Mallinckrodt Appeal Dated 06.02.20

USCA Case #20-5154 Document #1845229 Filed: 06/02/2020 Page 1 of 34
ORAL ARGUMENT NOT YET SCHEDULED

No. 20-5154
IN THE
United States Court of Appeals

for the District of Columbia Circuit
MALLINCKRODT ARD LLC,
Plaintiff-Appellant,
v.
SEEMA VERMA, in her official capacity as ADMINISTRATOR, CENTERS

FOR MEDICARE & MEDICAID SERVICES, and
ALEX M. AZAR II, in his official capacity as SECRETARY, UNITED STATES
DEPARTMENT OF HEALTH AND HUMAN SERVICES,
Defendants-Appellees,
On Appeal from the United States District Court

for the District of Columbia
No. 19-cv-1471, District Judge Thomas F. Hogan
EMERGENCY MOTION FOR INJUNCTION PENDING APPEAL

AND TO EXPEDITE BRIEFING AND ARGUMENT
CATHERINE E. STETSON
SUSAN M. COOK
KYLE M. DRUDING
HOGAN LOVELLS US LLP
555 Thirteenth Street, N.W.
Washington, D.C. 20004
(202) 637-5491
cate.stetson@hoganlovells.com
Counsel for Mallinckrodt ARD LLC

June 2, 2020
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CERTIFICATE OF PARTIES, RULINGS, AND RELATED CASES
Pursuant to Circuit Rule 28.1(a)(1), Mallinckrodt ARD LLC certifies that:
A. PARTIES
1. The following are parties in this Court:
a. Plaintiff-Appellant: Mallinckrodt ARD LLC
b. Defendant-Appellees: Seema Verma, in her official capacity as
Administrator, Centers for Medicare & Medicaid Services; and Alex M. Azar II, in
his official capacity as Secretary, United States Department of Health and Human
Services.
2. For purposes of Federal Rule of Appellate Procedure 26.1 and Circuit
Rule 26.1, Mallinckrodt ARD LLC states that it is a biopharmaceutical company.
Mallinckrodt ARD LLC is a wholly owned subsidiary of Mallinckrodt plc, a
publicly traded company.
B. RULINGS UNDER REVIEW
Mallinckrodt ARD LLC is appealing two rulings: The District Court’s
memorandum opinion and order granting the Government’s motion for summary
judgment and denying Mallinckrodt’s motion for summary judgment, Mallinckrodt
ARD LLC v. Verma, No. 19-CV-1471 (TFH), 2020 WL 1312716 (D.D.C. Mar. 13,
2020), Dkt. 36; and its memorandum opinion and order denying Mallinckrodt’s
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motion for reconsideration or, in the alternative, injunction pending appeal, entered
on May 29, 2020. Dkts. 46, 47.
C. RELATED CASES
Mallinckrodt ARD LLC is not aware of any related cases as that term is
defined in Circuit Rule 28(a)(1)(C).
/s/ Catherine E. Stetson

Catherine E. Stetson
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TABLE OF CONTENTS
Page
CERTIFICATE AS TO PARTIES, RULINGS, AND RELATED CASES ..........i
TABLE OF AUTHORITIES ...............................................................................v
GLOSSARY ........................................................................................................vii
INTRODUCTION ...............................................................................................1
BACKGROUND .................................................................................................4
Statutory and Regulatory Framework.............................................................4
Acthar’s Approval Under NDA 022432, And CMS’s Change In

Position.. ........................................................................................................6
Procedural History .........................................................................................8
ARGUMENT… ...................................................................................................9
I. MALLINCKRODT PRESENTS A SUBSTANTIAL

CHALLENGE TO THE DISTRICT COURT’S DECISION
AND IS LIKELY TO SUCCEED ON THE MERITS. .......................9
A. The District Court Ignored the Key Statutory

Definition of “Single Source Drug.” ...........................................9
B. The District Court Failed To Address The Argument

That CMS’s Determination Violates Its Regulations. ..................15
C. The District Court Overlooked CMS’s Inconsistent

Explanations For Its Position. .....................................................16
D. The District Court Shortchanged Core Fair-Notice

And Retroactivity Principles .......................................................18
II. MALLINCKRODT WILL SUFFER IRREPARABLE HARM

ABSENT PRELIMINARY INJUNCTIVE RELIEF. ..........................19
III. GRANTING PRELIMINARY INJUNCTIVE RELIEF

WOULD ADVANCE THE PUBLIC INTEREST. .............................22
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IV. DEFENDANTS WILL NOT BE SUBSTANTIALLY

HARMED BY INJUNCTIVE RELIEF. .............................................23
CONCLUSION ............................................................................................23
iv
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TABLE OF AUTHORITIES
Page(s)
Cases:
Christopher v. SmithKline Beecham Corp.,
567 U.S. 142 (2012) ......................................................................................... 18
General Elec. Co. v. EPA,

53 F.3d 1324 (D.C. Cir. 1995) ......................................................................... 18
Ipsen Biopharms., Inc. v. Azar,

943 F.3d 953 (D.C. Cir. 2019) ......................................................................... 11
National Med. Care, Inc. v. Shalala,

No. 95-0860 (WBB), 1995 WL 465650 (D.D.C. June 6, 1995) ........................ 23
Ramaprakash v. FAA,
346 F.3d 1121 (D.C. Cir. 2003) ....................................................................... 18
Retail, Wholesale and Dep’t Store Union, AFL-CIO v. NLRB,

466 F.2d 380 (D.C. Cir. 1972) ......................................................................... 18
Reuters Ltd. v. FCC,

781 F.2d 946 (D.C. Cir. 1986) ......................................................................... 15
Washington Metro. Area Transit Comm’n v. Holiday Tours, Inc.,

559 F.2d 841 (D.C. Cir. 1977) ...........................................................................9
Winter v. Natural Res. Def. Council, Inc.,

555 U.S. 7 (2008)...............................................................................................9
Wisconsin Gas Co. v. FERC,

758 F.2d 669 (D.C. Cir. 1985) ......................................................................... 19
Statutes:
21 U.S.C. § 331(d) ..................................................................................................4
21 U.S.C. § 355(a) ..................................................................................................4
21 U.S.C. § 355(b) ..................................................................................................4
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42 U.S.C. § 1396r-8(b) ..................................................................................... 4, 20
42 U.S.C. § 1396r-8(c) ............................................................................................5
42 U.S.C. § 1396r-8(c)(2)(A) ........................................................................... 5, 10
42 U.S.C. § 1396r-8(c)(2)(B) ......................................................................... 12, 13
42 U.S.C. § 1396r-8(d) ................................................................................... 20, 22
* 42 U.S.C. § 1396r-8(k)(7)(iv) ...................................................................... 5,10, 13
Other Authorities:
* 42 C.F.R. § 447.502..................................................................................... 5,10, 16
81 Fed. Reg. 5170-01, 5192 (Feb. 1, 2016) ....................................................... 5, 16
D.C. Cir. Practice & Internal Proc. R. VIII (B) ......................................................9
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GLOSSARY
AMP Average Manufacturer Price
ANDA Abbreviated New Drug Application
CMS Centers for Medicare & Medicaid Services
DDR Drug Data Reporting for Medicaid system
FDA U.S. Food and Drug Administration
IS Infantile Spasms
MDRP Medicaid Drug Rebate Program
NDA New Drug Application
NDC National Drug Code
NDRA National Drug Rebate Agreement
sNDA Supplemental New Drug Application
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INTRODUCTION
This appeal involves an old drug, a new approval, an agency flip-flop, and a
company on the edge of bankruptcy.
The District Court approved CMS’s directive that Mallinckrodt revise
certain pricing information in the Medicaid Drug Data Reporting system—despite
CMS having previously approved the data Mallinckrodt is reporting now. If
Mallinckrodt does not make those changes by June 14, CMS will “lock out”
Mallinckrodt from the system. If Mallinckrodt does make those changes, it will
trigger an obligation to pay hundreds of millions in retroactive Medicaid drug
rebates. Mallinckrodt accordingly requests an injunction preventing CMS from
“locking out” Mallinckrodt from its Drug Data Reporting system pending appeal.
Mallinckrodt produces Acthar® Gel (repository corticotropin) injection, a
costly drug for a rare and dangerous condition called Infantile Spasms. The
parties’ dispute has to do with the base date average manufacturer price (AMP) for
Acthar. Manufacturers who provide drug products to Medicaid patients pay
rebates to states based on a formula designed to capture the difference between the
base date AMP and the drug’s current AMP.
Acthar as a product has been around for decades, but its use to treat Infantile
Spasms was off-label until recently. About ten years ago, the then-owner of
Acthar, Questcor, sought and received FDA approval to treat Infantile Spasms
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pursuant to an application FDA classified as a New Drug Application. Following
FDA’s approval, Questcor sought and received CMS’s permission to begin
reporting a new base date AMP for the product.
Several years later, CMS equivocated. Without referencing the 2012
exchange between the agency and Questcor, CMS asked Mallinckrodt, by then
Acthar’s owner, to “review” the data then reported in the Drug Data Reporting
system and “make the necessary correction to ensure accurate information.” Over
the ensuing years, CMS offered various evolving statements on the issue, none of
them consistent and all of them refuted. Finally, in May 2019, CMS threatened
that if Mallinckrodt failed to adjust Acthar’s information in the drug reporting
system to reflect the pre-2012 base date AMP—triggering an increase in rebates
prospectively and retroactively—CMS would designate Mallinckrodt “out of
compliance.” That gave Mallinckrodt a Hobson’s choice: make $640 million (and
counting) in back payments to state Medicaid agencies or be suspended from the
Medicaid Drug Rebate Program.
Mallinckrodt sued for declaratory and injunctive relief, explaining that
CMS’s about-face violates the Administrative Procedure Act (APA) in multiple
respects. It is unmoored from the relevant statutory text. It contradicts the
agency’s own regulations. The agency’s failure to adequately explain its change in
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position is arbitrary and capricious. And its effort to impose its new policy
retroactively violates basic principles of fair notice and due process.
The District Court disagreed—but for a completely different reason than
anything CMS had offered in its defense. And when Mallinckrodt sought
reconsideration and pointed out the deficiencies in its new analysis, the District
Court largely doubled down, in an opinion that ran for 28 pages.
Because the District Court’s decision departs so sharply from the statute,
CMS’s regulatory practices, and this Court’s precedent, Mallinckrodt is likely to
prevail on the merits of this appeal. Mallinckrodt also will suffer irreparable injury
without an injunction. If it is forced to pay hundreds of millions of dollars in
retroactive rebates, the company will face an existential threat before it can be fully
heard out in this Court. And because the public interest and balance of equities
also weigh in favor of injunctive relief, an injunction pending appeal is warranted,
in the form of requiring CMS to temporarily refrain from locking Mallinckrodt out
of the Drug Data Reporting for Medicaid (DDR) system pending resolution of this
appeal. Mallinckrodt also requests a June 8, 2020 deadline for responding to this
emergency motion. Appellees do not consent to the proposed injunction; they have
consented to the proposed briefing schedule.
To ensure that the injunction lasts no longer than necessary while affording
Mallinckrodt meaningful judicial review, Mallinckrodt also requests expedited
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briefing and argument. Mallinckrodt proposes to file its opening brief on July 2;
that Appellees’ responsive brief be filed on August 7; and that Mallinckrodt file its
reply on August 21. Mallinckrodt further requests that argument be scheduled on
the earliest available date in the Fall. Appellees consent to this proposed schedule.
BACKGROUND
Statutory and Regulatory Framework
There are two separate agency processes in play here: FDA’s, and CMS’s.
FDA must approve all “new drugs.” 21 U.S.C. §§ 355(a), 331(d). A “new
drug” may be one that has never been approved, or it may be an approved product
with a change, like a new indication or a different strength. Approval for a “new
drug” may be sought through a New Drug Application, or NDA. See 21 U.S.C.
§ 355(b). FDA assigns each NDA a six-digit number.1 FDA also assigns each
NDA a Classification Code, categorizing them by “Type” depending on the nature
of the application. A392.
CMS administers the Medicaid statute. For a “covered outpatient drug” to
remain eligible for federal Medicaid payment, the drug’s manufacturer must
provide rebates to state Medicaid agencies based on each state’s Medicaid
beneficiaries’ utilization of the drug. See 42 U.S.C. § 1396r-8(b), (c). One such
1
See Drugs@FDA Glossary of Terms, available at
https://www.fda.gov/drugs/informationondrugs/ucm079436.htm.
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covered outpatient drug is known as a “single source drug,” defined as a “drug . . .
which is produced or distributed under a [NDA] approved by the [FDA].” Id.
§ 1396r-8(k)(7)(iv). The Medicaid rebate amount due for “each dosage form and
strength of a single source drug” is calculated based in part on the drug’s base date
AMP, a measure related to the drug’s price during a statutorily specified window
of time, adjusted by an inflation factor. See 42 U.S.C. § 1396r-8(c). Every “single
source drug” is entitled to its own base date AMP. Id. § 1396r-8(c)(2)(A).
In 2016, CMS finalized a rule explaining that a “single source drug” means:
[A] covered outpatient drug that is produced or distributed under an

original NDA approved by FDA and has an approved NDA number
issued by FDA . . . .
For purposes of this definition and the [Medicaid Drug Rebate

Program], an original NDA means an NDA, other than an ANDA,
approved by the FDA for marketing, unless CMS determines that a
narrow exception applies.2
42 C.F.R. § 447.502.
2
The statute previously defined “single source drug” as one produced or
distributed under an “original NDA.” 42 U.S.C. § 1396r-8(k)(7)(iv) (Nov. 5,
1990). The “narrow exception” does not apply to “drugs that received patent
protection or statutory exclusivity.” Medicaid Program; Covered Outpatient
Drugs, 81 Fed. Reg. 5170-01, 5192 (Feb. 1, 2016).
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Acthar’s Approval Under NDA 022432, And CMS’s Change In Position
FDA first approved H.P. Acthar Gel in 1952 under NDA 008372. A155,
A237, A242. It has been approved for use in treating numerous diseases over the
years. A270.
In 2006, Questcor sought to have Acthar approved by FDA for treating
Infantile Spasms (IS)—a rare seizure disorder that if left untreated can lead to
serious developmental and intellectual disabilities, and for which Acthar had
become the standard of care, even while off-label. Questcor filed its request as a
supplement to NDA 008372 (sNDA). A367. In 2008, FDA unilaterally converted
the sNDA to a distinct NDA. A287. FDA assigned the new NDA the number
022432 and classified it as “Type 6,” for products already approved or marketed
and intended for a new indication. 3
FDA approved NDA 022432 in October 2010, permitting Acthar to be
marketed and distributed for the treatment of IS. A361. FDA also granted Acthar
seven years of statutory “orphan drug” exclusivity effective upon approval of NDA
022432. A319.
Acthar is complex and expensive to produce; Questcor for years had lost
millions of dollars annually on the product. A295. In 2012, Questcor approached
3
Type 6 NDAs are obsolete; FDA now classifies similar NDAs as Type 9 or 10.
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CMS about establishing a new base date AMP for Acthar, to preserve its ability to
continue to manufacture this critical drug. CMS invited Questcor to present the
issue by letter, which Questcor did, offering two possible ways for CMS to
implement a new base date AMP. A295–296. CMS granted the request,
concluding that Acthar with the IS indication was a “single source drug” entitled to
a new base date AMP because it was “approved under” NDA 022432. A289; see
also A236 (reiterating same conclusion).
In reliance on CMS’s statements, Questcor reported Acthar’s new base date
AMP and began remitting rebates accordingly. Mallinckrodt continued that
practice when it acquired Questcor in 2014. But in April 2016, seemingly unaware
of the 2012 exchange between prior CMS officials and Questcor, CMS requested
that Mallinckrodt “review” Acthar’s data in the DDR “and make the necessary
correction to ensure accurate information is reported.” A232.
Over the ensuing years, Mallinckrodt made multiple attempts to seek
clarification of CMS’s request and to explain to CMS—in emails and letters, and
through an in-person meeting—that the agency’s 2012 decision was correct. CMS
offered a new and conflicting view each time, often separated by months of
silence. Ultimately, in May 2019, CMS informed Mallinckrodt that the company
would be declared “out of compliance” in the DDR unless it revised the base date
AMP for Acthar back to the original, pre-2012 base date AMP. A82.
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Procedural History
Mallinckrodt filed this lawsuit and sought a preliminary injunction to
prevent CMS from taking adverse action against the company. After a conference
and pursuant to representations made by CMS, the District Court ordered CMS to
refrain from locking Mallinckrodt out of the DDR pending a decision on the
merits. See June 7, 2019 Minute Order. The parties’ cross-motions for summary
judgment culminated in a hearing in early August 2019.
In March 2020, the District Court denied Mallinckrodt’s summary judgment
motion and granted CMS’s cross-motion. Despite the parties’ agreement that the
statutory and regulatory definitions of “single source drug” informed the inquiry,
the District Court deemed them irrelevant. A34. Instead it crafted its own test:
whether the drug is “an entirely new drug product.” A16, A31, A37–38, A40,
A42. That novel test infected the entire decision, resulting in the erroneous
conclusion that Acthar is not—and never was—entitled to a new base date AMP.
Mallinckrodt sought reconsideration, or in the alternative, injunctive relief
pending appeal, both of which were denied Friday, May 29. CMS agreed not to
lock Mallinckrodt out of the DDR until June 14, 2020 but has refused to extend
that agreement. Mallinckrodt seeks an injunction to maintain the status quo so the
company may pursue its appeal rights before facing bankruptcy.
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ARGUMENT
A motion for injunctive relief pending appeal is governed by the usual
factors: (1) likelihood of success on the merits, (2) irreparable harm, (3) whether
granting the requested relief would substantially harm other parties, and (4) the
public interest. Washington Metro. Area Transit Comm’n v. Holiday Tours, Inc.,
559 F.2d 841, 843 (D.C. Cir. 1977); see Winter v. Natural Res. Def. Council, Inc.,
555 U.S. 7 (2008). Each of these factors is met.
Mallinckrodt is also seeking expedited briefing and argument. That requires
showing that the decision under review “is subject to substantial challenge,” and
that the delay will cause irreparable injury. D.C. Cir. Practice & Internal Proc. R.
VIII (B). The Court may also expedite cases “in which the public generally” has
“an unusual interest in prompt disposition” and the reasons are “strongly
compelling.” Id. Each of these tests is met.
I. MALLINCKRODT PRESENTS A SUBSTANTIAL CHALLENGE TO

THE DISTRICT COURT’S DECISION AND IS LIKELY TO
SUCCEED ON THE MERITS.
A. The District Court Ignored the Key Statutory Definition of “Single

Source Drug.”
Following its approval by FDA under a separate NDA in 2010, Acthar
constituted a legally distinct “single source drug.” Because each single source
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drug is entitled to its own base date AMP, Acthar is eligible for a new base date
AMP. 42 U.S.C. § 1396r-8(c)(2)(A).
The District Court dismissed the statutory definition of “single source drug”
as irrelevant, claiming that Mallinckrodt had “misappropriate[d]” the definition to
support its analysis. See A34. That is wrong. The definition is the analysis.
Until 2019, the MDRP statute defined a “single source drug” to mean “a
covered outpatient drug . . . produced or distributed under an original [NDA]
approved by the [FDA].” 42 U.S.C. § 1396r-8(k)(7)(iv) (Nov. 5, 1990). That
section was recently updated—deleting the word “original”—to clarify that what
matters for purposes of qualifying as a “single source drug” is whether the drug is
approved under an NDA, unless an inapplicable “narrow exception” applies. 42
U.S.C. § 1396r-8(k)(7)(iv); 42 C.F.R. § 447.502. Acthar was approved under a
distinct NDA—NDA 022432. Thus, Acthar fits squarely within the statutory
definition of a “single source drug,” entitling it to a distinct base date AMP. 42
U.S.C. § 1396r-8(c)(2)(A).
CMS has always interpreted the Medicaid statute to require the base date
AMP to “follow the NDA of the product.” A372–373, A379–380. When CMS
approved Questcor’s request for a new base date AMP for Acthar in 2012, the
agency cited FDA’s approval of the drug under NDA 022432 and invoked
“Section 1927(c)(2)(A)”—aka 42 U.S.C. § 1396r-8(c)(2)(A)—as the basis for its
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approval of the new base date AMP. A289. CMS also noted: “[i]n accordance
with that provision, the base date AMP is calculated based on the new drug
application which is approved by the FDA.” Id. CMS has reiterated that position
in other litigation. See A344 (explaining that a pharmaceutical manufacturer “can
apply a different base-date [AMP] . . . only if it creates a new covered outpatient
drug by obtaining FDA approval of a separate NDA with a different six-digit NDA
number or if it changes the drug’s dosage form or strength”); Ipsen Biopharms.,
Inc. v. Azar, 943 F.3d 953, 955 (D.C. Cir. 2019) (noting CMS’s explanation that a
new base date AMP is not warranted following approval under a supplemental
NDA).
In its initial opinion, the District Court eschewed this straightforward
statutory analysis in favor of a different test: whether the drug is “an entirely new
drug.” A16, A31, A37–38, A40, A42. That standard has no basis in the statute.
Nor is it something that the agency has ever espoused. Indeed, CMS agrees that
the question whether a particular drug product is a “single source drug” is a critical
component of the inquiry here. See A289, Dkt. 20 at 17–19, 22–23. So the real
question under the governing statutory definition is whether FDA’s 2010 approval
of Acthar was of “an NDA.” It was.
This key error was compounded by related statutory missteps. For example,
the opinion points to a statutory provision tying a drug’s base date AMP “to the
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date when the FDA approved the drug and the drug was first marketed.” A35–36
(citing 42 U.S.C. § 1396r-8(c)(2)(B)). But the relevant question is whether a
change to a drug product entitles it to a new base date AMP. The provision the
opinion cites has to do with the time period during which the base date AMP is
calculated.
When Mallinckrodt sought reconsideration of the District Court’s decision,
the District Court tweaked its new test to focus on whether the drug product itself
was “new,” in the sense that it had never previously been “approved or marketed.”
A55–56 & n.2, A70. Rather than presume that Congress “says in a statute what it
means and means in a statute what it says there,” Barnhart v. Sigmon Coal Co.,
534 U.S. 438, 461–462 (2002), the District Court rejected what it called a “hyper-
literal interpretation of the definition of ‘single source drug’ ” in the governing
statute. A67. Citing an 1876 Supreme Court case, the District Court instead
offered a purposivist interpretation based on that term’s “ ‘implied’ ” meaning,
given the statute’s “legislative purpose” of “provid[ing] medical assistance to poor
people.” A71–72 (quoting Bd. of Sup’rs of Wood Cty. v. Lackawana Iron & Coal
Co., 93 U.S. 619, 624 (1876)). But the days when courts would “restrain the
words” of statutes based on notions of Congress’s unrevealed purposes are long
gone. Cf. Holy Trinity Church v. United States, 143 U.S. 457, 460 (1892).
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The court also observed that Congress “omitted the phrase ‘single source
drug’ from § 1396r-8(c)(2)(B), and instead, elected to use a different phrase—
‘covered outpatient drug.’” A70–71. But Subsection (c)(2)(B) merely modifies
language in Subsection (c)(2)(A), which expressly does apply to a “single source
drug.” In any event, the two terms are the same as applied to Acthar. “Single
source drugs” are a subset of “covered outpatient drugs.” 42 U.S.C. § 1396r-
8(k)(7)(A)(iv).
Acthar is thus a legally distinct “covered outpatient drug” from its
predecessor under the Medicaid statute. The definition of “single source drug”
matters, as the agency itself has long acknowledged. The drug product itself need
not somehow change physically to count as a separate covered outpatient drug or
to qualify for a new base date AMP.
Nor did the agency assert otherwise in the record. The District Court
suggests that CMS must have “assum[ed]” that, because Acthar was approved
under a different NDA, “that meant that Acthar with the [IS] indication must be a
different ‘product’ from the ‘original product.’ ” A37 (citing A289). From this the
court concluded that “[t]he only possible takeaway” from CMS’s 2012 letter “was
that CMS believed that Acthar with the [IS] indication was an entirely new drug
product.” Id.
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CMS never made this argument. For good reason. CMS knows its
governing statutes. And it always knew what Acthar was and was not: It was a
decades-old drug, approved for a new indication under a distinct NDA. See, e.g.,
A224, A291, A293, A296; A303–306, A308, A311. Questcor was clear with CMS
that NDA 022432 covered two changes: (i) approval of the IS indication and
(ii) new labeling. See A224, A289. When it sought permission for a new base date
AMP, Questcor specifically informed CMS:
Acthar was initially approved for multiple indications in 1952, under

NDA 08-372, and then in 1978, an NDA supplement was approved for
the use of Acthar to treat multiple sclerosis exacerbations. On October
15, 2010, Acthar was approved to treat infantile spasms under NDA 22-
432.
A224. Questcor never suggested that Acthar had a different formulation than the
previously approved product or was in any other way an “entirely new drug.”
The opinion also speculates that CMS must have assumed that Acthar was
an “entirely new drug product” because it had told Questcor that the agency
“ ‘does not have the current ability to allow a manufacturer to replace the original
reported base date AMP with a new base date AMP midway through the life of a
product.’ ” A37. But that statement has nothing to do with whether the agency
had the statutory authority to change the base date AMP for a drug product. It
relates to CMS’s rejection of Questcor’s proposal that the drug product be allowed
to retain the same National Drug Code (NDC) after the new base date AMP was
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implemented; there is no administrative mechanism for the DDR to assign two
different base date AMPs to the same NDC. CMS had to admit as much in
briefing on reconsideration. Dkt. 40 at 13.
CMS’s letter approving Acthar’s new base date AMP cannot be read as
secretly endorsing a previously unknown requirement that a drug product must be
an “entirely new drug product” to obtain a new base date AMP. Instead, that letter
reinforces the statutory interpretation long applied by the agency: what matters is
whether the drug is a separate “single source drug” because it was approved under
a separate NDA. A289, A236. That is why CMS cited “Section 1927(c)(2)(A)” as
the basis for its decision and said that “the base date AMP is calculated based on
the [NDA] which is approved by the FDA.” A289. The letter reflects the agency’s
acknowledgement that if a drug product is a distinct “single source drug,” it is
entitled to its own base date AMP—whether or not it is an “entirely new drug.”
B. The District Court Failed To Address The Argument That CMS’s

Determination Violates Its Regulations.
CMS’s determination also cannot be squared with its own regulations. “A
precept which lies at the foundation of the modern administrative state is that
agencies must abide by their rules and regulations.” Reuters Ltd. v. FCC, 781 F.2d
946, 947 (D.C. Cir. 1986).
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CMS has bound itself to the position that a drug product produced or
distributed under “an NDA, other than an ANDA” is eligible for its own base date
AMP, unless a “narrow exception” applies. See 42 C.F.R. § 447.502. Acthar
qualifies under these parameters: FDA approved Acthar for IS under “an NDA,”
and Acthar received statutory exclusivity upon approval of NDA 22432, rendering
the “narrow exception” inapplicable, see 81 Fed. Reg. at 5191.
CMS’s current position clashes with these regulations. But because the
District Court discarded the importance of the statutory phrase “single source
drug” to the base date AMP analysis, it also gave too short shrift to CMS’s own
regulations. See A42 n.23. The inescapable conclusion is that CMS ignored its
own regulations in forcing Mallinckrodt to restate Acthar’s base date AMP.
C. The District Court Overlooked CMS’s Inconsistent Explanations For Its

Position.
In 2012, CMS twice “agree[d] that Acthar is eligible for a new base date
AMP” because it was “approved under a new NDA.” A289, A236. Questcor (and
then Mallinckrodt) relied on that pronouncement by allowing Acthar to remain in
the Medicaid drug rebate program. The agency now asserts that Acthar is not
eligible for a new base date AMP, even though it was indisputably “approved
under a new NDA.” See A161. Mallinckrodt has repeatedly asked CMS to
16
(Page 24 of Total)
explain its abrupt change of position, and CMS has repeatedly offered baseless and
inconsistent justifications.
First, CMS cited the fact that the wrong NDA number briefly appeared in
the (self-reported) On-Line Label Repository. A231. That was corrected. Then
CMS maintained that Acthar was a “purchased product” under the terms of an
inapplicable guidance document. A213. Mallinckrodt explained that was wrong.
Then CMS admitted that Acthar had been approved under NDA 022432 but noted
that that NDA was “administratively closed upon approval” such that “marketing
of the drug” was under NDA 008372. A161. Mallinckrodt questioned this
explanation, given the agency’s 2012 position. Then CMS shifted again and
asserted that Acthar is currently being “produced or distributed” under NDA
008372. A93. Shortly thereafter, the agency asserted that its “final decision” had
actually been rendered three years earlier. A91.
The District Court acknowledged this series of shifting explanations. And
yet it concluded that “from the very outset CMS made clear that it was approving a
new base date AMP for Acthar because the agency believed that NDA number
022432 involved the FDA’s approval of a new drug product.” A43.
That conclusion is not supported by the record in the least. And the
assertion that CMS consistently “directed” Mallinckrodt to revise its base date
AMP, A43–45, does not mean that CMS consistently explained itself. See
17
(Page 25 of Total)
Ramaprakash v. FAA, 346 F.3d 1121, 1124–25 (D.C. Cir. 2003). An agency can
make the same baseless demand over and over, but repetition doesn’t make it legal.
D. The District Court Shortchanged Core Fair-Notice And Retroactivity

Principles.
CMS’s effort to punish Mallinckrodt retroactively for relying in good faith
on the agency’s prior representations violates principles of fair notice and due
process. CMS has worked a quintessential “unfair surprise” by first pronouncing
Acthar eligible for a new base date AMP and then, years later, reversing course
and demanding retroactive rebate adjustments. See Christopher v. SmithKline
Beecham Corp., 567 U.S. 142, 156 (2012). That is not fair notice. See General
Elec. Co. v. EPA, 53 F.3d 1324, 1334 (D.C. Cir. 1995).
The balance of factors announced in Retail Wholesale & Dep’t Store Union
v. NLRB, 466 F. 2d 380, 390 (D.C. Cir. 1972), strongly tilts towards denying
retroactive force to CMS’s new position. This is not a matter of first impression;
the agency twice considered this issue in 2012. Mallinckrodt and its predecessor
relied on CMS’s prior position. Retroactive enforcement of CMS’s new position
will impose an enormous burden. And CMS has no legitimate interest in applying
this new rule retroactively.
The District Court concluded that because the statute was purportedly clear
that only an “entirely new drug” qualifies for a base date AMP, Mallinckrodt had
18
(Page 26 of Total)
fair notice of the “correct” standard all along. A47. But the District Court’s new
statutory interpretation would never have been knowable to a regulated entity
before that opinion—not during the 2012–2016 time period, when the agency was
expressly applying the statutory definition of “single source drug” and focusing on
whether the drug product was marketed under an “original NDA,” A289, and not
even as of August 2017, when CMS stated in Ipsen that a drug product is entitled
to a new base date AMP when it is re-approved under an NDA. A344–345.
II. MALLINCKRODT WILL SUFFER IRREPARABLE HARM

ABSENT INJUNCTIVE RELIEF.
Mallinckrodt was in a fragile financial position even before the District
Court’s judgment. It is worse off now. This is that rare case where the looming—
and effectively non-recoverable—economic consequence of the District Court’s
judgment “threatens the very existence of the movant’s business.” Wisconsin Gas
Co. v. FERC, 758 F.2d 669, 674 (D.C. Cir. 1985).
Mallinckrodt has two paths forward following the District Court’s judgment:
It can decline to adjust the pricing data for Acthar in CMS’s reporting system and
be booted from the Medicaid program; or it can adjust the data, triggering an
obligation to pay hundreds of millions of dollars in rebates to the states. Both
choices carry grave consequences.
If Mallinckrodt fails to adjust Acthar’s base date AMP, it will be declared
“out of compliance,” meaning it will not be able to adjust drug pricing data for
19
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Acthar in the DDR system, and will face civil monetary penalties. 42 U.S.C.
§ 1396r-8(b)(3)(C)(i). Mallinckrodt’s National Drug Rebate Agreement (NDRA)
also will be suspended for at least thirty days until it reports the adjusted data. Id.
Suspension means states will no longer be generally required to cover Acthar. See
42 U.S.C. § 1396r-8(d). The financial harm to the company will be significant,
and will be compounded by irremediable harm to Mallinckrodt’s reputation and
market standing as a result of being publicly deemed “out of compliance.”
Reasons Declaration ¶¶ 3–4.
The second path—adjusting Acthar’s base date AMP—triggers a $640
million liability owed to state Medicaid agencies. Id. ¶ 4. Simply put:
Mallinckrodt cannot afford that.
The District Court’s judgment risks unwinding a $1.6 billion settlement in
principle Mallinckrodt reached in the opioid litigation, necessitating re-negotiation
with Mallinckrodt in a weakened position. Id. ¶ 9. Before the District Court’s
judgment, Mallinckrodt also had negotiated favorable loan terms to fund
approximately $615 million in debt payments due April 15. Id. ¶¶ 7–8. But after
re-negotiations necessitated by the judgment, Mallinckrodt was able to refinance
only a portion of the debt on less favorable terms, forcing Mallinckrodt to pay out
the remainder—worth approximately $120 million. Id. ¶ 8. That further hinders
Mallinckrodt’s ability to absorb the approximately $640 million in payments that
20
(Page 28 of Total)
will become due absent injunctive relief. Id. ¶ 12. Mallinckrodt will have no
option but to take drastic and painful measures, up to and including the prospect of
bankruptcy. Id. ¶¶ 3, 14.
And even if Mallinckrodt is vindicated on appeal, it will be too little too late.
Mallinckrodt could theoretically try to recoup rebate overpayments by offsetting
those amounts against future Acthar rebate payments. But CMS policy specifies
that manufacturers should offset no more than 25% of an amount owed to them by
a state Medicaid agency against a rebate amount due to that agency. CMS,
Manufacturer Release No. 80 (Jan. 5, 2010), at 2. Since Mallinckrodt pays
approximately $70-80 million in Medicaid rebates on Acthar annually, Reasons
Declaration ¶ 15, recouping Mallinckrodt’s $640 million would take approximately
32 years. The Government has hinted that states might be willing to return larger
sums to Mallinckrodt because the agency’s guidance is a “suggestion.” Dkt. 40 at
7–9. But why would any state agree to give back money faster than CMS
“suggest[s]”?
CMS also suggests that Mallinckrodt may not need to disperse all $640
million right away. But that ignores the reality that absent a stay, the entire
liability will go on Mallinckrodt’s books immediately, and Mallinckrodt’s net
liabilities will balloon overnight. Meanwhile, Mallinckrodt’s new liabilities to
state Medicaid agencies will exceed the company’s free cash flow over the course
21
(Page 29 of Total)
of an entire year, unless the company institutes severe structural and operational
changes. Reasons Declaration ¶¶ 11, 13.
At bottom, Mallinckrodt has been navigating a thin financial tightrope, and
absent injunctive relief the company could fail. The District Court’s decision will
push the company to the edge, and when the company accounts for other economic
factors the path forward is dark. Injunctive relief is needed to ensure that
Mallinckrodt does not suffer this debilitating harm before it can pursue its appeal.
III. GRANTING INJUNCTIVE RELIEF WOULD ADVANCE THE

PUBLIC INTEREST.
The country is currently battling an unprecedented public health crisis. If
Mallinckrodt no longer participates in the Medicaid program, Medicaid patients—
among the nation’s most vulnerable citizens—may lose critical access to necessary
drugs. See 42 U.S.C. § 1396r-8(d); Dkt. No. 4-1 at 37. Even temporary
interruption of access to Acthar could exacerbate certain autoimmune disorders,
like lupus, Dkt. No. 37-1 at 17–18, putting immune-compromised patients at a
higher risk of serious illness. See Joshua D. Rabinowitz & Caroline R. Bartman,
These Coronavirus Exposures Might Be the Most Dangerous, N.Y. Times (Apr. 1,
2020), https://tinyurl.com/tjadr9j. Patients will also suffer if Mallinckrodt instead
is forced into bankruptcy. Mallinckrodt is working to investigate whether an
22
(Page 30 of Total)
existing drug product can treat severe lung dysfunction caused by COVID-19.4 If
all of Mallinckrodt’s free cash flow is devoted to Acthar Medicaid payments, it
would put such research and development activities at risk.
IV. DEFENDANTS WILL NOT BE SUBSTANTIALLY HARMED BY

INJUNCTIVE RELIEF.
The balance of the equities also favors injunctive relief. Granting this
motion would preserve the status quo pending appellate review. The Government
does not face harm from that; CMS “will only have implemented its retroactive
policies . . . at a later date.” See National Med. Care, Inc. v. Shalala, No. 95-0860
(WBB), 1995 WL 465650, at *4 (D.D.C. June 6, 1995). CMS retains all the tools
necessary to recover any amount owed if it succeeds on appeal.
CONCLUSION
For these reasons, Mallinckrodt’s motion should be granted. This Court
should bar CMS from designating Mallinckrodt “out of compliance” in DDR or
suspending Mallinckrodt’s participation in the Medicaid Drug Rebate Program
with respect to Acthar’s base date AMP during the pendency of this appeal and set
this appeal for expedited briefing and argument.
4
Available at https://tinyurl.com/mnkcovid19. For an L.A. Times story on the
promise of nitric oxide as a potential remedy, see
https://www.latimes.com/science/story/2020-04-05/viagra-discovery-could-treat-
coronavirus-patients.
23
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Respectfully submitted,

Susan M. Cook
Kyle M. Druding
555 Thirteenth Street, NW
Phone: (202) 637-5491
Fax: (202) 637-5910
Dated: June 2, 2020
24
(Page 32 of Total)
CERTIFICATE OF COMPLIANCE
1. This document complies with the type-volume limits of Fed. R. App. P.
27(d)(2) because, excluding the parts of the document exempted by Fed. R. App.
P. 32(f), this document contains 5,164 words.
2. This document complies with the typeface requirements of Fed. R. App.
P. 32(a)(5) and the type-style requirements of Fed. R. App. P. 32(a)(6) because this
document has been prepared in a proportionally spaced typeface using Microsoft
Word 2010 in 14-point Times New Roman.

(Page 33 of Total)
CERTIFICATE OF SERVICE
I certify that on June 2, 2020, the foregoing was electronically filed through
this Court’s CM/ECF system, which will send a notice of filing to all registered
users.
I further certify that the foregoing was served by email on:
Joshua M. Salzman
Attorney, Civil Appellate Staff
U.S Department of Justice
950 Pennsylvania Ave., NW
Washington, DC 20530
Joshua.M.Salzman@usdoj.gov
Counsel for Defendants-Appellees

(Page 34 of Total)
IN THE UNITED STATES COURT OF APPEALS

FOR THE DISTRICT OF COLUMBIA
)
MALLINCKRODT ARD LLC, )
)
Plaintiff, )
)
v. ) No. 20-5154
)
SEEMA VERMA, )
in her official capacity as )
ADMINISTRATOR, CENTERS FOR )
MEDICARE & MEDICAID SERVICES, )
)
and )
)
ALEX M. AZAR II, )
in his official capacity as SECRETARY, )
UNITED STATES DEPARTMENT OF )
HEALTH AND HUMAN SERVICES, )
)
Defendants. )
)
DECLARATION OF BRYAN REASONS

IN SUPPORT OF PLAINTIFF’S EMERGENCY MOTION
FOR INJUNCTION PENDING APPEAL
(Page 35 of Total)
I, Bryan Reasons, declare as follow:
1. I am the Executive Vice President and Chief Financial Officer of
Mallinckrodt plc, the parent company of Mallinckrodt ARD LLC. In that role, I
am responsible for overseeing Mallinckrodt’s finances, including tracking cash
flow, analyzing the company’s financial status, and planning for significant
financial events. I have personal knowledge of the matters stated in this
declaration and would testify truthfully to them if called upon to do so.
2. Based on my knowledge and experience, I am familiar with the harm
that Mallinckrodt will suffer as a result of the recent decision by the Centers for
Medicare & Medicaid Services (CMS) to declare Mallinckrodt “out of
compliance” in the Drug Data Reporting for Medicaid (DDR) system based on the
dispute over the base date average manufacturer price (AMP) for Acthar® Gel
(repository corticotropin) injection (Acthar).
3. Absent injunctive relief, Mallinckrodt will suffer immediate
irreparable harm, and will likely face bankruptcy. CMS’s agreement to voluntarily
refrain from declaring Mallinckrodt “out of compliance” expires on June 14, 2020.
Ninety days after the next reporting period (or on approximately October 28,
2020), Mallinckrodt will automatically be suspended from the Medicaid Drug
Rebate Program (MDRP). Suspension from the MDRP will mean no federal
Medicaid payment for Acthar, and no general Medicaid utilization coverage for the
(Page 36 of Total)
drug product. That not only will cause significant (and unrecoverable) monetary
losses and reputational damage for Mallinckrodt, it also could jeopardize the
ability of Medicaid patients with a critical medical need to access Acthar. That
makes this option untenable for Mallinckrodt.
4. The only way that Mallinckrodt could avoid suspension from the
MDRP would be to revise Acthar’s base date AMP in the DDR. But doing so
would mean that the company would become immediately liable for roughly $640
million in retroactive increased charges to State Medicaid programs, as calculated
at the time of the district court decision in this case. Either option—suspension
from the MDRP or acceding to nearly $640 million in rebates to State Medicaid
programs—would be financially untenable for Mallinckrodt, particularly given its
present economic circumstances. If left to stand, the district court’s decision leaves
Mallinckrodt in certain peril.
6. Mallinckrodt faces a number of pressing financial uncertainties. First,
Mallinckrodt is involved in the major opioid litigation that has swept up a number
of pharmaceutical companies nationwide, in which it faces the potential for billions
of dollars in damages. Second, Mallinckrodt is struggling to juggle more than $5
billion in debt, which comes due in tranches over the next five years. Third,
Mallinckrodt is the defendant in the early stages of a False Claims Act case—
presenting more than $1 billion in potential liabilities—filed in the District of
(Page 37 of Total)
Massachusetts stemming from the very same base date AMP dispute that is
presently before this Court. And the company faces significant risk and
uncertainty from this litigation itself.
7. Before the district court’s decision in this case, Mallinckrodt had
made significant progress in resolving two of those financial uncertainties—the
opioid litigation and the company’s debt load. Mallinckrodt reached an agreement
in principle in the opioid litigation in February of this year, where the company,
among other things, would pay a total of $1.6 billion structured over eight years,
with $300 million due upon execution of the settlement—as early as next year.
The company had also reached favorable terms on an $800 million loan to fund its
approximately $615 million in debt payments due April 15, 2020, while also
strengthening the company’s liquidity.
8. But the district court’s judgment has had a severe and immediate
negative impact on both of these plans. Already the district court’s judgment has
required Mallinckrodt to re-negotiate financing on its near-term debts on far less
favorable terms. Indeed, Mallinckrodt was able to refinance only a portion of the
debt due in 2020, and it had to do so on significantly less favorable terms than
originally negotiated—including a higher-than-market 10% interest rate.
Moreover, the company was forced to use $120 million in cash in April to pay out
the portion of the debt it could no longer refinance. So, after the district court’s
(Page 38 of Total)
decision, Mallinckrodt’s favorable loan to pay down the company’s debt and
strengthen its liquidity was replaced by a loan with unfavorable terms that was
insufficient to cover Mallinckrodt’s debts and required the company to draw down
its cash reserves.
9. The district court’s judgment also risks unwinding Mallinckrodt’s
settlement in principle in the opioid litigation, which has the agreement of 48 state
and territory Attorneys General and plaintiffs’ counsel representing approximately
2,000 counties and cities. The settlement in principle between Mallinckrodt and
the opioid plaintiffs contains a litigation contingency for renegotiation in the event
of a decision just like this, allowing CMS to impose significant retroactive rebate
liability. Based on the company’s financial projections, and in the face of nearly
$640 million of retroactive rebates, the company will have no choice but to seek
that renegotiation. As such, as a result of the district court’s decision, Mallinckrodt
will need to return to the negotiating table in a severely weakened position—at risk
of unraveling the entire agreement in principle.
10. All of this is compounded by the global pandemic and worldwide
economic crisis, both of which have materially affected the company’s sales.
Because of the pandemic, there are fewer elective procedures, patients are unable
or unwilling to visit physicians, and the company’s sales force is unable to access
hospital or physician offices. Mallinckrodt has already begun to take significant
(Page 39 of Total)
actions affecting the company’s operations, including reducing expenses, delaying
R&D investments and implementing a reduction in force.
11. Unless the district court’s decision is enjoined pending appeal,
Mallinckrodt faces approximately $640 million in retroactive increased State
Medicaid rebates, even before this Court decides the case. In the absence of an
injunction pending appeal, that amount will go on Mallinckrodt’s books
immediately, and the company believes that states may issue invoices for those
retroactive rebates as early as August or September of this year. Moreover, there is
no established process known to the company to delay payments without risking
suspension of the company’s participation in the Medicaid program. The company
does not have the cash on hand to satisfy that liability and the other liabilities and
debt the Company must manage in the coming months and years; indeed, $640
million exceeds the company’s projected free cash flow over the course of the
entire year.
12. Coming up with the cash necessary to pay that liability is made even
harder due to Mallinckrodt’s inability to adequately re-finance its near term debt
earlier this year, resulting in the necessity to use $120 million in cash to pay for the
portion of its debt that it could not refinance. Worse still, the prospective change
to the Medicaid rebate calculation triggered by the change to Acthar’s base date
AMP will reduce Acthar’s net sales by roughly $90 to 100 million per annum,
(Page 40 of Total)
based on historical data. All of this is in the context of unexpectedly reduced sales
in 2020, resulting from the global pandemic and ensuing economic effects.
13. In summary, Mallinckrodt faces a perfect financial storm: The
company already must juggle more than $5 billion in debt over the next five years.
And significant additional liabilities loom. This case presents the prospect of
nearly $640 million in immediate additional rebate liability. Relatively soon,
Mallinckrodt will need to pay $300 million in cash to the plaintiffs in the opioid
litigation—assuming the settlement in principle can be renegotiated successfully—
with $1.3 billion in additional liabilities structured over the next eight years. And
Mallinckrodt faces more than $1 billion in potential liabilities from the pending
False Claims Act case. Satisfying the liabilities from this case alone will consume
Mallinckrodt’s projected free cash flow for the year, and the company has already
had to expend $120 million in cash to discharge debt it could not successfully
refinance due in part to the district court’s decision. Meanwhile, the company is
facing reduced sales because of the global pandemic, and it risks an additional $90
to $100 million loss in future sales if it revises Acthar’s base date AMP. Simply
put, Mallinckrodt has significant liabilities that are only growing while its ability to
satisfy those liabilities is being hindered.
14. If CMS is not enjoined from acting on the district court’s judgment
until conclusion of this appeal, Mallinckrodt faces the likelihood of bankruptcy,
(Page 41 of Total)
which would be the only option left to the company to attempt to stem what would
otherwise be an unmanageable call on cash.
15. Even if Mallinckrodt were to avoid bankruptcy long enough to win its
appeal, it would be too little too late. Under CMS policy, it could take decades for
Mallinckrodt to recover the disputed $640 million from State Medicaid agencies.
That policy specifies that manufacturers should offset no more than 25% of an
amount owed to them by a State Medicaid agency against a rebate amount due
invoiced to them by that State Medicaid agency. Mallinckrodt pays approximately
$70-80 million in rebates to Medicaid on Acthar annually. At that rate, recovering
$640 million will take more than 30 years.
16. Without injunctive relief, Mallinckrodt faces an existential crisis that
could lead to the demise of the company before it has the opportunity to exercise
its appellate rights. Injunctive relief is necessary to maintain the status quo so that
Mallinckrodt can be heard on the merits of its appeal.
I declare under penalty of perjury under the laws of the United States of America
that the foregoing is true and correct.
Executed this 1st day of June, 2020
Bryan Reasons
(Page 42 of Total)
ORAL ARGUMENT NOT YET SCHEDULED

No. 20-5154
IN THE
United States Court of Appeals
for the District of Columbia Circuit

Plaintiff-Appellant,
v.
SEEMA VERMA, in her official capacity as ADMINISTRATOR, CENTERS

FOR MEDICARE & MEDICAID SERVICES, and
ALEX M. AZAR II, in his official capacity as SECRETARY, UNITED STATES
DEPARTMENT OF HEALTH AND HUMAN SERVICES,
Defendants-Appellees,
On Appeal from the United States District Court

for the District of Columbia,
No. 19-cv-1471, District Judge Thomas F. Hogan
APPENDIX OF PERTINENT RECORD MATERIALS FOR APPELLANT

MALINCKRODT ARD LLC’S EMERGENCY MOTION FOR
INJUNCTION PENDING APPEAL AND TO EXPEDITE BRIEFING AND
ARUGMENT
CATHERINE E. STETSON
SUSAN M. COOK
KYLE M. DRUDING
555 Thirteenth Street, N.W.
(202) 637-5491

June 2, 2020
(Page 43 of Total)
TABLE OF CONTENTS
Page
Memorandum Opinion on Mallinkcrodt ARD LLC’s Motion for

Preliminary Injunction and Cross-Motion for Summary Judgment
(March 13, 2020), Dkt. No. 35 ........................................................................ A1
Order Denying Mallinkcrodt ARD LLC’s Motion for Preliminary

Injunction and Cross-Motion for Summary Judgment
(March 13, 2020), Dkt. No. 36 ...................................................................... A50
Memorandum Opinion on Mallinkcrodt ARD LLC’s Emergency

Motion for Reconsideration and Stay of Entry of Judgment
Pending Reconsideration or, Alternatively, Injunction Pending
Appeal (May 29, 2020), Dkt. No. 46 ............................................................. A52
Order Denying Mallinkcrodt ARD LLC’s Emergency Motion for

Reconsideration and Stay of Entry of Judgment Pending
Reconsideration or, Alternatively, Injunction Pending Appeal
(May 29, 2020), Dkt. No. 47 ......................................................................... A80
Email from John M. Coster, Director, Division of Pharm. Ctr. for

Medicaid & CHIP Servs., CMS, to Kathleen A. Schaefer, Sr. Vice
President and Corporate Controller, Mallinckrodt Pharm.
(May 10, 2019), AR 1–3 .............................................................................. A81
Email from Arathi Almli, Attorney, HHS Office of General Counsel,

to Mark Casey, General Counsel, Mallinckrodt Pharm.
(Apr. 29, 2019), AR 4–5 .............................................................................. A84
Email from Mark Casey, General Counsel, Mallinckrodt Pharm., to

Arathi Almli, Attorney, HHS Office of General Counsel,
(Apr. 25, 2019), AR 6 ................................................................................... A86
Email from Arathi Almli, Attorney, HHS Office of General Counsel,

to Mark Casey, General Counsel, Mallinckrodt Pharm.
(Apr. 24, 2019), AR 7 .................................................................................. A87
i
(Page 44 of Total)
Email from Mark Casey, General Counsel, Mallinckrodt Pharm., to

Christopher Traylor, Deputy Admin. and Director, Ctr. for
Medicaid & CHIP Servs., CMS
(Apr. 12, 2019), AR 8–10 ............................................................................. A88
Email from Robert Charrow, General Counsel, HHS, to Mark Casey,

General Counsel, Mallinckrodt Pharm.
(Mar. 27, 2019), AR 11 ................................................................................ A91
Email from CMS Rx Drug Policy (04) to Kathleen A. Schaefer,

Sr. Vice President and Corporate Controller, Mallinckrodt Pharm.
(Mar. 12, 2019), AR 12–14 .......................................................................... A92
Email from Alice Valder Curran, Partner, Hogan Lovells US LLP, to

John M. Coster, Director, Division of Pharm. Ctr. for Medicaid &
CHIP Servs., CMS
(Mar. 11, 2019), AR 15–16 .......................................................................... A95

John M. Coster, Director, Division of Pharm. Ctr. for Medicaid &
CHIP Servs., CMS
(Mar. 6, 2019), AR 17–42 ............................................................................ A97

Ruth Blatt, Pharmacist and Health Insurance Specialist, CMS
(Feb. 27, 2019), AR 43–89 ......................................................................... A123
CMS In-Person Meeting Request from Mallinckrodt Pharm.

(Dec. 4, 2018), AR 90–91 .......................................................................... A170
Email from Ruth Blatt, Pharmacist and Health Insurance Specialist,

CMS, to William Sarraille, Partner, Sidley Austin LLP
(Nov. 30, 2018), AR 92–95 ........................................................................ A172
Email from Diane Bass, Director of Govt. Reporting, Mallinckrodt

Pharm., to John M. Coster, Director, Division of Pharm. Ctr. for
Medicaid & CHIP Servs., CMS
(Nov. 12, 2018), AR 96–104 ....................................................................... A176
ii
(Page 45 of Total)
Email from CMS Rx Drug Policy (04) to Diane Bass, Director of

Govt. Reporting, Mallinckrodt Pharm.
(Nov. 6, 2018), AR 105–108 ....................................................................... A185
Email from CMS Rx Drug Policy (04) to Diane Bass, Director of

Govt. Reporting, Mallinckrodt Pharm.
(Nov. 6, 2018), AR 109–113 ....................................................................... A189
Email from Kay Forshée, Sr. Manager Govt. Reporting, Mallinckrodt

Pharm., to CMS MDROperations
(Apr. 14, 2017), AR 114–118 ..................................................................... A194
Email from Deborah G. Weston, Policy Analyst, Health Sys. Division,

State of Oregon, to CMS MDROperations
(Feb. 8, 2017), AR 119–132 ........................................................................ A199
Email from CMS MDROperations to Kay Forshée, Sr. Manager Govt.

Reporting, Mallinckrodt Pharm.
(June 2, 2016), AR 133–138 ....................................................................... A213
Email from Kay Forshée, Sr. Manager Govt. Reporting, Mallinckrodt

Pharm., to CMS MDROperations
(May 10, 2016), AR 139–149 ..................................................................... A219
Email from CMS MDROperations to Kay Forshée, Sr. Manager Govt.

Reporting, Mallinckrodt Pharm.
(Apr. 13, 2016), AR 150–153 ..................................................................... A230
Email from Susan B. Daugherty, Project Manager, Division of

Neurology, FDA/CDER/OND, to John M. Coster, Director,
Division of Pharm. Ctr. for Medicaid & CHIP Servs., CMS
(Nov. 25, 2015), AR 157–158 .................................................................... A234
Letter from Cindy Mann, Director, Ctr. for Medicaid and CHIP Servs.,
CMS, to Michael Mulroy, Sr. Vice President, CFO, and General
Counsel, Questcor Pharm., Inc.
(Sept. 19, 2012), AR 169 ............................................................................ A236
iii
(Page 46 of Total)
Email from Diane Schulman, Analyst, Indigao Group, to CMS

MDROperations, and Selected Attachments (Sept. 6, 2012),
AR 170–173, 314–330, 343–357, 360–373, 609–610 ................................. A237
Letter from Cindy Mann, Deputy Administrator, Ctr. for Medicaid

and CHIP Servs., CMS, to Michael Mulroy, Sr. Vice President,
CFO, and General Counsel, Questcor Pharm., Inc.
(Aug. 6, 2012), AR 617–618 ...................................................................... A289
Letter from Michael Mulroy, Sr. Vice President, CFO, and General
Counsel, Questcor Pharm., Inc., to Cindy Mann, Deputy
Administrator, Ctr. for Medicaid and CHIP Servs., CMS
(May 8, 2012), AR 619–625 ...................................................................... A291
Questcor PowerPoint Presentation “Medicaid Rebates for

H.P. Acthar® Gel” (Mar. 29, 2012), AR 626–646 ..................................... A298
Letter from Gayatri R. Rao, Acting Director, Office of Orphan

Products Development, FDA, to Sian Bigora, Vice President
Regulatory Affairs, Questcor Pharm., Inc.
(Nov. 17, 2011), AR 691–693 ..................................................................... A319
Memo. in Support of Defs.’ Cross-Motion for Summary Judgment

and Opp. to Pls.’ Mot. for Summary Judgment, Ipsen Biopharm.,
Inc. v. Price, No. 1:16-cv-2372-ABJ, ECF No. 16-1
(D.D.C. Aug. 14, 2017), Dkt. 37-1 .............................................................. A322
NDA 022432 Approval Letter from Russell Katz, Director, Division

of Neurology Products, CDER, to Sian Bigora, Vice President
Regulatory Affairs, Questcor Pharm., Inc.
(Oct. 15, 2010), AR 307–313 ...................................................................... A360
FDA Form 3542a: Patent Information Submitted with the Filing of an

NDA Amendment, or Supplement for H.P. Acthar® Gel
(June 6, 2006), AR 542–545 ....................................................................... A367
CMS, Medicaid Drug Rebate Program Release for Participating

Manufacturers No. 26
(Feb. 27, 1997), AR 928–935 ...................................................................... A371
iv
(Page 47 of Total)
CMS, Medicaid Drug Rebate Program Release for Participating

Manufacturers No. 48
(Nov. 15, 2000), AR 917–921 ..................................................................... A379
CDER, MAPP 5018.2: NDA Classification Manual

(Nov. 4, 2015), AR 936–945 ....................................................................... A384
Certificate of Service
v
(Page 48 of Total)
UNITED STATES DISTRICT COURT

Plaintiff,
Civil Action No. 19-cv-1471 (TFH)
v.
UNDER SEAL
SEEMA VERMA, et al.,
Defendants.
MEMORANDUM OPINION
Plaintiff Mallinckrodt ARD LLC filed this lawsuit challenging the Centers for Medicare
& Medicaid Services’ (CMS’s) conclusion that Mallinckrodt is using the wrong base date
Average Manufacturer Price (AMP) to calculate federally mandated rebates it must pay for the
H.P. Acthar Gel® pharmaceutical drug under the statutory Medicaid Drug Rebate Program.
Defendants Seema Verma, Administrator of CMS, and Alex M. Azar II, Secretary of the United
States Department of Health and Human Services (HHS), counter by alleging that Mallinckrodt
has been underpaying the required rebates and depriving Medicaid of hundreds of millions of
dollars since 2013.
Pending before the Court are the following three motions: (1) Mallinckrodt’s Motion for
Preliminary Injunction, ECF No. 4; (2) Government’s Motion for Summary Judgment, ECF No.
17; and (3) Mallinckrodt’s Cross Motion for Summary Judgment, ECF No. 22. Because there
are no material facts in dispute and CMS lawfully determined that the Medicaid Drug Rebate
Program statute requires that Acthar’s base date AMP be calculated based on the date the drug
was approved by the United States Food and Drug Administration (FDA) under New Drug
(Page 49 of Total) A1
Application (NDA) number 008372, the Court will deny Mallinckrodt’s motions and grant the
defendants’ motion.
STATUTORY AND REGULATORY STRUCTURE
Mallinckrodt ARD LLC is a pharmaceutical company that markets and sells a drug called
H.P. Acthar Gel® (Acthar), which is an adrenocorticotropic hormone (ACTH) analogue derived
from pigs’ pituitary glands. Administrative Record (“A.R.”) 28, 182. Mallinckrodt acquired
Acthar in 2014 when it purchased the drug’s prior manufacturer, Questcor Pharmaceuticals.
A.R. 54. Many of the relevant events in this case occurred while Questcor reigned as Acthar’s
manufacturer before merging with Mallinckrodt. At issue is whether CMS lawfully determined
that Questcor and Mallinckrodt have been miscalculating Acthar’s Medicaid rebates since 2013.
Resolving this issue implicates two federal statutes that are administered by operating
divisions of HHS. The first statute is the Federal Food, Drug, and Cosmetic Act, ch. 675, 52
Stat. 1040 (codified as amended at 21 U.S.C. § 301 et seq.), which governs drug applications and
is administered by the United States Food and Drug Administration (FDA). 1 The second statute
is Title XIX of the Social Security Act, 79 Stat. 343 (codified as amended at 42 U.S.C. §§ 1396–
1396v), which is commonly known as the “Medicaid Act.” The Medicaid Act establishes the
Medicaid Drug Rebate Program and specifies how drug rebates must be calculated. See 42
U.S.C. § 1396r-8. The Medicaid Act and Medicaid Drug Rebate Program are administered by
CMS. See Moore ex rel. Moore v. Reese, 637 F.3d 1220, 1235 (11th Cir. 2011) (stating that
1
Many documents in the Administrative Record contain acronyms. For ease, and to avoid
taxing the reader’s memory about what a particular acronym means, the Court will avoid using
all but the most readily recognized acronyms, such as CMS, HHS, FDA, and NDA. The first
time the Court mentions a phrase that is referred to in the record by acronym, however, the
associated acronym will be identified for cross reference even though that acronym might not be
used again in this opinion.
CMS “is charged with administering the Medicaid Act”). Because it is important to understand
the process to obtain FDA approval for new drugs, and labeling changes to add new indications
for previously approved drugs, as well as how the Medicaid Drug Rebate Program works, the
Court will begin with a brief discussion of both the Federal Food, Drug, and Cosmetic Act and
the Medicaid Act before proceeding to discuss the facts and the Court’s analysis of the legal
issues.
I. THE FEDERAL FOOD, DRUG, AND COSMETIC ACT AND ITS

IMPLEMENTING REGULATIONS
Section 505 of the Federal Food, Drug, and Cosmetic Act requires companies to apply for
FDA approval before marketing a “new drug” commercially. 21 U.S.C. § 355(a); accord United
States v. Rutherford, 442 U.S. 544, 551 (1979) (“By its terms, § 505 of the Act requires
premarketing approval for ‘any new drug’ unless it is intended solely for investigative use or is
exempt under one of the Act’s grandfather provisions.”). The Act defines “new drug” in relevant
part to mean “[a]ny drug . . . the composition of which is such that such drug is not generally
recognized, among experts qualified by scientific training and experience to evaluate the safety
and effectiveness of drugs, as safe and effective for use under the conditions prescribed,
recommended, or suggested in the labeling thereof.” 21 U.S.C. § 321(p).
A drug manufacturer may apply to the FDA for approval to market a new drug after the
manufacturer obtains sufficient evidence about the drug’s safety and effectiveness to satisfy the
FDA’s requirements. See New Drug Application (NDA), Drugs@FDA Glossary of Terms,
https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-terms. The
application for a new drug is subject to certain conditions and procedures outlined in the Federal
Food, Drug, and Cosmetic Act and the regulations that implement that Act. See 21 U.S.C.
§ 355(b); 21 C.F.R. §§ 314.50–314.99.
Although there are three types of drug marketing applications, the only one that is
relevant here is the type generically titled “New Drug Application” and referred to by the
acronym “NDA.” 2 The Federal Food, Drug, and Cosmetic Act’s regulations define the terms
“new drug application, or NDA” to mean in relevant part “the application described under [21
C.F.R.] § 314.50, including all amendments and supplements to the application.” 21 C.F.R.
§ 314.3(b). 21 C.F.R. § 314.50, in turn, is the federal regulation that sets forth the required
contents and format for NDAs and their supplements. 21 C.F.R. § 314.50 (stating that “NDAs
and supplements to approved NDAs are required to be submitted in the form and contain the
information, as appropriate for the particular submission, required under this section”). As
indicated, the statute and regulation contemplate that an NDA includes later amendments or
supplements rather than treating amendments or supplements as independent NDAs. 21 U.S.C.
§ 355(b); 21 C.F.R. § 314.50.
As will become clear, much of the dispute in this case revolves around numbers the FDA
assigns to NDAs and their supplements. When manufacturers like Mallinckrodt and Questcor
submit an NDA the FDA assigns the application a six-digit number. See New Drug Application
(NDA) Number, Drugs@FDA Glossary of Terms, https://www.fda.gov/ drugs/drug-approvals-
and-databases/drugsfda- glossary-terms (defining “New Drug Application Number” to mean a
“six digit number . . . assigned by FDA staff to each application for approval to market a new
drug in the United States”). “A drug can have more than one application number if it has
2
The other two types of applications are Abbreviated New Drug Applications (ANDAs), which
are governed by § 505(j) of the Federal Food, Drug, and Cosmetic Act and its implementing
regulations, and Biologic License Applications (BLAs), which are governed by § 351 of the
Public Health Service Act (PHSA), 42 U.S.C. § 262(a), and its implementing regulations.
different dosage forms or routes of administration.” Id. The FDA assigns NDA numbers “[f]or
internal tracking purposes.” Id.
When a company seeks to “make changes” to a drug “that already has an approved new
drug application (NDA)” the company may do so by submitting a “supplement” application to
the FDA’s Center for Drug Evaluation and Research (CDER). Supplement, Drugs@FDA
Glossary of Terms, https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-
terms. The Center for Drug Evaluation and Research “must approve all important NDA changes
(in packaging or ingredients, for instance) to ensure the conditions originally set for the product
are still met.” 3 Id.
Important to this case, when a drug manufacturer seeks to add a new indication 4 for a
drug that has an existing FDA-approved NDA and number, the Federal Food, Drug, and
Cosmetic Act’s implementing regulations contemplate that the request will be presented as an
“efficacy supplement,” which is defined to mean, in relevant part, a “supplement to an approved
NDA proposing to . . . [a]dd or modify an indication or claim.” 21 C.F.R. § 314.3(b). A
“supplement” is assigned a “supplement number” that is “associated with an existing FDA New
Drug Application (NDA) number.” Supplement Number, Drugs@FDA Glossary of Terms,
https://www.fda.gov/ drugs/drug-approvals-and-databases/drugsfda-glossary-terms. The
supplement number “is usually, but not always, sequential, starting with 001.” Id.
3
The FDA’s Center for Drug Evaluation and Research has numerous offices and divisions,
including the Division of Metabolism and Endocrinology Products (DMEP) and the Division of
Neurology Products (DNP). CDER Offices and Divisions, U.S. Food and Drug Administration,
https://www.fda.gov/about-fda/center-drug-evaluation-and-research/cder-offices-and-divisions.
4
An “indication” identifies “what the drug is used for.” Label, Drugs@FDA Glossary of Terms,
https://www.fda.gov/drugs/ drug-approvals-and-databases/ drugsfda-glossary-terms.
In addition to the Federal Food, Drug, and Cosmetic Act and its implementing
regulations, the FDA circulates additional guidance about matters related to NDAs in the form of
various agency manuals for industry. One such document is the Guidance for Industry
Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User
Fees (“Guidance for Industry”). A.R. 898–907. As the FDA explains in the Guidance for
Industry, “[b]ecause different user fees are assessed for original applications and supplements,
FDA believes it is useful to provide guidance to applicants on the Agency’s interpretation of
what constitutes a separate original application, amendment, or supplement.” A.R. 902.
Notably, the Guidance for Industry instructs drug manufacturer’s that changes to an approved
drug to add a new indication “should be submitted individually in a separate supplement to an
approved original application.” A.R. 906 (emphasis added).
Another example of an FDA document that provides guidance about NDAs is the Center
for Drug Evaluation and Research’s Manual of Policy and Procedures (MAPP). A.R. 936–45.
That manual “describes the new drug application (NDA) classification code assigned by the
Center for Drug Evaluation and Research (CDER) to an NDA based on characteristics of the
product in the application.” A.R. 936. The classification code is different from the NDA
number, see A.R. 937 – 42 (identifying the various current and obsolete codes), and “provides a
way of categorizing new drug applications . . . including their relationships to products already
approved or marketed in the United States,” A.R. 936. The Manual of Policy and Procedures
states that it is the FDA’s policy to “tentatively assign[] an NDA classification code by the filing
date for a new application and reassess[] the code at the time of approval.” A.R. 936. “The
reassessment will be based upon relationships of the drug product being approved to products
already approved or marketed in the United States at the time of approval.” A.R. 936–37. “FDA
may also reassess the code after approval.” A.R. 937.
The version of the Manual of Policy and Procedures that was submitted as part of the
Administrative Record in this case identifies the NDA classification codes to be Type 1 through
Type 10. A.R. 937–42. The only NDA classification code that is relevant here is Type 6, which
the Manual explains is now obsolete but was used through July 2009 “for a drug product that
duplicates a drug product already approved or marketed in the United States by the same
applicant, except that it is intended for a new indication or claim (same active moiety or
combination of active moieties, same salt(s), ester(s), or other noncovalent derivative(s), same
dosage form, and same formulation (including all ingredients used in the manufacturing process
whether or not they are present in the final dosage form)).” A.R. 940 & n.5 (noting that “July 27,
2009 is the date of implementation of the Document Archiving, Reporting and Regulatory
Tracking System (DARRTS), which made Type 6 obsolete” (emphasis in original)).
II. THE MEDICAID ACT AND THE MEDICAID DRUG REBATE PROGRAM
After the FDA approves a new drug under the Federal Food, Drug, and Cosmetic Act, the
drug’s manufacturer (also referred to as the drug’s “labeler”) may seek to have the drug covered
by Medicaid through the Medicaid Drug Rebate Program. See Medicaid National Drug Rebate
Agreement, CMS, https://www.medicaid.gov/ medicaid/prescription-drugs/medicaid-drug-
rebate-program/national-drug-rebate-agreement/index.html (discussing the requirements and
process to request a Medicaid National Drug Rebate agreement). “Medicaid, as everyone knows,
is a cooperative state-federal program designed to provide medical assistance to poor people.”
Indiana Family & Soc. Servs. Admin. v. Thompson, 286 F.3d 476, 477 (7th Cir. 2002). It was
established in 1965 when Congress amended the Social Security Act by adding Title XIX.
Pharm. Research & Mfrs. of Am. v. Walsh, 538 U.S. 644, 650 (2003). Each state establishes its
own Medicaid plan but plans that are approved by the federal government are eligible to receive
federal matching funds. Indiana Family & Soc. Servs. Admin., 286 F.3d at 477.
The Medicaid Drug Rebate Program—which, as already explained, is administered by
CMS—is set forth in the Medicaid Act and serves to offset federal and state agencies’ costs for
covered outpatient drugs prescribed to Medicaid patients. 42 U.S.C. § 1396r-8(b); see Verified
Compl. ¶ 16, ECF No. 1 (averring that drug manufacturers are required to “pay greater rebate
amounts where price increases outpace the rate of inflation”). To participate in the Medicaid
Drug Rebate Program a drug must be a “covered outpatient drug” as defined in the Medicaid Act
and its manufacturer must have a rebate agreement with the Secretary of HHS. 42 U.S.C. §§
1396r-8(a)(1), (k)(2)–k(4). Rebate agreements afford Medicaid coverage for qualifying drugs
but mandate that the drug’s manufacturer provide a rebate to participating states to reduce the
costs of dispensed outpatient drugs that a state expends under its Medicaid plan. 42 U.S.C. §
1396r-8(b)(1)(B).
The Medicaid Act mandates how drug manufacturers must calculate the amount of rebate
for “each dosage form and strength of a single source drug” under the Medicaid Drug Rebate
Program. 42 U.S.C. § 1396r-8(c)(1)(A). A “single source drug” is defined in relevant part to
mean a drug that is “produced or distributed under a new drug application approved by the Food
and Drug Administration.” 42 U.S.C. § 1396r-8(k)(7)(A)(iv). The Medicaid Act’s
implementing regulations state more particularly that a “single source drug means a covered
outpatient drug that is produced or distributed under an original NDA approved by FDA and has
an approved NDA number issued by FDA.” 42 C.F.R. § 447.502. The regulations further state
that “[f]or purposes of this definition and the MDR program, an original NDA means an NDA,
other than an ANDA, approved by the FDA for marketing, unless CMS determines that a narrow
exception applies.” 5 Id.
The Medicaid Act and its implementing regulations do not define “new drug application”
or “NDA.” As already discussed, however, the Food, Drug, and Cosmetic Act’s implementing
regulations define those terms to mean “the application described under § 314.50” including “all
supplements to the application.” 21 C.F.R. § 314.3(b). Accordingly, to summarize, a drug
manufacturer must calculate the required rebate for each dosage form and strength of a covered
outpatient drug that is being produced or distributed under an FDA-approved new drug
application, as described in 21 U.S.C. § 314.50, including all supplements.
The calculated rebate amount for single source drugs is referred to as a “unit rebate
amount (URA)” and consists of a basic rebate plus an additional rebate. 42 U.S.C. §§ 1396r-
8(c)(1), (c)(2). The basic rebate amount equals the number of a drug’s units the state paid for
under its Medicaid plan multiplied by the greater of (1) the AMP minus the best price for the
drug or (2) a statutorily set minimum rebate percentage of the drug’s AMP. 42 U.S.C. § 1396r-
8(c)(1). The additional rebate is the amount, if any, that the drug’s AMP for a particular quarter
exceeded the so-called “base date AMP,” which is a covered outpatient drug’s AMP for the third
quarter of 1990 if the drug was FDA-approved on or before October 1, 1990, or the AMP for the
5
In a response to comments accompanying CMS’s issuance of a final rule implementing
provisions of the Patient Protection and Affordable Care Act of 2010, as amended by the Health
Care and Education Reconciliation Act of 2010 (collectively the “Affordable Care Act”), the
agency stated that the narrow exception involves circumstances in which “for the purposes of the
Medicaid Drug Rebate (MDR) program, certain drugs might be more appropriately treated as if
they were approved under an ANDA and classified as a noninnovator multiple source drug.”
Medicaid Program; Covered Outpatient Drugs, 81 Fed. Reg. 5,170, 5,191 (Feb. 1, 2016) (to be
codified at 42 C.F.R. § 447).
9
first full quarter of sales if the drug was FDA-approved after that date, either of which is adjusted
by an inflation factor. 42 U.S.C. § 1396r-8(c)(2).
As the plaintiff concedes, “the base date AMP is generally used to calculate Medicaid
rebates for the entire life of the relevant drug product.” Verified Compl. ¶ 1.
BACKGROUND
I. H.P. ACTHAR GEL’S FDA APPROVAL UNDER ORIGINAL NDA NUMBER

008372 AND EFFICACY SUPPLEMENT APPROVAL UNDER NOW DEFUNCT
NDA NUMBER 022432
A. In 1952, the FDA Approved H.P. Acthar Gel to be Marketed as a New Drug
Under NDA Number 008372
Approximately 70 years ago, H.P. Acthar Gel’s original manufacturer applied to the FDA
for approval to market the drug commercially in the United States. A.R. 51. 6 The FDA assigned
the application a six-digit NDA number, which was 008372. A.R. 51. At that time—unlike
today—”drug manufacturers only had to show the drug was safe for use in humans” without
proving the drug’s efficacy. 7 A.R. 509.
In 1952, the FDA approved NDA number 008372, which allowed Acthar’s manufacturer
to market the drug to treat about 50 indications. 8 A.R. 29, 183, 355, 859. Infantile spasms (IS)
was not one of the approved indications. A.R. 183. By 1958, however, Acthar was regarded as a
6
Indicating that Acthar was approved in 1952, in which case the application was filed no later
than that year.
7
See United States v. Sage Pharm., Inc., 210 F.3d 475, 478 (5th Cir. 2000) (stating that, “[i]n
1962, the [Federal Food, Drug, and Cosmetic Act] was amended to require NDAs to show that a
drug is not only safe, but also effective for its intended uses”).
8
According to the FDA, a “label is the official description of a drug product [that] includes
indication (what the drug is used for); who should take it; adverse events (side effects);
instructions for uses in pregnancy, children, and other populations; and safety information for the
patient.”
10

successful off-label treatment for the disease. A.R. 29. Indeed, over time, Acthar became the
premier treatment for infantile spasms. A.R. 29, 344, 735.
Over the course of several decades, Acthar’s NDA number 008372 was the subject of
numerous supplement applications to make labeling and other changes, including expanding
Acthar’s label indications to add the treatment of multiple sclerosis. See A.R. 52 (indicating that
Acthar was never assigned a different NDA number until 2008), 723–26 (identifying supplement
applications), 859 (stating that Acthar’s label was expanded in 1972 to include multiple
sclerosis). The drug’s use to treat infantile spasms, however, continued to be off label. See A.R.
754 (noting “the continued off-label use of Acthar Gel” for infantile spasm treatment through
2010).
B. In 2006, Questcor Unsuccessfully Submitted an Efficacy Supplement to Add

Infantile Spasms to Acthar’s Label Indications
By 2003, Questcor owned Acthar and sought FDA approval to have the drug designated
an “orphan drug” to treat infantile spasms. 9 A.R. 710 (referring to Questcor’s February 24, 2003
request). The Office of Orphan Products Development granted the requested orphan drug
designation via a letter dated May 21, 2003. A.R. 710–11. The letter stated, however, that final
approval to market Acthar as an orphan drug would be reserved until Questcor secured FDA
approval to market Acthar to treat infantile spasms. A.R. 710.
Three years later, Questcor submitted an application to the FDA seeking approval to
market Acthar as an infantile spasm treatment by adding that indication to the drug’s existing
9
An “orphan drug” is a drug “intended for the safe and effective treatment, diagnosis or
prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that
affect more than 200,000 persons but are not expected to recover the costs of developing and
marketing a treatment drug.” Office of Orphan Products Development, U.S. Food and Drug
Administration, https://www.fda.gov/about-fda/office-special-medical-programs/office-orphan-
products-development.
11

label. A.R. 65 (stating that “[t]his supplemental application proposes to add the treatment of
infantile spasms to reduce or eliminate spasms and the hypsarrhythmic electroencephalogram
pattern to the indications and usage section of the package insert for H.P. Acthar® Gel”)
(formatting omitted), 577 (stating that Acthar’s label would be expanded by “adding the
indication of infantile spasms”), 856. A.R. 65. The application was dated June 16, 2006 and
was submitted to the FDA’s Division of Metabolism and Endocrinology Products. A.R. 65, 856.
Questcor’s application was presented as an “efficacy supplement” to NDA number 008372.
A.R. 188, 694, 735, 891. The FDA assigned the application Supplement Number S-039. A.R.
694, 735, 891.
On May 10, 2007, the FDA’s Division of Metabolism and Endocrinology Products
rejected Questcor’s application by issuing a “Not Approvable” letter that cited “numerous
deficiencies, including the lack of a bridge between this specific product and the products used in
the various published studies.” A.R. 344; accord A.R. 65–67, 856. Significantly, the Not-
Approvable letter stated that the Division of Metabolism and Endocrinology Products had
conferred with epilepsy subject-matter experts at the agency’s Division of Neurology Products
and determined that the Division of Neurology Products “should have regulatory and scientific
oversight” of Questcor’s application. A.R. 66.
C. In 2009, Questcor Resubmitted the Efficacy Supplement Application and the

FDA Assigned it an NDA Number for Administrative Tracking and to
Facilitate the FDA Division of Neurology Products’ Review
After the Not-Approvable letter notified Questcor that the Division of Neurology
Products should be handling the efficacy supplement application, Questcor began conferring
with that division about how to resubmit the application to secure FDA approval. See A.R. 189,
344, 875, 869. Questcor ultimately resubmitted the application on December 10, 2009. A.R.
869.
12

The Division of Neurology Products viewed Questcor’s resubmission to be a “response”
to the FDA’s May 10, 2007 Not-Approvable letter and “redesignated” it as a “Type 6 NDA” for
that division’s review. A.R. 344, 856–57, 869. A contemporaneous file memorandum that
discussed changing the resubmission’s regulatory classification noted that a “Type 6 NDA” was
“an efficacy supplement that is designated . . . as a new NDA and assigned a new NDA number
for administrative purposes (e.g., to facilitate the review of a supplement for an indication for
which the scientific expertise lies in a division different from the parent division for the original
application).” A.R. 857 n.* (emphasis added). And a later email from the FDA to a CMS
official confirmed that the agency “created Type-6 NDAs when an efficacy supplement was
submitted for an indication to be reviewed by [a] Division other than the Division responsible for
the parent (original) NDA to ensure that all of the documents submitted for review in support of
a new indication would be sent to the appropriate Division.” A.R. 157. The FDA explained that
“[i]n the case of Acthar Gel, the parent NDA (008372) and all of its supplements were reviewed
by the Division of Metabolic and Endocrine Products and review of the infantile spasms
indication was conducted by the Division of Neurology Products.” A.R. 157.
Mallinckrodt agrees that “[t]he agency took this action because it concluded the IS
[infantile spasm] indication was fundamentally different from the other uses for which the
product had been approved, and required review by a different component within FDA than had
to date been responsible for the drug.” Verified Compl. ¶ 30. Mallinckrodt also does not dispute
that the Type 6 designation “was used for drug products that had already been approved or
marketed by the same applicant, but were intended for a new indication or claim.” Verified
Compl. ¶ 30 (emphasis added).
13

The FDA assigned an administrative tracking number—NDA number 022432—to the
resubmission. A.R. 708.
D. In 2010, The FDA Approved Questcor’s Efficacy Supplement Application to

Add Infantile Spasms to Acthar’s Label and Directed Questcor to Stop Using
NDA Number 022432 in Favor of Acthar’s Original NDA Number 008372
In 2010, the FDA approved Questcor’s efficacy supplement application to add infantile
spasms to Acthar’s label indications. A.R. 702–707. Importantly, the FDA’s letter made clear
that the agency was phasing out its use of NDA number 022432, as demonstrated by the FDA’s
instructions to Questcor to address all submissions “to the original NDA 008372 for this drug
product” and to stop using NDA number 022432, A.R. 706 (stating “[i]n the future, do not make
submissions to this NDA [022432] except for the final printed labeling”). The FDA’s letter also
required Questcor to submit a risk evaluation and mitigation strategy (REMS) and directed the
company to identify the submission as an “NDA 008372 REMS Assessment,” “New Supplement
for NDA 008372,” and “New Supplement (New Indication for Use) for NDA 008372.” A.R.
705 (formatting omitted).
In early 2011, Questcor submitted the required final printed labeling under NDA
number 022432 and then submitted an application—referred to as a “Changes Being Effected
Labeling Supplement”—to revise the labeling for NDA number 008372. A.R. 700. Questcor
explained that it was requesting the labeling revision to NDA number 008372 “[i]n order for the
approval of the indication for the Treatment of Infantile Spasms to be associated with the parent
NDA number, 08-372, since the tracking NDA number [022432] will no longer be used.” A.R.
694 (emphasis added). The application further identified “tracking NDA 22,432” as a
“Supplemental NDA for Treatment of Infantile Spasms” and “efficacy supplement.” A.R. 700.
The FDA approved the labeling revision nearly four years later on March 24, 2015 and, once
again, reiterated that “the tracking NDA number 022432 will no longer be used.” A.R. 688.
14

II. QUESTCOR SEEKS TO RESET THE BASE DATE AMP FOR ACTHAR
About three months after the FDA first rejected Questcor’s initial efficacy supplement in
2007, Questcor raised Acthar’s price from $1,650 to $23,269 per vial. A.R. 144, 636. Despite
this price hike, however, Questcor grew antsy several years later about what it perceived to be
the drug’s curtailed profitability under the Medicaid Drug Rebate Program, as demonstrated by a
letter Questcor’s General Counsel 10 sent to CMS on May 8, 2012. See A.R. 141, 145.
Questcor’s letter sought to reset Acthar’s base date AMP—and thereby lower the
company’s Medicaid rebate liability—based on what Questcor characterized as the “significant
revisions to the Acthar label” that were required by the FDA’s 2010 approval to add infantile
spasms as an indication. A.R. 141–149. Questcor contended that Acthar’s rebate liability was
greater than its Medicaid revenue and, as a result, the company was losing money by
participating in the Medicaid Drug Rebate Program. A.R. 145. Questcor went on to insinuate
that Acthar’s ongoing participation in the program might be “untenable,” A.R. 142, if its rebate
liability was not reduced, A.R. 145. Questcor therefore proposed setting a new base date AMP
to decrease Acthar’s rebate liability, 11 A.R. 141, and “thereby ensure Questcor’s continued
participation in and payment of rebates under the MDRP [Medicaid Drug Rebate Program],”
A.R. 146.
10
Questcor’s General Counsel at that time also served as a Senior Vice President and Corporate
Secretary. A.R. 147.
11
Questcor’s letter seeking a new base date AMP went on to suggest that Questcor’s exit from
the Medicaid Drug Rebate Program was not “in the interest of CMS, as we believe state
Medicaid programs likely still will be required to cover Acthar’s use for infantile spasms even if
Questcor does exit the program.” A.R. 142. According to Questcor, the Early and Periodic
Screening, Diagnostic and Treatment (EPSDT) benefit would provide Medicaid coverage “for
children who need Acthar even if Questcor withdrew” from the Medicaid Drug Rebate Program.
A.R. 142 n.3.
15

Questcor, through its General Counsel, offered two alternative approaches to implement a
new base date AMP and keep Questcor in the Medicaid Drug Rebate Program. A.R. 141–142.
Questcor’s “preferred” approach was “for CMS to permit the Company to establish a new base
date AMP for the current Acthar NDC-9 [National Drug Code] 12 for use on a prospective basis
upon the issuance of the Covered Outpatient Drug final rule,” which Questcor noted was a
proposed rule that would allow manufacturers to reset the base date AMP for existing drugs
“using the revised definition of AMP included in the Patient Protection and Affordable Care Act
of 2010 (‘ACA’).” A.R. 141–42 (emphasis in original). The second approach would require
Questcor to obtain a new National Drug Code based on the “major label revision” required in the
FDA’s 2010 approval to add infantile spasms as an indication. A.R. 142. Upon receiving the
new National Drug Code, Questcor would then “calculate and report a new base date AMP for
the product in accordance with MDRP [Medicaid Drug Rebate Program] standards.” A.R. 142.
Although Questcor’s letter portrayed the FDA approval to add infantile spasms to
Acthar’s label as a “major label revision,” A.R. 142, and a “significant revision . . . in the
conditions under which [Acthar] will be marketed and distributed,” A.R. 144, at no point did
Questcor suggest that Acthar with the infantile spasm indication was an entirely new drug that
qualified for a new base date AMP based on the FDA’s assignment of NDA number 022432 to
12
The FDA’s National Drug Code Directory website explains that “[d]rug products are identified
and reported using a unique, three-segment number, called the National Drug Code (NDC),
which serves as a universal product identifier for drugs. FDA publishes the listed NDC numbers
and the information submitted as part of the listing information in the NDC Directory[,] which is
updated daily.” Nat’l Drug Code Directory, U.S. Food & Drug Admin., https://www.fda.gov/
drugs/drug-approvals-and-databases/national-drug-code-directory (last visited July 30, 2019).
The National Drug Code consists of digits that identify the labeler, product, and package size and
type. See 21 C.F.R. § 207.33(a). The FDA assigns the labeler code. 21 C.F.R.
§ 207.33(b)(1)(i). The drug manufacturer proposes the product and packaging codes. 21 C.F.R.
§ 207.33(d).
16

the supplement application approved in 2010. To the contrary, Questcor expressly stated that it
was “the FDA’s recent expansion and revision of the Acthar label” that “provide Questcor and
CMS with the ability to reset the Acthar base date AMP going forward.” 13 A.R. 146.
On August 6, 2012, CMS responded to Questcor’s request to set a new base date AMP
for Acthar. A.R. 148. CMS granted the request but jettisoned Questcor’s two proposed
approaches. A.R. 148. Instead, CMS indicated that it was granting the request because Acthar
with the infantile spasm indication was a new drug product that the FDA had approved under a
different NDA “from the original product”:
As noted in your letter, the Food and Drug Administration (FDA) recently approved
Acthar Gel for use in treating infantile spasms. It is your position in light of FDA’s
approval that Acthar is eligible for a new base[] date AMP.
We have reviewed your request and agree that Acthar Gel is eligible for a new base
date AMP. Section 1927(c)(2)(A) defines the base date AMP, in part, for each
single source or innovator multiple source drug approved by the FDA before or
after October 1, 1990. In accordance with that provision, the base date AMP is
calculated based on the new drug application which is approved by the FDA, not
the national drug code (NDC). Therefore, given that the recently approved Acthar
Gel was approved under a different [NDA 14] from the original product, Questcor
may set a new base date AMP for this drug.
...
For the purpose of the Medicaid Drug Rebate Program we believe the assignment
of a new NDC-9 to the recently approved Acthar Gel would be necessary. We
13
Indeed, Questcor’s outside counsel contacted officials at CMS in January 2012 to request a
meeting to discuss whether Acthar was entitled to a new base date AMP in light of the fact that it
“recently received FDA approval for a revised label for its product H.P. Acthar Gel . . . .” A.R.
648 (emphasis added). And Questcor’s letter requesting to change Acthar’s base date AMP
contained a footnote stating that “Questcor believes that the FDA’s changes to the Acthar label,
including the addition of the infantile spasms indication, qualify the drug for a new product code
or NDC-9.” A.R. 77 n.10 (emphasis added).
14
CMS’s response inadvertently referred to a National Drug Code (NDC) rather than New Drug
Application (NDA), see A.R. 148, but that error was later corrected in a letter dated September
19, 2012, which stated that “we would like to correct our earlier reply to note that because
Acthar was approved under a new NDA, Questcor may set a new base date AMP,” A.R. 169.
17

understand Questcor’s concerns regarding how this option might create some
confusion; however, the Centers for Medicare & Medicaid Services (CMS) does
not have the current capability to allow a manufacturer to replace the original
reported base date AMP with a new base date AMP midway through the life of a
product.
A.R. 617 (emphases added). Accordingly, CMS authorized Questcor to set a new base date
AMP for Acthar based on the now defunct NDA number 022432, but directed Questcor to secure
a new National Drug Code for the drug. A.R. 148–49. At that time, Acthar’s National Drug
Code was 63004-7731-01. See A.R. 151 (identifying the “original NDC 63004-7731-01”).
Questcor obtained a new National Drug Code for Acthar in 2013, which was 63004-8710-01.
A.R. 30, 54, 137.
III. CMS DISCOVERS THAT NDA NUMBER 002432 WAS RENDERED OBSOLETE
UPON APPROVAL AND THE LABEL REVISION AUTHORIZING QUESTCOR
TO MARKET ACTHAR FOR INFANTILE SPASMS WAS CONSOLIDATED
UNDER NDA NUMBER 008372
Over the next several years, it became apparent that CMS might have been misguided in
its decision to allow Questcor to reset Acthar’s base date AMP based on the fact that Questcor’s
efficacy supplement application was provisionally assigned a different NDA number. First, the
FDA’s October 15, 2010 letter approving Questcor’s application to revise Acthar’s label to
include infantile spasms as an indication expressly stated that Questcor should use NDA number
008372 and not NDA number 002432 for all future submissions. A.R. 312. Although Questcor
arguably alluded to this fact in a footnote to its May 2012 letter requesting to change Acthar’s
base date AMP, see A.R. 74 n.4, that footnote did not make clear that, with the exception of
Questcor’s submission of final carton and container labels, 15 NDA number 002432 became
15
The FDA’s October 15, 2010 approval letter directed Questcor to submit final carton and
container labels and designate the submission as “for approved NDA 022432.” A.R. 309. The
letter mandated, however, that all “other submissions should be addressed to the original NDA
008372 for this drug product, not to this NDA.” A.R. 312.
18

obsolete upon approval. See A.R. 74 n.4 (stating that “Acthar’s original NDA is number 08-372,
and the FDA has informed Questcor that the agency intends to revise its record so that the
approval for infantile spasms is reflected as part of the product’s original NDA, No. 08-372” but
“[t]hat has not yet occurred”).
In addition, a private research analyst contacted CMS by email on September 6, 2012—
only a month after CMS approved Questor’s request to lower Acthar’s base date AMP—and
questioned CMS’s rationale for authorizing Questcor to reset Acthar’s base date AMP based on
the provisional NDA number given that the drug had not otherwise changed. See A.R. 170–72.
The analyst stated that she was “trying to understand the circumstances under which Medicaid
would pay MORE for this drug that was first approved by FDA in 1952.” A.R. 170 (emphasis in
original). She then posed several queries, including: “If a type 6 NDA is an administrative
change . . . is it really possible that this type of NDA could possibly trigger a 76.9% loss to
Medicaid on each Medicaid vial, with a current AWP of more than $34,000?” The analyst
commented that “[i]t’s hard to imagine that there is any common sense rationale that would
permit this.” A.R. 172. She also asked whether there was “some other change from sNDA 8372
and NDA 22432 in the drug beyond the wrong FDA reviewing department” and expressed her
opinion that “[t]here is no doubt that taxpayer dollars will be wasted.” A.R. 172.
About nine months later, on May 28, 2013, a CMS official emailed Questcor’s Director
of Business Analytics and Evaluation to request that Questcor correct Acthar’s base date AMP.
A.R. 164. The CMS official observed that Acthar’s National Drug Code number was associated
with a product that was approved under NDA 008372 and stated that Questcor therefore needed
to “follow the baseline data” for Acthar that was historically associated with that NDA number at
the time Questcor purchased the drug. A.R. 165. The CMS official directed Questcor to several
19

numbered agency publications for guidance about a drug product’s base date AMP being tied to
the NDA number rather than the National Drug Code number. A.R. 165.
Later that same year, an official from the Ohio Department of Medicaid contacted CMS
by email to ask why Acthar’s National Drug Codes 63004-7731-01 and 63004-8710-01 had
different base date AMPs when both products appeared to be the same drug. A.R. 163. A CMS
official responded and said that “[t]he new Acthar H.P. NDC is being marketed pursuant to a
new NDA, and therefore the product has a different base AMP quarter.” A.R. 163.
Another year or two passed before a CMS official emailed the FDA’s Center for Drug
Evaluation and Research on October 9, 2015 and requested that the Center identify the correct
NDA number for Acthar. A.R. 159. The CMS official pointed out that searches for Acthar on
the FDA’s website drugs@fda.gov resulted in “two different NDA numbers [being] referenced—
008372 and 022432.” A.R. 159. The CMS official noted that the approval letter associated with
NDA number 022432 “indicates that NDA number 022432 will no longer be used.” A.R. 159–
60. The CMS official then asked whether “that mean[s] tha[t] the only NDA used for the
marketing of Acthar HP gel is 008372?” A.R. 160. The CMS official also asked whether “the
information referencing NDA 022432 [will] be removed from drugs@fda?” A.R. 160. A Drug
Information Specialist from the Center responded and said that he “confirmed that the only
active NDA for HP Acthar Gel is 008372” and he was “notifying the Drugs@FDA team about
the older NDA”—i.e., NDA number 022432. A.R. 159.
A couple of months later, on November 24, 2015, CMS’s Director for the Division of
Pharmacy at the Center for Medicaid and CHIP Services contacted the official who signed the
FDA’s March 24, 2015 letter approving Questcor’s “Changes Being Effected” supplemental new
drug application—which effectively consolidated under NDA number 008372 the labeling
20

revision that added infantile spasms to Acthar’s indications 16—to ask when NDA number
022432 became obsolete and the reason for its demise. A.R. 158 (“Is it the date you signed on
3/24/2015, or does this letter invalidate NDA number 022432 altogether since it’s first approval
back on October 15, 2010?”). A project manager at the Center for Drug Evaluation and
Research responded and stated, among other things, that “Type-6 NDAs are administratively
closed upon approval.” A.R. 157. The project manager further explained that, “[u]pon approval
of the infantile spasms efficacy supplement we requested that the sponsor submit a labeling
supplement to the parent NDA [008372] for administrative purposes to update the labeling under
the parent NDA.” A.R. 157.
Two weeks later, on December 8, 2015, the same CMS official who previously alerted
the FDA’s Center for Drug Evaluation and Research that two different NDA numbers were
associated with Acthar on the Drugs@FDA.gov website once again contacted the Center by
email to advise that “Drugs@FDA is still showing that the NDA number for HP Acthar Gel is
022432.” A.R. 154. The Center responded by confirming that, although both NDA numbers
008372 and 022432 were listed on the website Drugs@FDA.gov, NDA number 022432 was “no
longer used.” A.R. 154 (bracketing omitted). The Center explained that NDA number 022432
was still appearing on the website because there were ongoing agency deliberations about how to
“list” the “Type 6 approvals” on the site. 17 A.R. 154 (stating “I was informed that the policy on
16
See A.R. 30 (acknowledging that the FDA intended to “consolidate NDA 022432 with NDA
008372” and ultimately did consolidate the two applications in 2015).
17
Mallinckrodt’s claim that the “FDA repeatedly refused to answer” CMS’s questions about
whether Acthar was being marketed under NDA number 008372 versus NDA number 022432 is
not credible upon examination. As already discussed, the FDA unequivocally confirmed that:
“the only active NDA for HP Acthar Gel is 008372,” A.R. 159; Type 6 NDAs like NDA number
022432 “are administratively closed upon approval” and NDA number 008372 was the “parent”
of NDA number 022432, A.R. 157; and NDA number 022432 was “no longer used” by the
21

how to list these Type 6 approvals is still being deliberated” but “[f]eel free to check back in a
few months or periodically at the NDA listings for further updates”).
IV. CMS DIRECTS QUESTCOR TO CORRECT ITS MEDICAID PROGRAM

REPORTING DATA TO REFLECT THAT ACTHAR IS BEING MARKETED
UNDER NDA NUMBER 008372
These events culminated in CMS formally notifying Questcor and Mallinckrodt, which
had merged, that they were reporting the wrong base date AMP for Acthar. A.R. 151. That
notice came in the form of a letter dated April 13, 2016, in which CMS directed the companies to
correct the data they had reported in the Medicaid Drug Rebate Program’s Drug Data Reporting
for Medicaid (DDR) system to reflect that Acthar was being marketed under NDA number
008372—not NDA number 022432:
It has recently come to our attention that even though H.P. Acthar Gel is shown to
be approved under NDA 022432 on Drugs@FDA, NDC 63004-8710-01 is listed
as approved under NDA 008372 on FDA Online Label Repository at
http://labels.fda.gov/getPackageCode.cfm. As a result of this discrepancy, we have
reviewed the approval status of H.P. Acthar Gel and it is our understanding that
H.P. Acthar Gel is marketed under NDA 008372 not NDA 022432. In the FDA
approval letter for H.P. Acthar Gel provided by Drugs@FDA at
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/022432x000ltr.pd,
the approval letter shows that although the NDA for the use of H.P. Acthar Gel for
infantile spasms was initially assigned number 022432, that any future submissions
“should be addressed to the original NDA 008372 for this drug product, not to this
NDA [022432]”.
When reviewing the reporting of NDC 63004-8710 to the Medicaid Drug Rebate
(MDR) program in the Drug Data Reporting for Medicaid (DDR) system, we
noticed that this NDC has NDA 022432 reported as its FDA application number,
which is incorrect pursuant to the FDA approval letter indicated above and the
listing information provided by the manufacturer to FDA Online Label Repository.
Therefore, we are requesting the manufacturer to review and correct the reporting
of its product data in DDR to ensure that accurate information is reported to the
MDR program.
agency but was appearing on the Drugs@FDA website simply because the agency had not yet set
a policy about how it should “list” NDA Type 6 applications there, A.R. 159.
22

A.R. 151 (formatting omitted). The letter also advised the companies that the base date AMP
associated with Acthar’s reported National Drug Code needed to be revised to reflect the base
date AMP that applied to NDA number 008372:
Additionally, as provided in Manufacturer Release No. 90 . . . baseline data of an

NDC for a single source drug or innovator multiple source drug must follow the
NDA. Therefore, the baseline data of NDC 63004-8710 need to follow the baseline
data of the original NDC 63004-7731-01, which includes revision to the base AMP
of NDC 63004-8710.
A.R. 151.
What ensued over the course of the next three years were a series of communications—
via emails, letters, and meetings—between Mallinckrodt officials and CMS officials, all of
whom asserted and reasserted their respective, albeit opposing, positions about whether Acthar
was entitled to a new base date AMP consistent with CMS’s 2012 determination. A.R. 12–150.
Whether intentional or not, a July 6, 2016 email from Mallinckrodt to CMS made the inexact
statement that NDA number 022432 involved the FDA’s “approval” of “the product that was
discussed in the CMS letter of August 6, 2012.” A.R. 83. CMS was not misled, however, and
responded by email on March 20, 2017 to explain that:
[I]t is our understanding that the marketing of the drug has always been under the
auspices of NDA 008372, regardless of the administratively assigned NDA 022432,
which was only for the purpose of FDA approval of the new indication, but not for
the approval and marketing of the drug itself.
The baseline information for a drug that was approved prior to the effective date of
section 1927 of the Social Security Act is established using the data of the drug as
of 9/30/1990. It is our understanding that NDA 008372 for Acthar was approved
on April 29, 1952, therefore, the baseline data for the drug that is marketed under
that NDA would be based on data from 9/30/1990 as the approval of NDA 022432
in 2010 was not for approval of a new drug.
23

A.R. 81. Throughout these communications, Mallinckrodt appears to have believed that it was
engaged in negotiations with CMS, 18 whereas CMS remained resolute and, on March 12, 2019,
sent Mallinckrodt a letter stating that, “[a]s we have said in our prior communications of April
13, 2016, June 2, 2016, and March 20, 2017, and as we reiterated at the March 7th meeting, the
base date AMP of H.P. Acthar Gel should reflect the base date AMP for the drug that was first
produced or distributed under new drug application (NDA) 008372.” A.R. 13. CMS maintained
that, “[b]ecause H.P. Acthar gel is currently, and always has been, produced or distributed under
NDA 008372, the base date AMP Mallinckrodt is reporting to the Drug Data Reporting for
Medicaid (DDR) system does not reflect the appropriate base date AMP, and Mallinckrodt has
been underpaying Medicaid rebates for H.P. Acthar Gel.” A.R. 13.
CMS effectively shut down any further discussions between the parties via a March 27,
2019 email that HHS’s General Counsel sent to Mallinckrodt’s General Counsel and the
company’s outside counsel. A.R. 11. The email canceled a planned meeting between the parties
in light of the HHS General Counsel’s conclusion that CMS’s April 13, 2016 letter to Questcor
was the agency’s final decision. See A.R. 11 (“I’ve reviewed the underlying documents and
have concluded that the April 13, 2016 letter from CMS to Mallinckrodt constituted CMS’ final
decision on the relevant issue. Therefore . . . any meeting . . . would not and could not be
productive.”).
Mallinckrodt nevertheless took one last run at CMS’s position in an April 12, 2019 letter
in which Mallinckrodt’s General Counsel sought “to engage with [CMS] to discuss a potential
middle ground where Mallinckrodt would agree to a pathway for implementing Acthar’s pre-
18
See Mallinckrodt’s Mot. for Prelim. Inj. Br. 19 (stating that “[a]lthough Mallinckrodt has
continued to seek further dialogue with the agency since then, those efforts have been rebuffed”).
24

2013 base date AMP on a prospective basis only.” A.R. 9. Mallinckrodt’s General Counsel
proposed that CMS “acknowledge that, under its interpretation of the law to date, Mallinckrodt’s
use of Acthar’s post-2012 base date AMP was appropriate, but would take appropriate steps to
change its interpretation of the law, on a prospective basis, such that, going forward, Acthar’s
pre-2013 base date AMP would be implemented.” A.R. 9. CMS declined to consider
Mallinckrodt’s proposal and, instead, reaffirmed that its “position remains the same, as reflected
in [the HHS General Counsel’s] March 27, 2019 email . . . .” A.R. 4.
CMS cemented its position on May 10, 2019 by sending Mallinckrodt a letter notifying
the company that it must correct the information in the Drug Data Reporting Medicaid system in
14 days or risk having its National Drug Codes flagged as “out of compliance” in the system.
A.R. 2. CMS added that it “may also refer Mallinckrodt to the Department of Justice and/or U.S.
Department of Health and Human Services—Office of Inspector General for further review and
investigation.” A.R. 2. CMS now characterizes this letter as the agency’s final decision, see
Gov’t’s Reply Br. 15 (stating that “the relevant date for purposes of final agency action is May
2019 when the agency threatened to find Mallinckrodt out of compliance in the drug data
reporting system”), which Mallinckrodt has not disputed in its legal briefs or during oral
arguments.
Ten days after receiving CMS’s final decision, Mallinckrodt filed this lawsuit. See
Verified Compl., ECF No. 1. Mallinckrodt then immediately moved for a preliminary injunction
to enjoin the government from “suspending Mallinckrodt’s participation in the Medicaid Drug
Rebate Program and/or taking any other action as a result of a recent determination by the
Centers for Medicare & Medicaid Services (CMS) regarding the base date average
manufacturing price (AMP) for Mallinckrodt’s drug product Acthar Gel® (repository
25

corticotropin) injection (Acthar).” Mallinckrodt’s Mot. for Prelim. Inj. 1, ECF No. 4. During a
teleconference that took place on May 24, 2019, however, the then-presiding judge secured the
parties’ agreement to consolidate the issues raised in Mallinckrodt’s preliminary injunction
motion with a decision on the merits of summary judgment motions. See Teleconference Tr. 5–
9, May 24, 2019, ECF No. 9.
Mallinckrodt’s Verified Complaint alleges two claims. Mallinckrodt’s first claim is that
CMS’s (1) 2016 determination that Acthar was not a distinct single source drug entitled to
establish a new base date AMP, (2) ambition to recover the underpaid rebates from Mallinckrodt,
and (3) indication that it might take enforcement action against Mallinckrodt were all unlawful,
arbitrary, and capricious under the Administrative Procedure Act (APA), 5 U.S.C. §§ 700–706.
Verified Compl. ¶¶ 94–106 (Count I). Mallinckrodt’s second claim is that it relied on CMS’s
2010 authorization granting Questcor approval to establish a new base date AMP and CMS’s
subsequent “failure to give Mallinckrodt advance notice of its newfound interpretation of ‘single
source drug’ violates basic principles of fair notice.” Verified Compl. ¶ 110 (Count II).
Mallinckrodt also takes issue with CMS’s “effort to seek enforcement action,” which
Mallinckrodt asserts “violates the procedural due process guarantees of the Fifth Amendment to
the United States Constitution and the APA.” Verified Compl. ¶ 111 (Count III). At stake are
potentially hundreds of millions of dollars in retroactive rebate adjustments dating back to 2013
that Mallinckrodt will owe Medicaid agencies. See Mallinckrodt’s Prelim. Inj. Br. 2, ECF No. 4-
1 (arguing that if Mallinckrodt is forced to correct Acthar’s base date AMP in the Drug Data
Reporting for Medicaid (DDR) system, “[i]t would automatically trigger adjustments to the
Acthar rebate calculations—not just prospectively, but retroactively, all the way back to 2013,
26

resulting in losses totaling in the hundreds of millions of dollars for Mallinckrodt” (emphasis in
original)).
LEGAL STANDARDS
I. PRELIMINARY INJUNCTIONS
Preliminary injunctions are “extraordinary” remedies that are awarded “only . . . upon a
clear showing that the plaintiff is entitled to such relief.” Guedes v. Bureau of Alcohol, Tobacco,
Firearms & Explosives, 920 F.3d 1, 10 (D.C. Cir. 2019) (quoting Winter v. Nat. Res. Def.
Council, Inc., 555 U.S. 7, 24 (2008)), cert. denied, No. 19-296, 2020 WL 981797 (U.S. Mar. 2,
2020). To make this showing the plaintiff bears the burden of persuading the court that (1) the
plaintiff is likely to succeed on the merits, (2) the plaintiff is likely to suffer irreparable harm if
there is no preliminary relief, (3) the balance of equities favor the plaintiff, and (4) it is in the
public interest to grant a preliminary injunction. Id. If, however, the plaintiff fails to establish
the first factor—a likelihood of success on the merits—the court “need not proceed to review the
other three preliminary injunction factors.” Arkansas Dairy Co-op Ass’n v. U.S. Dep’t of Agric.,
573 F.3d 815, 832 (D.C. Cir. 2009).
II. SUMMARY JUDGMENT
Rule 56 of the Federal Rules of Civil Procedure mandates that a federal court grant
summary judgment in favor of a moving party when there are no genuine disputes about material
facts and the movant is entitled to judgment as a matter of law. Fed. R. Civ. P. 56(a). A dispute
is genuine if “a reasonable jury could return a verdict for the nonmoving party.” Anderson v.
Liberty Lobby, Inc., 477 U.S. 242, 248 (1986). A fact is material if it “might affect the outcome
of the suit under the governing law.” Id.
27

The party moving for summary judgment bears the burden of showing that there are no
genuine disputes about material facts. Adickes v. S. H. Kress & Co., 398 U.S. 144, 157 (1970).
To determine whether a dispute about a material fact is genuine, the Court must view the
evidence in the light that is most favorable to the party opposing the motion and draw all
reasonable inferences in that party’s favor. Tolan v. Cotton, 572 U.S. 650, 651, 656 (2014) (per
curiam). The Court may not weigh the evidence or make credibility determinations. Allen v.
Johnson, 795 F.3d 34, 38 (D.C. Cir. 2015).
To successfully oppose a motion for summary judgment, the nonmoving party must offer
sufficient evidence of a factual dispute—not mere allegations—such that a jury or judge is
necessary “to resolve the parties’ differing versions of the truth at trial.” First Nat. Bank of Ariz.
v. Cities Serv. Co., 391 U.S. 253, 289 (1968). Although the evidence need not be “in a form that
would be admissible at trial, the evidence still must be capable of being converted into
admissible evidence.” Gilmore v. Palestinian Interim Self-Gov’t Auth., 843 F.3d 958, 969 (D.C.
Cir. 2016) (emphasis in original) (quoting Gleklen v. Democratic Cong. Campaign Comm., Inc.,
199 F.3d 1365, 1369 (D.C. Cir. 2000)). “[T]he mere existence of some alleged factual dispute
between the parties will not defeat an otherwise properly supported motion for summary
judgment; the requirement is that there be no genuine issue of material fact.” Anderson, 477
U.S. at 247–48 (emphases in original).
III. APA REVIEW
The standard of review for summary judgment under the APA requires the Court to hold
unlawful and set aside agency action, findings, and conclusions that the Court finds to be
arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law.
AstraZeneca Pharm. LP v. Food & Drug Admin., 713 F.3d 1134, 1139 (D.C. Cir. 2013); 5
28

U.S.C. § 706(2)(A). An agency action is arbitrary and capricious when the agency “entirely
fail[s] to consider an important aspect of the problem, offer[s] an explanation for its decision that
runs counter to the evidence before the agency, or is so implausible that it could not be ascribed
to a difference in view or the product of agency expertise[.]” Motor Vehicle Mfrs. Assn. of U.S.,
Inc. v. State Farm Mut. Auto. Ins. Co., 463 U.S. 29, 43 (1983); Gresham v. Azar, No. 19-5094,
2020 WL 741278, at *4, ___ F.3d ___ (D.C. Cir. Feb. 14, 2020).
To be sure, the scope of arbitrary and capricious review is narrow, Dep’t of Commerce v.
New York, 139 S. Ct. 2551, 2569 (2019), and “highly deferential,” Holy Land Found. for Relief
& Dev. v. Ashcroft, 333 F.3d 156, 162 (D.C. Cir. 2003). The Court’s role is to “determine only
whether the [agency] examined ‘the relevant data’ and articulated ‘a satisfactory explanation’ for
[its] decision, ‘including a rational connection between the facts found and the choice made.’”
Id. (quoting Motor Vehicle Mfrs. Assn. of U.S., Inc., 463 U.S. at 43). It is well established that a
court may not substitute its own judgment for that of federal agencies and “may not supply a
reasoned basis for the agency’s action that the agency itself has not given.” Bowman Transp.,
Inc. v. Arkansas-Best Freight Sys., Inc., 419 U.S. 281, 285 (1974). It is also well established,
however, that an agency’s decision need not “be a model of analytic precision to survive a
challenge.” Dickson v. Sec’y of Def., 68 F.3d 1396, 1404 (D.C. Cir. 1995). Courts will “uphold
a decision of less than ideal clarity if the agency’s path may reasonably be discerned.” Bowman
Transp., 419 U.S. at 286.
The APA mandates that courts must “review the whole record or those parts cited by a
party” when reviewing an agency’s action. 5 U.S.C. § 706. The Court’s review is therefore
confined to the Administrative Record, which “includes all materials compiled by the agency
that were before the agency at the time the decision was made.” James Madison Ltd. by Hecht v.
29

Ludwig, 82 F.3d 1085, 1095 (D.C. Cir. 1996) (internal citations and quotation marks omitted).
“[T]he function of the district court is to determine whether or not as a matter of law the
evidence in the administrative record permitted the agency to make the decision it did.”
Occidental Eng’g Co. v. I.N.S., 753 F.2d 766, 769 (9th Cir. 1985). The Court will not consider
post hoc agency rationalizations that the Administrative Record does not support. See Caiola v.
Carroll, 851 F.2d 395, 400 (D.C. Cir. 1988).
ANALYSIS
Mallinckrodt contends that CMS correctly decided in 2012 that Acthar was eligible for a
new base date AMP after the FDA approved Questcor’s efficacy supplement application to
revise the drug’s label by adding infantile spasms as a new indication. The gist of
Mallinckrodt’s argument is this: When the FDA approved Questcor’s efficacy supplement
application to add infantile spasms as an indication after converting it into a Type 6 “new drug
application” and assigning it a new (albeit now defunct 19) NDA number—022432—the result
was a “new drug application” approved by the FDA. And, because Questcor and Mallinckrodt
thereafter began producing and distributing Acthar using that NDA number, Acthar with the
infantile spasm indication satisfied the statute’s definition of a “single source drug” eligible for a
new base date AMP because it was a “drug” that was being “produced and distributed” under a
“new drug application” approved by the FDA. See Mallinckrodt’s Prelim. Inj. Br. 20–28;
Mallinckrodt’s Summ. J. Br. 4–7, ECF No. 22-1. Mallinckrodt therefore challenges CMS’s later
decision requiring the manufacturer to correct its reporting and apply the base date AMP
associated with Acthar’s FDA approval under NDA number 008372. Id. Mallinckrodt argues
19
An FDA letter dated March 24, 2015 and addressed to Questcor states that “tracking NDA
number 022432 will no longer be used.” A.R. 688–690.
30

that CMS’s change of heart was unlawful, arbitrary, and capricious for three reasons: (1) the
agency’s determination that Acthar is not a distinct single source drug is contrary to the terms of
the statutory Medicaid Drug Rebate Program; (2) the agency’s decision violates CMS’s own
regulations; and (3) CMS failed to explain why its position changed. Mallinckrodt’s Prelim. Inj.
Br. 21–29. Mallinckrodt also separately claims that CMS’s decision violates principles of fair
notice and will be impermissibly retroactive. Id. at 29–36.
CMS resists Mallinckrodt’s challenge by pointing out that the agency’s 2012 decision
allowing Questcor to set a new base date AMP for Acthar was based on facts Questcor presented
that “showed that the U.S. Food and Drug Administration . . . recently had approved Acthar as an
entirely new drug” versus simply approving a label revision to add an indication for infantile
spasms. Gov’t’s Opp’n Br. 1, ECF No. 18 (Sealed). CMS interprets the Medicaid Drug Rebate
Program statute as “set[ting] the base date AMP for each dosage form and strength of a single
source drug, such as Acthar, by reference to the FDA’s approval of an NDA under which the
drug is marketed.” Gov’t’s Opp’n Br. 17–18. According to CMS, “[c]hanges to an existing
product result in a new base date AMP only if those changes result in a new drug being marketed
under a new NDA or the changes are to dosage form or strength.” Id. at 18. CMS concludes
that, regardless of whether the FDA assigned a provisional NDA number to Questcor’s efficacy
supplement application to revise Acthar’s label by adding infantile spasms as an indication, the
FDA’s approval of that application “did not create a new drug” because “the drug’s composition
remained the same and the drug has been marketed only under the original FDA approval from
1952, NDA 008372.” Id. And once CMS became aware that NDA number 022432 was obsolete
and did not involve a new drug approval, the agency directed both Questcor and Mallinckrodt to
correct their drug reporting for the Medicaid Drug Rebate Program. Id. at 26. CMS therefore
31

defends both its 2012 and 2019 decisions as consistent interpretations of the statute, lawful,
adequately explained, and supported by the Administrative Record. Id. at 17–23.
I. CMS COMPLIED WITH THE MEDICAID DRUG REBATE PROGRAM

STATUTE AND THE ADMINISTRATIVE PROCEDURE ACT
A. CMS Lawfully Determined that the Medicaid Drug Rebate Program Statute
Requires that Acthar’s Base Date AMP be Calculated Based on the Date
When the FDA Approved the Drug Under NDA Number 008372
Turning first to Mallinckrodt’s allegation that CMS failed to comply with the Medicaid
Drug Rebate Program statute when it reversed its 2012 decision allowing Acthar’s base date
AMP to be reset, Mallinckrodt asserts that this claim “turns on whether FDA’s approval of NDA
022432 entitles Acthar to be treated as a distinct ‘single source drug.’” Mallinckrodt’s Summ. J.
Br. 4. Framed this way, the question for the Court is whether the Medicaid Drug Rebate
Program statute contemplates that, if the FDA approves an efficacy supplement application to
add a new indication to an existing drug’s label after converting that application to a Type 6
NDA and assigning it a different NDA number from the number of the NDA under which the
drug received FDA approval for marketing, is that same drug thereby transformed into a new
“single source drug” entitled to a new base date AMP. This is a question of statutory
interpretation and, although both parties subscribe to the theory that the Medicaid Drug Rebate
Program statute is clear and unambiguous, their views about what the statute means diverge. 20
20
Mallinckrodt argues that the Court need not give deference to CMS’s interpretation of the
Medicaid Drug Rebate Program statute pursuant to the Supreme Court’s decision in Chevron
U.S.A. Inc. v. Nat. Res. Def. Council, Inc., 467 U.S. 837 (1984), because the government has
forfeited Chevron’s application by failing to invoke it. Mallinckrodt’s Summ. J. Br. 6 n. 3. The
Court does not apply Chevron, however, when Congress’s intent is clear from the statute; rather,
in such situations, the Court applies the ordinary tools of statutory interpretation. Safari Club
Int’l v. Zinke, 878 F.3d 316, 326 (D.C. Cir. 2017). Furthermore, the D.C. Circuit’s decision in
Guedes, 920 F.3d 1, establishes that government counsel cannot waive or forfeit the applicability
of Chevron deference “unless the underlying agency action fails to manifests its engagement in
the kind of interpretive exercise to which review under Chevron generally applies—i.e.,
32

“In the interpretation of statutes, the function of the courts is easily stated. It is to
construe the language so as to give effect to the intent of Congress.” United States v. Am.
Trucking Ass’ns, 310 U.S. 534, 542 (1940). To do so, the Court adheres to the “preeminent
canon of statutory interpretation” that requires the Court to “‘presume that [the] legislature says
in a statute what it means and means in a statute what it says there.’” BedRoc Ltd., LLC v.
United States, 541 U.S. 176, 183 (2004) (quoting Connecticut Nat. Bank v. Germain, 503 U.S.
249, 253–254 (1992)). The Court’s analysis therefore “begins with the statutory text, and ends
there as well if the text is unambiguous.” Id. Ultimately, “[a]s in all cases of statutory
construction, [the Court’s] task is to interpret the words of . . . statutes in light of the purposes
Congress sought to serve.” Chapman v. Houston Welfare Rights Org., 441 U.S. 600, 608 (1979).
Congress’s purpose for enacting the Medicaid Drug Rebate Program was “to further
reduce Medicaid spending.” Iowa Dep’t of Human Servs. v. Centers for Medicare & Medicaid
Servs., 576 F.3d 885, 886 (8th Cir. 2009). The program achieves this purpose by mandating that
drug manufacturers that seek to have their drugs covered by Medicaid must agree to provide
rebates to states to offset the rising costs of those drugs. See 42 U.S.C. §§ 1396r-8(a)(1),
(b)(1)(B).
42 U.S.C. § 1396r-8(c) is the section of the Medicaid Drug Rebate Program statute that
governs how rebates are determined—including a drug’s so-called “base date AMP.” As already
discussed in the section of this decision addressing the statutory and regulatory structure of the
case, the relevant provisions in 42 U.S.C. § 1396r-8(c) set forth the rebate amount a drug
manufacturer must pay for “each dosage form and strength of a single source drug.” 42 U.S.C.
interpreting a statute it is charged with administering in a manner (and through a process)

evincing an exercise of its lawmaking authority.” Id. at 22 (internal quotation marks omitted).
33

§ 1396r-8(c)(1)(A). The statute currently defines the phrase “single source drug” to mean in
relevant part “a covered outpatient drug . . . which is produced or distributed under a new drug
application approved by the Food and Drug Administration.” 42 U.S.C. § 1396r-8(k)(7)(iv).
Mallinckrodt seizes on the statute’s definition of “single source drug” as the linchpin of
its claim that CMS correctly determined in 2012 that Acthar with the infantile spasm indication
qualified for a new base date AMP. Mallinckrodt’s Mot. for Prelim. Inj. Br. 22–23. Unpacking
Mallinckrodt’s argument proceeds thusly: NDA number 022432 was, on its face, a “new drug
application” that was “approved by the Food and Drug Administration.” Id. at 22. Acthar with
the infantile spasm indication could not be “lawfully marketed” until the FDA approved NDA
number 022432. Id. After the FDA approved NDA number 022432, Questcor and Mallinckrodt
began “producing and distributing” Acthar using that NDA number, including by importing the
drug’s bulk active ingredient “under” that number. 21 Id. at 23. As a result, because Acthar was
“produced and distributed” under a “new drug application” (i.e., NDA number 022432) that was
“approved by the Food and Drug Administration,” see A.R. 702, the drug thereby qualified as a
distinct “single source drug” that was “eligible for its own base date AMP under the plain
meaning of the statute,” Mallinckrodt’s Mot. for Prelim. Inj. Br. 23.
Mallinckrodt’s approach to the statute’s interpretation misappropriates the definition of
“single source drug” and extrapolates it to mean that a drug’s base date AMP may be reset any
time the FDA approves an application that has been administratively categorized as an “NDA”—
regardless of what action related to a drug was actually occasioned by the approval. Such an
21
Mallinckrodt never explains what, precisely, it means to “import” Acthar’s active ingredient
“under” NDA number 022432. All indications, however, suggest that anything Mallinckrodt is
doing “under” NDA number 022432 is the product of its own agenda and self-reporting given
that the FDA has made clear that number is obsolete for the agency’s purposes, A.R. .
34

interpretation runs counter to the purpose of the Medicaid Drug Rebate Program, however,
because it would empower both the agency and drug manufacturers to circumvent Congress’s
intent to reduce Medicaid spending via drug rebates by simply manipulating how a submitted
drug application was administratively categorized. And “[a] statute should ordinarily be read to
effectuate its purposes rather than to frustrate them.” Motor Vehicle Mfrs. Ass’n of U.S., Inc.,
719 F.2d at 1165.
Mallinckrodt’s urged interpretation also fails to account for the fact that the FDA’s 2010
letter approving NDA number 022432 makes clear that the FDA viewed Acthar with the infantile
spasm indication to be the same “drug product” that was originally approved in 1952 under NDA
008372. See A.R. 706. This is demonstrated by the FDA’s statement in the approval letter that
“[a]ll . . . submissions should be addressed to the original NDA 008372 for this drug product, not
to this NDA.” A.R. 706 (emphasis added). In other words, the FDA expressly viewed the drug
approved under NDA number 008372 and the drug with the label revision adding infantile
spasms as an indication that was approved under NDA number 022432 to be one and the same
“drug product.” A.R. 706.
Moreover, Mallinckrodt’s interpretation overlooks the statute’s straightforward textual
language dictating that a drug’s base date AMP is tied to the date when the FDA approved the
drug and the drug was first marketed—not when the FDA approved any so-titled “new drug
application” that relates to the drug—although these events might well coincide. The statute
provides that the rebate amount for single source drugs consists of the sum of two calculations:
(1) the “basic rebate” plus (2) an “additional rebate.” 42 U.S.C. §§ 1396r-8(c)(1)(A), (2). The
base date AMP only comes into play in the calculation of the “additional rebate.” See 42 U.S.C.
§ 1396r-8(c)(2)(A)(ii); see also A.R. 1020 (defining “Base Date AMP” in the national Drug
35

Rebate Agreement to have the meaning set forth in 42 U.S.C. § 1396r-8(c)(2)(A)(ii)(II)). For
drugs that were FDA approved on or before October 1, 1990, the statute states that the base date
AMP is:
[T]he average manufacturer price for such dosage form and strength for the
calendar quarter beginning July 1, 1990 (without regard to whether or not the drug
has been sold or transferred to an entity, including a division or subsidiary of the
manufacturer, after the first day of such quarter), increased by the percentage by
which the consumer price index for all urban consumers (United States city
average) for the month before the month in which the rebate period begins exceeds
such index for September 1990.
42 U.S.C. § 1396r-8(c)(2)(A)(ii)(II). Relevant here, however, the statute further states that if a
“covered outpatient drug” is “approved by the FDA” after October 1, 1990 (as would be the case
if Acthar with the infantile spasm indication was a new drug), the drug’s base date AMP is set
based on the “day on which the drug was first marketed”:
In the case of a covered outpatient drug approved by the Food and Drug
Administration after October 1, 1990, clause (ii)(II) of subparagraph (A) shall be
applied by substituting “the first full calendar quarter after the day on which the
drug was first marketed” for “the calendar quarter beginning July 1, 1990” and “the
month prior to the first month of the first full calendar quarter after the day on which
the drug was first marketed” for “September 1990”. 22
42 U.S.C. § 1396r-8(c)(2)(B).
The plain meaning of this statutory language makes clear that the operative event that
determines if and when a drug’s base date AMP may be set is the date on which the “covered
outpatient drug” was “approved by the Food and Drug Administration.” 42 U.S.C. § 1396r-
8(c)(2)(B). If a “covered outpatient drug” was “approved by” the FDA after October 1, 1990, as
22
Legislation enacted after the Medicaid Drug Rebate Program statute appears to refine this
calculation based on the dates of the first full calendar quarter that apply but do not otherwise
alter the fact that the base date AMP is set based on when the “covered outpatient drug” was
“approved by the FDA” and “first marketed.” See, e.g., A.R. 983 (discussing the agency’s
guidance about how to use the correct baseline AMP and Consumer Price Index Urban (CPI-U)
factors).
36

would be the case if Mallinckrodt’s theory about Acthar was valid, then the base date AMP must
be calculated in accordance with the substitute language found in 42 U.S.C. § 1396r-8(c)(2)(B),
which provides that the base date AMP is triggered by the “day on which the drug was first
marketed.” Aside from the catalyst event of a “covered outpatient drug” being “approved by the
FDA,” however, the statute does not expressly contemplate any other events that would allow a
manufacturer to reset a single source drug’s base date AMP during the lifecycle of that drug
absent a new formulation, see 42 U.S.C. § 1396r-8(c)(2)(C) (providing for the calculation of a
base date AMP for new formulations of a single source drug), or, as the government correctly
noted, a new dosage form and strength, Gov’t’s Summ. J. Br. 18 (arguing that “[c]hanges to an
existing product result in a new base date AMP only if those changes result in a new drug being
marketed under a new NDA or the changes are to dosage form or strength”).
The Administrative Record confirms that CMS’s 2012 decision allowing Questcor to
reset Acthar’s base date AMP was premised on the agency’s assumption that, because the
infantile spasm indication “was approved under a different [NDA] from the original product,”
that meant that Acthar with the infantile spasm indication must be a different “product” from the
“original product.” A.R. 617 (emphasis added). CMS put Questcor on notice that the agency
was relying on this assumption by stating that the agency “does not have the current ability to
allow a manufacturer to replace the original reported base date AMP with a new base date AMP
midway through the life of a product.” A.R. 617 (emphasis added). The only possible takeaway
from this statement was that CMS believed that Acthar with the infantile spasm indication was
an entirely new drug product. Given Mallinckrodt’s concession that CMS’s rationale was a
departure from the two approaches that Questcor’s General Counsel had identified and proposed
when he advocated for a new base date AMP, see Mallinckrodt’s Summ. J. Br. 2 (arguing that
37

“[w]e know that CMS rejected both of Questcor’s suggested legal pathways for a new base date
AMP and reached its own, unprompted conclusion”), and given that Questcor (and Mallinckrodt)
knew all along that NDA number 022432, although titled a “new drug application,” was in fact
an efficacy supplement to NDA number 008372 that sought the FDA’s approval to revise
Acthar’s label to add infantile spasms as an indication, see id. at 3 (challenging CMS’s claim that
it was ignorant of the fact that Acthar was not “an entirely new drug” on the ground that this
claim was “not right” because “Questcor repeatedly told the agency that the drug was first
approved in 1952 and received a new indication for infantile spasms in 2010”), 12 (arguing that
that “the administrative record makes clear” that the 2010 FDA approval authorizing Questcor to
add infantile spasms to Acthar’s label “was not [an approval] of an ‘entirely new drug’ but
simply added IS to the labeling”), it would have behooved the companies to clarify the agency’s
understanding, if only to insulate them from a dispute down the road, as has now come to pass.
Mallinckrodt cites record documents numbered A.R. 621, 622, and 632 as evidence that it
clearly disclosed to CMS that Acthar with the infantile spasm indication was not “an entirely
new drug.” Mallinckrodt’s Summ. J. Br. 3. This argument is unavailing upon inspection. Both
A.R. 621 and A.R. 622 are pages from Questcor’s May 8, 2012 letter requesting to set a new
base date AMP for Acthar. A.R. 621 reflects that Questcor told CMS the following:
The FDA granted Acthar an orphan drug designation for IS in 2003 and approved
Acthar under NDA 22-432 for treatment of infantile spasms 4 on October 15, 2010.
We believe that prior owners of Acthar did not pursue an approval with FDA based
on their view that the economics of obtaining the approval were too burdensome.
A.R. 621. Footnote 4 on that same page stated:
Acthar’s original NDA is number 08-372, and the FDA has informed Questcor that
the agency intends to revise its record so that the approval for infantile spasms is
reflected as part of the product’s original NDA, 08-372. That has not yet occurred.
A.R. 621 n.4. On the next page, Questcor stated:
38

Acthar was initially approved for multiple indications in 1952, under NDA 08-372,
and then in 1978, an NDA supplement was approved for the use of Acthar to treat
multiple sclerosis exacerbations. On October 15, 2010, Acthar was approved to
treat infantile spasms under NDA 22-432. The FDA’s approval of Acthar for this
indication reflects the agency’s conclusion, based on data supplied by Questcor,
that the product is safe and effective for that use. Upon this approval, however, the
FDA also significantly revised Acthar’s label and required the implementation [of]
a Risk Evaluation and Mitigation Strategy (“REMS”), which the agency
determined was necessary for the product’s safe use. These changes represent a
significant revision in the product’s labeling and in the conditions under which it
will be marketed and distributed.
A.R. 622. Lastly, A.R. 632 consists of a chart titled “History of Acthar” that states in relevant
part “2010 IS Approval Label Modernized.”
The Court does not share Mallinckrodt’s confidence that these statements alerted CMS to
the fact that Acthar with the infantile spasm indication was not a new drug, particularly in light
of the way the 1978 approval to add multiple sclerosis as an indication was identified as an
“NDA supplement” to NDA number 008372. A.R. 622. In contrast, the statements addressing
the approval of NDA number 022432, which was also technically a supplement to NDA number
008372, see, e.g., A.R. 157 (stating that NDA number 022432 “was created for administrative
purposes when the sponsor submitted an efficacy supplement for the treatment of infantile
spasms), 869 (characterizing Questcor’s NDA number 022432 as a “resubmission to your
supplemental new drug application for H.P. Acthar® Gel”), discusses the FDA’s review of the
safety and effectiveness of Acthar for infantile spasm treatment and thereby made the approval
under that NDA number appear to involve something more than a label revision to add a new
indication. In addition, an email that Mallinckrodt sent to CMS on July 6, 2016 characterized the
FDA approval of NDA number 022432 as approving “the product” that was “discussed in the
CMS letter of August 6, 2012,” thereby suggesting that the FDA approval was for a new drug
product rather than a label revision. A.R. 83.
39

Furthermore, the statements Mallinckrodt cites were made in documents CMS had before
it issued the August 6, 2012 letter approving a new base date AMP for Acthar, which, as
discussed, makes clear that CMS viewed Acthar with the infantile spasm treatment to be a new
drug product. See A.R. 617. It therefore should have been obvious to Questcor that, however
clearly the company thought it had been that Acthar with the infantile spasm indication was not
“an entirely new drug,” Mallinckrodt’s Summ. J. Br. 3, that clarity had bypassed CMS, see A.R.
617. It was also apparent that CMS erroneously assumed that the FDA’s approval of an NDA
that was assigned a different NDA number signaled that the approval was for a new drug
product. Placed on notice of that erroneous assumption via CMS’s 2012 approval letter,
Questcor (and later Mallinckrodt) gambled by implementing a new base date AMP for Acthar
without first clarifying this point, particularly in light of the statute’s clear language stating that
the base date AMP for a single source drug depends on when the “covered outpatient drug” was
“approved by” the FDA and, if that approval was after October 1, 1990, the base date AMP is
triggered by the date that covered outpatient drug was “first marketed,” 42 U.S.C. §§ 1396r-
8(c)(2)(A)(ii)(II), (B). Nowhere in the Medicaid Drug Rebate Program statute does it provide for
a single source drug’s base date AMP to be reset based solely on the FDA approving a so-titled
“New Drug Application” that does something other than “approve” a “covered outpatient drug,”
as occurred here. See 42 U.S.C. §§ 1396r-8(c)(2).
The upshot is that CMS correctly assessed in its 2012 approval letter to Questcor that
§ 1396r-8(c)(2)(A) of the Medicaid Drug Rebate Program statute (cited by reference to § 1927 of
the Social Security Act) establishes when a drug’s base date AMP attaches. A.R. 617. CMS
repeated that correct assessment five years later in a March 20, 2017 email to Mallinckrodt. A.R.
81. CMS also correctly assessed that the base date AMP attaches to a drug in relation to when
40

the drug was approved by the FDA and the agency lacked authority to change a drug’s base date
AMP during that drug’s lifecycle. A.R. 617 (stating that the base date AMP applies to “each
single source or innovator multiple source drug approved by the FDA before or after October 1,
1990” and that CMS lacked authority to “replace the original . . . base date AMP with a new base
date AMP midway through the life of a product”).
The Court stated at the beginning of this discussion that the legal question was whether
the Medicaid Drug Rebate Program statute contemplates that when the FDA approves an
efficacy supplement application to add a new indication to an existing drug’s label that drug is
then entitled to a new base date AMP. As framed specifically with respect to this case, the
question is whether Acthar with the infantile spasm indication became a distinct single source
drug entitled to a new base date AMP by virtue of the FDA approving Questcor’s efficacy
supplement application after converting it into a Type 6 NDA and assigning it NDA number
022432. The Court answers that legal question in the negative because the plain language of the
statute provides that a single source drug’s base date AMP is set based on when the “covered
outpatient drug” was “approved by the FDA” and, if approved after October 1, 1990, when that
“covered outpatient drug” was “first marketed.” 42 U.S.C. §§ 1396r-8(c)(2)(A)(ii)(II), (B).
Mallinckrodt and Questcor cannot avoid application of the base date AMP that attached when
Acthar was approved by the FDA under NDA number 008372 by manufacturing the existence of
a distinct “single source drug” through their own self-interested actions in continuing to use
NDA number 022432 despite the FDA’s direction otherwise, see A.R. 706, and notwithstanding
Questcor’s own contemporaneous acknowledgment that NDA number 022432 was a “tracking
number” that would “no longer be used,” A.R. 694.
41

It is to no avail whether Mallinckrodt continued to produce and distribute Acthar using
defunct NDA number 022432 because, regardless of whether the Medicaid Drug Rebate
Program statute’s definition of “single source drug” could be interpreted in the crafted way that
Mallinckrodt advocates, the statute nonetheless makes clear that the base date AMP is triggered
by the dates on which the “covered outpatient drug” was “approved by” the FDA and “first
marketed”—and it remains undisputed that the date when Acthar was “approved by” the FDA
was 1952 when the FDA approved NDA number 008372. See Mallinckrodt’s Summ. J. Br. 12
(conceding that “the 2010 approval was not of an ‘entirely new drug’ but simply added IS to the
labeling”). Because Acthar was first marketed well before October 1, 1990, its base date AMP
under the statute is “the average manufacturer price for . . . the calendar quarter beginning July 1,
1990 . . . increased by the percentage by which the consumer price index for all urban consumers
(United States city average) for the month before the month in which the rebate period begins
exceeds such index for September 1990.” 42 U.S.C. § 1396r-8(c)(2)(ii)(II). As a result, CMS’s
decision requiring Mallinckrodt and Questcor to correct their Medicaid Drug Rebate Program
reporting for Acthar to reflect this base date AMP, which was triggered by the FDA’s approval
of NDA number 008372, was consistent with the statute and not arbitrary, capricious, or an
abuse of discretion. For these same reasons CMS’s decision also complied with its agency
regulations. 23
23
Mallinckrodt argues that CMS’s decision violated its own agency regulations because those
“regulations make clear that a ‘single source drug’ is ‘a covered outpatient drug that is produced
or distributed under an original NDA approved by FDA and has an approved NDA number
issued by FDA.” Mallinckrodt’s Summ. J. Br. 9. This argument does not further Mallinckrodt’s
case, though, in light of the clear statutory language the Court has already discussed that ties a
drug’s base date AMP to the date when that drug was approved by the FDA and first marketed.
42

B. CMS Adequately Explained Why Acthar’s Base Date AMP Must Follow the
FDA’s Approval of NDA Number 008372
Mallinckrodt also protests that CMS’s decision requiring the company to correct Acthar’s
base date AMP to reflect the base date AMP associated with NDA number 008372 was arbitrary,
capricious, and unreasonable because the agency vacillated about its rationale for the decision
and never actually explained it. Mallinckrodt’s Summ. J. Br. 11–17. The Administrative
Record, however, demonstrates otherwise.
To reiterate, from the very outset CMS made clear that it was approving a new base date
AMP for Acthar because the agency believed that NDA number 022432 involved the FDA’s
approval of a new drug product to treat infantile spasms. A.R. 169 (stating that CMS was
approving a new base date AMP because “[a]s noted in [Questcor’s] letter of May 8, 2012, the
FDA approved Acthar Gel through a New Drug Application (NDA) for use in treating the
orphan condition of infantile spasms”), 617 (stating that, in accordance with the Medicaid Drug
Rebate Program statute, “the base date AMP is calculated based on the new drug application
which is approved by the FDA” and “given that the recently approved Acthar Gel was approved
under a different [NDA] from the original product, Questcor may set a new base date AMP for
this drug” (emphases added)). That CMS believed NDA number 022432 involved a different
“drug product” from the drug approved under NDA number 008372 is substantiated by CMS’s
statement in its 2012 approval letter that the agency “does not have the current capability to
allow a manufacturer to replace the original reported base date AMP with a new base date AMP
midway through the life of a product.” A.R. 617 (emphasis added).
After CMS verified that NDA number 022432 was defunct and did not involve the
approval of a new drug, the agency properly directed both Mallinckrodt and Questcor to correct
how they were reporting the drug’s base date AMP for the Medicaid Drug Rebate Program. See
43

A.R. 2 (referring to the agency’s March 12, 2019 letter (A.R. 13) and directing Mallinckrodt to
report the appropriate base date AMP for Acthar), 13 (stating that “[b]ecause H.P. Acthar gel
[sic] is currently, and always has been, produced or distributed under NDA 008372, the base date
AMP Mallinckrodt is reporting to the Drug Data Reporting for Medicaid (DDR) system does not
reflect the appropriate base date AMP, and Mallinckrodt has been underpaying Medicaid rebates
for H.P. Acthar Gel”), 81 (noting that “FDA has informed us that type-6 NDAs are
administratively closed upon approval,” “the administratively assigned NDA 022432 . . . was
only for the purpose of FDA approval of the new indication, but not for the approval and
marketing of the drug itself,” and “the approval of NDA 022432 in 2010 was not for approval of
a new drug”), 84 (stating that the “baseline data of a purchased product should be the same as the
baseline data of a product marketed previously under the same NDA”), 88 (instructing Questcor
and Mallinckrodt that the “baseline data of an NDC for a single source drug . . . must follow the
NDA”), 89 (stating that “although the NDA for the use of H.P. Acthar Gel for infantile spasms
was initially assigned number 022432” the FDA’s approval letter stated that “any future
submissions ‘should be addressed to the original NDA 008372 for this drug product’”), 106 (“On
April 13, 2016 and March 20, 2017 CMS informed Mallinckrodt LLC that it was reporting
incorrect base Average Manufacturer Price (base AMP) information and an incorrect FDA
application number in the Drug Data Reporting for Medicaid (DDR) system.”), 115 (“It is our
understanding that NDA 008372 for Acthar was approved on April 29, 1952, therefore, the
baseline data for the drug that is marketed under that NDA would be based on data from
9/30/1990 as the approval of NDA 022432 in 2010 was not for approval of a new drug.”), 154
(stating that NDA number 022432 was “no longer used”).
44

Thereafter, CMS consistently directed the manufacturers to calculate Acthar’s Medicaid
rebates using the base date AMP associated with the NDA under which Acthar was approved by
the FDA for marketing, which was NDA number 008372. A.R. 2, 13, 81, 106, 115, 133. This
direction was compliant with the clear provisos set forth in the Medicaid Drug Rebate Program
statute that tether the base date AMP to the date when a “covered outpatient drug” is “approved
by” the FDA and, if approved after October 1, 1990, when that “covered outpatient drug” was
“first marketed.” 42 U.S.C. §§ 1396r-8(c)(2)(A)(ii)(II), (B). However phrased, CMS’s message
was always the same—(1) the statute requires a single source drug’s base date AMP to be set
based on the when the FDA approved the drug for marketing, (2) the agency lacked authority to
change a drug’s base date AMP midway through the life of the drug, and (3) with respect to
Acthar, the FDA approved the drug for marketing pursuant to NDA number 008372, not defunct
NDA number 022432, which was an efficacy supplement application seeking to revise Acthar’s
label to add a new treatment indication. A.R. 13, 81, 88, 115. Thus, CMS never wavered from
the Medicaid Drug Rebate Program statute’s plain language and, contrary to Mallinckrodt’s
insistence that CMS unfairly and unlawfully changed its position, the record demonstrates that
simply was not so. And the path CMS took to reach its decision requiring Questcor and
Mallinckrodt to correct the way they were reporting Acthar’s base date AMP can be readily and
reasonably be discerned. See Bowman Transp., 419 U.S. at 286.
II. CMS COMPLIED WITH THE STATUTE AND DID NOT VIOLATE
PRINCIPLES OF FAIR NOTICE OR RETROACTIVE APPLICATION WHEN
IT DIRECTED MALLINCKRODT TO CORRECT ACTHAR’S BASE DATE
AMP
Mallinckrodt advances two final arguments. The first is that CMS failed to give
Mallinckrodt fair notice that the agency’s interpretation of the Medicaid Drug Rebate Program
statute had changed after it approved Questcor’s request to establish a new base date for Acthar
45

based on the FDA’s approval of defunct NDA number 022432. Mallinckrodt’s Summ. J. Br. 17–
21. Mallinckrodt’s second argument is that CMS’s decision requiring Mallinckrodt to correct
Acthar’s base date AMP and face the retroactive rebate payments and possible penalties that
would result is “impermissibly retroactive.” Id. at 22.
A. CMS’s 2012 Approval Letter, Pre-Enforcement Efforts, and the Medicaid

Drug Rebate Program Statute Supplied Fair Notice that a Single Source
Drug’s Base Date AMP is Tethered to the Date the Drug was Approved by
the FDA and First Marketed
Addressing Mallinckrodt’s fair notice argument first, Mallinckrodt is correct that the
requirement that federal agencies provide “fair notice” of their regulatory interpretations “has
now been thoroughly incorporated into administrative law.” Gen. Elec. Co. v. U.S. E.P.A., 53
F.3d 1324, 1329 (D.C. Cir. 1995), as corrected (June 19, 1995). It is, however, well recognized
that “in many cases the agency’s pre-enforcement efforts to bring about compliance will provide
adequate notice.” Id. Furthermore, “[i]f, by reviewing the regulations and other public
statements issued by the agency, a regulated party acting in good faith would be able to identify,
with ‘ascertainable certainty,’ the standards with which the agency expects parties to conform,
then the agency has fairly notified [that party] of the agency’s interpretation.” Id.
As an initial matter, the doctrine serves to prevent “deference to an agency’s
interpretation of its own regulations” from “validating the application of a regulation that fails to
give fair warning of the conduct it prohibits or requires.” Gates & Fox Co. v. Occupational
Safety & Health Review Comm’n, 790 F.2d 154, 156 (D.C. Cir. 1986). It therefore follows that,
if the Court is not applying a standard of deference—for example by applying Chevron, see infra
n. 20—because the statute at issue is clear and unambiguous, then the doctrine would not apply.
But even if the doctrine does apply, fair notice was supplied by the clarity of the Medicaid Drug
46

Rebate Program statute, CMS’s 2012 approval letter, and the agency’s pre-enforcement efforts to
bring about compliance.
To establish a lack of fair notice, Mallinckrodt first argues that “CMS made no mention
of its current legal position, which is that a drug might in theory be ‘marketed’ under an NDA
that differs from the one under which it was ‘approved.’” Id. at 11. But that was never CMS’s
position, at least according to the Administrative Record. As the Court has repeatedly observed,
CMS’s 2012 letter approving Questcor’s request to set a new base date AMP for Acthar indicates
that the approval was premised on CMS’s erroneous belief that a “drug product” was approved
under NDA number 022432 and, moreover, that this approved “drug product” was different from
the “drug product” approved under NDA number 008372, A.R. 617.
Another problem with Mallinckrodt’s argument is that CMS’s 2012 approval letter put
Acthar’s manufacturers on fair notice that CMS lacked the authority to change a drug product’s
base date AMP midway through the life of that product. A.R. 617. As a result, Questcor and
Mallinckrodt had fair notice that if Acthar with the infantile spasm indication was not an entirely
new drug product, CMS could not authorize a new base date AMP for it.
CMS’s pre-enforcement efforts to secure Questcor’s and Mallinckrodt’s compliance with
the Medicaid Drug Rebate Program statute by correcting Acthar’s base date AMP to reflect that
the drug was approved in 1952 under NDA number 008372 also provided the required fair
notice. From 2016 through 2019, CMS gave the manufacturers more than ample opportunity to
bring its reporting into compliance so it would not continue to accrue rebate underpayments for
which it would be liable.
Of course, fair notice was most certainly supplied by the Medicaid Drug Rebate Program
statute, which the Court has explained clearly and unambiguously sets a single source drug’s
47

base date AMP based on the date the “covered outpatient drug” was “approved by” the FDA. 42
U.S.C. §§ 1396r-8(c)(2)(A)(ii)(II), (B). Mallinckrodt has never disputed that H.P. Acthar Gel®
was approved for marketing when the FDA approved NDA number 008372 in 1952. Setting
aside Mallinckrodt’s attempt to mold a new drug out of the statutory and regulatory definitions
of “single source drug” and the FDA’s approval of now defunct NDA number 022432, which by
all accounts was actually an efficacy supplement application to revise Acthar’s label under NDA
number 008372 (and, indeed, the two NDAs were eventually consolidated), the plain language of
the statute confirms that there was never a statutory basis to set a new base date AMP for Acthar.
To the extent Mallinckrodt views this issue to be an arguable one of statutory interpretation, its
proffered interpretation is not only inconsistent with the purpose of the statute, but would
actually thwart Congress’s intent to minimize the costs of drugs under Medicaid by, as the Court
has already noted, empowering the agency and drug manufacturers to avoid the statutory rebates
by manipulating how applications involving existing drugs are administratively classified.
B. CMS’s Decision Requiring Mallinckrodt to Correct Acthar’s Base Date AMP

was not a Newly Adopted Rule or Policy to Which Concerns about
Retroactivity Apply
Mallinckrodt’s final argument is that CMS’s decision requiring Questcor and
Mallinckrodt to correct Acthar’s base date AMP reflects a change in policy that is being
improperly applied retroactively. Mallinckrodt’s Summ. J. Mot. 20. Mallinckrodt cites Retail
Wholesale & Dep’t Store Union v. NLRB, 466 F.2d 380 (D.C. Cir. 1972) (“Retail Union”), and
contends that the factors set forth in that case counsel against allowing CMS to retroactively
penalize Mallinckrodt based on the agency’s new policy. Mallinckrodt’s Summ. J. Mot. 22. The
principle of retroactivity applies, however, to newly adopted rules and policies. See Retail
Union, 466 F.2d at 389 (discussing the principle). Here, though, CMS’s decision was not the
product of a change in policy or a new policy—and the Court has concluded that Mallinckrodt
48

had fair notice about how CMS was interpreting the Medicaid Drug Rebate Program statute via
the agency’s 2012 letter authorizing Questcor to establish a new base date AMP, among other
indications. Consequently, the retroactivity principle is inapplicable when considered in light of
the particular facts of this case.
CONCLUSION
For all the foregoing reasons, the Court will deny Mallinckrodt’s Motion for Preliminary
Injunction, ECF No. 4, grant the Government’s Motion for Summary Judgment, ECF No. 17,
and deny Mallinckrodt’s Cross Motion for Summary Judgment, ECF No. 22. An appropriate
order will be entered in the public docket.
March 13, 2020 ___________________________________

Thomas F. Hogan
SENIOR UNITED STATES DISTRICT JUDGE
49


Plaintiff,
v.
Defendants.
Upon consideration of Mallinckrodt’s Motion for Preliminary Injunction, the
Government’s Motion for Summary Judgment, Mallinckrodt’s Cross Motion for Summary
Judgment, the responses thereto, the Administrative Record, and the entire record in this case,
and for the reasons set forth in the Memorandum Opinion that was issued today under seal, it is
ORDERED that Mallinckrodt’s Motion for Preliminary Injunction, ECF No. 4, is
DENIED. It is
FURTHER ORDERED that the Government’s Motion for Summary Judgment, ECF
No. 17 is GRANTED. Accordingly, the Clerk of the Court shall enter JUDGMENT IN
FAVOR OF the defendants. It is
FURTHER ORDERED that Mallinckrodt’s Cross Motion for Summary Judgment, ECF
No. 22, is DENIED. It is finally
ORDERED that the parties shall confer and jointly submit a proposed redacted version

of the Memorandum Opinion. The joint submission shall be filed under seal on or before May
13, 2020, absent the parties’ agreement to an earlier date.
SO ORDERED.
March 13, 2020 ___________________________________

Thomas F. Hogan

Case 1:19-cv-01471-TFH Document 46 Filed 05/29/20 Page 1 of 28

Plaintiff,
v. Civil Action No. 19-cv-1471 (TFH)
Defendants.
MEMORANDUM OPINION
Pending before the Court is plaintiff Mallinckrodt ARD LLC’s (Mallinckrodt’s)
Emergency Motion for Reconsideration and Stay of Entry of Judgment Pending Reconsideration
or, Alternatively, Injunction Pending Appeal, ECF No. 37. Mallinckrodt invokes Rules 59, 60,
and 62(c) of the Federal Rules of Civil Procedure, along with Rule 8(a)(1) of the Federal Rules
of Appellate Procedure, to request that the Court do the following three things: (1) reconsider its
March 13, 2020, memorandum opinion granting summary judgment in favor of defendants
Seema Verma, Administrator of the Centers for Medicare & Medicaid Services (CMS), and Alex
M. Azar II, Secretary of the United States Department of Health and Human Services (HHS);
(2) stay the entry of judgment pending reconsideration; and (3) issue an injunction prohibiting
CMS from “locking” Mallinckrodt out of the Drug Data Reporting for Medicaid (DDR) system
or otherwise enforcing the judgment before Mallinckrodt can litigate an appeal. Mem. of P. &
A. in Support of Pl.’s Emergency Mot. 1, ECF No. 37-1 (hereinafter cited as “Mallinckrodt’s
Br.”). Mallinckrodt contends that these judicial actions are warranted because the Court
“fundamental[ly] misread[]” the controlling statute and the company faces an “existential threat”

of financial ruin if CMS locks the company out of the Drug Data Reporting for Medicaid system
before an appeal is resolved. Mallinckrodt’s Br. 3. The defendants oppose the motion.
Because the Court holds that Mallinckrodt failed to carry its burden of establishing that
reconsideration is appropriate, that it is likely to succeed on the merits of an appeal, or that it is
likely to be irreparably harmed absent a stay pending appeal, the Court will deny Mallinckrodt’s
motion for the reasons that follow.
DISCUSSION 1
I. MALLINCKRODT FAILED TO ESTABLISH THAT RECONSIDERATION IS

WARRANTED
Mallinckrodt’s motion is titled as one for “reconsideration” but, aside from vague first-
paragraph citations to Rules 59 and 60 of the Federal Rules of Civil Procedure, Mallinckrodt
never identifies the relevant provisions of these rules that it believes authorize reconsideration,
the legal standards associated with those provisions, or how it believes it has satisfied those
standards. See Mallinckrodt’s Mot. 1; Mallinckrodt’s Br. 1, 3–12; Mallinckrodt’s Reply Br. 1–
10, ECF No. 41. Because Mallinckrodt failed to specify the relevant provisions of the rules that
it is relying on, the Court is left to assume that they are Rule 59’s subparagraph (e) and Rule 60’s
subparagraph (b), although it is unclear which of subparagraph (b)’s enumerated provisions
Mallinckrodt is advancing. Regardless, reconsideration under either Rule 59(e) or Rule 60(b) is
considered “extraordinary” and unwarranted when a litigant simply recycles legal arguments that
were previously considered and rejected by a court, as is the case here. See, e.g., Leidos, Inc. v.
Hellenic Republic, 881 F.3d 213, 217 (D.C. Cir. 2018) (stating that reconsideration under Rule
59(e) is an “extraordinary measure” that cannot be used to reargue matters a court already
1
This opinion assumes that the reader is familiar with the facts of the case, which are discussed
at length in the Court’s March 13, 2020, memorandum opinion. See Mem. Op., ECF No. 35.

considered); Kramer v. Gates, 481 F.3d 788, 790 (D.C. Cir. 2007) (“[R]elief under Rule 60(b)(6)
is appropriate only in ‘extraordinary circumstances.’” (quoting Ackermann v. United States, 340
U.S. 193, 199 (1950))); Howard v. U.S. Dep’t of Educ., 756 F. Supp. 2d 72, 74 (D.D.C. 2010)
(rejecting reconsideration under Rule 60(b) when a plaintiff “rehash[ed] the same argument”
made in a prior motion).
A. Rule 59(e) of the Federal Rules of Civil Procedure
Addressing Rule 59(e) first, this rule permits a court to exercise the discretion to alter or
amend a judgment when (1) the controlling law has changed, (2) new evidence has become
available, or (3) the court needs to correct a clear error or prevent manifest injustice. Firestone v.
Firestone, 76 F.3d 1205, 1208 (D.C. Cir. 1996) (per curiam); Fed. R. Civ. P. 59(e). Absent one
of these three circumstances, though, “[a] district court need not grant a Rule 59(e) motion.”
Mohammadi v. Islamic Republic of Iran, 782 F.3d 9, 17 (D.C. Cir. 2015). And it is well
established that the rule is not available to “relitigate old matters.” Exxon Shipping Co. v. Baker,
554 U.S. 471, 486 (2008) (quoting 11 C. Wright & A. Miller, Federal Practice and Procedure
§ 2810.1, pp. 127–128 (2d ed.1995)).
As the Court already noted, absent from Mallinckrodt’s motion and supporting legal
briefs is any discussion about the legal standards that apply to a Rule 59(e) motion or how
Mallinckrodt believes that it has satisfied them. See Mallinckrodt’s Mot.; Mallinckrodt’s Br.;
Mallinckrodt’s Reply Br., ECF No. 41. Mallinckrodt offers nothing in the way of an argument
hinting at the possibility that the controlling law has changed or that new evidence is available.
Moreover, a word search of Mallinckrodt’s motion, supporting legal brief, and reply brief reveals
that the terms “clear error” and “manifest injustice” are nowhere to be found. See id.

At best, Mallinckrodt argues that the Court’s “construction of the [Medicaid Drug Rebate
Program] statute as focusing on whether the drug is ‘an entirely new drug’ is simply unfounded”
therefore “[r]econsideration should be granted in order to permit the Court to engage again with
the relevant statutory language, with the parties’ briefs, and with the transcript of the August 2,
2019 argument on this critical point of statutory interpretation.” Mallinckrodt’s Mot. 9. But the
Court’s opinion never focused on whether Acthar was an entirely new drug. Instead, it focused
on what the statute actually says, which is that the base date Average Manufacturer Price (AMP)
is set on the date the “covered outpatient drug” was “approved by” the United States Food and
Drug Administration (FDA) and “first marketed.” Mem. Op. 35–37, ECF No. 35.
The statute plainly does not contemplate that a covered outpatient drug’s base date AMP
can be “reset” later during that drug’s lifecycle, as CMS correctly cautioned Mallinckrodt in
2012, A.R. 617, absent, perhaps, FDA-approved new dosage forms or strengths, see 42 U.S.C.
§ 1396r-8(c)(2), which are not at issue here. And fatal to Mallinckrodt’s case are its concessions
that (1) the covered outpatient drug H.P. Acthar Gel® was “approved by” the FDA in 1952
under New Drug Application (NDA) number 008372 and (2) the only things the FDA approved
under defunct NDA number 022432 were the addition of an infantile spasm indication along
with other label revisions to a “decades-old drug.” 2 Verified Compl. ¶ 27, ECF No. 1;
2
Paragraphs 29 and 30 of Mallinckrodt’s Verified Complaint summarize the very facts that
reveal as a charade Mallinckrodt’s contention that the FDA approved a “distinct”—i.e., new—
drug under NDA 022432:
Questcor acquired H.P. Acthar Gel in 2001, and in 2006 sought to have the product
approved for the treatment of IS. The request for approval, which presented
information and data from published literature on the use of H.P. Acthar Gel for IS,
was submitted as a supplement to the existing NDA (sNDA). In May 2007, FDA
issued what is now called a “Complete Response Letter” (CRL), in which the
agency declined to approve Questcor’s sNDA, explaining that the company had not
4

Mallinckrodt’s Reply Br. 5 (admitting that what the FDA approved in 2010 were label revisions
for a “decades-old drug product,” including adding an infantile spasm indication).
Divested of its reliance on sheer insistence, Mallinckrodt’s argument amounts to a bald
disagreement with the outcome that fails to establish, or even present, a clear error or manifest
injustice, neither of which can be “demonstrated by the disappointment of the losing party.” Oto
v. Metro. Life Ins. Co., 224 F.3d 601, 606 (7th Cir. 2000). Upon careful consideration of
Mallinckrodt’s motion and supporting legal briefs, it is clear to the Court that the company
shown a sufficient nexus between the product and the relied-upon studies to meet
the standards for approval.
Consistent with FDA procedure, the sNDA remained pending while Questcor and
FDA reached agreement on how to address the asserted inadequacy, and the
company set about developing the necessary data. During this period, FDA
unilaterally converted the sNDA to a new, separate NDA, to which (consistent with
standard procedures) the agency assigned a distinct NDA number: NDA 022432.
The agency took this action because it concluded the IS indication was
fundamentally different from the other uses for which the product had been
approved, and required review by a different component within FDA than had to
date been responsible for the drug. The new NDA was classified as a “Type 6”
NDA, which was used for drug products that had already been approved or
marketed by the same applicant, but were intended for a new indication or claim.
Verified Comp. ¶¶ 29, 30 (emphases added). These paragraphs serve as an express admission
that no distinct “drug” was “approved by” the FDA under defunct provisional NDA number
022432; rather, NDA number 022432 served solely as a ministerial (and temporary) mechanism
for the FDA to facilitate another division reviewing what Mallinckrodt does not dispute was, in
fact, “a supplement to the existing NDA”—i.e., NDA number 008372. More to the point,
Mallinckrodt admits that NDA number 022432 involved a “drug product” that “had already been
approved or marketed” but was “intended for a new indication or claim,” Verified Compl. ¶ 30,
which means that there was no new (or, as Mallinckrodt seeks to characterize it, “distinct”) drug
that could qualify as a separate “covered outpatient drug . . . approved by” the FDA after October
1, 1990 for the purpose of resetting the base date AMP pursuant to 42 U.S.C. § 1396r-
8(c)(2)(A)(ii)(II), as amended by 42 U.S.C. § 1396r-8(c)(2)(B), see infra Part II(A). There is no
mistaking that the statute expressly requires that the FDA “approval” be of a “covered outpatient
drug” under 42 U.S.C. § 1396r-8(c)(2)(A)(ii)(II) and not simply be “approval” of an NDA, as
Mallinckrodt urges.

“merely [takes] umbrage with the court’s ruling and rehashe[s] old arguments” without ever
establishing a legal basis for reconsideration under Rule 59(e). Id. As a result, Mallinckrodt
failed to carry its burden of demonstrating that reconsideration is warranted under that rule. See,
e.g., Schoenman v. F.B.I., 857 F. Supp. 2d 76, 80 (D.D.C. 2012) (stating that “[m]otions under
Rule 59(e) are disfavored and the moving party bears the burden of establishing extraordinary
circumstances warranting relief from a final judgment” (internal quotation marks omitted));
Niedermeier v. Office of Baucus, 153 F. Supp. 2d 23, 28 (D.D.C. 2001) (same).
B. Rule 60(b) of the Federal Rules of Civil Procedure
Turning to Rule 60(b), this rule is “intended to preserve the delicate balance between the
sanctity of final judgments . . . and the incessant command of the court’s conscience that justice
be done in light of all the facts.” Good Luck Nursing Home, Inc. v. Harris, 636 F.2d 572, 577
(D.C. Cir. 1980) (quotation marks omitted). Rule 60(b) sets forth six grounds upon which a
litigant may obtain relief from a final judgment, order, or proceeding, only two of which are
potentially relevant here. The first ground is Rule 60(b)(1), which provides that the court may
relieve a litigant from a final judgment, order, or proceeding for “mistake, inadvertence, surprise,
or excusable neglect.” Fed. R. Civ. P. 60(b)(1). The second ground is Rule 60(b)(6), which
allows the Court to relieve a litigant from a final judgment, order, or proceeding for “any other
reason that justifies relief.” Rule 60(b)(6). Mallinckrodt again neglects to identify which ground
it is invoking to seek relief and fails to argue—much less establish—that relief is warranted
under either.
Notwithstanding that Rule 60(b) “grants federal courts broad authority to relieve a party
from a final judgment upon such terms as are just,” Liljeberg v. Health Services Acquisition
Corp., 486 U.S. 847, 863 (1988), a litigant nevertheless “must clear a very high bar” to secure

this relief, Kramer, 481 F.3d at 792. With respect to Rule 60(b)(1), relief resulting from mistake,
inadvertence, surprise, or excusable neglect is “rare” because district courts are permitted to
“correct only limited types of substantive errors.” Hall v. C.I.A., 437 F.3d 94, 99 (D.C. Cir.
2006). And as far as Rule 60(b)(6) is concerned, relief under that provision “is even more rare,
being available only in ‘extraordinary circumstances.’” Owens v. Republic of Sudan, 864 F.3d
751, 818 (D.C. Cir. 2017), certified question answered, 194 A.3d 38 (D.C. App. 2018) (quoting
Ackermann v. United States, 340 U.S. 193, 199 (1950)). Furthermore, the United States Court of
Appeals for the District of Columbia Circuit has noted that “a dispute over the proper
interpretation of a statute, by itself, does not likely justify relief under Rule 60(b)(6).” Id. at 818
n.11. Precedent also “makes clear that Rule 60(b)(6) is not an opportunity for unsuccessful
litigants to take a mulligan,” Kramer, 481 F.3d at 792, nor can it serve to “rescue a litigant from
strategic choices that later turn out to be improvident,” Good Luck Nursing Home, Inc., 636 F.2d
at 577.
Faced with insufficient legal arguments from which the Court can discern (1) which Rule
60(b) provisions Mallinckrodt is invoking and (2) whether relief is warranted under any such
provisions, the Court is deprived of any legal basis to grant the requested reconsideration.
C. Summary Conclusion
Whether Mallinckrodt intended to lend an air of mystery to its motion or to obfuscate an
argument it viewed as weak, the fact of the matter is that, as the Seventh Circuit aptly observed
nearly three decades ago, “[j]udges are not like pigs, hunting for truffles buried in briefs.”
United States v. Dunkel, 927 F.2d 955, 956 (7th Cir. 1991). The Court is not obligated to divine
from Mallinckrodt’s briefs a viable legal argument that it failed to adequately present. To the
contrary, the burden to demonstrate that reconsideration is warranted under either Rule 59 or

Rule 60 belongs to Mallinckrodt. See, e.g., Schoenman, 857 F. Supp. 2d at 80; Niedermeier, 153
F. Supp. 2d at 28; Owens, 864 F.3d at 819.
Because Mallinckrodt failed to provide any legal discussion about how or why Rules 59
and 60 apply, it failed to carry its burden of supplying the “extraordinary” circumstances that
justify relief under either rule and, in any event, reconsideration is not available to reargue
grounds the Court already considered and found unconvincing. See, e.g., Leidos, 881 F.3d at
217; Kramer, 481 F.3d at 790; Howard, 756 F. Supp. 2d at 74. For all the foregoing reasons, the
Court will decline Mallinckrodt’s invitation to exercise judicial discretion by granting
reconsideration under either rule. Mallinckrodt’s motion for reconsideration will therefore be
denied.
II. A STAY PENDING APPEAL IS NOT WARRANTED
In addition to reconsideration, Mallinckrodt also seeks to stay the entry of judgment
pending reconsideration and enjoin the defendants from “locking” the company out of the federal
database that governs Medicaid rebates until the company can resolve an appeal of the Court’s
March 13, 2020, decision granting summary judgment in the defendants’ favor. Mallinckrodt’s
Mot. 1. On May 8, 2020, the parties filed a Joint Notice of Parties, ECF No. 45, which advised
the Court that the defendants “agreed to refrain from locking Mallinckrodt out of CMS’s online
data reporting system until June 14, 2020.” The Court commends the parties for collaborating to
reach this intermediate resolution without the need for judicial intervention. Although the
parties’ agreement and this opinion appear to moot Mallinckrodt’s requested stay of the Court’s
judgment pending reconsideration, see, e.g., Reporters Comm. for Freedom of Press v. Sampson,
591 F.2d 944, 950 (D.C. Cir. 1978) (“[A]n issue is moot if it has lost its character as a present,
live controversy.”), Mallinckrodt’s request for an injunction to prevent the defendants from
locking the company out of the database pending the resolution of an appeal remains a live issue.
8

Mallinckrodt asserts that it is entitled to an injunction because it is likely to succeed on
the merits of an appeal and would suffer irreparable harm if during an appeal it is unable to
report or revise Acthar’s drug pricing in the Drug Data Reporting for Medicaid database, it is
subjected to civil monetary penalties, and its National Drug Rebate Agreement (NDRA) is
suspended. 3 Mallinckrodt’s Mot. 13. The defendants counter by arguing that, among other
points, “a stay would inflict immense harm upon the Government and the public,” Gov’t’s Opp’n
Br. 4, “equity clearly tips against permitting Mallinckrodt to continue course by withholding
payment pending appeal to the detriment of the Medicaid Program,” id. at 4–5, and the
“magnitude of the harm to the Government and public is severe and continuing to grow” given
that “Mallinckrodt has effectively retained an interest-free loan at taxpayers’ expense to date—
indeed, CMS may never be able to recover interest on Mallinckrodt’s past underpayment,” id. at
5. The defendants also challenge Mallinckrodt’s claim that if an injunction is not granted
Mallinckrodt’s immediate liability for approximately $600 million in Medicaid rebate
underpayments would threaten the company’s existence, id. at 6, particularly when the company
recently stated that 2019 was a successful year, id. at 6–7.
As an initial matter, Mallinckrodt’s request to prohibit CMS from “altering the status quo
by locking [Mallinckrodt] out of the Drug Data Reporting for Medicaid (DDR) system or taking
any other enforcement action pending appeal” is presented as an “alternative” request for an
3
Mallinckrodt argues that “because it is the NDRA that is the condition precedent to states’
obligation to cover a manufacturer’s covered outpatient drugs, when Mallinckrodt’s NDRA is
suspended, states will no longer be required to cover Mallinckrodt’s covered outpatient drugs,
including Acthar.” Mallinckrodt’s Mot. 13. The irony of this argument cannot elude
Mallinckrodt in light of its veiled threat to quit the Medicaid Drug Rebate Program in 2012. See
A.R. 142 (insinuating that Acthar’s ongoing participation in the program might be “untenable” if
CMS refused to reduce its rebate liability but that its departure was not “in the interest of CMS,
as we believe state Medicaid programs likely still will be required to cover Acthar’s use for
infantile spasms even if Questcor does exit the program”).

“injunction.” Mallinckrodt’s Mot. 1. Mallinckrodt cites, however, Rule 62 of the Federal Rules
of Civil Procedure, which governs “stays” of judicial proceedings. Although an injunction “has
some functional overlap” with a stay pending appeal, the Supreme Court’s decision in Nken v.
Holder, 556 U.S. 418, 429 (2009), indicates that, in circumstances like this one where the
moving party is asking the Court to maintain the status quo by suspending the opposing party’s
authority to act—i.e., by suspending the Court’s March opinion and judgment—the appropriate
remedy is a stay, albeit the same legal standards apply to stays pending appeal and injunctions,
see Washington Metro. Area Transit Comm’n v. Holiday Tours, Inc., 559 F.2d 841, 842 n.1
(D.C. Cir. 1977) (noting that the factors to establish the stay of the administrative order at issue
in Virginia Petroleum Jobbers Ass’n v. Fed. Power Comm’n, 259 F.2d 921 (D.C. Cir. 1958),
“also apply to motions for preliminary injunctions and motions for stays of district court orders
pending appeal”).
The D.C. Circuit has characterized the legal standards to obtain a stay as “stringent” 4 and
identified the following four factors as determinative:
(1) Has the petitioner made a strong showing that it is likely to prevail on the merits
of its appeal? Without such a substantial indication of probable success, there would
be no justification for the court’s intrusion into the ordinary processes of
administration and judicial review. (2) Has the petitioner shown that without such
relief, it will be irreparably injured? . . . (3) Would the issuance of a stay
substantially harm other parties interested in the proceedings? . . . (4) Where lies
the public interest?
Washington Metro. Area Transit Comm’n, 559 F.2d at 842–43 (quoting Virginia Petroleum
Jobbers Ass’n, 259 F.2d at 925). Historically, courts in this jurisdiction applied a so-called
4
See, e.g., Advanta Bank v. F.D.I.C., No. 10-5051, 2010 WL 1050253, at *1 (D.C. Cir. Mar. 11,
2010) (per curiam) (referring to the “stringent standards required for a stay pending appeal”);
Kiyemba v. Bush, No. 08-5424, 2008 WL 4898963, at *1 (D.C. Cir. Oct. 20, 2008) (per curiam)
(same); Al-Bandar v. Bush, No. 06 5425, 2006 WL 3986241, at *1 (D.C. Cir. Dec. 29, 2006) (per
curiam) (same).
10

“sliding scale” analysis to these factors whereby “a strong showing on one factor could make up
for a weaker showing on another.” Sherley v. Sebelius, 644 F.3d 388, 392 (D.C. Cir. 2011).
After the Supreme Court’s decision in Winter v. Natural Res. Def. Council, Inc., 555 U.S. 7
(2008), however, the D.C. Circuit questioned this approach on the ground that “Winter could be
read to create a more demanding burden than the sliding-scale analysis requires.” Sherley, 644
F.3d at 392 (internal quotation marks omitted). The D.C. Circuit has not yet decided, however,
whether Winter requires that the sliding scale approach be “abandoned.” Archdiocese of
Washington v. Washington Metro. Area Transit Auth., 897 F.3d 314, 334 (D.C. Cir. 2018), cert.
denied, 140 S. Ct. 1198 (2020). At a minimum, though, the D.C. Circuit has stated that it
“read[s] Winter at least to suggest if not to hold that a likelihood of success is an independent,
free-standing requirement for a preliminary injunction.” Id. at 393.
Indeed, the Supreme Court made clear in Winter that a movant must establish that it is
“likely” both that he will succeed on the merits and that irreparable harm will follow if the
requested stay is withheld. 555 U.S. at 21–22. The Supreme Court rejected as “too lenient” a
standard according to which a movant who makes a “strong” showing that success on the merits
is “likely” would then be permitted to make a lesser showing that irreparable harm is merely
“possible.” Id. at 22; see also id. at 20 (stating that “[a] plaintiff seeking a preliminary injunction
must establish that the is likely to succeed on the merits” and “that he is likely to suffer
irreparable harm,” as well as “that the balance of equities tips in his favor” and “that an
injunction is in the public interest”). Because the movant must demonstrate both of these factors
to a degree of probability characterized as “likely,” there appears to be no room for the Court to
assess that a more robust showing of one opens the door to a lesser showing of the other, at least
to the extent that the lesser showing is something that falls below “likely.” See Davis v. Pension
11

Ben. Guar. Corp., 571 F.3d 1288, 1296 (D.C. Cir. 2009) (Kavanaugh, J., concurring)
(“Importantly, the Winter Court rejected the idea that a strong likelihood of success could make
up for showing only a possibility (rather than a likelihood) of irreparable harm. In other words,
the Court ruled that the movant always must show a likelihood of irreparable harm.”).
Over the course of the dozen years or so since the Supreme Court’s decision in Winter,
however, the D.C. Circuit has not found an occasion to expressly resolve the fate of the sliding-
scale approach. See Archdiocese of Washington, 897 F.3d at 334 (stating that the case presented
no occasion to decide whether the sliding-scale approach has continuing vitality after Winter);
League of Women Voters of United States v. Newby, 838 F.3d 1, 7 (D.C. Cir. 2016) (same).
Instead, it has left the question open and avoided it in at least one case by holding that the
moving party failed to establish that injunctive relief was appropriate “even under the less
demanding sliding-scale analysis.” Sherley, 644 F.3d at 393; see also Aamer v. Obama, 742
F.3d 1023, 1043 (D.C. Cir. 2014) (stating that the fate of the sliding-scale approach “remains an
open question”). Applying the sliding-scale approach means that “in cases where the other three
factors strongly favor issuing an injunction, a plaintiff need only raise a ‘serious legal question’
on the merits” rather than demonstrating that success is “likely.” Aamer, 742 at 1043 (quoting
Sherley, 644 F.3d at 393, 398)). In any event, the Court need not attempt to reconcile the tension
between the Supreme Court’s decision in Winter and the D.C. Circuit’s sliding-scale approach
because Mallinckrodt cannot establish that the required factors favor a stay even if the sliding-
scale approach is applied.
The Court will address each of the factors in turn, beginning, as it must, with the
likelihood of success on the merits and irreparable harm, which the prior discussion foreshadows
as being “the most critical.” Nken, 556 U.S. at 434. If Mallinckrodt satisfies these two factors,
12

“the traditional stay inquiry calls for assessing the harm to the opposing party and weighing the
public interest,” although “[t]hese factors merge when the Government is the opposing party,” as
is the case here. Id. at 435.
A. Likelihood of Success on the Merits
Mallinckrodt must demonstrate that it is likely to succeed on the merits of its appeal to
prevail on its motion for a stay. See Citizens for Responsibility & Ethics in Washington v. Fed.
Election Comm’n, 904 F.3d 1014, 1019 (D.C. Cir. 2018) (noting that when an appeal “shows
little prospect for success” that is “an arguably fatal flaw for a stay”); Apotex, Inc. v. Food &
Drug Admin., 449 F.3d 1249, 1253 (D.C. Cir. 2006) (dispensing with the need to consider the
other stay factors when success on the merits was unlikely). Mallinckrodt contends that it will
succeed on the merits of an appeal because the Court misinterpreted the provisions of the
Medicaid Drug Rebate Program statute that apply to “single source drugs” and “[t]here simply
can be no dispute at this point that under 42 U.S.C. § 1396r-8(c)(2)(A), if a drug product is a
distinct ‘single source drug,’ it is entitled to its own base date AMP—whether or not it is an
‘entirely new drug.’” Mallinckrodt’s Br. 4, 9 (quotation). Mallinckrodt also argues that the
Court “gave too short shrift to CMS’s own regulations,” id. at 9, and overlooked what
Mallickrodt views to be inconsistent explanations CMS advanced for initially authorizing the
company to set a new base date AMP for Acthar but then later negating that authorization, id. at
10. Mallinckrodt further challenges the Court’s determinations that CMS’s actions did not
violate principles of fair notice and retroactivity. Id. at 12.
Like Mallinckrodt’s request for reconsideration, its request for a stay reprises the same
arguments the company presented to the Court during the litigation of the parties’ motions for
summary judgment, which were considered and resolved in the Court’s March 13, 2020
13

memorandum opinion. Mallinckrodt offers nothing new in the way of legal arguments and the
Court stands by the analyses set forth in that opinion, which explains why Mallinckrodt’s
arguments are unconvincing and forestalled by the Medicaid Drug Rebate Program statute’s
plain language. See Mem. Op. 30–49. Nevertheless, confronted by Mallinckrodt’s persistent
effort to convince the Court that the statute says something that it does not, the Court will walk
through some of the essential points of the analyses again.
To reiterate, the question in this case is whether CMS properly determined that
Mallinckrodt has been using the wrong base date AMP to calculate federally mandated rebates
that Mallinckrodt must pay for the H.P. Acthar Gel® pharmaceutical drug under the statutory
Medicaid Drug Rebate Program, which is part of the Medicaid Act, otherwise known as Title
XIX of the Social Security Act, 79 Stat. 343 (codified as amended at 42 U.S.C. §§ 1396–1396v).
Mallinckrodt agrees that the relevant section of the Medicaid Drug Rebate Program statute that
establishes how it must calculate Achtar’s rebates is 42 U.S.C. § 1396r-8(c), which is the section
that applies to “single source drugs.” See Mallinckrodt’s Br. 4. The statute currently defines the
phrase “single source drug” to mean in relevant part “a covered outpatient drug . . . which is
produced or distributed under a new drug application [NDA] approved by the Food and Drug
Administration.” 42 U.S.C. § 1396r-8(k)(7)(iv).
Mallinckrodt’s entire case is premised on convincing the Court that Acthar with the infantile
spasm indication qualifies as a “distinct” single source drug from the version of Acthar that the FDA
approved in 1952 under NDA number 008372. See Mallinckrodt’s Br. 4 (asserting that “because
Acthar constitutes a legally distinct ‘single source drug,’ it is entitled to a new base date AMP based
on the plain language of the statute”). To get there, Mallinckrodt claims that Acthar has been
“produced and distributed” under NDA number 022432, which was an efficacy supplement
application that started out as Supplement Number S-039 to NDA number 008372 but was later
14

provisionally categorized as a “Type 6 NDA” by the FDA and assigned number 022432 solely as
a bureaucratic mechanism to secure the application’s review by a different FDA division from
the one that first evaluated it. 5 See supra n. 3; A.R. 157, 344, 856–57, 869. Importantly,
Mallinckrodt does not dispute that the Type 6 designation “was used for drug products that had
already been approved or marketed by the same applicant, but were intended for a new indication or
claim,” id. ¶ 30 (emphasis added). Equally important is the fact that Mallinckrodt has never disputed
that Acthar with the infantile spasm indication is not a new drug, see Mallinckrodt’s Reply Br. 5
(arguing that CMS “could not possibly have assumed that it was approving an ‘entirely new drug’”
based on “references” to Acthar’s history in the record), and that what the FDA approved in 2010
was the drug’s use for a new indication and revised labeling, see id. (conceding that the 2010
approval involved “a decades-old drug, approved for a new orphan indication under a distinct
NDA”).
Additionally, Mallinckrodt has never disputed the fact that, when the FDA approved the
efficacy supplement application that was provisionally assigned NDA number 022432, the agency
told Mallinckrodt’s predecessor, Questcor, to address all submissions “to the original NDA 008372
for this drug product” 6 and stop using NDA number 022432, A.R. 706 (stating “[i]n the future, do
5
The FDA explained that “[i]n the case of Acthar Gel, the parent NDA (008372) and all of its
supplements were reviewed by the Division of Metabolic and Endocrine Products” but “review
of the infantile spasms indication was conducted by the Division of Neurology Products.” A.R.
157. Mallinckrodt does not dispute that “[t]he agency took this action because it concluded the
IS [infantile spasm] indication was fundamentally different from the other uses for which the
product had been approved, and required review by a different component within FDA than had
to date been responsible for the drug.” Verified Compl. ¶ 30.
6
The Court noted in the memorandum opinion that the FDA’s October 15, 2010 letter approving
NDA number 022432 made clear that the agency viewed Acthar with the infantile spasm
indication to be the same drug product as the version of Acthar that was approved in 1952.
Mem. Op. 18 (quoting A.R. 312 (stating that “all ‘other submissions should be addressed to the
original NDA 008372 for this drug product, not to this NDA’” (emphasis added))), 35.
15

not make submissions to this NDA [022432] except for the final printed labeling”) (emphasis added).
Thus, as of date the efficacy supplement application was approved in 2010, NDA number 022432
became obsolete and neither Questcor nor Mallinckrodt should have used it.
As the Court discussed in its memorandum opinion, absent Questcor’s and
Mallinckrodt’s self-interested acts of “producing and distributing” Acthar using NDA number
022432 in defiance of the FDA’s direction not to, the companies lack any plausible hook to
claim that Acthar with the infantile spasm indication is a new or distinct “single source drug.”
Mallinckrodt’s position is viable only if the Court either accepts or ignores the company’s
manipulation of the statute by producing and distributing Acthar using the defunct provisional
NDA number that the FDA told the company not to use—a manipulation that Mallinckrodt seeks
to further by applying a hyper-literal interpretation of the definition of “single source drug.”
Surely it is implicit in the statute that the covered outpatient drug at issue is legitimately and lawfully
being “produced or distributed” under the claimed “new drug application” and “what is . . . implied
in a statute . . . is as effectual as what is expressed.” Bd. of Sup’rs of Wood Cty. v. Lackawana Iron
& Coal Co., 93 U.S. 619, 624 (1876). Otherwise, the purposes of the Medicaid Drug Rebate
Program statute to provide medical assistance to the poor and facilitate that effort by minimizing
drug costs could be easily avoided and even preposterous scenarios would permit manufacturers to
lay claim to a new base date AMP.
For example, Mallinckrodt’s theory would accommodate a less than honest manufacturer
resetting a drug’s base date AMP by suddenly producing and distributing an existing drug using an
FDA-approved NDA number that applied to an entirely different drug. There might be other
regulatory mechanisms that make that scenario improbable if not impossible, but one can see the
point. By Mallinckrodt’s reckoning, such a scenario would satisfy the statute because all that is
required to set a new base date AMP, so Mallinckrodt argues, is a literal showing that a covered
16

outpatient drug is being “produced or distributed” under a “new drug application approved by the
FDA”—and it does not matter whether that NDA involved the FDA approving something other than
a “drug” (such as a label revision, as is the case here), or that the application was rendered obsolete
upon approval so no drug could be “produced or distributed” under it (as is also the case here), or
that the application was for a different drug entirely (hypothetical). Mallinckrodt has reaped a true
windfall to the determent of both the nation’s poor and its taxpayers by adhering to this legally
untenable position. 7
Moreover, as the Court explained in its memorandum opinion, even if Mallinckrodt’s
interpretation of the “single source drug” definition could carry the day, it still cannot prevail on the
merits because a single source drug’s base date AMP is set based on when the relevant “covered
outpatient drug” was “approved by” the FDA and it is not, as Mallinckrodt insists, automatically set
based on whether a covered outpatient drugs qualifies as a “single source drug.” 8 Mem. Op. 32–42.
Contrary to Mallinckrodt’s position, this is what the Medicaid Drug Rebate Program statute
actually says about the additional rebate for single source drugs and, in particular, when the base
date AMP may be set:
7
The Court finds it noteworthy that Mallinckrodt has never come forward with an example of an
occasion when CMS authorized a new base date AMP for a drug based solely on the FDA
approving an efficacy supplement application for that drug, whether in the form of a “new drug
application” or otherwise.
8
Mallinckrodt characterizes this as a “different test.” Mallinckrodt’s Br. 4. The only test the
Court applied in this case, however, was a test that asked what the statute actually says. The
issue the Court “homed in on,” Mallinckrodt’s Br. 5, was whether the statutory definition of
“single source drug” can be satisfied when the FDA-approved NDA at issue does something
other than “approve” a “drug,” such as by approving a label revision, as is the case here, Mem.
Op. 40 (stating that “[n]owhere in the Medicaid Drug Rebate Program statute does it provide for
a single source drug’s base date AMP to be reset based solely on the FDA approving a so-titled
‘New Drug Application’ that does something other than ‘approve’ a ‘covered outpatient drug,’ as
occurred here”).
17

(A) In general
The amount of the rebate specified in this subsection for a rebate period, with
respect to each dosage form and strength of a single source drug or an innovator
multiple source drug, shall be increased by an amount equal to the product of--
(i) the total number of units of such dosage form and strength dispensed
after December 31, 1990, for which payment was made under the
State plan for the rebate period; and
(ii) the amount (if any) by which--
(I) the average manufacturer price for the dosage form and
strength of the drug for the period, exceeds
(II) the average manufacturer price for such dosage form and
strength for the calendar quarter beginning July 1, 1990
(without regard to whether or not the drug has been sold or
transferred to an entity, including a division or subsidiary of
the manufacturer, after the first day of such quarter),
increased by the percentage by which the consumer price
index for all urban consumers (United States city average)
for the month before the month in which the rebate period
begins exceeds such index for September 1990.
(B) Treatment of subsequently approved drugs
In the case of a covered outpatient drug approved by the Food and Drug
Administration after October 1, 1990, clause (ii)(II) of subparagraph (A) shall be
applied by substituting “the first full calendar quarter after the day on which the
drug was first marketed” for “the calendar quarter beginning July 1, 1990” and “the
month prior to the first month of the first full calendar quarter after the day on which
the drug was first marketed” for “September 1990”.
42 U.S.C. § 1396r-8(c)(2).
The first highlighted subsection—§ 1396r-8(c)(2)(A)(ii)(II)—is the statutory base date
AMP for drugs that the FDA approved on or before October 1, 1990. 9 See, e.g., A.R. 1020
(National Drug Rebate Agreement). The second highlighted subsection—
9
Mallinckrodt contends that this provision merely “sets the time period during which the base
date AMP is calculated,” Mallinckrodt’s Br. 6 (emphasis in original), but the National Drug
Rebate Agreement, to which Mallinckrodt is a party, says otherwise and states that this provision
is the “base date AMP.” See A.R. 1020 (defining the term “base date AMP” to mean 42 U.S.C.
18

§ 1396r-8(c)(2)(B)—amends the language of the base date AMP (i.e., it modifies § 1396r-
8(c)(2)(A)(ii)(II)) to cover outpatient drugs that the FDA approved after October 1, 1990. In
other words, for outpatient drugs that the FDA approved after October 1, 1990, § 1396r-
8(c)(2)(A)(ii)(II), as amended by § 1396r-8(c)(2)(B), states that the base date AMP is:
[T]he average manufacturer price for such dosage form and strength for the first
full calendar quarter after the day on which the drug was first marketed (without
regard to whether or not the drug has been sold or transferred to an entity, including
a division or subsidiary of the manufacturer, after the first day of such quarter),
increased by the percentage by which the consumer price index for all urban
consumers (United States city average) for the month before the month in which
the rebate period begins exceeds such index the month prior to the first month of
the first full calendar quarter after the day on which the drug was first marketed.
42 U.S.C. §§ 1396r-8(c)(2)(A)(ii)(II), (B) (emphases added).
Importantly, the language in the second highlighted subsection—§ 1396r-8(c)(2)(B)—
expressly states that a covered outpatient drug’s base date AMP is set in relation to when the
“covered outpatient drug” was “approved by” the FDA and “first marketed.” Thus, the plain
language of the statute cannot be harmonized with Mallinckrodt’s theory that the base date AMP
is tied to whether a drug satisfies the statutory definition of “single source drug” and, if so, then a
new base date AMP is automatic. Mallinckrodt’s Br. 4. That is simply not what the statute says.
Mallinckrodt’s argument might be viable if § 1396r-8(c)(2)(B) stated that “[i]n the case
of a single source drug approved by the Food and Drug Administration after October 1, 1990,
clause (ii)(II) of subparagraph (A) shall be applied by substituting ‘the first full calendar quarter
after the day on which the drug was first marketed’ for ‘the calendar quarter beginning July 1,
1990’ and ‘the month prior to the first month of the first full calendar quarter after the day on
which the drug was first marketed’ for ‘September 1990.’” But Congress omitted the phrase
§ 1396r-8(c)(2)(A)(ii)(II)).
19

“single source drug” from § 1396r-8(c)(2)(B) and, instead, elected to use a different phrase—
“covered outpatient drug.” And it is well established that “[w]hen Congress uses explicit
language in one part of a statute to cover a particular situation and then uses different language in
another part of the same statute, a strong inference arises that the two provisions do not mean the
same thing.” Persinger v. Islamic Republic of Iran, 729 F.2d 835, 843 (D.C. Cir. 1984).
Congress could have used the phrase “single source drug” in § 1396r-8(c)(2)(B) but it chose not
to, and that has meaning. Id.
Consequently, even assuming for the sake of argument that Mallinckrodt was legitimately
producing and distributing Acthar under defunct and provisional Type 6 NDA number 022432,
the drug’s base date AMP nevertheless would still be tethered to the date the FDA approved
Acthar, which there is no dispute was 1952. See, e.g., A.R. 51; Mallinckrodt’s Br. 7 (conceding
that “the second NDA covered only two changes: (i) approval of the infantile spasm indication
and (ii) new labeling”); Mallinckrodt’s Reply Br. 5 (conceding that Acthar was a “decades-old
drug product”). That is what the Medicaid Drug Rebate Program statute’s plain and
unambiguous language demands.
Mallinckrodt cited no precedent, statutory provision, or any other authority to support its
self-serving theory that a new base date AMP is automatic if the definition of single source drug
is triggered and notwithstanding that the “new drug application” used to trigger it did something
other than seek FDA approval of a covered outpatient drug, see Mallinckrodt’s Br. 6 (arguing
without cited authority that “[t]he drug product itself need not somehow change physically in
order to count as a separate covered outpatient drug or qualify for a new base date AMP”). And,
as the Court stated in its memorandum opinion, Mallinckrodt’s theory flies in the face of the
Medicaid Drug Rebate Program statute’s legislative purpose, which is “to provide medical
20

assistance to poor people,” Mem. Op. 7 (quoting Indiana Family & Soc. Servs. Admin. v.
Thompson, 286 F.3d 476, 477 (7th Cir. 2002)), and to accomplish this in part by minimizing
drug costs, see 42 U.S.C. § 1396r-8(b) (explaining that drug rebates serve to offset drug costs).
Mallinckrodt’s theory would not just circumvent the statute’s goal of minimizing drug costs—it
would defeat it.
The Medicaid Drug Rebate Program statute is technical and complex, but it is not
ambiguous or silent. A single source drug gets a new base date AMP when the relevant “covered
outpatient drug” is “approved by” the FDA and “first marketed” if that approval occurred after
October 1, 1990. The statute expressly provides that the base date AMP attaches only once
absent an FDA-approved new dosage form or strength. 42 U.S.C. § 1396r-8(c)(2). Again, it
remains undisputed that no covered outpatient drug was approved by the FDA in 2010 under
defunct and provisional NDA number 022432. To the contrary, in Mallinckrodt’s own words,
“the 2010 approval covered [1] a new IS indication; and [2] new labeling for a decades-old drug
product.” Mallinckrodt’s Reply Br. 5 (emphasis added).
From the outset, CMS properly adhered to the statute and told Mallinckrodt that it could
not change the base date AMP of a drug product during that drug product’s lifecycle, which is
entirely consistent and compliant with the statute’s plain language. 10 A.R. 617 (stating that the
10
Mallinckrodt claims that “the agency’s reference to replacing base date AMPs ‘midway
through the life of a product’—has nothing at all to do with how to set the base date AMP” and,
instead, “relates to its rejection of Questcor’s proposal that it be allowed to retain the same
National Drug Code (NDC) for Acthar after the new base date AMP was implemented.”
Mallinckrodt’s Br. 8. This is but one example of how Mallinckrodt appears to be dazzled by its
own litigation strategy much like the proverbial emperor who is wearing no clothes but is
convinced he is wearing a new suit that is invisible to the commoners. CMS’s letter allowing
Questcor to set a new base date AMP for Acthar with the infantile spasm indication stated that
the agency could not replace the “original” base date AMP for a drug product with a new base
date AMP midway through the life of a product. A.R. 617. That statement means exactly what
it says. It was made in the context of CMS explaining why Questcor could not keep the same
21

base date AMP applies to “each single source or innovator multiple source drug approved by the
FDA before or after October 1, 1990” and that CMS lacked authority to “replace the original . . . base
date AMP with a new base date AMP midway through the life of a product”). And, as the Court
previously found, “[f]or the[] same reasons” that CMS’s decision complied with the statute it “also
complied with its agency regulations,” which follow the language of the statute. Mem. Op. 42; see
also 42 C.F.R. § 447.509.
The Court is not immune to the fact that, aside from the parties’ discussions of the legal
proceedings in Ipsen Biopharms., Inc. v. Price, No. 16-cv-2372 (DLF), the statutory question in
this case does not appear to have been tested by other federal courts, although that might be
because the statute is clear. At best, though, the potential novelty of the question inches the
probability of Mallinckrodt’s success on the merits closer to “possible,” but nowhere near
“likely,” as required to establish that a stay is warranted pending appeal, see Winter, 555 U.S. at
21–22. The Court simply cannot conclude on this record that Mallinckrodt raises issues “so
National Drug Code after setting a new base date AMP for Acthar, but its meaning is clear and
has everything to do with the agency’s view about when a new base date AMP could be set for a
drug product. CMS was telling Questcor that, because the existing National Drug Code
associated with Acthar was linked to Achtar’s original NDA number 008372, in order to set a
new base date AMP for the “recently approved Acthar Gel” (note that CMS did not say the
“recently approved label revision” or “recently approved addition of an infantile spasm
indication,” suggesting, again, that CMS was under the mistaken impression that Acthar with the
infantile spasm indication was approved as an entirely new drug product) Questcor would, as a
corollary, have to obtain a new National Drug Code to go with what CMS understood to be the
new NDA number—022432—because it could not change the base date AMP for NDA number
008372 during the lifecycle of that drug product. A.R. 617. At that point, Questcor was on
obvious notice that CMS interpreted the Medicaid Drug Rebate Program statute to permit the
calculation of a new base date AMP for Acthar with the infantile spasm indication only because
CMS viewed Acthar with the infantile spasm indication to be a different “drug product” from the
“original product,” based on the fact that Questcor had reported that the drug was approved
under a different NDA, in which case it would need a new National Drug Code associated with
the new NDA because the “original” drug product’s base date AMP could not be changed during
its lifecycle. A.R. 617 (distinguishing Acthar with the infantile spasm indication as different
“from the original product”).
22

serious, substantial, difficult and doubtful, as to make them a fair ground for litigation and thus
for more deliberative investigation.” Washington Metro. Area Transit Comm’n v. Holiday
Tours, Inc., 559 F.2d 841, 844 (D.C. Cir. 1977). Finally, in light of the Court’s statutory analysis
and for the reasons set forth in the Court’s March 13, 2020 memorandum opinion, Mallinckrodt is
also not likely to prevail on its requests for relief pursuant to asserted fair notice and retroactivity
principles.
B. Irreparable Harm
With respect to Mallinckrodt’s requirement to establish that it will be irreparably harmed
unless the Court issues a stay of its judgment, Mallinckrodt claims that it faces an “existential
threat” posed by “significant financial, structural, and reputational harms to the company” if
CMS declares it to be out of compliance with the Medicaid Drug Rebate Program requirements,
which might occur if the defendants act to enforce the Court’s judgment and Mallinckrodt fails
to correct Acthar’s base date AMP. Mallinckrodt’s Br. 13. In particular, Mallinckrodt states that
it will (1) be unable to report or revise Acthar’s drug pricing data if CMS locks it out of the
federal database that administers the drug rebate program, (2) risk being subjected to civil
monetary penalties for its noncompliance, and (3) risk that its National Drug Rebate Agreement
will be temporarily suspended, which means states “will no longer be required to cover
Mallinckrodt’s covered outpatient drugs, including Acthar.” Id.
Moreover, even if Mallinckrodt alternatively elects to revise Acthar’s base date AMP to
comply with the statute, the company asserts that the revised based date AMP will trigger
irreparable injury in the form of liability for “more than $600 million in additional Medicaid
rebates that would come due to State Medicaid agencies almost immediately.” Id. Mallinckrodt
laments that this would cause a “cash-flow problem for the company” and, if paid, “would be
recoverable only very slowly, over many years, from State Medicaid agencies, because of how
23

the recovery process works,” which would entail offsetting the rebate overpayments against
future Acthar rebate payments. Id. at 13–14.
The D.C. Circuit “has said time and again that the degree of proof required for
‘irreparable harm’ is ‘high,’ and that a failure to surmount it provides ‘grounds for refusing to
issue a preliminary injunction, even if the other three factors entering the calculus merit such
relief.’” Olu-Cole v. E.L. Haynes Pub. Charter Sch., 930 F.3d 519, 529 (D.C. Cir. 2019)
(quoting Chaplaincy of Full Gospel Churches v. England, 454 F.3d 290, 297 (D.C. Cir. 2006)).
As the D.C. Circuit has explained:
Although the concept of irreparable harm does not readily lend itself to definition,
the courts have developed several well known and indisputable principles to guide
them in the determination of whether this requirement has been met.
First, the injury must be both certain and great; it must be actual and not theoretical.
Injunctive relief will not be granted against something merely feared as liable to
occur at some indefinite time . . .; the party seeking injunctive relief must show that
the injury complained of is of such imminence that there is a clear and present need
for equitable relief to prevent irreparable harm.
It is also well settled that economic loss does not, in and of itself, constitute
irreparable harm. As this court has noted:
The key word in this consideration is irreparable. Mere injuries,

however substantial, in terms of money, time and energy necessarily
expended in the absence of a stay are not enough. The possibility
that adequate compensatory or other corrective relief will be
available at a later date, in the ordinary course of litigation weighs
heavily against a claim of irreparable harm.
Virginia Petroleum Jobbers Ass’n v. FPC, 259 F.2d at 925. Recoverable monetary
loss may constitute irreparable harm only where the loss threatens the very
existence of the movant’s business.
Implicit in each of these principles is the further requirement that the movant
substantiate the claim that irreparable injury is “likely” to occur. Bare allegations
of what is likely to occur are of no value since the court must decide whether the
harm will in fact occur. The movant must provide proof that the harm has occurred
in the past and is likely to occur again, or proof indicating that the harm is certain
to occur in the near future. Further, the movant must show that the alleged harm
will directly result from the action which the movant seeks to enjoin.
24

Wisconsin Gas Co. v. F.E.R.C., 758 F.2d 669, 674 (D.C. Cir. 1985) (per curiam) (citations and
internal quotation marks omitted, alterations adopted). To be sure, the harms must be “beyond
remediation” to qualify as “irreparable.” Chaplaincy of Full Gospel Churches v. England, 454
F.3d 290, 297 (D.C. Cir. 2006). Accordingly, the Court will assess whether Mallinckrodt’s
asserted harms are actual, certain, imminent, beyond remediation, and, because most of the
asserted harms are economic, threaten Mallinckrodt’s very existence.
The only support Mallinckrodt proffers to prove its alleged harms are (a) the Declaration
of Kathleen A. Schaefer in Support of Plaintiff’s Motion for Preliminary Injunction, ECF No. 4-
2, which was attached as Exhibit 2 to Mallinckrodt’s original motion for a preliminary
injunction, and (b) a transcript of Mallinckrodt’s 2019 fourth quarter earnings call for investors,
ECF No. 37-3, which was attached as Exhibit 3 to Mallinckrodt’s motion for reconsideration.
See Mallinckrodt’s Br. 15 (citing the declaration and transcript), 17, 18. Kathleen Schaefer is
Mallinckrodt’s President. Schaefer Decl. ¶ 3. Her declaration lays out the harms that
Mallinckrodt will suffer if CMS “declare[s] Mallinckrodt ‘out of compliance’ in the Drug Data
Reporting for Medicaid (DDR) system based on the dispute over the base date average
manufacturer price (AMP) for Acthar Gel® (repository corticotropin) injection (Acthar).”
Schaefer Decl. ¶ 3. Those harms include: financial losses and reputational damage to
Mallinckrodt if it is suspended from the Medicaid Drug Rebate Program, Schaefer Decl. ¶¶ 5, 6;
loss of research and development investments, marketing efforts, and workforce, Schaefer Decl.
¶ 6; negative credit ratings, investment ratings, and declining stock prices, Schaefer Decl. ¶¶ 7, 8;
reputational stigma and loss of good will among patients, healthcare professionals, and others,
Schaefer Decl. ¶ 10; and civil monetary penalties to the tune of $10,000 per day, Schaefer Decl.
¶ 13. If Mallinckrodt revises Acthar’s base date AMP to comply with the statute, Shaefer offers
25

that “[t]hat presents its own risks and liabilities,” including “losses totaling in the hundreds of
millions of dollars for Mallinckrodt.” Schaefer Decl. ¶ 14.
With respect to the asserted economic harms, although Schaefer states that “CMS
therefore has put Mallinckrodt between the proverbial rock and a hard place,” Schaefer Decl.
¶ 14, nowhere does she state that the company’s demise is or would be imminent, whether
Mallinckrodt elects to correct Acthar’s base date AMP or not. As a result, her declaration fails to
corroborate the notion that Mallinckrodt will confront imminent demise absent a stay, and the
economic harms otherwise do not demonstrate “irreparable” harm under this Circuit’s precedent,
see, e.g., Wisconsin Gas Co., 758 F.2d at 674 (stating that “[r]ecoverable monetary loss may
constitute irreparable harm only where the loss threatens the very existence of the movant’s
business”).
Furthermore, Schaefer generally presents the reputational harms as possible, but not
necessarily certain, stating that losses related to CMS enforcing the statute “could impact
investor confidence” and prescribers and patients who switch to other treatments “may never
return to Acthar.” Schaefer Decl. ¶¶ 7, 10. Although she also states that a loss of investor
confidence has resulted in a stock price decline and the loss of goodwill “can never be
remedied,” she fails to back that up with evidence or an explanation showing how or why the
stock decline is irreversible or Mallinckrodt’s reputation is forever tarnished. Schaefer Decl.
¶¶ 7–10. As a consequence, the Schaefer declaration does not adequately support granting a stay
on the ground that Mallinckrodt will suffer irreparable harm without one. Trudeau v. Fed. Trade
Comm’n, 384 F. Supp. 2d 281, 297 (D.D.C. 2005), aff'd, 456 F.3d 178 (D.C. Cir. 2006) (stating
that “the showing of reputational harm must be concrete and corroborated, not merely
speculative”).
26

The transcript of the 2019 fourth quarter earnings call with investors that Mallinckrodt
submitted fares no better and belies the notion that the company is facing imminent demise.
That transcript reveals that Mallinckrodt’s Vice President-Investor Relations and Investor
Relations Officer, Daniel Speciale, reported that, “[w]hile we are not providing specific guidance
due to the complexities of the settlement of financing in the Acthar CMS matter . . . [i]n general,
total net sales for 2020 are expected to be in line with present consensus” and “we expect
performance across the products to be weaker on a year-over-year basis in the first half of the
year and rebounding in the back half of the year.” Q4 2019 Earnings Call Tr. 2. Mallinckrodt’s
Chief Executive Officer, Mark Trudeau, was similarly equivocal but optimistic, referencing the
“strong fourth quarter and full-year 2019 results,” announcing a settlement of the opioid
litigation that “is financially manageable and removes a significant uncertainty related to our
business that will better enable us to move forward with our strategic plans and drive shareholder
value,” and stating that, while “there could be pressure on Acthar . . . [d]epending on the
outcome of the CMS” litigation he nevertheless “do[es] expect the business to, overall, continue
to generate significant cash flows.” 11 Q4 2019 Earnings Call Tr. 2–3, 16.
As demonstrated, Mallinckrodt’s two supplied sources of evidence offered to corroborate
that it will be harmed without a stay plainly fail to establish that the asserted harm rises to the
11
Mallinckrodt initially suggested that the potential $600 million rebate liability risked
“disrupting other efforts by the company to right its financial ship,” including the company’s
efforts to refinance its near-term debts. See Mallinckrodt’s Reply Br. 10–11. The risk of that
particular harm appears to have been resolved, however, at least in principle, by the company’s
reported negotiation of an exchange agreement to refinance nearly $500 million in debt. See
Surreply in Opp’n to Pl.’s Emergency Mot. 2, ECF No. 44 (providing a link to a Securities and
Exchange Commission (SEC) filing in which Mallinckrodt reported that the company entered
into an exchange agreement to refinance nearly $500 million in debt).
27

level of “irreparable.” See, e.g., Wisconsin Gas Co., 758 F.2d at 674. As a result, the Court
cannot find that a stay is either warranted or appropriate under this factor.
C. Summary Conclusion
For all the foregoing reasons, the Court holds that Mallinckrodt has failed to establish
that either success on the merits of an appeal or irreparable harm absent a stay are likely, in
which case it cannot prevail regardless of whether the Court applies the legal standards set forth
in Winter, 555 U.S. at 21–22, or the D.C. Circuit’s sliding-scale approach, see, e.g., Sherley, 644
F.3d at 392. The Court therefore need not consider the remaining factors, CityFed Fin. Corp. v.
Office of Thrift Supervision, 58 F.3d 738, 747 (D.C. Cir. 1995), albeit suffice it to say that there
is a strong public interest in ensuring that pharmaceutical companies are not circumventing the
Medicaid Drug Rebate Program’s purpose of minimizing Medicaid—and thereby taxpayers’—
costs and diminishing the nation’s ability to provide the medical services to the poor that
Congress intended.
CONCLUSION
For the reasons set forth herein, the Court will deny Mallinckrodt ARD LLC’s
Emergency Motion for Reconsideration and Stay of Entry of Judgment Pending Reconsideration
or, Alternatively, Injunction Pending Appeal, ECF No. 37. An appropriate order will be filed
forthwith.
May 29, 2020 ___________________________________

Thomas F. Hogan
28


Plaintiff,
v.
Defendants.
ORDER
Upon consideration of Mallinckrodt ARD LLC’s Emergency Motion for Reconsideration
and Stay of Entry of Judgment Pending Reconsideration or, Alternatively, Injunction Pending
Appeal, ECF No. 37, the responses thereto, the Administrative Record, and the entire record in
this case, and for the reasons set forth in the accompanying Memorandum Opinion, it is
ORDERED that Mallinckrodt ARD LLC’s Emergency Motion for Reconsideration and
Stay of Entry of Judgment Pending Reconsideration or, Alternatively, Injunction Pending
Appeal, ECF No. 37, is DENIED.
SO ORDERED.
March 29, 2020 ___________________________________

Thomas F. Hogan

From: Coster, John M. (CMS/CMCS)

To: Schaefer, Kathy A
Cc: Coster, John M. (CMS/CMCS); Blatt, Ruth (CMS/CMCS)
Subject: Letter from CMS on Acthar Gel
Date: Friday, May 10, 2019 9:33:10 AM
Attachments: acthar May2019.pdf
TEMPLATE FOR BASE AMP CHANGE REQUEST - (S & I Drugs).xlsx
Please see attached letter. Thank you.
John M. Coster, Ph.D., R.Ph.

Director, Division of Pharmacy
Center for Medicaid & CHIP Services
Centers for Medicare & Medicaid Services
7500 Security Blvd
Mail Stop S2-14-26
Baltimore, MD 21244
john.coster@cms.hhs.gov
410-786-1121
443=615-1257 – cell
(Page 129 of Total) A81 HHS - 000001

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TEMPLATE FOR BASE AMP CHANGE REQUEST (S and I Drugs only)
1. Date of Request:
2. Labeler Name:
3. Labeler Technical Contact (Name & Phone #):
(Page 131 of Total)

4. Labeler 5. Product 6. Product Name 7a. COD 7b. FDA 8. Does this NDC have a 9. If product is 10. OBRA ’90 11. 12a. 12b. If no 13. OBRA ’93 14. Current 15a. 15b. If no PPD 16. Esimated 17. Estimated
Code Code Status Application No. reference NDC, such as acquired from Base AMP Current Revised PPD provided Base AMP OBRA '93 Revised provided in Amount Due to Amount Due to
(NDA/ANDA)/OT did you acquire this another company Quarter OBRA '90 OBRA '90 in #9, please Quarter Base AMP OBRA '93 #9, please States from Labeler from
C Mongraph product from another as provided in #8, Base AMP Base AMP provide BP Base AMP provide BP Labeler States
company? If yes, please then please value value
provide the old provide the
company's NDC. Or if Product Purchased If there is NO AMOUNT DUE
USCA Case #20-5154
your product is an Date (PPD). either to States from Labeler or

Authorized Generic, to Labeler from States, please
please provide the NDC of provide the reason why no
the Brand Product. amount is due in the reason
box.
20. Labeler’s Reason to Request for a Change (please provide as much detail as possible):
Document #1845229
Filed: 06/02/2020
Page 89 of 400
Updated September 2017
A83 HHS - 000003

From: Almli, Arathi (HHS/OGC)

Sent: Monday, April 29, 2019 10:15 AM
To: mark.casey@mnk.com
Subject: RE: Mallinckrodt -- base AMP of Acthar gel
Mark,
To be clear, while I did refer to a response to your letter, that does not mean that CMS is considering your
proposal. CMS’ position remains the same, as reflected in Bob Charrow’s March 27, 2019 email to you.
Thanks – Arathi
From: Casey, Mark [mailto:Mark.Casey@mnk.com]

Sent: Thursday, April 25, 2019 8:19 AM
To: Almli, Arathi (HHS/OGC)
Arathi,
Thank you for the update. We appreciate the agency’s consideration of our proposal. Can you give
us an approximate timeframe in which we might expect the agency’s response? Please do not
hesitate to reach out to me if it would be helpful to discuss our proposal.
Best regards,
Mark
Mark J. Casey | General Counsel

Mallinckrodt Pharmaceuticals
T: 908.997.9296 | M: 908.200.0012
mark.casey@mnk.com | https://protect2.fireeye.com/url?k=5d74144a-01211d59-5d742575-0cc47adb5650-
a8d8767dbbb2f590&u=http://www.mallinckrodt.com/
From: Almli, Arathi (HHS/OGC) <Arathi.Almli@HHS.GOV>

Sent: Wednesday, April 24, 2019 9:45 AM

To: Casey, Mark <Mark.Casey@mnk.com>
Subject: [EXTERNAL] Mallinckrodt -- base AMP of Acthar gel
CAUTION: This email originated from Arathi.Almli@hhs.gov which is outside of the Mallinckrodt system. Do
not click on any links or attachments unless you know the source and are very confident that the
links/attachments are safe. If you have any doubts, please contact SuspiciousEmail@mnk.com for assistance.
Mark – Bob Charrow asked me to respond to your inquiries in regards to your letter dated April 12, 2019.
We understand that in your letter you requested a response from the agency by April 19, however, the
agency is not in a position to respond in that timeframe.
Thank you.
Arathi
Arathi D. Almli
Attorney
U.S. Department of Health and Human Services
Office of the General Counsel
Centers for Medicare & Medicaid Services Division
(410) 786-8860
Arathi.almli@hhs.gov

From: Casey, Mark

To: Almli, Arathi (HHS/OGC)
Date: Thursday, April 25, 2019 8:20:09 AM
Arathi,
Thank you for the update. We appreciate the agency’s consideration of our proposal. Can you give
us an approximate timeframe in which we might expect the agency’s response? Please do not
hesitate to reach out to me if it would be helpful to discuss our proposal.
Best regards,
Mark
Mark J. Casey | General Counsel

T: 908.997.9296 | M: 908.200.0012
mark.casey@mnk.com | https://protect2.fireeye.com/url?k=5d74144a-01211d59-5d742575-0cc47adb5650-
a8d8767dbbb2f590&u=http://www.mallinckrodt.com/
From: Almli, Arathi (HHS/OGC) <Arathi.Almli@HHS.GOV>

Sent: Wednesday, April 24, 2019 9:45 AM
To: Casey, Mark <Mark.Casey@mnk.com>
Subject: [EXTERNAL] Mallinckrodt -- base AMP of Acthar gel
CAUTION: This email originated from Arathi.Almli@hhs.gov which is outside of the Mallinckrodt system. Do
not click on any links or attachments unless you know the source and are very confident that the
Thank you.
Arathi
Arathi D. Almli
Attorney
(410) 786-8860

From: Almli, Arathi (HHS/OGC)

To: mark.casey@mnk.com
Subject: Mallinckrodt -- base AMP of Acthar gel
Date: Wednesday, April 24, 2019 9:44:59 AM
Thank you.
Arathi
Arathi D. Almli
Attorney
(410) 786-8860

From: Casey, Mark <Mark.Casey@mnk.com>

Sent: Friday, April 12, 2019 3:08 PM
To: Traylor, Christopher (CMS/CMCS) <Christopher.Traylor@cms.hhs.gov>; Charrow, Robert
(HHS/OGC) <Robert.Charrow@hhs.gov>
Subject: Letter from Mallinckrodt regarding the base date average manufacturer price of Acthar Gel
Dear Messrs. Traylor and Charrow,
Please see the attached letter regarding the base date average manufacturer price of Acthar Gel.
I look forward to your reply.
Best regards,
Mark
0DUN-&DVH\_*HQHUDO&RXQVHO
T: 908.997.9296 | M: 908.200.0012
mark.casey@mnk.com | https://protect2.fireeye.com/url?k=6da417d1-31f00ead-6da426ee-0cc47adc5fa2-
7a5ef9b914a7795d&u=http://www.mallinckrodt.com/



_____________________________________________
From: Charrow, Robert (HHS/OGC)
Sent: Wednesday, March 27, 2019 9:19 AM
To: Casey, Mark <Mark.Casey@mnk.com>; alice.valder.curran@hoganlevells.com
Cc: Charrow, Robert (HHS/OGC) <Robert.Charrow@hhs.gov>
Subject: Mallinckrodt Meeting
Dear Mark and Alice,
Sorry to be the bearer of less than stellar news. I’ve reviewed the underlying documents and
have concluded that the April 13, 2016 letter from CMS to Mallinckrodt constituted CMS’
final decision on the relevant issue. Therefore, given that there is a final CMS decision on this
issue, any meeting with me would not and could not be productive. Accordingly, I am
canceling the meeting. Bob
Robert P. Charrow
General Counsel
Department of Health and Human Services
200 Independence Avenue, S.W.
(202) 690-7741
Email: Robert.Charrow@hhs.gov

From: CMS RxDRUGPolicy

To: Schaefer, Kathy A
Cc: Coster, John M. (CMS/CMCS); Blatt, Ruth (CMS/CMCS)
Subject: H.P. Acthar gel
Date: Tuesday, March 12, 2019 9:55:34 AM
Attachments: TEMPLATE FOR BASE AMP CHANGE REQUEST - (S & I Drugs).xlsx
acthar March 2019.doc.pdf
Ms. Schaefer,
Please find attached an advance copy of a letter that you will be receiving by U.S. Mail.
Thank you,
CMS Rx Drug Policy (04)
The information in this response is limited to and based upon the facts described in this email and any attachments
provided and our understanding of the facts as described in the emails and attachments submitted. If a subsequent
review by CMS, by the Office of Inspector General, or another authorized government agency determines or reveals
that additional adjustments or revisions are necessary, the manufacturer is responsible for complying with that
determination. This response cannot be considered an advisory opinion under section 1128D(b) of the Social
Security Act, since only the Inspector General of the U.S. Department of Health and Human Services has been
authorized to issue advisory opinions relating to health care fraud and abuse under that section. This response
should not be interpreted as acquiescence by the Government to the arrangements described herein. Further, this
response is not a release of any liability.
NOTICE: The contents of this message and any attachments may be privileged and confidential. If you are not an
intended recipient, or have received this message in error, please delete it without reading it and please do not print,
copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that you have received this
communication in error. Your receipt of this message is not intended to waive any applicable privilege.

DEPARTMENT OF HEALTH & HUMAN SERVICES

7500 Security Boulevard, Mail Stop S2-14-26
Baltimore, Maryland 21244-1850
March 12, 2019
Kathy A. Schaefer
Senior Vice President, Finance and Corporate Controller
1425 U.S. Route 206
Bedminster, New Jersey 07921
Dear Ms. Schaefer:
We thank Mallinckrodt Pharmaceuticals (Mallinckrodt) for meeting with us on March 7, 2019 to

present its position regarding the base date Average Manufacturer Price (AMP) of H.P. Acthar
Gel.
As we have said in our prior communications of April 13, 2016, June 2, 2016, and March 20,
2017, and as we reiterated at the March 7th meeting, the base date AMP of H.P. Acthar Gel
should reflect the base date AMP for the drug that was first produced or distributed under new
drug application (NDA) 008372. Because H.P. Acthar gel is currently, and always has been,
produced or distributed under NDA 008372, the base date AMP Mallinckrodt is reporting to the
Drug Data Reporting for Medicaid (DDR) system does not reflect the appropriate base date
AMP, and Mallinckrodt has been underpaying Medicaid rebates for H.P. Acthar Gel.
We are enclosing a template for you to complete and return to ruth.blatt@cms.hhs.gov in order
for Mallinckrodt to report the correct baseline information to the Medicaid Drug Rebate
Program.
Sincerely,
/s/
John M. Coster, Ph.D, RPh

cc: Alice Valder Curran
1|Page
TEMPLATE FOR BASE AMP CHANGE REQUEST (S and I Drugs only)
1. Date of Request:
2. Labeler Name:
(Page 142 of Total)

4. Labeler 5. Product 6. Product Name 7a. COD 7b. FDA 8. Does this NDC have a 9. If product is 10. OBRA ’90 11. 12a. 12b. If no 13. OBRA ’93 14. Current 15a. 15b. If no PPD 16. Esimated 17. Estimated
Code Code Status Application No. reference NDC, such as acquired from Base AMP Current Revised PPD provided Base AMP OBRA '93 Revised provided in Amount Due to Amount Due to
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USCA Case #20-5154
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Document #1845229
Filed: 06/02/2020
Page 100 of 400
Updated September 2017
A94 HHS - 000014

From: Curran, Alice Valder

To: Coster, John M. (CMS/CMCS)
Cc: Blatt, Ruth (CMS/CMCS); Choe, Kenneth Y.
Subject: Acthar Base Date AMP
Date: Monday, March 11, 2019 9:16:17 AM
Attachments: image007.jpg
image008.jpg
image009.jpg
FOIA-EXEMPT CONFIDENTIAL COMMERCIAL INFORMATION
John,
On behalf of Mallinckrodt, thanks again to you and your team for taking the time to meet to discuss
Acthar’s base date AMP.
Please know that we will soon be sending a follow-up letter to address the issues raised by the
agency during the meeting. In addition, please know that we are in the process of requesting a
meeting with Chris Traylor, as well as a meeting with OGC.
We would appreciate if the agency were to hold off on any enforcement action with respect to this
matter until we have had an opportunity to present our concerns to the Deputy Administrator and
to OGC. In any event, we would appreciate confirmation that the agency would notify Mallinckrodt
before taking any such action.
Thank you again.
Alice
Alice Valder Curran

Partner
Hogan Lovells US LLP

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
Email: alice.valder.curran@hoganlovells.com
https://protect2.fireeye.com/url?k=f830825a-
a464ab71-f830b365-0cc47a6d17cc-
216fcc2c75dcff2e&u=http://www.hoganlovells.com/
Please consider the environment before printing this e-mail.
Follow Hogan Lovells Life Sciences and Health Care

for the latest industry news and updates:

About Hogan Lovells

Hogan Lovells is an international legal practice that includes Hogan Lovells US LLP and Hogan Lovells International LLP.
For more information, see https://protect2.fireeye.com/url?k=e1011167-bd55384c-e1012058-0cc47a6d17cc-
13c2242a61ff5fc5&u=http://www.hoganlovells.com/.
CONFIDENTIALITY. This email and any attachments are confidential, except where the email states it can be disclosed; it
may also be privileged. If received in error, please do not disclose the contents to anyone, but notify the sender by return
email and delete this email (and any attachments) from your system.


To: Blatt, Ruth (CMS/CMCS); Coster, John M. (CMS/CMCS)
Cc: Choe, Kenneth Y.
Subject: RE: Mallinckrodt Pharmaceuticals Meeting - Tuesday, 9 AM January 22
Date: Wednesday, March 06, 2019 2:53:48 PM
image011.jpg
image012.jpg
image001.jpg
image002.jpg
image003.jpg
13864691_1.pdf
Confidential/FOIA-Exempt
Ruth and John,
Attached are the slides we will use for our meeting tomorrow at 2 PM at the Humphrey Building in
Washington, D.C. Please circulate them to the attendees, and let me know if you have any
questions.
Best regards,
Alice
Alice Valder Curran

Partner

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
https://protect2.fireeye.com/url?k=080208e9-
545621c2-080239d6-0cc47a6d17cc-
0b845b1c8e7c49d9&u=http://www.hoganlovells.com/


From: Blatt, Ruth (CMS/CMCS) [mailto:Ruth.Blatt@cms.hhs.gov]

Sent: Friday, February 08, 2019 4:43 PM
To: Curran, Alice Valder
Confirmed for March 7th at 2 PM in DC at the Humphrey building. Will provide further details when I
get a room set up.
Thanks!
Ruth
From: Curran, Alice Valder [mailto:alice.valder.curran@hoganlovells.com]

To: Blatt, Ruth (CMS/CMCS) <Ruth.Blatt@cms.hhs.gov>
Thank you Ruth! We would like to do the meeting on the 7th at 2 PM in Washington. If you can
confirm that, I will get you in the revised meeting request form.
Alice

Sent: Thursday, February 07, 2019 6:24 PM
Would one of these work- in DC, at the Humphrey Building at 200 Independence Avenue S.W.
March 7th 10 or 11 AM or 2PM

March 14 10 or 11 AM
Ruth

Subject: Mallinckrodt Pharmaceuticals Meeting - Tuesday, 9 AM January 22
Confidential
Ruth,
Thank you for clarifying. Mallinckrodt has a strong preference to have John attend in person given
the significance of the Acthar base date AMP matter to the company. However, travel schedules

and other commitments make an earlier meeting date very challenging for the Mallinckrodt
attendees. Would it be possible to consider the next earliest date after the 26th when John could
meet in person?
Many thanks for your help in managing this.
Alice

Sent: Wednesday, February 06, 2019 9:32 AM
Alice,
I’m sorry I wasn’t clear. John will only be available by phone on the 26th.
My option to meet in DC would have to be on a date that does not fall within the week of the 25th.
Ruth

Thank you Ruth. We would prefer to stick with the 26th and meet with John in DC with the
Pharmacy team dialing in. Please confirm that still works at 11 AM on the 26th.
I will get the meeting request form to you no later than the end of this week.
Best regards,
Alice

Sent: Tuesday, February 05, 2019 3:58 PM
Alice,
Unfortunately, John will now be out of the office on February 26th but would be able to call in to a
meeting on that date.
He will be in Baltimore on February 20th. Another possibility is to meet with him in DC and the
Baltimore staff can call in.
Additionally, I’ve attached the meeting request form which I’ll need you to return prior to the

meeting.
Thank you,
Ruth
From: Blatt, Ruth (CMS/CMCS)

Sent: Friday, January 18, 2019 10:04 AM
To: Curran, Alice Valder <alice.valder.curran@hoganlovells.com>
Confirming February 26th at 11 AM.
Since the players have changed, could you complete the attached meeting request form and return
to me?

Ruth – Thank you for getting back to me so quickly yesterday, and for providing the February dates
this morning. We would like to schedule the in-person meeting, including John, for Tuesday the
26th, at 11 AM. I understand from your message that CMS will not take any action on the base date
AMP matter until that meeting has occurred. If my understanding is incorrect, please let me know.
In the meantime, we will get started on the letter and get that to you and your colleagues ahead of
the February 26th meeting.
Best regards,
Alice
Alice Valder Curran

Partner

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
https://protect2.fireeye.com/url?k=fe314e8d-
a26567a6-fe317fb2-0cc47a6d17cc-
eff4795872ef5e7a&u=https://protect2.fireeye.com/url?
k=153dc589-4969dcf5-153df4b6-0cc47adc5fa2-

22748fdf897a81ac&u=https://protect2.fireeye.com/url?
k=22446b8b-7e1072f7-22445ab4-0cc47adc5fa2-
9e468c3c14af615e&u=http://www.hoganlovells.com/


Hi Alice,
It was nice speaking with you yesterday. We can offer the following dates/times for a meeting:
February 5th 11 AM
February 12th 11AM
February 26th 11AM
Kindly let me know at your earliest convenience which date you prefer.
Ruth

Sent: Thursday, January 17, 2019 1:52 PM
Ruth,
I am writing on behalf of Mallinckrodt Pharmaceuticals, which recently changed its outside counsel

to Hogan Lovells for the purpose of assisting in the ongoing dialogue between CMS and Mallinckrodt
regarding a base date AMP determination by the agency in 2012.
As you know, Mallinckrodt is currently scheduled to meet with you and your colleagues about this
matter at 9:00 a.m. on Tuesday, January 22. To maximize efficient use of the agency’s time, we
propose instead to send CMS a letter that details the relevant considerations, and to postpone the
meeting until after the agency has had an opportunity to review the letter.
Please advise at your earliest convenience if the agency is amenable to this alternative way of
proceeding. Thank you for your consideration. Please let me know if we could connect by phone to
discuss the pathway forward. I am happy to do so at your convenience.
Alice
Alice Valder Curran

Partner

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
https://protect2.fireeye.com/url?k=9b9a4646-c7ce6f6d-
9b9a7779-0cc47a6d17cc-
ca4f875a21268424&u=https://protect2.fireeye.com/url?
k=056de981-5939f0fd-056dd8be-0cc47adc5fa2-
dbe25fc5e4820ea6&u=https://protect2.fireeye.com/url?
k=24e805b7-78bc1ccb-24e83488-0cc47adc5fa2-
7b73369042327b75&u=http://www.hoganlovells.com/

About Hogan Lovells

Hogan Lovells is an international legal practice that includes Hogan Lovells US LLP and Hogan Lovells International LLP.

For more information, see https://protect2.fireeye.com/url?k=48d45c09-14807522-48d46d36-0cc47a6d17cc-

290abf4fdafd7296&u=https://protect2.fireeye.com/url?k=15b17ea0-49e567dc-15b14f9f-0cc47adc5fa2-
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ca984a2959323926&u=http://www.hoganlovells.com/.
CONFIDENTIALITY. This email and any attachments are confidential, except where the email states it can be disclosed; it
may also be privileged. If received in error, please do not disclose the contents to anyone, but notify the sender by return
email and delete this email (and any attachments) from your system.

(Page 152 of Total)
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Document #1845229
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A122 HHS - 000042

To: Blatt, Ruth (CMS/CMCS); Coster, John M. (CMS/CMCS)
Cc: Choe, Kenneth Y.
Date: Wednesday, February 27, 2019 5:53:44 PM
image001.jpg
image009.jpg
image010.jpg
Letter from Mallinckrodt to CMS Re Acthar Base Date AMP (2019-02-27).pdf
Ruth and John,
Attached is Mallinckrodt’s letter addressing the base date AMP for H.P. Acthar Gel. We look forward
to discussing the matter with the CMS Division of Pharmacy team on March 7th at 2 PM. Please do
not hesitate to contact me in the interim with any questions you may have.
Alice
Alice Valder Curran

Partner

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
www.hoganlovells.com



To: Blatt, Ruth (CMS/CMCS)
Subject: Re: Mallinckrodt Pharmaceuticals Meeting - Tuesday, 9 AM January 22
Thank you very much Ruth. Have a good weekend.
Alice
Sent from my iPad
On Feb 8, 2019, at 9:44 PM, Blatt, Ruth (CMS/CMCS) <Ruth.Blatt@cms.hhs.gov> wrote:
Confirmed for March 7th at 2 PM in DC at the Humphrey building. Will provide further
details when I get a room set up.
Thanks!
Ruth

Thank you Ruth! We would like to do the meeting on the 7th at 2 PM in Washington. If
you can confirm that, I will get you in the revised meeting request form.
Alice

Would one of these work- in DC, at the Humphrey Building at 200 Independence
Avenue S.W.
March 7th 10 or 11 AM or 2PM

March 14 10 or 11 AM
Ruth


Confidential
Ruth,
Thank you for clarifying. Mallinckrodt has a strong preference to have John attend in
person given the significance of the Acthar base date AMP matter to the company.
However, travel schedules and other commitments make an earlier meeting date very
challenging for the Mallinckrodt attendees. Would it be possible to consider the next
earliest date after the 26th when John could meet in person?
Many thanks for your help in managing this.
Alice

Alice,
I’m sorry I wasn’t clear. John will only be available by phone on the 26th.
My option to meet in DC would have to be on a date that does not fall within the week
of the 25th.
Ruth

Thank you Ruth. We would prefer to stick with the 26th and meet with John in DC with
the Pharmacy team dialing in. Please confirm that still works at 11 AM on the 26th.
I will get the meeting request form to you no later than the end of this week.
Best regards,
Alice

Sent: Tuesday, February 05, 2019 3:58 PM
Alice,

Unfortunately, John will now be out of the office on February 26th but would be able to
call in to a meeting on that date.
He will be in Baltimore on February 20th. Another possibility is to meet with him in DC
and the Baltimore staff can call in.
Additionally, I’ve attached the meeting request form which I’ll need you to return prior
to the meeting.
Thank you,
Ruth
From: Blatt, Ruth (CMS/CMCS)

To: Curran, Alice Valder <alice.valder.curran@hoganlovells.com>
Confirming February 26th at 11 AM.
Since the players have changed, could you complete the attached meeting request
form and return to me?

Ruth – Thank you for getting back to me so quickly yesterday, and for providing the
February dates this morning. We would like to schedule the in-person meeting,
including John, for Tuesday the 26th, at 11 AM. I understand from your message that
CMS will not take any action on the base date AMP matter until that meeting has
occurred. If my understanding is incorrect, please let me know.
In the meantime, we will get started on the letter and get that to you and your
colleagues ahead of the February 26th meeting.
Best regards,
Alice
Alice Valder Curran

Partner


Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
https://protect2.fireeye.com/url?k=153dc589-
4969dcf5-153df4b6-0cc47adc5fa2-
22748fdf897a81ac&u=https://protect2.fireeye.com/url?
k=22446b8b-7e1072f7-22445ab4-0cc47adc5fa2-
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<image003.jpg>

Hi Alice,
It was nice speaking with you yesterday. We can offer the following dates/times for a
meeting:
February 5th 11 AM
February 12th 11AM
February 26th 11AM
Kindly let me know at your earliest convenience which date you prefer.
Ruth

Sent: Thursday, January 17, 2019 1:52 PM

Ruth,
I am writing on behalf of Mallinckrodt Pharmaceuticals, which recently changed its

outside counsel to Hogan Lovells for the purpose of assisting in the ongoing dialogue
between CMS and Mallinckrodt regarding a base date AMP determination by the
agency in 2012.
As you know, Mallinckrodt is currently scheduled to meet with you and your colleagues
about this matter at 9:00 a.m. on Tuesday, January 22. To maximize efficient use of the
agency’s time, we propose instead to send CMS a letter that details the relevant
considerations, and to postpone the meeting until after the agency has had an
opportunity to review the letter.
Please advise at your earliest convenience if the agency is amenable to this alternative
way of proceeding. Thank you for your consideration. Please let me know if we could
connect by phone to discuss the pathway forward. I am happy to do so at your
convenience.
Alice
Alice Valder Curran

Partner

Columbia Square
Tel: +1 202 637 5600

Direct: +1 202 637 5997
Fax: +1 202 637 5910
https://protect2.fireeye.com/url?k=056de981-5939f0fd-
056dd8be-0cc47adc5fa2-
dbe25fc5e4820ea6&u=https://protect2.fireeye.com/url?
k=24e805b7-78bc1ccb-24e83488-0cc47adc5fa2-
7b73369042327b75&u=http://www.hoganlovells.com/

<image002.jpg>
<image003.jpg>

About Hogan Lovells

Hogan Lovells is an international legal practice that includes Hogan Lovells US LLP and Hogan Lovells
International LLP. For more information, see https://protect2.fireeye.com/url?k=15b17ea0-49e567dc-
15b14f9f-0cc47adc5fa2-0c3e2507500399c1&u=https://protect2.fireeye.com/url?k=f4a2694f-a8f67033-
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CONFIDENTIALITY. This email and any attachments are confidential, except where the email states it can
be disclosed; it may also be privileged. If received in error, please do not disclose the contents to anyone,
but notify the sender by return email and delete this email (and any attachments) from your system.

FOIA-EXEMPT CONFIDENTIAL COMMERCIAL INFORMATION
February 27, 2019
Via Electronic and U.S. Mail

Director
Division of Pharmacy
Center for Medicaid and CHIP Services
7500 Security Boulevard
Mail Stop S2-14-26
Baltimore, MD 21244
Re: H.P. Acthar Gel® Base Date Average Manufacturer Price
Dear Dr. Coster:
I am writing on behalf of Mallinckrodt ARD Inc. (Mallinckrodt) (labeler code 63004) regarding its product
H.P. Acthar Gel® (Acthar) in advance of our meeting on March 7, 2019, to set forth Mallinckrodt’s position
regarding Acthar’s base date average manufacturer price (AMP).
Mallinckrodt is an innovation-driven specialty pharmaceutical company focused on improving outcomes

for patients with severe and critical conditions. We are guided by a set of four values: patient-centricity,
integrity, innovation, and collaboration. In support of all of these values, Mallinckrodt is committed to
compliance with its statutory and regulatory obligations under the Medicaid drug rebate (MDR) program.
In 2012, the Centers for Medicare & Medicaid Services (CMS) affirmatively and specifically determined
that Acthar with the infantile spasms (IS) indication qualifies for a new base date AMP. Mallinckrodt has
reasonably and in good faith relied on this determination, as did Questcor Pharmaceuticals (Questcor),
the then-sponsor of the product that had engaged CMS on the issue and that Mallinckrodt acquired on
August 14, 2014. The CMS determination was correct at the time and remains so today. The agency’s
communications with Mallinckrodt (and Questcor before it) have provided no meaningful explanation for
any change in CMS’s position, nor have there been any changes in law or fact that would justify such a
reversal. As addressed below, and as we look forward to discussing during our upcoming meeting, both
the facts and the law supported – and continue to support – establishing and maintaining a new base date
AMP for Acthar with the IS indication.
1
(Page 178 of Total) FOIA-EXEMPT CONFIDENTIAL COMMERCIAL INFORMATION
A130
1425 U.S. Route 206 • Bedminster, New Jersey HHS - 000050
07921 • 908.238.6600 • www.mallinckrodt.com
I. FACTUAL BACKGROUND
A. Acthar and Infantile Spasms
Acthar, an adrenocorticotropic hormone (ACTH) analogue, is approved for nineteen indications in a range
of patients, including infantile spasms in children under two years of age. 1 Infantile spasms is a rare and
devastating seizure disorder that occurs in young children and greatly increases the risk of developmental
disability if left untreated. Acthar is a first-line therapy for infantile spasms; the Food and Drug
Administration (FDA) recognizes that Acthar “has been the treatment of choice for IS for many years.” 2
B. Timeline
In addition to providing factual background, the following timeline of key events demonstrates Questcor’s,
and later Mallinckrodt’s, good faith and transparent engagement with CMS regarding the base date AMP
for Acthar.
x 1952: FDA first approves H.P. Acthar Gel® under new drug application (NDA) 008372. 3
x 1958: The active ingredient in Acthar, ACTH, is first reported as a successful treatment for IS. 4
Over time, it becomes the treatment of choice for infantile spasms. 5
x 2001: Questcor acquires Acthar from Aventis.
x 2003: FDA grants orphan drug designation to Acthar to convey exclusivity upon approval for the
treatment of infantile spasms. 6
x 2007: Questcor increases the price of Acthar from $1,650/unit to $23,269/unit to ensure the
continued commercial availability of the product and to reflect the investment in
modernizing the product and its manufacturing.
1 Acthar Prescribing Information (Acthar PI), available at

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s000LBL.pdf.
2 FDA, Memorandum (Apr. 5, 2010) (NDA 022432 Summary Review) at 1, available at
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s0900SumR.pdf (PDF p.4).
3 FDA, Drugs@FDA (Approval Date(s) and History, Letters, Labels, Reviews for NDA 008372), available
at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008372.
4 See, e.g., C. Tsao, Current trends in the treatment of infantile spasms, NEUROPSYCHIATR DIS
TREAT. 2009;5:289-299, available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695218/, citing L. Sorel
& A. Dusaucy-Bauloye, Findings in 21 cases of Gibbs’ hypsarrhythmia: spectacular effectiveness of ACTH, ACTA
NEUROL PSYCHIATR BELG. 1958 Feb;58(2):130-41.
5 See, e.g., NDA 022432 Summary Review at 1; D. Shields, “Infantile Spasms,” Child Neurology
Foundation (referring to 1958 publication and stating that “ACTH was used for more than 50 years before it
was approved by the FDA in 2010 for the treatment of infantile spasms”), available at
https://www.childneurologyfoundation.org/disorders/infantile-spasms/.
6 FDA, Search Orphan Drug Designations and Approvals, available at
https://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm.
2
A131
x 2010: FDA approves Acthar with the IS indication under NDA 022432.7
o On June 16, 2006, Questcor submitted a supplemental NDA (sNDA) seeking approval of
Acthar with the IS indication. 8
o On May 10, 2007, FDA issued a Not Approvable (NA) letter.9
The letter cited the absence of a sufficient nexus between the product and
published studies.
The letter encouraged Questcor to meet with FDA to discuss the deficiencies in
the application. 10
o Questcor and FDA thereafter “entered into discussions regarding how [the IS] indication
could be pursued,” during which FDA “determined that the sponsor should attempt to
obtain primary data for several trials published in archival literature that, potentially,
could provide substantial evidence of effectiveness for Acthar Gel for IS.” 11
o On August 8, 2008, FDA unilaterally converted the sNDA to an NDA, to which it assigned
NDA number 022432. 12
o On December 10, 2009, Questcor submitted NDA 022432 in response to the NA letter,
based on, among other things, the data that FDA had determined Questcor should obtain
and submit. 13
o On October 15, 2010, FDA approved NDA 022432 for Acthar to treat IS. This approval
included significant revisions to the Acthar’s PI, including: 14
x Removal of more than thirty indications;
x Addition of the IS indication;
7 Letter from FDA to Questcor (Oct. 15, 2010) (NDA 022432 Approval Letter), available at
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s000Approv.pdf (PDF pp. 4-8).
8 NDA 022432 Summary Review at 1 (PDF p.2).
9 Attachment 1 (Letter from FDA to Questcor (May 10, 2007)).
10 Id. at 2 (“We strongly encourage you to meet with review staff from both the Division of Metabolism
and Endocrinology Products and Division of Neurology Products to discuss the deficiencies of the
application.”).
12 FDA, Memorandum (Aug. 8, 2008) at 1 (“. . . sNDA 08-372/S-039 has been converted to the new NDA
22-432 for the 2nd cycle.”) (emphasis added), available at
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s000AdminCorres.pdf
(Administrative Documents and Correspondence (PDF p.69)).
14 See NDA 022432 Approval Letter (PDF pp. 4-8); Acthar PI.
3
A132
x Imposition of a risk evaluation and mitigation strategy (REMS) for the new IS
indication;
x New “Medication Guide” requirement for the new IS indication;
x Revisions to the “Dosage and Administration” section; and
x New section on pediatric indications.
o NDA 022432 received seven years of orphan drug exclusivity upon approval.15
x 2012: CMS confirms in writing that Acthar with the IS indication qualifies for a new base date
AMP and directs Questcor to assign a new National Drug Code (NDC)-9 to the product to
effectuate the new base date AMP. 16
o On March 29, 2012, Questcor met with CMS and proceeded to engage with the agency in
good faith and with transparency regarding Acthar’s base date AMP and the company’s
ability to continue to participate in the MDR program. 17
At that time, Questcor conveyed to the agency that the product accounted for
more than 99% of Questcor’s sales revenue, and MDR program rebates for the
product exceeded Questcor’s Medicaid revenue, noting the following:
x There was a high incidence of Medicaid utilization of Acthar for treatment

of infantile spasms, given the pediatric patient population.
x The MDR program unit rebate amount (URA) was 100% of AMP.
x Questcor lost money on Medicaid utilization where Medicaid was the

primary payor because of distribution costs incurred on every unit in
addition to the 100% of AMP rebate, and even more so where Medicaid
was a secondary payor and the full rebate nevertheless was due.
Questcor laid out the reasoning as to why Acthar with the IS indication qualifies
for a new base date AMP.
Subject to CMS’s agreement with such reasoning, Questcor proffered a choice

between effectuating the new base date AMP using the existing NDC-9 or doing
so using a new NDC-9.

16 Attachment 2 (Letter from CMS to Questcor (Aug. 6, 2012)).
17 See Attachment 3 (Letter from Questcor to CMS (May 8, 2012)).
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o On May 8, 2012, Questcor sent a letter to CMS in follow up to the March 29, 2012 meeting
and, at the agency’s suggestion, addressed the letter to the CMS Deputy Administrator
and Center for Medicaid and CHIP Services (CMCS) Director. 18 The letter:
Memorialized the reasoning as to why Acthar with the IS indication qualifies for
a new base date AMP;
Reiterated the proffered alternatives for how to effectuate the new base date
AMP; and
Disclosed to CMS the fact that FDA would be consolidating NDA 022432 with NDA
008372, stating: “[T]he FDA has informed Questcor that the agency intends to
revise its record so that the approval for infantile spasms is reflected as part of
the product’s original NDA, No. 08-372. That has not yet occurred.” 19
o On August 6, 2012, the CMS Deputy Administrator and CMCS Director sent a letter to
Questcor. 20 The letter:
Confirmed that Acthar with the IS indication qualifies for a new base date AMP;
Directed Questcor to assign a new NDC-9 to the product to effectuate the new
base date AMP; and
Confirmed that “[t]he [Acthar new base date AMP] decision in this letter is . . .
based on the facts and information presented to us . . . .” 21
x 2013: Questcor effectuates the new base date AMP using the new NDC-9 that it had assigned
to the product.
x 2014: Mallinckrodt acquires Questcor for $5.8 billion on August 14, 2014.
o In doing so, Mallinckrodt relied in good faith on the 2012 determination by CMS that a
new base date AMP was appropriate.
o Mallinckrodt would not have engaged in the Questcor transaction as it occurred but for
the 2012 determination.
o Mallinckrodt has since invested more than $500 million in modernizing the product and
its manufacturing.
x 2015: FDA consolidates NDA 022432 with NDA 008372. 22
18 Id.
19 Id. at 3 n.4.
20 Attachment 2.
21 Id. at 1.
22 See Letter from FDA to Questcor (Mar. 24, 2015) at 1 (“This [sNDA] provides for the indication for the
treatment of infantile spasms to be associated with the parent NDA number 08372, since the tracking NDA
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x 2016: Mallinckrodt conforms the NDA number listing for Acthar with the IS indication in the FDA
Online Label Repository to that in Drugs@FDA – NDA number 022432 – in response to a
CMS observation that the listings were inconsistent. 23
II. LEGAL BACKGROUND
In order for federal payment to be available under Medicaid or Medicare Part B for the covered outpatient
drugs of a manufacturer, the manufacturer must, among other things, enter into a National Drug Rebate
Agreement (NDRA) with CMS. 24 Under the NDRA, the manufacturer must, among other things, provide
rebates to state Medicaid agencies on Medicaid utilization of the manufacturer’s covered outpatient
drugs during each calendar quarter. 25
The Medicaid statute sets forth the formula under which the URA for each covered outpatient drug is
calculated. 26 A distinct URA is calculated for each dosage form and strength of each single source or
innovator multiple source drug as follows:
x The basic rebate: The greater of:
o The difference between the AMP and the best price of the dosage form or strength of the
drug; or
o The statutorily specified minimum rebate percentage of AMP; 27 plus
x The additional rebate: The amount (if any) by which the AMP of the dosage form or strength of
the drug for the reporting quarter exceeds the base date AMP of the dosage form or strength of
the drug (without regard to whether the product has been sold or transferred), increased by an
inflation factor. 28
The URA is capped at 100% of AMP. 29
For a covered outpatient drug approved on or before October 1, 1990, base date AMP is AMP for the third
quarter of 1990. 30 For a covered outpatient drug approved after October 1, 1990, base date AMP is AMP
for the first full calendar quarter of sales. 31 Base date AMP is not otherwise defined in statute or
regulation.
number 022432 will no longer be used”), available at

https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/008372Orig1s044ltr.pdf.
23 FDA, FDA Online Label Repository, available at https://labels.fda.gov/.
24 Social Security Act (SSA) § 1927(a)(1).
25 Id. § 1927(b)(1)(A).
26 Id. § 1927(c).
27 Id. § 1927(c)(1)(A)(ii).
28 Id. § 1927(c)(2)(A)(ii).
29 Id. § 1927(c)(2)(D).
30 Id. § 1927(c)(2)(A)(ii)(II).
31 Id. § 1927(c)(2)(B).
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Each dosage form and strength of each single source or innovator multiple source drug has a distinct URA
– and therefore a distinct base date AMP. Accordingly, as CMS has confirmed, a distinct base date AMP
is appropriate where a product is:
x A distinct dosage form or strength of a single source or innovator multiple source drug; or
x A distinct single source or innovator multiple source drug. 32
As set forth below, Acthar with the IS indication is a distinct single source drug. It therefore properly has
its own base date AMP, distinct from that of the pre-2010 Acthar product.
III. CMS CORRECTLY DETERMINED IN 2012 THAT ACTHAR WITH THE IS INDICATION QUALIFIES FOR
A NEW BASE DATE AMP
On August 6, 2012, the CMS Deputy Administrator and CMCS Director confirmed in writing on behalf of
the agency that Acthar with the IS indication qualifies for a new base date AMP. 33 Specifically, the agency
“agree[d] that Acthar Gel is eligible for a new base date AMP.” 34 In explaining its reasoning, the agency
stated:
Section 1927(c)(2)(A) defines the base date AMP, in part, for each single source of
innovator multiple source drug approved by the FDA before or after October 1, 1990. In
accordance with that provision, the base date AMP is calculated based on the new drug
application which is approved by the FDA, not the national drug code (NDC). Therefore,
given that the recently approved Acthar Gel was approved under a different ND[A][35]
from the original product, Questcor may set a new base date AMP for this drug. 36
The agency went on to direct Questcor to assign a new NDC-9 to Acthar with the IS indication to effectuate
the new base date AMP:
[Y]ou proposed two options with respect to the calculation of a new base date AMP. First,
you note that based on the proposed rule, Questcor could revise its base date based on
revisions in the Affordable Care Act. Second, you note that Questcor could create a new
NDC-9 based on the recent FDA approval. For the purpose of the Medicaid Drug Rebate
32 Mem. in Supp. of Def.’s Cross-Mot. for Summ. J. & Opp’n to Pl.’s Mot. for Summ. J. at 18, Ipsen
Biopharmaceuticals v. Price, Civ. Action No. 1:16-cv-02372-ABJ (D.D.C. Aug. 14, 2017) (“[A manufacturer] can
apply a different base-date average manufacturer price for [a] product only if it creates a new covered
outpatient drug by obtaining FDA approval of a separate NDA with a different six-digit NDA number or if it
changes the drug’s dosage form or strength.”) (citation omitted) (emphasis added).
33 Attachment 2.
34 Id. at 1 (emphasis added).
35 Here, the agency referred to an “NDC,” instead of an NDA. In context, this appears to be a scrivener’s
error.
36 Id. (emphasis added).
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Program we believe the assignment of a new NDC-9 to the recently approved Acthar Gel
would be necessary. 37
CMS correctly determined in 2012 that Acthar with the IS indication qualifies for a new base date AMP.
As set forth below:
x Acthar with the IS indication was approved under an original NDA, both in fact and as a matter of
law; and
x It is reasonable to treat Acthar with the IS indication as a distinct single source drug because it is
in fact a distinct product.
A. Acthar with the IS Indication Was Approved Under an Original NDA
A distinct single source drug is entitled to its own base date AMP. 38 The statute defines the term “single
source drug,” in relevant part, as “a covered outpatient drug which is produced or distributed under an
original new drug application approved by the Food and Drug Administration . . . .” 39 In regulation, CMS
has interpreted this statutory definition, in relevant part, as follows:
Single source drug means a covered outpatient drug that is produced or distributed under
an original NDA approved by FDA and has an approved NDA number issued by FDA . . . .
For purposes of this definition and the MDR program, an original NDA means an NDA,
other than an [abbreviated new drug application (ANDA)], approved by the FDA for
marketing, unless CMS determines that a narrow exception applies. 40
Accordingly, a product qualifies as a distinct single source drug if it: (1) is produced or distributed under
an original NDA approved by FDA, and (2) has an approved NDA number issued by FDA.
37 Id. (emphasis added); see also id. (“We request that Questcor notify CMS about the new NDC-9 and
baseline data when Questcor has this information and is ready to report the information into the Drug Data
Reporting for Medicaid system.”) (emphasis added).
38 See § II supra.
39 SSA § 1927k)(7)(A)(iv) (emphasis added).
40 42 C.F.R. § 447.502 (emphasis added). This regulatory definition became effective on April 1, 2016.
See 81 Fed. Reg. 5170 (Feb. 1, 2016). Prior to April 1, 2016, CMS’s regulatory definition, in relevant part, simply
parroted the statutory definition. See 42 C.F.R. § 447.502 (2015). In establishing the current regulatory
definition, CMS explained that no change in policy was intended, stating, “this final rule is designed to clarify
existing policy regarding the definitions of original NDA and single source drugs, innovator multiple source
drugs, and noninnovator multiple source drugs.” 81 Fed. Reg. at 5193; see also id. at 5196 (“Our proposed
language was not designed to change CMS policy, but rather to provide further clarification that an ‘original
NDA’ means an NDA, other than an ANDA, approved by the FDA for marketing, unless the narrow exception
discussed above applies.”); id. at 5336 (“[W]e believe that manufacturers should have been reporting drugs
marketed under an original NDA as either single source or innovator multiple source drugs prior to this
rulemaking . . . .”). Accordingly, the 2016 revision to the regulatory definition is not material to the analysis at
hand.
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Here, Acthar with the IS indication is in fact produced and distributed under NDA 022432,41 which is an
NDA that FDA has approved 42 and for which FDA has issued an NDA number. 43 And, of critical importance
here, Acthar with the IS indication was approved under an original NDA, both in fact and as a matter of
law, as set forth below. It therefore qualifies as a distinct single source drug, and is properly associated
with a distinct base date AMP.
1. Acthar with the IS indication was approved under an original NDA in fact
On October 15, 2010, FDA approved Acthar for treating IS under NDA 022432, an NDA distinct from NDA
008372. 44 In determining that Acthar with the IS indication qualifies for a new base date AMP, CMS
expressly acknowledged, and based its determination on, the fact that “the recently approved Acthar Gel
was approved under a different ND[A] from the original product.” 45 CMS has since expressly confirmed
that its understanding remains the same: “We understand and agree that the new indication for Acthar
was approved under NDA 022432.” 46
Drugs@FDA confirms that Acthar was approved to treat IS under NDA 022432. According to FDA, “the
purpose of Drugs@FDA” is to provide “official information about FDA approved innovator (brand name)
and generic drugs and therapeutic biological products,” including the NDA number under which a drug
was approved.47 As CMS has expressly recognized,48 Drugs@FDA lists the NDA under which Acthar was
approved to treat IS as NDA 022432. 49
It is undisputed that Acthar with the IS indication was approved under NDA 022432 – a distinct NDA.
Because Acthar with the IS indication is produced and distributed under this distinct FDA-approved NDA
with a distinct FDA-issued NDA number 50 – i.e., under this original NDA in fact – the product qualifies as a
distinct single source drug, and therefore properly has its own base date AMP.
41 See FDA, National Drug Code Directory, available at

https://www.accessdata.fda.gov/scripts/cder/ndc/; FDA, FDA Online Label Repository, available at
https://labels.fda.gov/.
42 NDA 022432 Approval Letter (PDF pp. 4-8).
43 FDA, Memorandum (Aug. 8, 2008) at 1 (“. . . sNDA 08-372/S-039 has been converted to the new NDA
22-432 for the 2nd cycle.”) (emphasis added), available at
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s000AdminCorres.pdf
(Administrative Documents and Correspondence (PDF p.69)).
44 NDA 022432 Approval Letter (PDF pp. 4-8).
45 Attachment 2 at 1 (emphasis added).
46 Attachment 4 (E-mail from CMS to Mallinckrodt (Mar. 20, 2017)) at 2 (emphasis added).
47 FDA, Drugs@FDA Frequently Asked Questions (emphasis added), available at
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=faq.page.
48 Attachment 5 (Letter from CMS to Mallinckrodt (Apr. 13, 2016)) at 1.
49 FDA, Drugs@FDA, available at
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022432.
50 See n.41 supra.
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2. Acthar with the IS indication was approved under an original NDA as a matter
of law
Under the regulatory definition of “original NDA” – which applies for purposes of both the definition of
“single source drug” and the MDR program in general 51 – the NDA under which FDA approved a drug
qualifies as an original NDA if it is:
x An NDA (other than an ANDA) approved by FDA for marketing;
x Unless CMS determines that a narrow exception applies. 52
This regulatory definition establishes (1) an expansive default rule and (2) a narrow exception policy. The
NDA under which FDA approved Acthar with the IS indication qualifies as an original NDA under the
expansive default rule, and the narrow exception does not apply.
Under the regulatory definition of the term “original NDA,” the default rule – to which CMS has bound
itself through rulemaking 53 – is that a product qualifies as a drug approved under an original NDA if it is
approved by FDA for marketing under “an” NDA (other than an ANDA). 54 Neither the type of NDA (so long
as it is not an ANDA) nor subsequent consolidation with another NDA is material or relevant to the
analysis. 55
The regulatory definition of the term “original NDA” directs that the default rule applies “unless CMS
determines that a narrow exception applies.” 56 The preamble to the rule in which CMS established this
regulatory definition makes clear that this exception clause is intended to be read in a “very limited” and
“very narrow” manner. 57 Indeed, CMS embraced a sweeping definition of the term “original NDA,”
explaining that any departures from the default rule are permitted only in “very limited circumstances”
to ensure only “very narrow exceptions to the rule that drugs marketed under NDAs . . . , other than
ANDAs, should be classified as either single source or innovator multiple source drugs.” 58 Moreover, as
reflected in both the preamble and subsequent guidance, CMS has carefully interpreted the exception
clause to specifically restrict its application in a way that makes the narrow exception policy categorically
inapplicable to Acthar.
51 42 C.F.R. § 447.502.
52 Id.
53 See, e.g., Nat’l Fair Hous. All. v. Carson, 330 F. Supp. 3d 14, 54 (D.D.C. 2018) (“An agency issuing a
legislative rule is itself bound by the rule until that rule is amended or revoked and may not alter such a rule
without notice and comment.”).
54 42 C.F.R. § 447.502 (emphasis added).
55 See also SSA § 1927k)(7)(A)(iv) (defining the term “single source drug” by reference to “an” original
NDA, without regard to type of original NDA or subsequent consolidation with another original NDA) (emphasis
added).
56 42 C.F.R. § 447.502.
57 81 Fed. Reg. at 5191; see also id. at 5202-03 (incorporating by reference the discussion of the term
“innovator multiple source drug” into that of the term “single source drug”); Tex. Children’s Hosp. v. Azar, 315
F. Supp. 3d 322, 334 (D.D.C. 2018) (“To be clear, the preamble to a . . . rule may be used to help inform the
proper interpretation of an ambiguous text.”) (citation omitted).
58 81 Fed. Reg. at 5191.
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First, in the preamble, CMS categorically stated that “the narrow exception will not be considered
applicable . . . for drugs that received patent protection or statutory exclusivity.” 59 Its subsequent
guidance reflects the same categorical interpretation of the exception clause: “The narrow exception will
not be granted under the following circumstances: . . . Drugs that received patent protection or statutory
exclusivity, regardless of whether the protection or exclusivity is currently in effect.” 60 Acthar with the IS
indication received statutory exclusivity – orphan drug exclusivity,61 which is granted under section 527
of FDCA. 62 Accordingly, under CMS’s categorical interpretation of the exception clause, as repeatedly
expressed in the preamble and its subsequent guidance, this is not a circumstance in which an exception
to the default rule could conceivably apply.
Second, in the preamble, CMS made clear that any determination by CMS that an exception to the default
rule applies “requires the manufacturer’s written submission to CMS, and CMS’s response confirming that
the exception applies.” 63 Here, neither Mallinckrodt nor Questcor made any submission to CMS seeking
an exception to the default rule – to reclassify Acthar as a noninnovator multiple source drug (the only
exception circumstance contemplated by the preamble and the subsequent guidance 64) or otherwise.
Again, under CMS’s categorical interpretation of the exception clause, this is not a circumstance in which
CMS may determine that an exception to the default rule applies.
* * * * *
It is undisputed that Acthar with the IS indication was approved under NDA 022432. Under the default
rule, it is immaterial and irrelevant whether this NDA is a certain type of NDA or that it was subsequently
consolidated with NDA 008372. It is material only that it is “an” NDA. Because Acthar with the IS
indication is in fact marketed under this FDA-approved NDA, 65 and because no exception to the default
rule applies, it was approved under an original NDA as a matter of law. Acthar with the IS indication
otherwise meets the regulatory definition of the term “single source drug” and therefore is entitled to its
own base date AMP.66
59 Id..
60 CMS, Manufacturer Release No. 98 (May 2, 2016) at 2, available at
https://www.medicaid.gov/medicaid-chip-program-information/by-topics/prescription-drugs/downloads/rx-
releases/mfr-releases/mfr-rel-098.pdf.
62 21 U.S.C. § 360cc.
63 81 Fed. Reg. at 5192 (emphasis added).
64 See id. at 5190-97, 5202-03; Manufacturer Release No. 98.
65 See n.41 supra.
66 The same conclusion applies to the period before the April 1, 2016 adoption of the current regulatory
definition of “single source drug” because, as discussed above, CMS has confirmed that the regulatory revisions
to the definition merely clarified existing policy. See n.40 supra. Moreover, before the adoption of the current
regulatory definition, CMS’s only pronouncement regarding the term “original NDA” was a proposal to define
the term “original NDA” by reference to patent protection or marketing exclusivity. See 81 Fed. Reg. at 5194
(citing 60 Fed. Reg. 48442, 48453 (Sept. 19, 1995)). Under that proposed definition, the NDA under which FDA
approved Acthar to treat IS would qualify as an “original NDA” because the product received orphan drug
exclusivity with the approval of NDA 022432. See n.61 supra.
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B. It Is Reasonable to Treat Acthar with the IS Indication as a Distinct Single Source Drug
Because It Is In Fact a Distinct Product
The reasonableness of the conclusion that Acthar with the IS indication is a distinct single source drug –
entitled to its own base date AMP – is bolstered by:
x The definition of the term “new drug”; and
x The distinct NDC-9 assigned to Acthar with the IS indication at the direction of CMS.
1. Acthar with the IS indication meets the definition of the term “new drug”
The NDRA in effect at the time of CMS’s 2012 determination defined the term “new drug” as “a Covered
Outpatient Drug approved as a new drug under section 201(p) of the Federal Food, Drug, and Cosmetic
Act [(FDCA)].” 67 Section 201(p) of the FDCA in turn defines the term “new drug,” in relevant part, as “[a]ny
drug . . . the composition of which is such that such drug is not generally recognized, among experts
qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe
and effective under the conditions prescribed, recommended, or suggested in the labeling thereof . . . .” 68
A new drug may not be marketed or distributed without FDA approval. 69
Here, Acthar with the IS indication meets the definition of the term “new drug” under section 201(p) of
the FDCA and, accordingly, was not marketed or distributed for that use until it was approved – via NDA
022432 – by FDA. The significant revisions to Acthar’s PI at the time of FDA’s 2010 approval necessarily
rendered the product a new drug under section 201(p) of the FDCA: The product was not generally
recognized as safe and effective under the new conditions under which FDA granted approval prior to
2010. These new conditions reflected numerous material differences between Acthar with the IS
indication and the previously approved product, which precluded marketing or distribution absent FDA
approval. Chief among these differences was the addition of the IS indication. Other significant
differences include:
x Removal of more than thirty indications;
x Imposition of a REMS for the new IS indication;
x New “Medication Guide” requirement for the new IS indication;
x Revisions to the “Dosage and Administration” section; and
x New section on pediatric indications.
In light of these significant revisions to Acthar’s PI, which required FDA’s 2010 approval, Acthar with the
IS indication meets the definition of the term “new drug.” That Acthar with the IS indication is, by
67 56 Fed. Reg. 7049, 7051 (Feb. 21, 1991). Although the current NDRA does not continue to define the
term “new drug,” the concept of a new drug, as defined under section 201(p) of the FDCA, remains compatible
with the MDR program regulatory scheme. See 57 Fed. Reg. 12770 (Mar. 23, 2018).
68 21 U.S.C. §321(p)(1) (emphasis added).
69 Id. § 355(a); see also id. § 331(d).
12
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definition, a new drug only reinforces the conclusion that it is a distinct single source drug – and therefore
properly associated with a distinct base date AMP.
2. The distinct NDC-9 assigned to Acthar with the IS indication confirms that
Acthar with IS indication is in fact a distinct product
The MDR program routinely looks to a distinct NDC-9 as a proxy for a distinct product. For example:
x Monthly AMP is calculated at the NDC-9 level; 70
x The 5i AMP “not generally dispensed” determination is made at the NDC-9 level; 71
x “Drugs of different types” are identified by distinct NDC-9s for bundled sales purposes; 72 and
x The NDRA in effect at the time of CMS’s 2012 determination expressly recognized that the product
code portion of an NDC (i.e., the NDC at the NDC-9 level) identifies a “specific product or
formulation.” 73
There are only two recognized circumstances under which a distinct NDC-9 does not represent a distinct
product:
x Where a drug has been sold or transferred; 74 and
x An authorized generic. 75
Here, CMS itself expressly directed the assignment of a new NDC-9 as the means of effectuating the new
base date AMP for Acthar as approved to treat IS. 76 The assignment of the new NDC-9 did not reflect
either a sale or transfer of the product or an authorized generic of the product. Rather, it reflected a
material difference between Acthar with the IS indication and the previously approved product,
warranting a new NDC-9 (in addition to requiring approval under a new NDA). Accordingly, here, the new
NDC-9 represents a distinct product. This only bolsters the conclusion that Acthar with the IS indication
is in fact a distinct single source drug – and therefore properly associated with a distinct base date AMP. 77
70 42 C.F.R. § 447.510(d)(2)(iii).
71 Id. § 447.506(b)(1).
72 Id. § 447.502.
73 56 Fed. Reg. at 7051; see also id. at 7053.
74 SSA § 1927(c)(2)(B).
75 Id. § 1927(k)(1)(C).
76 Attachment 1 at 1.
77 CMS’s only guidance regarding base date AMP provides that base date AMP follows the NDA – but this
is so only in the circumstances contemplated in CMS’s guidance: (1) where a drug has been assigned a new
NDC-9 because it has been sold or transferred, or (2) where a drug has been assigned a new NDC-9 because it
is an authorized generic. See, e.g., CMS, Manufacturer Releases No. 90 (Apr. 18, 2014), available at
https://www.medicaid.gov/medicaid-chip-program-information/by-topics/prescription-drugs/downloads/rx-
releases/mfr-releases/mfr-rel-090.pdf, 38 (Nov. 20. 1998), available at https://www.medicaid.gov/medicaid-
chip-program-information/by-topics/prescription-drugs/downloads/rx-releases/mfr-releases/mfr-rel-038.pdf,
26 (Feb. 27, 1997), available at https://www.medicaid.gov/medicaid-chip-program-information/by-
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ATTACHMENT 1

A144



ATTACHMENT 2

A148


ATTACHMENT 3

A151







ATTACHMENT 4

A159
From: Forshee, Kay

To: CMS MDROperations
Cc: Landolt, Jamie; Matasi, Twayler; "CMS MDROperations"
Subject: RE: MDR 04 RE: Acthar gel final.doc
Proprietary and Confidential—Not to Be Released under FOIA or Otherwise
Thank you for your email on March 20, 2017.
We appreciate CMS’ confirmation that “the new indication for Acthar was approved under NDA
022432.” We see this as significant, because it confirms the basis CMS gave in its August 6, 2012
communication to Questcor that explicitly approved the appropriateness of a new base date AMP.
CMS concluded there that “[w]e have reviewed your request and agree that Acthar Gel is eligible for
a new base date AMP.” Mallinckrodt, which purchased Acthar from Questcor in August 2014, has
relied upon that agency determination.
We believe the agency’s conclusion was correct in 2012 and remains correct now. NDA 022432
represented a very significant set of events. Acthar’s label, indications, and approval for marketing
underwent a fundamental revision, including all of the following changes under that NDA:
• Addition of the infantile spasms indication;
• Removal of more than 30 indications that previously were approved for marketing;
• Revised “Dosage and Administration” section;
• New and separate section on pediatric indications;
• New FDA requirement for a “Medication Guide” relating to the new infantile spasms
indication;
• New, indication-specific Risk Evaluation and Mitigation Strategy (REMS) for the new
infantile spasms indication;
• Addition of the route of administration for Acthar; and
• Addition of the “Mechanism of Action” section.
Your email dated March 20, 2017 also indicates that FDA has reportedly suggested to CMS that NDA
022432 was a “type-6 NDA”. As an initial matter, we do not see any significance in this observation,
even if correct. The plain language of the Medicaid drug rebate statute speaks directly to the
importance of an approval of an NDA; it is irrelevant under the statute whether an NDA was a "type
6".
We will continue to review your email, however, and we may have some additional thoughts to
share with you as part of this ongoing dialogue. Thank you for your engagement with us on this
important issue.

Best regards,
Kay Forshée | Sr. Manager, Government Reporting

325 McDonnell Blvd. | Hazelwood, MO 63042 | USA
T: 314.654.6592 / M: 314.780-1630
kay.forshee@mallinckrodt.com l www.mallinckrodt.com
This information may be confidential and/or privileged. Use of this information by anyone other
than the intended recipient is prohibited. If you receive this in error, please inform the sender and
remove any record of this message.
From: CMS MDROperations [mailto:MDROperations@cms.hhs.gov]

Sent: Monday, March 20, 2017 5:18 PM
To: Forshee, Kay
Cc: Lough, Mairi; Landolt, Jamie; Lasker, Karen L; CMS MDROperations
Kay,
Thank you for your emails on July 6, 2016 and July 29, 2016. We understand and agree that
the new indication for Acthar was approved under NDA 022432. We also note that the SPL
information submitted to FDA by the manufacturer currently reflects NDA 022432. However
FDA has confirmed that NDA 022432, a type-6 NDA, was created for administrative purposes
because an FDA division other than the division responsible for NDA 008372 was reviewing
the application for the new indication. FDA has informed us that type-6 NDAs are
administratively closed upon approval. Therefore, it is our understanding that the marketing
of the drug has always been under the auspices of NDA 008372, regardless of the
administratively assigned NDA 022432, which was only for the purpose of FDA approval of
the new indication, but not for the approval and marketing of the drug itself.
The baseline information for a drug that was approved prior to the effective date of section
1927 of the Social Security Act is established using the data of the drug as of 9/30/1990. It is
our understanding that NDA 008372 for Acthar was approved on April 29, 1952, therefore,
the baseline data for the drug that is marketed under that NDA would be based on data from
9/30/1990 as the approval of NDA 022432 in 2010 was not for approval of a new drug.
Thank you,
CMS MDR Operations
The decision in this response is limited to and based upon the facts described in this email and any
attachments provided and our understanding of the facts as described in the emails and attachments
submitted. If a subsequent review by CMS, by the Office of Inspector General, or another authorized
government agency determines or reveals that additional adjustments or revisions are necessary, the
manufacturer is responsible for complying with that determination. This response cannot be considered an
advisory opinion under section 1128D(b) of the Social Security Act, since only the Inspector General of the

U.S. Department of Health and Human Services has been authorized to issue advisory opinions relating to
health care fraud and abuse under that section. This response should not be interpreted as acquiescence
by the Government to the arrangements described herein. Further, this response is not a release of any
liability.
NOTICE: The contents of this message and any attachments may be privileged and confidential. If you are
not an intended recipient, or have received this message in error, please delete it without reading it and please
do not print, copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that
you have received this communication in error. Your receipt of this message is not intended to waive any
applicable privilege.
From: Forshee, Kay [mailto:Kay.Forshee@mallinckrodt.com]

Sent: Friday, July 29, 2016 8:02 PM
To: CMS MDROperations <MDROperations@cms.hhs.gov>
Cc: Lough, Mairi <Mairi.Lough@mallinckrodt.com>; Landolt, Jamie
<Jamie.Landolt@mallinckrodt.com>; Lasker, Karen L <Karen.Lasker@mallinckrodt.com>
Subject: MDR 04 RE: Acthar gel final.doc
Proprietary and Confidential—Not to Be Released, in Whole or in Part, under FOIA or

Otherwise
Good evening,
We wanted to briefly follow up on our email below. As we indicated there, we have

continued to look into your correspondence. As part of that effort, we have clarified the pre-
existing FDA Online Label Repository listing to list NDA 022432, consistent with CMS' letter
and analysis dated August 6, 2012.
Thank you,

T: 314.654.6592
This information may be confidential and/or privileged. Use of this information by anyone
other than the intended recipient is prohibited. If you receive this in error, please inform the
sender and remove any record of this message.
From: Forshee, Kay

Sent: Wednesday, July 06, 2016 6:12 PM
To: 'CMS MDROperations'

Cc: Lough, Mairi; Landolt, Jamie; Lasker, Karen L

Proprietary and Confidential—Not to Be Released, in Whole or in Part, under

FOIA or Otherwise
Good Evening,
Thank you for your email below. As we continue to research the points CMS has
raised, we want to clarify a point that seems to be the basis for the agency’s
request. In your email, you indicate that the base date AMP for a “purchased
product” should not be altered. We want to note that Mallinckrodt’s purchase of
Acthar from Questcor in August 2014 was not the basis of CMS’ confirmation to
Questcor of the appropriateness of a new base date AMP in the agency’s letter to
Questcor dated August 6, 2012, which was two years before Mallinckrodt’s
acquisition of Questcor.
In the April 13, 2016 letter, CMS also stated that it believed that it was potentially
incorrect to have listed the product as “ha[ving] NDA 022432 as its FDA application
number.” We have gone back and confirmed that this was, in fact, the correct FDA
assigned application number for the approval of the product that was discussed in
the CMS letter of August 6, 2012 and that CMS cited in determining that “[w]e have
reviewed your request and agree that Acthar Gel is eligible for a new based date
AMP.”
However, we continue to look further into your correspondence, and will offer
additional thoughts, as they may be helpful to you, at a later date when we have
completed our work.
Thank you,

T: 314.654.6592
This information may be confidential and/or privileged. Use of this information by

anyone other than the intended recipient is prohibited. If you receive this in error,
please inform the sender and remove any record of this message.

Sent: Thursday, June 02, 2016 5:33 PM
To: Forshee, Kay; CMS MDROperations
Kay,

We are aware of the correspondence between Questcor and CMS that you
provided. However, as stated in Manufacturer Release #90 at
http://www.medicaid.gov/Medicaid-CHIP-Program-Information/By-
Topics/Benefits/Prescription-Drugs/Downloads/Rx-Releases/MFR-
Releases/mfr-rel-090.pdf, the baseline data of a purchased product should
be the same as the baseline data of a product marketed previously under
the same NDA. Therefore, we are requesting that you complete and return
the attached template so that the baseline information for the NDC matches
the baseline information of the NDC that was originally used for marketing
the product under the same NDA.
Thank you,
CMS MDR Operations
The decision in this response is limited to and based upon the facts described in this
email and any attachments provided and our understanding of the facts as described in
the emails and attachments submitted. If a subsequent review by CMS, by the Office of
Inspector General, or another authorized government agency determines or reveals that
additional adjustments or revisions are necessary, the manufacturer is responsible for
complying with that determination. This response cannot be considered an advisory
opinion under section 1128D(b) of the Social Security Act, since only the Inspector
General of the U.S. Department of Health and Human Services has been authorized to
issue advisory opinions relating to health care fraud and abuse under that section. This
response should not be interpreted as acquiescence by the Government to the
arrangements described herein. Further, this response is not a release of any liability.
NOTICE: The contents of this message and any attachments may be privileged and
confidential. If you are not an intended recipient, or have received this message in error,
please delete it without reading it and please do not print, copy, forward, disseminate, or
otherwise use the information. Also, please notify the sender that you have received this
communication in error. Your receipt of this message is not intended to waive any

Sent: Tuesday, May 10, 2016 4:26 PM
<Jamie.Landolt@mallinckrodt.com>; Lasker, Karen L
<Karen.Lasker@mallinckrodt.com>
Subject: RE: Acthar gel final.doc

Good afternoon,
Attached please find correspondence between Questcor/Mallinckrodt and

CMS regarding the approved NDC changes and new base AMP for Acthar.
Please advise if we are required to make any changes to the DDR.
Please feel free to contact me directly with any questions.
Thanks,

T: 314.654.6592

Sent: Wednesday, April 13, 2016 1:44 PM
To: Forshee, Kay
Cc: CMS MDROperations
Subject: Acthar gel final.doc
Kay,
Attached, please find an advance copy of a letter that you will be

receiving by U.S. Mail. Also attached is a template, for your use in
requesting the changes referenced in the letter.
Thank you,
CMS MDR Operations
The decision in this response is limited to and based upon the facts described in
this email and any attachments provided and our understanding of the facts as
described in the emails and attachments submitted. If a subsequent review by
CMS, by the Office of Inspector General, or another authorized government
agency determines or reveals that additional adjustments or revisions are
necessary, the manufacturer is responsible for complying with that
determination. This response cannot be considered an advisory opinion under
section 1128D(b) of the Social Security Act, since only the Inspector General of
the U.S. Department of Health and Human Services has been authorized to
issue advisory opinions relating to health care fraud and abuse under that
section. This response should not be interpreted as acquiescence by the
Government to the arrangements described herein. Further, this response is
not a release of any liability.
NOTICE: The contents of this message and any attachments may be privileged
and confidential. If you are not an intended recipient, or have received this

message in error, please delete it without reading it and please do not print, copy,
forward, disseminate, or otherwise use the information. Also, please notify the
sender that you have received this communication in error. Your receipt of this
message is not intended to waive any applicable privilege.

ATTACHMENT 5

A167

April 13, 2016
Kay Forshee
Technical Contact
Questcor Pharmaceuticals/Mallinckrodt
675 McDonnell Blvd
Hazelwood, MO 63042
Dear Kay:
It has recently come to our attention that even though H.P. Acthar Gel is shown to be approved
under NDA 022432 on Drugs@FDA, NDC 63004-8710-01 is listed as approved under NDA
008372 on FDA Online Label Repository at http://labels.fda.gov/getPackageCode.cfm. As a
result of this discrepancy, we have reviewed the approval status of H.P. Acthar Gel and it is our
understanding that H.P. Acthar Gel is marketed under NDA 008372 not NDA 022432. In the
FDA approval letter for H.P. Acthar Gel provided by Drugs@FDA at
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/022432s000ltr.pdf, the approval
letter shows that although the NDA for the use of H.P. Acthar Gel for infantile spasms was
initially assigned number 022432, that any future submissions “should be addressed to the
original NDA 008372 for this drug product, not to this NDA [022432]”.
When reviewing the reporting of NDC 63004-8710 to the Medicaid Drug Rebate (MDR)
program in the Drug Data Reporting for Medicaid (DDR) system, we noticed that this NDC has
NDA 022432 reported as its FDA application number, which is incorrect pursuant to the FDA
approval letter indicated above and the listing information provided by the manufacturer to FDA
Online Label Repository. Therefore, we are requesting the manufacturer to review and correct
the reporting of its product data in DDR to ensure that accurate information is reported to the
MDR program.
Additionally, as provided in Manufacturer Release No. 90 at

Topics/Benefits/Prescription-Drugs/Downloads/Rx-Releases/MFR-Releases/mfr-rel-090.pdf, the
baseline data of an NDC for a single source drug or innovator multiple source drug must follow
the NDA. Therefore, the baseline data of NDC 63004-8710 need to follow the baseline data of
the original NDC 63004-7731-01, which includes revision to the base AMP of NDC 63004-
8710.

As requested above, please review the data reported in the DDR system as soon as possible and
make the necessary correction to ensure accurate information is reported to the MDR program.
Also, please send a reply e-mail to advise us when the correction has been completed.
If you have any questions or concerns, or would like to discuss further, please contact Ruth Blatt
at 410-786-1767 or ruth.blatt@cms.hhs.gov.
Sincerely,
/s/
John M. Coster, Ph.D.,R.Ph.

Director

CONFIDENTIAL AND PROPRIETARY

NOT SUBJECT TO RELEASE OR DISCLOSURE UNDER FOIA OR OTHERWISE
Please provide all the information below to Division of Pharmacy, so our team can respond appropriately.
Please note, due to the high volume of meeting requests, there may be a delay in our response to you. Thank
you for your continued commitment to improving our nation’s health care delivery system.
Requested Information: Please Enter Information Here:

Name of Person and/or Organization Making Mallinckrodt Pharmaceuticals
Request:
Background Information and/or Brief Description Mallinckrodt Pharmaceuticals (Mallinckrodt) is a specialty
of the Person and/or Organization Making pharmaceutical company focused on our mission:
Request: Managing Complexity. Improving Lives. We provide
medicines to address unmet patient needs, stemming from
150 years of using our unique strengths, experience and
expertise to help improve people’s lives. Areas of focus
include autoimmune and rare diseases in specialty areas
like neurology, rheumatology, nephrology, pulmonology
and ophthalmology; immunotherapy and neonatal
respiratory critical care therapies; analgesics and
gastrointestinal products.
Type of Organization: Pharmaceutical Manufacturer
(e.g., Hospital, Specialty Care, IT, Pharmaceutical,
Association, University, etc.)
Address and Phone Number: Mallinckrodt Pharmaceuticals
Specialty Brands Principal Office
1405 U.S. 206
Bedminster Township, NJ 07921
USA
Phone: 908.238.6600
Website of Organization: http://www.mallinckrodt.com/
Discussion Topic: (e.g., AMP/BP calculation, Medicaid Drug Rebate Program: Base Date AMP for One of
Medicaid Reimbursement, Coverage, DUR, Medicaid Mallinckrodt’s Products
Drug Rebate Price reporting etc.)
What are the main questions you want answered We hope to discuss Mallinckrodt’s and CMS’s perspectives
during the meeting? (This is needed for internal CMS regarding the base date AMP for one of Mallinckrodt’s
planning purposes so we can ensure the appropriate products, including Mallinckrodt’s points as reflected in
Division of Pharmacy staff are invited to the the prior correspondence with CMS on this issue and
meeting.) CMS’s responses to Mallinckrodt’s points and concerns
about the current position reflected in CMS’s
correspondence.
Preferred Meeting Type: In-Person Meeting
In-Person Meeting (Baltimore Office) w/
teleconference
By Phone Only
Page 1 of 2
CONFIDENTIAL AND PROPRIETARY

NOT SUBJECT TO RELEASE OR DISCLOSURE UNDER FOIA OR OTHERWISE
If you are requesting specific dates/times for the December 4, 2018, at 11:00 AM Eastern
meeting, please list them here. We will do our best (per our prior emails exchanged with CMS (Ruth Blatt) on
to work within these dates: November 12–15, 2018, confirming this date and time)
Requested Division of Pharmacy Staff (if known): John Coster, Director
Wendy Tuttle, Acting Deputy Director
Ruth Blatt, Pharmacist, Health Insurance Specialist
Have you met with any CMS Staff in the past and if No, Mallinckrodt has not had a prior in-person meeting
so, who and when? (e.g., Medicaid Division of with CMS on this issue.
Pharmacy, CMMI, Part B or Part D staff etc.)
Point of Contact for Logistics:
Name: Name: Bill Sarraille and Stephanie Hales, Sidley Austin LLP
Phone: Phone: 202-736-8195; 202-736-8349
Email: Email: wsarraille@sidley.com; shales@sidley.com
Point of Contact for Day of Meeting:
Name: Name: Bill Sarraille and Stephanie Hales
Title: Title: Partner, Sidley Austin LLP (same for both)
Phone: Phone: 202-736-8195; 202-736-8349
Email: Email: wsarraille@sidley.com; shales@sidley.com
Attendees from Organization: x Mark Casey, General Counsel, Mallinckrodt
Name(s): x Mark Tyndall, Vice President, Government Affairs,
Title(s): Policy & Advocacy, Mallinckrodt
Organization(s): x Michele Robertson, Vice President, General Counsel of
Commercial Operations, Mallinckrodt
x Bill Sarraille, Partner, Sidley Austin LLP
x Paul Zidlicky, Partner, Sidley Austin LLP
x Stephanie Hales, Partner, Sidley Austin LLP
Agenda for Meeting: x Discussion of Base Date AMP for One of Mallinckrodt’s
Products
x Discussion of Recent Correspondence Between CMS
and Mallinckrodt
x Discussion of a Pathway Forward
Any Additional Information:
(If Applicable)
NOTE:
x If applicable, please provide an Agenda and/or Materials 3 days before the scheduled meeting
Page 2 of 2
! "# $#%& '()" *

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Hello, and thank you again for the January 22 date. We have been able to reschedule some things and we can
make that day and time. Thank you for rescheduling.
I assume that, in light of the rescheduled date, that the reference to a December 17 action date in Mr. Coster’s
letter is tolled?
Thank you so much.
Best regards,
Bill
A172 HHS - 000092
(Page 220 of Total)

Case 1:19-cv-01471 Document 1-15 Filed 05/20/19 Page 3 of 5
Sent with BlackBerry Work

(www.blackberry.com)
From: Blatt, Ruth (CMS/CMCS) <Ruth.Blatt@cms.hhs.gov>

Date: Friday, Nov 30, 2018, 11:23 AM
To: Sarraille, William <wsarraille@sidley.com>, CMS RxDRUGPolicy <rxdrugpolicy@cms.hhs.gov>
Cc: Michele.Robertson@mnk.com <Michele.Robertson@mnk.com>, Mark.Casey@mnk.com <Mark.Casey@mnk.com>,
Mark.Tyndall@mnk.com <Mark.Tyndall@mnk.com>, Zidlicky, Paul <pzidlicky@sidley.com>, Hales, Stephanie
<shales@sidley.com>
Subject: RE: Confidential and Proprietary - CMS Meeting Request Form - Mallinckrodt Pharmaceuticals
3 2! ! 39 3 $$3 DE C
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Dear Ms. Blatt,
I hope this finds you well. Thank you so much for your message.
I appreciate how busy Mr. Coster’s schedule is. We know the demands on his time. Given the serious issues
presented and Mr. Coster’s importance to a discussion of them, we do think we should reschedule.
I understand that Mr. Coster’s time in office is limited. We would really appreciate an in person meeting,
however. The questions presented here are enormously important and threaten to have seriously adverse effects
on patients.
What meeting options could you offer? I will check on our end regarding our group’s schedules.
Thank you so much.
Best regards,
Bill Sarraille
Sent with BlackBerry Work

(www.blackberry.com)
From: CMS RxDRUGPolicy <rxdrugpolicy@cms.hhs.gov>

Date: Thursday, Nov 29, 2018, 3:12 PM
To: Sarraille, William <wsarraille@sidley.com>, Blatt, Ruth (CMS/CMCS) <Ruth.Blatt@cms.hhs.gov>
Cc: Michele.Robertson@mnk.com <Michele.Robertson@mnk.com>, Mark.Casey@mnk.com <Mark.Casey@mnk.com>,
Mark.Tyndall@mnk.com <Mark.Tyndall@mnk.com>, Zidlicky, Paul <pzidlicky@sidley.com>, Hales, Stephanie
<shales@sidley.com>

Subject: RE: Confidential and Proprietary - CMS Meeting Request Form - Mallinckrodt Pharmaceuticals
5 34
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5 34
WILLIAM A. SARRAILLE
Partner
SIDLEY AUSTIN LLP

1501 K Street, N.W.
+1 202 736 8195
wsarraille@sidley.com
www.sidley.com
******************************************************************************************
**********
This e-mail is sent by a law firm and may contain information that is privileged or confidential.

If you are not the intended recipient, please delete the e-mail and any attachments and notify us
immediately.
******************************************************************************************
**********

From: Bass, Diane M

To: CMS RxDRUGPolicy
Cc: Schaefer, Kathy A; Robertson, Michele; Matasi, Twayler
Subject: RE: Action Required- NDC 63004-8710
Date: Monday, November 12, 2018 7:18:09 PM
Attachments: Letterhead_DBass_wemails.pdf
Importance: High
Dear Mr. Coster,
Please see attached response to the letter we received from you dated November 6, 2018. I will also
send you this response letter by certified mail.
Please acknowledge receipt of this response letter via email.
Thank you,
Diane M. Bass| Director of Government Reporting, Contract Operations and Gross to Net Accounting
675 McDonnell Blvd | Hazelwood, MO 63042
T: 314.654.7348
Diane.Bass@mnk.com | www.mallinckrodt.com
Note all email addresses for Mallinckrodt are now @mnk.com rather than @mallinckrodt.com. Please change your
contact lists accordingly.
This information may be confidential and/or privileged. Use of this information by anyone other than the intended recipient is
prohibited. If you receive this in error, please inform the sender and remove any record of this message.
From: CMS RxDRUGPolicy <rxdrugpolicy@cms.hhs.gov>

Sent: Tuesday, November 6, 2018 2:55 PM
To: Bass, Diane M <Diane.Bass@mnk.com>
Cc: Schaefer, Kathy A <Kathy.Schaefer@mnk.com>; CMS RxDRUGPolicy
<rxdrugpolicy@cms.hhs.gov>
Subject: [EXTERNAL] RE: Action Required- NDC 63004-8710
Importance: High
CAUTION: This email originated from rxdrugpolicy@cms.hhs.gov which is outside of the Mallinckrodt system.
Do not click on any links or attachments unless you know the source and are very confident that the
Ms. Bass,
Please find attached an advance copy of a letter you will be receiving by U.S. Mail.
Thank you,
The decision in this response is limited to and based upon the facts described in this email and any attachments


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ATTACHMENT

From: Forshee, Kay <kay.forshee@mallinckrodt.com>
Sent: Friday, April 14, 2017 2:07 PM
Cc: Landolt, Jamie; Matasi, Twayler; CMS MDROperations
communication to Questcor that explicitly approved the appropriateness of a new base date AMP. CMS
concluded there that “[w]e have reviewed your request and agree that Acthar Gel is eligible for a new
base date AMP.” Mallinckrodt, which purchased Acthar from Questcor in August 2014, has relied upon
that agency determination.
represented a very significant set of events. Acthar’s label, indications, and approval for
marketing underwent a fundamental revision, including all of the following changes under that
NDA:
· Addition of the infantile spasms indication;

· Removal of more than 30 indications that previously were approved for marketing;
· Revised “Dosage and Administration” section;
· New and separate section on pediatric indications;
· New FDA requirement for a “Medication Guide” relating to the new infantile spasms indication;
· New, indication-specific Risk Evaluation and Mitigation Strategy (REMS) for the new infantile
spasms indication;
· Addition of the route of administration for Acthar; and
· Addition of the “Mechanism of Action” section.
importance of an approval of an NDA; it is irrelevant under the statute whether an NDA was a "type 6".
We will continue to review your email, however, and we may have some additional thoughts to share
with you as part of this ongoing dialogue. Thank you for your engagement with us on this important
issue.
Best regards,
.D\)RUVKpH_6U0DQDJHU*RYHUQPHQW5HSRUWLQJ
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ND\IRUVKHH#PDOOLQFNURGWFRPOZZZPDOOLQFNURGWFRP
This information may be confidential and/or privileged. Use of this information by anyone other
than the intended recipient is prohibited. If you receive this in error, please inform the sender
and remove any record of this message.

To: Forshee, Kay
Kay,
Thank you for your emails on July 6, 2016 and July 29, 2016. We understand and agree that the new
indication for Acthar was approved under NDA 022432. We also note that the SPL information
submitted to FDA by the manufacturer currently reflects NDA 022432. However FDA has confirmed
that NDA 022432, a type-6 NDA, was created for administrative purposes because an FDA division other
than the division responsible for NDA 008372 was reviewing the application for the new indication. FDA
has informed us that type-6 NDAs are administratively closed upon approval. Therefore, it is our
understanding that the marketing of the drug has always been under the auspices of NDA 008372,
regardless of the administratively assigned NDA 022432, which was only for the purpose of FDA
approval of the new indication, but not for the approval and marketing of the drug itself.
The baseline information for a drug that was approved prior to the effective date of section 1927 of
the Social Security Act is established using the data of the drug as of 9/30/1990. It is our
understanding that NDA 008372 for Acthar was approved on April 29, 1952, therefore, the baseline
data for the drug that is marketed under that NDA would be based on data from 9/30/1990 as the
approval of NDA 022432 in 2010 was not for approval of a new drug.
Thank you,
CMS MDR Operations
review by CMS, by the Office of Inspector General, or another authorized government agency determines or
reveals that additional adjustments or revisions are necessary, the manufacturer is responsible for complying with
that determination. This response cannot be considered an advisory opinion under section 1128D(b) of the Social
intended recipient, or have received this message in error, please delete it without reading it and please do not print, copy,
forward, disseminate, or otherwise use the information. Also, please notify the sender that you have received this
3DJH2RI7

Cc: Lough, Mairi <Mairi.Lough@mallinckrodt.com>; Landolt, Jamie <Jamie.Landolt@mallinckrodt.com>;
Lasker,
Karen L <Karen.Lasker@mallinckrodt.com>
Proprietary and Confidential—Not to Be Released, in Whole or in Part, under FOIA or Otherwise
Good evening,
We wanted to briefly follow up on our email below. As we indicated there, we have continued to look
into your correspondence. As part of that effort, we have clarified the pre-existing FDA Online Label
Repository listing to list NDA 022432, consistent with CMS' letter and analysis dated August 6, 2012.
Thank you,
0F'RQQHOO%OYG _ +D]HOZRRG02
_ 86$7
This information may be confidential and/or privileged. Use of this information by anyone other than
the intended recipient is prohibited. If you receive this in error, please inform the sender and remove
any record of this message.
From: Forshee, Kay


Otherwise
Good Evening,
Thank you for your email below. As we continue to research the points CMS has raised, we
want to clarify a point that seems to be the basis for the agency’s request. In your email, you
indicate that the base date AMP for a “purchased product” should not be altered. We want to
note that Mallinckrodt’s purchase of Acthar from Questcor in August 2014 was not the basis of
CMS’ confirmation to Questcor of the appropriateness of a new base date AMP in the agency’s
letter to Questcor dated August 6, 2012, which was two years before Mallinckrodt’s acquisition
of Questcor.
In the April 13, 2016 letter, CMS also stated that it believed that it was potentially incorrect to
have listed the product as “ha[ving] NDA 022432 as its FDA application number.” We have
gone back and confirmed that this was, in fact, the correct FDA assigned application number
3DJH3RI7
for the approval of the product that was discussed in the CMS letter of August 6, 2012 and that
CMS cited in determining that “[w]e have reviewed your request and agree that Acthar Gel is
eligible for a new based date AMP.”
However, we continue to look further into your correspondence, and will offer additional
thoughts, as they may be helpful to you, at a later date when we have completed our work.
Thank you,
_ 86$7

Kay,
We are aware of the correspondence between Questcor and CMS that you provided.
However, as stated in Manufacturer Release #90 at http://www.medicaid.gov/Medicaid-
CHIP-Program- Information/By-Topics/Benefits/Prescription-Drugs/Downloads/Rx-
Releases/MFR-Releases/mfr-
rel-090.pdf, the baseline data of a purchased product should be the same as the baseline
data of a product marketed previously under the same NDA. Therefore, we are requesting
that you complete and return the attached template so that the baseline information for the
NDC matches the baseline information of the NDC that was originally used for marketing the
product under the same NDA.
Thank you,
CMS MDR Operations
manufacturer is responsible for complying with that determination. This response cannot be
considered an advisory opinion under section 1128D(b) of the Social Security Act, since only the
Inspector General of the
U.S. Department of Health and Human Services has been authorized to issue advisory opinions
relating to health care fraud and abuse under that section. This response should not be interpreted
as acquiescence by the Government to the arrangements described herein. Further, this response is
not a release of any liability.
3DJH4RI7

Good afternoon,
Attached please find correspondence between Questcor/Mallinckrodt and CMS regarding

the approved NDC changes and new base AMP for Acthar. Please advise if we are
required to make any changes to the DDR.
Please feel free to contact me directly with any
questions. Thanks,
_ 86$7

To: Forshee, Kay
Kay,
Attached, please find an advance copy of a letter that you will be receiving by U.S.
Mail. Also attached is a template, for your use in requesting the changes
referenced in the letter.
Thank you,
CMS MDR Operations
3DJH5RI7
The decision in this response is limited to and based upon the facts described in this email and
any attachments provided and our understanding of the facts as described in the emails and
attachments submitted. If a subsequent review by CMS, by the Office of Inspector General, or
another authorized government agency determines or reveals that additional adjustments or
revisions are necessary, the manufacturer is responsible for complying with that
determination. This response cannot be considered an advisory opinion under section
1128D(b) of the Social Security Act, since only the Inspector General of the U.S. Department
of Health and Human Services has been authorized to issue advisory opinions relating to
health care fraud and abuse under that
section. This response should not be interpreted as acquiescence by the Government
to the arrangements described herein. Further, this response is not a release of any
liability.
NOTICE: The contents of this message and any attachments may be privileged and confidential. If
you are not an intended recipient, or have received this message in error, please delete it without
reading it and please do not print, copy, forward, disseminate, or otherwise use the information.
Also, please notify the sender that you have received this communication in error. Your receipt of
this message is not intended to waive any applicable privilege.

3DJH6RI7

To: DIANE.BASS@MNK.COM
Cc: KATHY.SCHAEFER@MNK.COM; CMS RxDRUGPolicy
Subject: Action Required- NDC 63004-8710
Date: Tuesday, November 06, 2018 3:18:00 PM
Attachments: acthar 11_6_18.docx
TEMPLATE FOR FDA APPROVAL_MARKET DATE CHANGE REQUEST - (S & I Drugs).xlsx
Importance: High
Ms. Bass,
Thank you,


November 6, 2018
Diane Bass, Technical Contact

Mallinckrodt LLC
675 McDonnell Blvd
Hazelwood, MO 63042
Dear Ms. Bass:
On April 13, 2016 and March 20, 2017 CMS informed Mallinckrodt LLC that it was reporting
application number in the Drug Data Reporting for Medicaid (DDR) system. This is a notice
that Mallinckrodt LLC has not taken action to date to correct this information and must do so
within 30 days of receiving this notice and notify CMS of its action, otherwise CMS will identify
the following national drug code (NDC) as “out of compliance” in the DDR system as of
December 17, 2018. When an NDC is identified as out of compliance, the submission of pricing
records or updates to product data will not be allowed online or via file transfer. The NDC will
remain out of compliance until Mallinckrodt LLC takes the necessary steps to bring the NDC’s
product information into compliance. CMS may also consider referring Mallinckrodt LLC to the
Department of Justice and/or the Office of the Inspector General of the U.S. Department of
Health and Human Services (HHS-OIG), as appropriate.
The NDC is as follows:
63004-8710 H.P. Acthar Gel
We have enclosed a template for you to complete and return to rxdrugpolicy@cms.hhs.gov so
that we can enter the corrected base AMP information, FDA approval date, and market date into
DDR. Once we have done so, we will notify you that the corrected information is awaiting
Mallinckrodt’s certification. The FDA application number may be corrected in DDR by
Mallinckrodt LLC without CMS assistance. Once Mallinckrodt certifies the corrected
information, states will receive notification on the subsequent rebate file, in the form of prior
period adjustments, which indicate that the Unit Rebate Amount (URA) has changed for the
drug. Mallinckrodt will be responsible for adjusting previous payments to the states using the
Prior Quarter Adjustment Statement (PQAS) in accordance with the URA changes. We believe
that such changes would be applicable for every quarter for which the base date AMP should
have been established based on a market date of 9/30/1990 and not 1/7/2013.

Please review your records and contact CMS at rxdrugpolicy@cms.hhs.gov if you have any
questions regarding this email.
Sincerely,
/s/
John M. Coster, PhD, RPh
cc: Kathy Schaefer, Legal Contact

TEMPLATE FOR FDA APPROVAL/MARKET DATE CHANGE REQUEST (S & I Drugs)
1. Date of Request:
2. Labeler Name:
4. 5. Product 6. Product Name 7a. COD 7b. FDA 8. OLD FDA 9. NEW FDA 10. FDA Approval 11. Is there 12. Did you acquire 13. If product is 14. Change Market Date - 15. Market Date Change Necessitates a Change in Base AMP 16. Estimated 17. Estimated
Labeler Code Status Application No. Approval Approval Date Change State this product from acquired from Please note when Amount Due to Amount Due to
(Page 236 of Total)

Code (NDA/ANDA)/ Date: Date: Necessitates a Utilization another company? If another company providing a New Market States from Labeler from
OTC Mongraph Mo/Day/Yr Mo/Day/Yr Change in Market Prior to yes, please provide as provided in #12, Date, the New Market Date Labeler States
Date? Y/N Changed the old company's then please has to be equal to at least
Market Date? NDC. Or if your provide the one of the Package Size
Y/N product is an Product Purchased Intro Date.
Authorized Generic, Date (PPD).
please provide the From To If there is NO AMOUNT DUE
NDC of the Brand either to States from Labeler or
USCA Case #20-5154
Product. to Labeler from States, please

provide the reason why no
OBRA amount is due in the reason
'90 Base OBRA '93 DRA Base ACA Base box.
Mo/Day/Yr Mo/Day/Yr Quarter Year AMP Base AMP AMP AMP
Document #1845229
Filed: 06/02/2020
Page 194 of 400
A188 HHS - 000108

Created June 2008

Cc: KATHY.SCHAEFER@MNK.COM; CMS RxDRUGPolicy
Subject: FW: Action Required- NDC 63004-8710
Date: Tuesday, November 06, 2018 4:39:48 PM
Attachments: acthar 11_6_18.docx
TEMPLATE FOR FDA APPROVAL_MARKET DATE CHANGE REQUEST - (S & I Drugs).xlsx
Importance: High
Apologies, please see attached.
Thank you,

Sent: Tuesday, November 6, 2018 3:18 PM
Cc: KATHY.SCHAEFER@MNK.COM; CMS RxDRUGPolicy <rxdrugpolicy@cms.hhs.gov>
Subject: Action Required- NDC 63004-8710
Importance: High
Ms. Bass,
Thank you,



November 6, 2018
Diane Bass, Technical Contact

Mallinckrodt LLC
675 McDonnell Blvd
Hazelwood, MO 63042
Dear Ms. Bass:
On April 13, 2016 and March 20, 2017 CMS informed Mallinckrodt LLC that it was reporting
application number in the Drug Data Reporting for Medicaid (DDR) system. This is a notice
that Mallinckrodt LLC has not taken action to date to correct this information and must do so
within 30 days of receiving this notice and notify CMS of its action, otherwise CMS will identify
the following national drug code (NDC) as “out of compliance” in the DDR system as of
December 17, 2018. When an NDC is identified as out of compliance, the submission of pricing
records or updates to product data will not be allowed online or via file transfer. The NDC will
remain out of compliance until Mallinckrodt LLC takes the necessary steps to bring the NDC’s
product information into compliance. CMS may also consider referring Mallinckrodt LLC to the
Department of Justice and/or the Office of the Inspector General of the U.S. Department of
Health and Human Services (HHS-OIG), as appropriate.
The NDC is as follows:
63004-8710 H.P. Acthar Gel
We have enclosed a template for you to complete and return to rxdrugpolicy@cms.hhs.gov so
that we can enter the corrected base AMP information, FDA approval date, and market date into
DDR. Once we have done so, we will notify you that the corrected information is awaiting
Mallinckrodt’s certification. The FDA application number may be corrected in DDR by
Mallinckrodt LLC without CMS assistance. Once Mallinckrodt certifies the corrected
information, states will receive notification on the subsequent rebate file, in the form of prior
period adjustments, which indicate that the Unit Rebate Amount (URA) has changed for the
drug. Mallinckrodt will be responsible for adjusting previous payments to the states using the
Prior Quarter Adjustment Statement (PQAS) in accordance with the URA changes. We believe
that such changes would be applicable for every quarter for which the base date AMP should
have been established based on a market date of 9/30/1990 and not 1/7/2013.

Please review your records and contact CMS at rxdrugpolicy@cms.hhs.gov if you have any
questions regarding this email.
Sincerely,
/s/
John M. Coster, PhD, RPh
cc: Kathy Schaefer, Legal Contact

TEMPLATE FOR FDA APPROVAL/MARKET DATE CHANGE REQUEST (S & I Drugs)
1. Date of Request:
2. Labeler Name:
(Page 241 of Total)

USCA Case #20-5154

Document #1845229
Filed: 06/02/2020
Page 199 of 400
A193 HHS - 000113

Created June 2008
From: Forshee, Kay

Cc: Landolt, Jamie; Matasi, Twayler; CMS MDROperations
Date: Friday, April 14, 2017 2:07:15 PM

communication to Questcor that explicitly approved the appropriateness of a new base date AMP.
CMS concluded there that “[w]e have reviewed your request and agree that Acthar Gel is eligible for
a new base date AMP.” Mallinckrodt, which purchased Acthar from Questcor in August 2014, has
relied upon that agency determination.
represented a very significant set of events. Acthar’s label, indications, and approval for marketing
underwent a fundamental revision, including all of the following changes under that NDA:
• Addition of the infantile spasms indication;
• Removal of more than 30 indications that previously were approved for marketing;
• Revised “Dosage and Administration” section;
• New and separate section on pediatric indications;
• New FDA requirement for a “Medication Guide” relating to the new infantile spasms
indication;
• New, indication-specific Risk Evaluation and Mitigation Strategy (REMS) for the new
infantile spasms indication;
• Addition of the route of administration for Acthar; and
• Addition of the “Mechanism of Action” section.
importance of an approval of an NDA; it is irrelevant under the statute whether an NDA was a "type
6".
We will continue to review your email, however, and we may have some additional thoughts to
share with you as part of this ongoing dialogue. Thank you for your engagement with us on this
important issue.
Best regards,
T: 314.654.6592 / M: 314.780-1630

This information may be confidential and/or privileged. Use of this information by anyone other than
the intended recipient is prohibited. If you receive this in error, please inform the sender and
remove any record of this message.
To: Forshee, Kay
Kay,
Thank you for your emails on July 6, 2016 and July 29, 2016. We understand and agree that
the new indication for Acthar was approved under NDA 022432. We also note that the SPL
information submitted to FDA by the manufacturer currently reflects NDA 022432. However
FDA has confirmed that NDA 022432, a type-6 NDA, was created for administrative purposes
because an FDA division other than the division responsible for NDA 008372 was reviewing
the application for the new indication. FDA has informed us that type-6 NDAs are
administratively closed upon approval. Therefore, it is our understanding that the marketing
of the drug has always been under the auspices of NDA 008372, regardless of the
administratively assigned NDA 022432, which was only for the purpose of FDA approval of
the new indication, but not for the approval and marketing of the drug itself.
The baseline information for a drug that was approved prior to the effective date of section
1927 of the Social Security Act is established using the data of the drug as of 9/30/1990. It is
our understanding that NDA 008372 for Acthar was approved on April 29, 1952, therefore,
the baseline data for the drug that is marketed under that NDA would be based on data from
9/30/1990 as the approval of NDA 022432 in 2010 was not for approval of a new drug.
Thank you,
CMS MDR Operations
health care fraud and abuse under that section. This response should not be interpreted as acquiescence by
the Government to the arrangements described herein. Further, this response is not a release of any
liability.
intended recipient, or have received this message in error, please delete it without reading it and please do not
print, copy, forward, disseminate, or otherwise use the information. Also, please notify the sender that you have
received this communication in error. Your receipt of this message is not intended to waive any applicable privilege.


Otherwise
Good evening,
We wanted to briefly follow up on our email below. As we indicated there, we have
continued to look into your correspondence. As part of that effort, we have clarified the pre-
existing FDA Online Label Repository listing to list NDA 022432, consistent with CMS' letter
and analysis dated August 6, 2012.
Thank you,

T: 314.654.6592
From: Forshee, Kay
Proprietary and Confidential—Not to Be Released, in Whole or in Part, under
FOIA or Otherwise
Good Evening,
Thank you for your email below. As we continue to research the points CMS has
raised, we want to clarify a point that seems to be the basis for the agency’s request.
In your email, you indicate that the base date AMP for a “purchased product” should
not be altered. We want to note that Mallinckrodt’s purchase of Acthar from
Questcor in August 2014 was not the basis of CMS’ confirmation to Questcor of the
appropriateness of a new base date AMP in the agency’s letter to Questcor dated
August 6, 2012, which was two years before Mallinckrodt’s acquisition of Questcor.
In the April 13, 2016 letter, CMS also stated that it believed that it was potentially
incorrect to have listed the product as “ha[ving] NDA 022432 as its FDA application
number.” We have gone back and confirmed that this was, in fact, the correct FDA
assigned application number for the approval of the product that was discussed in
the CMS letter of August 6, 2012 and that CMS cited in determining that “[w]e have
reviewed your request and agree that Acthar Gel is eligible for a new based date
AMP.”
However, we continue to look further into your correspondence, and will offer
additional thoughts, as they may be helpful to you, at a later date when we have
completed our work.
Thank you,
T: 314.654.6592

This information may be confidential and/or privileged. Use of this information by
anyone other than the intended recipient is prohibited. If you receive this in error,
please inform the sender and remove any record of this message.
Kay,
We are aware of the correspondence between Questcor and CMS that you
provided. However, as stated in Manufacturer Release #90 at
Topics/Benefits/Prescription-Drugs/Downloads/Rx-Releases/MFR-
Releases/mfr-rel-090.pdf, the baseline data of a purchased product should
be the same as the baseline data of a product marketed previously under
the same NDA. Therefore, we are requesting that you complete and return
the attached template so that the baseline information for the NDC matches
the baseline information of the NDC that was originally used for marketing
the product under the same NDA.
Thank you,
CMS MDR Operations
The decision in this response is limited to and based upon the facts described in this email
and any attachments provided and our understanding of the facts as described in the
emails and attachments submitted. If a subsequent review by CMS, by the Office of
Inspector General, or another authorized government agency determines or reveals that
additional adjustments or revisions are necessary, the manufacturer is responsible for
complying with that determination. This response cannot be considered an advisory
opinion under section 1128D(b) of the Social Security Act, since only the Inspector
General of the U.S. Department of Health and Human Services has been authorized to
issue advisory opinions relating to health care fraud and abuse under that section. This
response should not be interpreted as acquiescence by the Government to the
arrangements described herein. Further, this response is not a release of any liability.
NOTICE: The contents of this message and any attachments may be privileged and confidential.
If you are not an intended recipient, or have received this message in error, please delete it
without reading it and please do not print, copy, forward, disseminate, or otherwise use the
information. Also, please notify the sender that you have received this communication in error.
Your receipt of this message is not intended to waive any applicable privilege.
<Jamie.Landolt@mallinckrodt.com>; Lasker, Karen L
<Karen.Lasker@mallinckrodt.com>
Good afternoon,
Attached please find correspondence between Questcor/Mallinckrodt and

CMS regarding the approved NDC changes and new base AMP for Acthar.
Please advise if we are required to make any changes to the DDR.
Thanks,
T: 314.654.6592
To: Forshee, Kay
Kay,
Attached, please find an advance copy of a letter that you will be
receiving by U.S. Mail. Also attached is a template, for your use in
requesting the changes referenced in the letter.
Thank you,
CMS MDR Operations
The decision in this response is limited to and based upon the facts described in
this email and any attachments provided and our understanding of the facts as
described in the emails and attachments submitted. If a subsequent review by
CMS, by the Office of Inspector General, or another authorized government
agency determines or reveals that additional adjustments or revisions are
necessary, the manufacturer is responsible for complying with that
determination. This response cannot be considered an advisory opinion under
section 1128D(b) of the Social Security Act, since only the Inspector General of
the U.S. Department of Health and Human Services has been authorized to issue
advisory opinions relating to health care fraud and abuse under that section.
This response should not be interpreted as acquiescence by the Government to
the arrangements described herein. Further, this response is not a release of
any liability.
NOTICE: The contents of this message and any attachments may be privileged and
confidential. If you are not an intended recipient, or have received this message in
error, please delete it without reading it and please do not print, copy, forward,
disseminate, or otherwise use the information. Also, please notify the sender that you
have received this communication in error. Your receipt of this message is not
intended to waive any applicable privilege.

From: Weston Deborah G

Subject: Acthar and Additional Rebate Due
Date: Wednesday, February 08, 2017 7:45:19 PM
Attachments: image001.png
NDA approval 022432Orig1s000Approv.pdf
Tracking number 022432 no longer used 008372Orig1s044ltr.pdf
To Whom it May Concern:

I am a Policy Analyst with Oregon’s Medicaid pharmacy program. I am also a
member of Western Medicaid Pharmacy Administrators Association (WMPAA).
Through WMPAA, I recently learned of a possible MDRP problem with HP
Acthar Gel.
I question if Questcor acted consistently with MDRP requirements. In
particular, can a supplemental NDA act to reset the “initial” price for purposes
of calculating “additional rebate” for an innovator multisource product? If this
is improper, Questcor has underpaid Medicaid drug rebates since 2013, and
continues to do so. Below is a brief timeline.
• April 29, 1952: Original approval of H.P. Acthar Gel (repository
corticotropin). NDA 008372.
• 1972: The FDA expanded approved indications to include multiple
sclerosis. Numerous other indications were already approved.
• In or around 2001: Questcor bought H.P. Acthar Gel from Sanofi-Aventis.
NDC 63004773101
• June 2006 – October 2010: Various communications between the FDA and
Questcor regarding a request to add an additional indication for infantile
spasms (IS) in pediatric patients. NDA 022432.
• 2007: Questcor began to dramatically increase the drug price. Thanks to
brand CPI penalty, Medicaid’s cost, net of rebate, remained the same as
the original (after adjusting for inflation) until the NDC was terminated in
2013.
• October 2010: NDA Approval letter from DHHS, approving the additional IS
indication. The letter used NDA 022432 for tracking purposes only, and
tied all future submissions and communications to the original NDA
008372:
“All 15-day alert reports, periodic (including quarterly) adverse
drug experience reports, field alerts, annual reports, supplements,
and other submissions should be addressed to the original NDA

008372 for this drug product, not to this NDA. In the future, do not
make submissions to this NDA except for the final printed labeling
requested above.”
NDA approval 022432, Page 5 (attached).
• 2013: NDC 63004773101 terminated and NDC 63004871001 began. The
price picked up where the original product left off. The “initial” 2013
price is the one used to determine CPI penalty. Thus Medicaid is only
now protected against price hikes since 2013.
• March 24, 2015: Supplement Approval letter from DHHS, approving the
supplemental new drug application (022432) to be associated with the
parent NDA (008372). The Letter clearly states the tracking NDA number
022432 will no longer be used.
If Questcor’s H.P. Acthar Gel (NDC 63004871001) is tied to NDA 008372, which
dates back to 1952, why is Questcor using the AMP established in 2013 as the
“initial” price for purposes of MDRP additional rebate? This does not seem
consistent with Manufacturer Release #90.
Thank you for your attention to this matter.
Sincerely,
Dee
Deborah Weston
Policy Analyst
Health Systems Division
deborah.g.weston@state.or.us
Cell: 503-884-5405
CONFIDENTIALITY NOTICE
This e-mail may contain information that is privileged, confidential, or otherwise exempt from disclosure under
applicable law. If you are not the addressee or it appears from the context or otherwise that you have received this
e-mail in error, please advise me immediately by reply e-mail, keep the contents confidential, and immediately
delete the message and any attachments from your system.

CENTER FOR DRUG EVALUATION AND RESEARCH
Approval Package for:
APPLICATION NUMBER:
022432Orig1s000
Trade Name: H.P. Acthar Gel
Generic Name: Repository Corticotropin Injection
Sponsor: Questcor Pharmaceuticals, Inc.
Approval Date: October 15, 2010
Indications: an adrenocorticotropic hormone (ACTH) analogue

indicated as monotherapy for the treatment of infantile
spasms in infants and children under 2 years of age;
Indicated for the treatment of exacerbations of

multiple
sclerosis in adults;
May be used for the following disorders and diseases:

rheumatic; collagen; dermatologic; allergic states;
ophthalmic; respiratory; and edematous state

CENTER FOR DRUG EVALUATION AND

RESEARCH
APPLICATION NUMBER:
022432Orig1s000
CONTENTS
Reviews / Information Included in this NDA Review.
Approval Letter X
Other Action Letters
Labeling X
REMS X
Summary Review X
Officer/Employee List X
Office Director Memo
Cross Discipline Team Leader Review X
Medical Review(s) X
Chemistry Review(s) X
Environmental Assessment
Pharmacology Review(s) X
Statistical Review(s) X
Microbiology Review(s)
Clinical Pharmacology/Biopharmaceutics Review(s) X
Other Reviews X
Risk Assessment and Risk Mitigation Review(s) X
Proprietary Name Review(s)
Administrative/Correspondence Document(s) X


RESEARCH
APPLICATION NUMBER:
022432Orig1s000
APPROVAL LETTER

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Silver Spring MD 20993
NDA 022432
NDA APPROVAL
Questcor Pharmaceuticals, Inc.

Attention: Sian Bigora, Pharm.D.
Vice President, Regulatory Affairs
3260 Whipple Road
Union City, CA 94587
Dear Dr. Bigora:
Please refer to your New Drug Application (NDA) dated June 16, 2006, received June 23, 2006,
submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for H.P. Acthar®
Gel (repository corticotropin) Injection.
We acknowledge receipt of your amendments dated December 10, 2009, and January 19, April
1, 22, and 28, June 8, and August 10, 2010.
The December 10, 2009, submission constituted a complete response to our May 10, 2007,
action letter.
This new drug application provides for the use of H.P. Acthar® Gel (repository corticotropin) to
treat infantile spasms.
We have completed our review of this application, as amended, and it is approved, effective on
the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
prescribing information. This waiver applies to all future supplements containing revised
labeling unless we notify you otherwise.
CONTENT OF LABELING
As soon as possible, but no later than 14 days from the date of this letter, submit, via the FDA
automated drug registration and listing system (eLIST), the content of labeling
[21 CFR 314.50(l)] in structured product labeling (SPL) format, as described at
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
identical to the enclosed labeling (text for the package insert and Medication Guide).
Information on submitting SPL files using eLIST may be found in the guidance for industry
titled “SPL Standard for Content of Labeling Technical Qs and As” at

NDA 022432
Page 2
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM072392.pdf.
The SPL will be accessible via publicly available labeling repositories.
We request that the labeling approved today be available on your website within 10 days of
receipt of this letter.
CARTON AND IMMEDIATE CONTAINER LABELS
Submit final printed carton and container labels that are identical to the enclosed carton and
immediate container labels, except with the revisions listed below, as soon as they are available,
but no more than 30 days after they are printed.
1. Because H.P. Acthar Gel is a multiple-dose injectable product, the strength per total
volume should be the primary and prominent expression on the principle display panel,
followed in close proximity by the strength per mL enclosed by parenthesis per USP
standards. Please revise the strength expression on all labels and labeling to read as
follows:
400 USP units/5 mL

(80 USP units/mL)
2. Relocate the strength expression immediately following the established name

presentation in all labels and labeling.
Please submit these labels electronically according to the guidance for industry titled “Providing
Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications
and Related Submissions Using the eCTD Specifications (June 2008).” Alternatively, you may
submit 12 paper copies, with 6 of the copies individually mounted on heavy-weight paper or
similar material. For administrative purposes, designate this submission “Final Printed Carton
and Container Labels for approved NDA 022432.” Approval of this submission by FDA is
not required before the labeling is used.
Marketing the product with FPL that is not identical to the approved labeling text may render the
product misbranded and an unapproved new drug.
REQUIRED PEDIATRIC ASSESSMENTS
Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
administration are required to contain an assessment of the safety and effectiveness of the
product for the claimed indication(s) in pediatric patients unless this requirement is waived,
deferred, or inapplicable.
Because this drug product for this indication has an orphan drug designation, you are exempt

NDA 022432
Page 3
from this requirement.
RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
Section 505-1 of the FDCA authorizes FDA to require the submission of a risk evaluation and
mitigation strategy (REMS), if FDA determines that such a strategy is necessary to ensure that
the benefits of the drug outweigh the risks [section 505-1(a)]. The details of the REMS
requirements were outlined in our REMS notification letter dated September 27, 2010.
H.P. Acthar Gel (repository corticotrophin) was approved on April 29, 1952, for multiple
indications. The label was later expanded to include multiple sclerosis (MS) in 1972. We are
now adding the indication of infantile spasms in pediatric patients. The known risks of
infections and blood pressure elevation in MS patients have also been identified as risks in the
pediatric population based on clinical trial data. Additionally, the risk of adrenal insufficiency
seen in other patient populations is an important potential serious adverse event in the pediatric
population. The extension of the indication to pediatrics changes the risk benefit profile of H.P.
Acthar Gel (repository corticotrophin) and is considered to be “new safety information” as
defined in section 505-1(b)(3) of the FDCA.
Your proposed REMS, submitted on September 28, 2010, and appended to this letter, is
approved. The REMS consists of a Medication Guide and timetable for submission of
assessments of the REMS.
The REMS assessment plan should include, but is not limited to, the following:
An evaluation of patients’ understanding of the serious risks of H.P. Acthar® Gel (repository
corticotropin).
Assessments of an approved REMS must also include, under section 505-1(g)(3)(B) and (C),
information on the status of any postapproval study or clinical trial required under section 505(o)
or otherwise undertaken to investigate a safety issue. With respect to any such postapproval
study, you must include the status of such study, including whether any difficulties completing
the study have been encountered. With respect to any such postapproval clinical trial, you must
include the status of such clinical trial, including whether enrollment has begun, the number of
participants enrolled, the expected completion date, whether any difficulties completing the
clinical trial have been encountered, and registration information with respect to requirements
under subsections (i) and (j) of section 402 of the Public Health Service Act. You can satisfy
these requirements in your REMS assessments by referring to relevant information included in
the most recent annual report required under section 506B and 21 CFR 314.81(b)(2)(vii) and
including any material or significant updates to the status information since the annual report was
prepared. Failure to comply with the REMS assessments provisions in section 505-1(g) could
result in enforcement action.
We remind you that in addition to the assessments submitted according to the timetable included
in the approved REMS, you must submit a REMS assessment and may propose a modification to
the approved REMS when you submit a supplemental application for a new indication for use as
described in section 505-1(g)(2)(A) of FDCA.

NDA 022432
Page 4
If you currently distribute or plan to distribute an authorized generic product under this NDA,
you will also need to submit a REMS, REMS supporting document, and any required appended
documents for that authorized generic, to this NDA. In other words, you must submit a complete
proposed REMS that relates only to the authorized generic product. Review and approval of the
REMS is required before you may market your product.
Prominently identify the submission containing the REMS assessments or proposed

modifications with the following wording in bold capital letters at the top of the first page of the
submission as appropriate:
NDA 008372 REMS ASSESSMENT
NEW SUPPLEMENT FOR NDA 008372

PROPOSED REMS MODIFICATION
REMS ASSESSMENT
NEW SUPPLEMENT (NEW INDICATION FOR USE)

FOR NDA 008372
REMS ASSESSMENT
PROPOSED REMS MODIFICATION (if included)
If you do not submit electronically, please send 5 copies of REMS-related submissions.
PROMOTIONAL MATERIALS
You may request advisory comments on proposed introductory advertising and promotional
labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
proposed materials in draft or mock-up form with annotated references, and the package insert
to:

Center for Drug Evaluation and Research
Division of Drug Marketing, Advertising, and Communications
5901-B Ammendale Road
Beltsville, MD 20705-1266
As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
information about submission of promotional materials to the Division of Drug Marketing,
Advertising, and Communications (DDMAC), see
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.

NDA 022432
Page 5
LETTERS TO HEALTH CARE PROFESSIONALS
If you decide to issue a letter communicating important safety-related information about this
drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
24 hours prior to issuing the letter, an electronic copy of the letter to this NDA to the following
address:
MedWatch Program
Office of Special Health Issues
10903 New Hampshire Ave
Building 32, Mail Stop 5353
Silver Spring, MD 20993
REPORTING REQUIREMENTS
We remind you that you must comply with reporting requirements for an approved NDA
(21 CFR 314.80 and 314.81).
All 15-day alert reports, periodic (including quarterly) adverse drug experience reports, field
alerts, annual reports, supplements, and other submissions should be addressed to the original
NDA 008372 for this drug product, not to this NDA. In the future, do not make submissions to
this NDA except for the final printed labeling requested above.
If you have any questions, call Susan Daugherty, Regulatory Project Manager, at
(301) 796-0878.
Sincerely,
{See appended electronic signature page}
Russell Katz, M.D.

Director
Division of Neurology Products
Office of Drug Evaluation I
ENCLOSURES:
Content of Labeling
Carton and Container Labeling
REMS

---------------------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
RUSSELL G KATZ
10/15/2010
Reference ID: 2850370


NDA 008372/S-044
SUPPLEMENT APPROVAL

6011 University Boulevard
Suite 260
Ellicott City, MD 21043
Dear Dr. Bigora:
Please refer to your Supplemental New Drug Application (sNDA) dated May 3, 2011, received
May 4, 2011, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
(FDCA) for H.P. Acthar Gel (respository corticotropin injection).
We acknowledge receipt of your amendment dated October 21, 2014.
The October 21, 2014, submission constituted a complete response to our October 22, 2013,
action letter.
This “Changes Being Effected” supplemental new drug application provides for the indication
for the treatment of infantile spasms to be associated with the parent NDA number 008372, since
the tracking NDA number 022432 will no longer be used.
APPROVAL & LABELING
We have completed our review of this supplemental application. It is approved, effective on the
date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
Submit final printed carton and immediate container labels that are identical to the enclosed
carton and immediate container labels, as soon as they are available, but no more than 30 days
after they are printed. Please submit these labels electronically according to the guidance for
industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical
Product Applications and Related Submissions Using the eCTD Specifications (June 2008).
Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
heavy-weight paper or similar material. For administrative purposes, designate this submission
“Final Printed Carton and Container Labels for approved NDA 008372/S-044.” Approval
of this submission by FDA is not required before the labeling is used.

NDA 008372/S-044
Page 2
Marketing the product(s) with FPL that is not identical to the approved labeling text may render
the product misbranded and an unapproved new drug.
(21 CFR 314.80 and 314.81).
If you have any questions, contact Stephanie N. Parncutt, M.H.A., Regulatory Health Project
Manager, at (301) 796-4098.
Sincerely,
Eric Bastings, M.D.

Deputy Director
ENCLOSURE(S):

---------------------------------------------------------------------------------------------------------
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
ERIC P BASTINGS
03/24/2015

From: CMS MDROperations

To: "Forshee, Kay"; CMS MDROperations
Date: Thursday, June 02, 2016 6:32:33 PM
Attachments: TEMPLATE FOR FDA APPROVAL_MARKET DATE CHANGE REQUEST.XLSX
Acthar gel final.doc
Kay,
We are aware of the correspondence between Questcor and CMS that you provided. However, as
stated in Manufacturer Release #90 at http://www.medicaid.gov/Medicaid-CHIP-Program-
Information/By-Topics/Benefits/Prescription-Drugs/Downloads/Rx-Releases/MFR-Releases/mfr-rel-
090.pdf, the baseline data of a purchased product should be the same as the baseline data of a
product marketed previously under the same NDA. Therefore, we are requesting that you complete
and return the attached template so that the baseline information for the NDC matches the baseline
information of the NDC that was originally used for marketing the product under the same NDA.
Thank you,
CMS MDR Operations


Good afternoon,
Attached please find correspondence between Questcor/Mallinckrodt and CMS regarding the
approved NDC changes and new base AMP for Acthar. Please advise if we are required to make any
changes to the DDR.
Thanks,

T: 314.654.6592

To: Forshee, Kay
Kay,
Attached, please find an advance copy of a letter that you will be receiving by U.S. Mail. Also
attached is a template, for your use in requesting the changes referenced in the letter.
Thank you,
CMS MDR Operations
health care fraud and abuse under that section. This response should not be interpreted as acquiescence
by the Government to the arrangements described herein. Further, this response is not a release of any
liability.


TEMPLATE FOR FDA APPROVAL/MARKET DATE CHANGE REQUEST
1. Date of Request:
2. Labeler Name:
(Page 264 of Total)

USCA Case #20-5154

Document #1845229
Filed: 06/02/2020
Page 222 of 400
A216 HHS - 000136

Created June 2008

April 13, 2016
Kay Forshee
Technical Contact
675 McDonnell Blvd
Hazelwood, MO 63042
Dear Kay:
MDR program.

8710.

Sincerely,
/s/

Director


Good afternoon,
Attached please find correspondence between Questcor/Mallinckrodt and CMS regarding the
approved NDC changes and new base AMP for Acthar. Please advise if we are required to make any
changes to the DDR.
Thanks,
T: 314.654.6592
To: Forshee, Kay
Kay,
Thank you,
CMS MDR Operations
health care fraud and abuse under that section. This response should not be interpreted as acquiescence by
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ZDLYHDQ\DSSOLFDEOHSULYLOHJH



[3.2.2] [Questcor Letter.pdf] [Page 1 of 7]







[3.2.1] [89 - CMS Letter rec'd 08-16-12 (2).pdf] [Page 1 of 2]

[3.2.1] [89 - CMS Letter rec'd 08-16-12 (2).pdf] [Page 2 of 2]
From: CMS MDROperations

To: "KAY.FORSHEE@MALLINCKRODT.COM"
Date: Wednesday, April 13, 2016 2:44:07 PM
Attachments: Acthar gel final.doc
TEMPLATE FOR FDA APPROVAL_MARKET DATE CHANGE REQUEST.xlsx
Kay,
Thank you,
CMS MDR Operations


April 13, 2016
Kay Forshee
Technical Contact
675 McDonnell Blvd
Hazelwood, MO 63042
Dear Kay:
MDR program.

8710.

Sincerely,
/s/

Director

TEMPLATE FOR FDA APPROVAL/MARKET DATE CHANGE REQUEST
1. Date of Request:
2. Labeler Name:
(Page 281 of Total)

USCA Case #20-5154

Document #1845229
Filed: 06/02/2020
Page 239 of 400
A233 HHS - 000153

Created June 2008
From: Daugherty, Susan B (CSO) (FDA/CDER)

To: Coster, John M. (CMS/CMCS)
Cc: Dunn, Billy (FDA/CDER); Bastings, Eric (FDA/CDER); Ware, Jacqueline H (FDA/CDER); Khau, Meagan T.
(CMS/OMH); Blatt, Ruth (CMS/CMCS)
Subject: RE: Issues with Acthar gel
Date: Wednesday, November 25, 2015 9:23:07 AM
Hello Dr. Coster,
HP Acthar Gel was originally approved under NDA 008372. NDA 008372 is
considered to be the original or parent NDA.
A type-6 NDA (022432) was created for administrative purposes when the sponsor
submitted an efficacy supplement for the treatment of infantile spasms. The definition
of a Type-6 NDA is, “A drug product that duplicates a drug product already approved or marketed
in the United States by the same applicant, except that it is intended for a new indication or claim
(same active moiety or combination of active moieties, same salt(s), same dosage form, and same
formulation (including all ingredients used in the manufacturing process whether or not they are
present in the final dosage form)).”
Back In the days of paper submissions, we created Type-6 NDAs when an efficacy
supplement was submitted for an indication to be reviewed by A Division other than
the Division responsible for the parent (original) NDA to ensure that all of the
documents submitted for review in support of a new indication would be sent to the
appropriate Division. In the case of Acthar Gel, the parent NDA (008372) and all of its
supplements were reviewed by the Division of Metabolic and Endocrine Products and
review of the infantile spasms indication was conducted by the Division of Neurology
Products.
Type-6 NDAs are administratively closed upon approval. The approval letter for NDA
022432 states, “All 15-day alert reports, periodic (including quarterly) adverse drug experience
reports, field alerts, annual reports, supplements, and other submissions should be addressed to the
original NDA 008372 for this drug product, not to this NDA. In the future, do not make submissions
to this NDA except for the final printed labeling requested above.” This letter may be accessed
@ http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/022432s000ltr.pdf
Upon approval of the infantile spasms efficacy supplement we requested that the
sponsor submit a labeling supplement to the parent NDA for administrative purposes
to update the labeling under the parent NDA.
Please let me know whether you have additional questions.
Best Regards,
Susan
Susan Daugherty
Project Manager
FDA/CDER/OND


10903 New Hampshire Avenue, Bldg. 22, Rm. 4348
Silver Spring, MD 20993-0002
(301)796-0878
From: Coster, John M. (CMS/CMCS) [mailto:John.Coster@cms.hhs.gov]

Sent: Tuesday, November 24, 2015 9:49 AM
To: Bastings, Eric
Cc: Khau, Meagan T (CMS); Blatt, Ruth (CMS)
Subject: Issues with Acthar gel
Dear Eric:
We came across the attached letter from FDA, signed by you, stating that the NDA
number 022432 for Acthar Gel is no longer being used and we would like some
additional information regarding this decision as this letter has an impact on the
manufacturer reporting of Acthar Gel to the Medicaid Drug Rebate Program at CMS.
What is the effective date of NDA number 022432 no longer being used? Is it the date
you signed on 3/24/2015, or does this letter invalidate NDA number 022432 altogether
since it’s first approval back on October 15, 2010?
Additionally, what is the basis for this decision? The letter did not provide this
information and it would be very helpful for us to have this information as we will
have to reach out to the manufacturer regarding the reporting of Acthar Gel and any
information from FDA would be helpful for us to support our discussion with the
manufacturer.
Thank you for your help



From: Diane Schulman

Cc: CMS RxDRUGPolicy
Subject: H.P. Acthar Gel
Date: Thursday, September 06, 2012 1:55:51 PM
Attachments: QUESTCOR 8K 9-4-12 SEC-ABEA-2S424C-1193125-12-378223-2.pdf
20100506-PCNS-S1-01-Questcor-CoreSlides.pdf
Questcor-022432Orig1_Original_Approval_Pkg.pdf
Memorandum re Acthar sNDA to NDA s Susan B. Daugherty 8808.pdf
To: Medicaid Drug Rebate Operations

From: Diane Schulman
Re: H.P. Acthar Gel
On Tuesday, September 4, 2012, Questcor Pharmaceuticals Inc. announced to investors (see

attached) that it had been informed by the government that its primary drug, Acthar (99% of
revenue) is "eligible for a lower Medicaid rebate amount."
Questcor Pharmaceuticals, Inc. (the “Company”) is providing the following update

regarding its Medicaid rebate position with respect to the Company’s primary product,
H.P. Acthar Gel (repository corticotropin injection) (“Acthar”):
As previously disclosed, we currently provide Acthar to Medicaid participants and pay

mandatory rebates to state Medicaid programs on the Acthar provided to those patients.
Currently, the rebate amount is approximately 100% of the amount we charge our
distributor for Acthar.
The government has informed the Company that Acthar is eligible for a lower
Medicaid rebate amount. Therefore, the Company is in the process of taking the
necessary steps to effect this change. We estimate that it will take approximately 3 – 6
months to implement this change and that the new rebate may become 23.1%. If we
ultimately implement this change in the Medicaid rebate amount for Acthar, such
change could have a materially positive impact on our financial results.
I'm trying to understand the circumstances under which Medicaid would pay MORE for this
drug that was first approved by FDA in 1952. As you know, in 2007 Questcor implemented
what it called its new Acthar marketing and pricing "strategy" raising the retail price of the
drug from ~$1600/vial to ~$24,000/vial overnight. This increase was implemented despite the
fact that the cost per vial is well under $200 and that there has been no appreciable research
and development required or executed on this 60 year old drug.
Questcor sought and received Orphan Drug Designation in 2003 for Acthar in connection with
its off-label use to treat Infantile Spasms (IS.) It filed an sNDA with FDA for approval of IS as
an on label indication in 2006 and was not approved. Questcor subsequently filed additional
documentation and received label approval for IS in 2010. Notably, in 2008, the application
was converted from an sNDA to a Type 6 NDA since the sNDA was reviewed by the wrong
department at FDA (see below.)
I now understand that because it was an NDA not an sNDA approved in 2010, Acthar's
medicaid rebate calculation is being reset to reflect the modest price increases (between 5 -
10% in a year) since 2010 and ignore the 2000% price increase from August 26, 2007 to
August 27, 2007.

From the Questcor-022432Orig1_Original_Approval_Pkg:
Application
Type/Number
--------------------
NDA-22432
NDA-8372
Submission
Type/Number
--------------------
ORIG-1
ORIG-1
Submitter Name
------------------------------------------
QUESTCOR PHARMACEUTICALS INC
QUESTCOR PHARMACEUTICA LS INC
Product Name
--------------------
H.P.ACTHAR GEL (Repository

Corticotropin Injection)
H.P. ACTHAR GEL

---------------------------------------------------------------------------------------------------------
With respect to the nonclinical data that support this application, which is an efficacy
supplement designated as a Type 6 NDA for administrative purposes, Questcor
implicitly
cross-references the nonclinical data in its previously approved 505(b)(1) application.

*A Type 6 NDA is an efficacy supplement that is designated in CDER’s database

as a
new NDA and assigned a new NDA number for administrative purposes (e.g., to
facilitate the review of a supplement for an indication for which the scientific expertise
lies in a division different from the parent division for the original application).
Please help me with some questions:
If a type 6 NDA is an administrative change (above), is it really possible that this type of
NDA could possibly trigger a 76.9% loss to Medicaid on each Medicaid vial, with a
current AWP of more than $34,000 ? It's hard to imagine that there is any common
sense rationale that would permit it.
Was there some other change from sNDA 8372 and NDA 22432 in the drug beyond the
wrong FDA reviewing department? What was that? I note in the 24432 file that Acthar
is referred to as H.P. Acthar Gel in the sNDA and H.P. Acthar Gel (respository
corticotropin) in the NDA. Is there a difference between the two?
I also note that Questcor says it has to take "steps" to implement a change in order to get
the windfall. Can you help me understand what that might be?
Please share with me any guidance, explanation, correspondence with the company with
regard to government reimbursement of this drug.
You should know that I have done a fair amount research into this company, drug and its
practices (which I'd be happy to discuss further with CMS.) For instance, in spite of its long
label, Acthar is marketed off-label for its most profitable indications. Also, numerous private
payers refuse to cover this drug for indications such as MS since there is no scientific evidence
that it is as effective or more effective than the much cheaper IV steroids. If commercial
insurers question covering this drug, shouldn't CMS do the same? There is no doubt that
taxpayer dollars will be wasted.
My office in Boston is 617-965-5113. For the next few days, I will be working at the number
508-255-2699. Please don't hesitate to call with any questions you may have.
Best regards,
Diane
--
Diane Schulman
41 East 11th Street 11th Floor

New York, NY 10003

diane.schulman@theindagogroup.com
617.965.5113 Direct phone


RESEARCH
APPLICATION NUMBER:
022432Orig1s000
LABELING

HIGHLIGHTS OF PRESCRIBING INFORMATION hypothalamic-pituitary-axis suppression after stopping treatment. (5 2)
These highlights do not include all the information needed to use H.P. x Cushing’s Syndrome: May occur after prolonged therapy. Monitor for
Acthar Gel safely and effectively. See full prescribing information for signs and symptoms. (5.2)
H.P. Acthar Gel. x Elevated Blood Pressure, Salt and Water Retention and Hypokalemia:
H.P. Acthar Gel (repository corticotropin) INJECTION, GEL for Monitor blood pressure and sodium and potassium levels. (5.3)
INTRAMUSCULAR | SUBCUTANEOUS use x Vaccination: Do not administer live or attenuated vaccines to patients on
Initial U.S. Approval: 1952 immunosuppressive doses. (5.4)
x Masking of Symptoms of Other Underlying Disease/Disorders. Monitor
----------------------------RECENT MAJOR CHANGES-------------------------- patients for signs of other underlying disease/disorders that may be
x Indications and Usage, (1) 10/10 masked. (5.5)
x Dosage and Administration, (2) 10/10 x Gastrointestinal Perforation and Bleeding: There is a risk for gastric ulcers
x Contraindications, Infantile Spasms (4) 10/10 and bleeding. There is an increased risk of perforation in patients with
x Warnings and Precautions (5) 10/10 certain GI disorders. Signs and symptoms may be masked. Monitor for
signs of perforation and bleeding. (5.6)
----------------------------INDICATIONS AND USAGE--------------------------- x Behavioral and Mood Disturbances: May include euphoria, insomnia,
x H.P. Acthar Gel is an adrenocorticotropic hormone (ACTH) analogue mood swings, personality changes, severe depression and psychosis.
indicated as monotherapy for the treatment of infantile spasms in infants Existing conditions may be aggravated (5.7)
and children under 2 years of age. (1.1) x Comorbid Diseases: Symptoms of diabetes and myasthenia gravis may be
x H.P. Acthar Gel is indicated for the treatment of exacerbations of multiple worsened with treatment. (5.8)
sclerosis in adults. (1.2) x Ophthalmic Effects: Monitor for cataracts, infections and glaucoma. (5.9)
x H.P. Acthar Gel may be used for the following disorders and diseases: x Immunogenicity Potential: Neutralizing antibodies with chronic
rheumatic; collagen; dermatologic; allergic states; ophthalmic; respiratory; administration may lead to a loss of endogenous ACTH activity. (5.10)
and edematous state; (1.3 to 1.9) x Use in Patients with Hypothyroidism or Liver Cirrhosis: May result in an
enhanced effect. (5.11)
----------------------DOSAGE AND ADMINISTRATION----------------------- x Negative Effects on Growth and Physical Development: Monitor pediatric
x In the treatment of infantile spasms, the recommended dose is 150 U/m2 patients on long term therapy. (5.12)
divided into twice daily intramuscular injections of 75 U/m2. After 2 x Decrease in Bone Density: Monitor for osteoporosis in patients on long
weeks of treatment, dosing should be gradually tapered and discontinued term therapy. (5.13)
over a 2-week period. (2.1) x Use in Pregnancy: Embryocidal effect. Apprise women of potential harm
x In the treatment of acute exacerbations of multiple sclerosis, daily to the fetus. (5.14)
intramuscular or subcutaneous doses of 80-120 units for 2-3 weeks may be
administered. It may be necessary to taper the dose. (2.2) ------------------------------ADVERSE REACTIONS-------------------------------
x In the treatment of other disorders and diseases, dosing will need to be x Common adverse reactions for Acthar Gel are similar to those of
individualized depending on the disease under treatment and the medical corticosteroids and include fluid retention, alteration in glucose tolerance,
condition of the patient. It may be necessary to taper the dose. (2.3) elevation in blood pressure, behavioral and mood changes, increased
appetite and weight gain. (6)
---------------------DOSAGE FORMS AND STRENGTHS---------------------- x Specific adverse reactions resulting from drug use in children under 2
x 5 mL multi-dose vial containing 80 USP units per mL (3) years of age are increased risk of infections, hypertension, irritability,
Cushingoid symptoms, cardiac hypertrophy and weight gain. (6.1.1)
------------------------------CONTRAINDICATIONS------------------------------ x
x H.P. Acthar Gel should never be given intravenously. To report SUSPECTED ADVERSE REACTIONS, contact Questcor
x H.P. Acthar Gel is contraindicated in patients with scleroderma, Pharmaceuticals, Inc. at (800) 411-3065 or (510) 400-0700 or FDA at
osteoporosis, systemic fungal infections, ocular herpes simplex, recent 1-800-FDA-1088 or www.fda.gov/medwatch
surgery, history of or the presence of a peptic ulcer, congestive heart
failure, uncontrolled hypertension, or sensitivity to proteins of porcine ------------------------------DRUG INTERACTIONS-------------------------------
origin. x H.P. Acthar Gel may accentuate the electrolyte loss associated with
x Administration of live or live attenuated vaccines is contraindicated in diuretic therapy. (7)
patients receiving immunosuppressive doses of H.P Acthar Gel.
x H.P. Acthar Gel is contraindicated in children under 2 years of age with -----------------------USE IN SPECIFIC POPULATIONS------------------------
suspected congenital infections. (4) x Pregnancy: H.P. Acthar Gel has been shown to have an embryocidal effect
x Treatment of conditions listed within the INDICATIONS section is and should be used during pregnancy only if the potential benefit justifies
contraindicated when they are accompanied by primary adrenocortical the potential risk to the fetus. (8.1)Pediatric Use: Prolonged use of H.P.
insufficiency or adrenocortical hyperfunction. (4) Acthar Gel in children may inhibit skeletal growth. If use is necessary, it
should be given intermittently with careful observation. (5.12 and 8.3)
-----------------------WARNINGS AND PRECAUTIONS------------------------
x Infections: Increased susceptibility to new infection and increased risk of See 17 for Patient Counseling Information and FDA-approved
exacerbation, dissemination or reactivation of latent infections. Signs and Medication Guide
symptoms of infection may be masked. (5.1)
x Adrenal Insufficiency after Prolonged Therapy: Monitor for effects of
FULL PRESCRIBING INFORMATION: CONTENTS*
FULL PRESCRIBING INFORMATION 2.1 Specific Recommended Dosage Regimen for Infantile Spasms
1 INDICATIONS AND USAGE in Infants and Children Under 2 Years of Age
1.1 Infantile spasms: 2.2 Recommended Dosage Regimen for the Treatment of Acute
1.2 Multiple Sclerosis: Exacerbations in Adults with Multiple Sclerosis.
1.3 Rheumatic Disorders: 2.3 Recommended Dosage Regimen for Other Indications for
1.4 Collagen Diseases: Adults and Children Over 2 Years of Age
1.5 Dermatologic Diseases: 2.4 Preparation
1.6 Allergic States: 3 DOSAGE FORMS AND STRENGTHS
1.7 Ophthalmic Diseases: 4 CONTRAINDICATIONS
1.8 Respiratory Diseases: 5 WARNINGS AND PRECAUTIONS
1.9 Edematous State: 5.1 Infections
2 DOSAGE AND ADMINISTRATION 5.2 Cushing’s Syndrome and Adrenal Insufficiency Upon
Withdrawal
Page 1
5.3 Elevated Blood Pressure, Salt and Water Retention and 6.2.7 Musculoskeletal
Hypokalemia 6.2.8 Neurological
5.4 Vaccination 6.3 Possible Additional Steroidogenic Effects
5.5 Masking Symptoms of Other Diseases 6.3.1 Dermatologic
5.6 Gastrointestinal Perforation and Bleeding 6.3.2 Endocrine
5.7 Behavioral and Mood Disturbances 6.3.3 Metabolic
5.8 Comorbid Diseases 6.3.4 Musculoskeletal
5.9 Ophthalmic Effects 6.3.5 Neurological
5.10 Immunogenicity Potential 6.3.6 Ophthalmic
5.11 Use in Patients with Hypothyroidism or Liver Cirrhosis 7 DRUG INTERACTIONS
5.12 Negative Effects on Growth and Physical Development 8 USE IN SPECIFIC POPULATIONS
5.13 Decrease in Bone Density 8.1 Pregnancy
5.14 Use in Pregnancy 8.3 Nursing Mothers
6 ADVERSE REACTIONS 8.4 Pediatric Use
6.1 Clinical Studies Experience 10 OVERDOSAGE
6.1.1 Adverse Reactions in Infants and Children Under 2 Years 11 DESCRIPTION
of Age 12 CLINICAL PHARMACOLOGY
6.2 Postmarketing Experience 12.1 Mechanism of Action
6.2.1 Allergic Reactions 13 NONCLINICAL TOXICOLOGY
6.2.2 Cardiovascular 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
6.2.3 Dermatologic 14 CLINICAL STUDIES
6.2.4 Endocrine 16 HOW SUPPLIED / STORAGE AND HANDLING
6.2.5 Gastrointestinal 17 PATIENT COUNSELING INFORMATION
6.2.6 Metabolic
*Sections or subsections omitted from the full prescribing information are not
listed
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Infantile spasms:
H.P. Acthar Gel (repository corticotropin injection) is indicated as monotherapy for the treatment
of infantile spasms in infants and children under 2 years of age.
1.2 Multiple Sclerosis:
H.P. Acthar Gel (repository corticotropin injection) is indicated for the treatment of acute
exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown H.P. Acthar
Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis.
However, there is no evidence that it affects the ultimate outcome or natural history of the
disease.
1.3 Rheumatic Disorders:
As adjunctive therapy for short-term administration (to tide the patient over an acute episode or
exacerbation) in: Psoriatic arthritis, Rheumatoid arthritis, including juvenile rheumatoid arthritis
(selected cases may require low-dose maintenance therapy), Ankylosing spondylitis.
1.4 Collagen Diseases:
During an exacerbation or as maintenance therapy in selected cases of: systemic lupus

erythematosus, systemic dermatomyositis (polymyositis).
1.5 Dermatologic Diseases:
Severe erythema multiforme, Stevens-Johnson syndrome.
Page 2
1.6 Allergic States:
Serum sickness.
1.7 Ophthalmic Diseases:
Severe acute and chronic allergic and inßammatory processes involving the eye and its adnexa
such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis; optic neuritis;
chorioretinitis; anterior segment inßammation.
1.8 Respiratory Diseases:
Symptomatic sarcoidosis
1.9 Edematous State:
To induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of

the idiopathic type or that due to lupus erythematosus.
2 DOSAGE AND ADMINISTRATION
2.1 Specific Recommended Dosage Regimen for Infantile Spasms in Infants and
Children Under 2 Years of Age
In the treatment of infantile spasms, H.P. Acthar Gel must be administered intramuscularly. The
recommended regimen is a daily dose of 150 U/m2 (divided into twice daily intramuscular
injections of 75 U/m2) administered over a 2-week period. Dosing with H.P. Acthar Gel should
then be gradually tapered over a 2-week period to avoid adrenal insufficiency. The following is
one suggested tapering schedule: 30 U/m2 in the morning for 3 days; 15 U/m2 in the morning for
3 days; 10 U/m2 in the morning for 3 days; and 10 U/m2 every other morning for 6-days.
H.P. Acthar Gel is typically dosed based on body surface area (BSA). For calculation of body
surface area, use the following formula
2.2 Recommended Dosage Regimen for the Treatment of Acute Exacerbations in Adults
with Multiple Sclerosis.
The recommended dose is daily intramuscular or subcutaneous doses of 80-120 units for 2-3
weeks for acute exacerbations.
Dosage should be individualized according to the medical condition of each patient. Frequency
and dose of the drug should be determined by considering the severity of the disease and the
initial response of the patient.
Page 3
Although drug dependence does not occur, sudden withdrawal of H.P. Acthar Gel after
prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to
stop the treatment. It may be necessary to taper the dose and increase the injection interval to
gradually discontinue the medication.
2.3 Recommended Dosage Regimen for Other Indications for Adults and Children Over
2 Years of Age
Dosage should be individualized according to the disease under treatment and the general
medical condition of each patient. Frequency and dose of the drug should be determined by
considering severity of the disease and the initial response of the patient.
The usual dose of H.P. Acthar Gel is 40-80 units given intramuscularly or subcutaneously every
24-72 hours.
Although drug dependence does not occur, sudden withdrawal of H.P. Acthar Gel after
prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to
stop the treatment. It may be necessary to taper the dose and increase the injection interval to
gradually discontinue the medication.
2.4 Preparation
H.P. Acthar Gel should be warmed to room temperature before using.
Caution should be taken not to over-pressurize the vial prior to withdrawing the product.
3 DOSAGE FORMS AND STRENGTHS
5 mL multi-dose vial containing 80 USP Units per mL.
4 CONTRAINDICATIONS
H.P. Acthar Gel is contraindicated for intravenous administration.
H.P. Acthar Gel is contraindicated where congenital infections are suspected in infants.
Administration of live or live attenuated vaccines is contraindicated in patients receiving

immunosuppressive doses of H.P Acthar Gel.
H.P. Acthar Gel is contraindicated in patients with scleroderma, osteoporosis, systemic fungal
infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer,
congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency,
adrenocortical hyperfunction or sensitivity to proteins of porcine origin.
Page 4
5 WARNINGS AND PRECAUTIONS
The adverse effects of H.P. Acthar Gel are related primarily to its steroidogenic effects. Not all
of the adverse events described below have been seen after treatment with H.P. Acthar Gel, but
might be expected to occur. [see Adverse Reactions (6.3)].
5.1 Infections
H.P. Acthar Gel may increase the risks related to infections with any pathogen, including viral,
bacterial fungal, protozoan or helminthic infections. Patients with latent tuberculosis or
tuberculin reactivity should be observed closely, and if therapy is prolonged, chemoprophylaxis
should be instituted.
5.2 Cushing’s Syndrome and Adrenal Insufficiency Upon Withdrawal
Treatment with H.P. Acthar Gel can cause hypothalamic-pituitary-axis (HPA) suppression and
Cushing’s syndrome. These conditions should be monitored especially with chronic use.
Suppression of the HPA may occur following prolonged therapy with the potential for adrenal
insufficiency after withdrawal of the medication. Patients should be monitored for signs of
insufficiency such as weakness, hyperpigmentation, weight loss, hypotension and abdominal
pain.
The symptoms of adrenal insufficiency in infants treated for infantile spasms can be difficult to
identify. The symptoms are non-specific and may include anorexia, fatigue, lethargy, weakness,
excessive weight loss, hypotension and abdominal pain. It is critical that parents and caregivers
be made aware of the possibility of adrenal insufficiency when discontinuing Acthar Gel and
should be instructed to observe for, and be able to recognize, these symptoms [see Information
for Patients (17)]
The recovery of the adrenal gland may take from days to months so patients should be protected
from the stress (e.g. trauma or surgery) by the use of corticosteroids during the period of stress.
The adrenal insufficiency may be minimized in adults and infants by tapering of the dose when
discontinuing treatment.
Signs or symptoms of Cushing’s syndrome may occur during therapy but generally resolve after
therapy is stopped. Patients should be monitored for these signs and symptoms such as
deposition of adipose tissue in characteristics sites (e.g., moon face, truncal obesity), cutaneous
striae, easy bruisability, decreased bone mineralization, weight gain, muscle weakness,
hyperglycemia, and hypertension.
5.3 Elevated Blood Pressure, Salt and Water Retention and Hypokalemia
H.P. Acthar Gel can cause elevation of blood pressure, salt and water retention, and increased
excretion of potassium and calcium. Dietary salt restriction and potassium supplementation may
Page 5
be necessary. Caution should be used in the treatment of patients with hypertension, congestive
heart failure, or renal insufficiency.
5.4 Vaccination
Administration of live or live attenuated vaccines is contraindicated in patients receiving

immunosuppressive doses of H.P. Acthar Gel. Killed or inactivated vaccines may be
administered; however, the response to such vaccines can not be predicted. Other immunization
procedures should be undertaken with caution in patients who are receiving H.P. Acthar Gel,
especially when high doses are administered, because of the possible hazards of neurological
complications and lack of antibody response.
5.5 Masking Symptoms of Other Diseases
H.P. Acthar Gel often acts by masking symptoms of other diseases/disorders without altering the
course of the other disease/disorder. Patients should be monitored carefully during and for a
period following discontinuation of therapy for signs of infection, abnormal cardiac function,
hypertension, hyperglycemia, change in body weight and fecal blood loss.
5.6 Gastrointestinal Perforation and Bleeding
Acthar Gel can cause GI bleeding and gastric ulcer. There is also an increased risk for
perforation in patients with certain gastrointestinal disorders. Signs of gastrointestinal
perforation, such as peritoneal irritation, may be masked by the therapy. Use caution where there
is the possibility of impending perforation, abscess or other pyogenic infections, diverticulitis,
fresh intestinal anastomoses, and active or latent peptic ulcer.
5.7 Behavioral and Mood Disturbances
Use of H.P. Acthar Gel may be associated with central nervous system effects ranging from
euphoria, insomnia, irritability (especially in infants), mood swings, personality changes, and
severe depression, to frank psychotic manifestations. Also, existing emotional instability or
psychotic tendencies may be aggravated.
5.8 Comorbid Diseases
Patients with a comorbid disease may have that disease worsened. Caution should be used when
prescribing H.P. Acthar Gel in patients with diabetes and myasthenia gravis.
5.9 Ophthalmic Effects
Prolonged use of H.P. Acthar Gel may produce posterior subcapsular cataracts, glaucoma with
possible damage to the optic nerves and may enhance the establishment of secondary ocular
infections due to fungi and viruses.
Page 6
5.10 Immunogenicity Potential
H.P. Acthar Gel is immunogenic. Limited available data suggest that a patient may develop
antibodies to H.P. Acthar Gel after chronic administration and loss of endogenous ACTH and
H.P. Acthar Gel activity. Prolonged administration of H.P. Acthar Gel may increase the risk of
hypersensitivity reactions. Sensitivity to porcine protein should be considered before starting
therapy and during the course of treatment should symptoms arise.
5.11 Use in Patients with Hypothyroidism or Liver Cirrhosis
There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the
liver.
5.12 Negative Effects on Growth and Physical Development
Long-term use of H.P. Acthar Gel may have negative effects on growth and physical
development in children. Changes in appetite are seen with H.P. Acthar Gel therapy, with the
effects becoming more frequent as the dose or treatment period increases. These effects are
reversible once H.P. Acthar Gel therapy is stopped. Growth and physical development of
pediatric patients on prolonged therapy should be carefully monitored.
5.13 Decrease in Bone Density
Decrease in bone formation and an increase in bone resorption both through an effect on calcium
regulation (i.e. decreasing absorption and increasing excretion) and inhibition of osteoblast
function may occur. These, together with a decrease in the protein matrix of the bone (secondary
to an increase in protein catabolism) and reduced sex hormone production, may lead to inhibition
of bone growth in children and adolescents and to the development of osteoporosis at any age.
Special consideration should be given to patients at increased risk of osteoporosis (i.e.,
postmenopausal women) before initiating therapy, and bone density should be monitored in
patients on long term therapy.
5.14 Use in Pregnancy
H.P. Acthar Gel has been shown to have an embryocidal effect. Apprise women of potential
harm to the fetus. [see Use in Specific Populations (8.1)]
6 ADVERSE REACTIONS
Please refer to Adverse Reactions in Infants and Children Under 2 Years of Age (Section 6.1.1)
for consideration when treating patients with Infantile Spasms. The adverse reactions presented
in Section 6.2 are primarily provided for consideration in use in adults and in children over 2
years of age, but these adverse reactions should also be considered when treating infants and
children under 2 years of age.
Page 7
H.P. Acthar Gel causes the release of endogenous cortisol from the adrenal gland. Therefore all
the adverse effects known to occur with elevated cortisol may occur with H.P. Acthar Gel
administration as well. Common adverse reactions include fluid retention, alteration in glucose
tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and
weight gain.
6.1 Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug, and may not reflect the rates observed in practice.
6.1.1 Adverse Reactions in Infants and Children Under 2 Years of Age
While the types of adverse reactions seen in infants and children under age 2 treated for infantile
spasms are similar to those seen in older patients, their frequency and severity may be different
due to the very young age of the infant, the underlying disorder, the duration of therapy and the
dosage regimen. Below is a summary of adverse reactions specifically tabulated from source data
derived from retrospective chart reviews and clinical trials in children under 2 years of age
treated for infantile spasms. The number of patients in controlled trials at the recommended dose
was too few to provide meaningful incidence rates or to permit a meaningful comparison to the
control groups.
TABLE: Incidence (%) of Treatment Emergent Adverse Events Occurring in 2% of H.P.

Acthar Gel (repository corticotropin injection) Infants and Children under 2 years of Age
Recommended 150 U/m2 qd

75 U/m2 bid n=37 (%)
System Organ Class n=122, (%)
Cardiac disorders
Cardiac Hypertrophy 3 0
Endocrine disorders
Cushingoid 3 22
Gastrointestinal disorders
Constipation 0 5
Diarrhea 3 14
Vomiting 3 5
General disorders and administration site conditions
Irritability 7 19
Pyrexia 5 8
Infections and infestations
Infection 1 20 46
Page 8
Recommended 150 U/m2 qd

75 U/m2 bid n=37 (%)
System Organ Class n=122, (%)
Investigations
Weight gain 1 3
Metabolism and nutrition disorders
Increased appetite 0 5
Decreased appetite 3 3
Nervous system disorders
Convulsion2 12 3
Respiratory, thoracic and mediastinal disorders
Nasal Congestion 1 5
Skin and subcutaneous tissue disorders
Acne 0 14
Rash 0 8
Vascular disorders
Hypertension 11 19
1
Specific infections that occurred at 2% were candidiasis, otitis media, pneumonia and upper respiratory tract
infections.2 In the treatment of Infantile Spasms, other types of seizures/convulsions may occur because some
patients with infantile spasms progress to other forms of seizures (for example, Lennox-Gastaut Syndrome).
Additionally the spasms sometimes mask other seizures and once the spasms resolve after treatment, the other
seizures may become visible.
These adverse reactions may also be seen in adults and children over 2 years of age when treated
for other purposes and with different doses and regimens.
6.2 Postmarketing Experience
The following adverse reactions associated with the use of H.P. Acthar Gel have been identified
from postmarketing experience with H.P. Acthar Gel. Only adverse events that are not listed
above as adverse events reported from retrospective chart reviews and non-sponsor conducted
clinical trials and those not discussed elsewhere in labeling, are listed in this section. Because
the adverse reactions are reported voluntarily from a population of uncertain size, it is not always
possible to estimate their frequency or establish a causal relationship to use with H.P. Acthar
Gel. Events are categorized by system organ class. Unless otherwise noted these adverse events
have been reported in infants, children and adults.
6.2.1 Allergic Reactions
Allergic responses have presented as dizziness, nausea and shock (adults only).
Page 9
6.2.2 Cardiovascular
Necrotizing angitis (adults only) and congestive heart failure.
6.2.3 Dermatologic
Skin thinning (adults only), facial erythema and increased sweating (adults only).
6.2.4 Endocrine
Decreased carbohydrate tolerance (infants only) and hirsutism.
6.2.5 Gastrointestinal
Pancreatitis (adults only), abdominal distention and ulcerative esophagitis.
6.2.6 Metabolic
Hypokalemic alkalosis (infants only).
6.2.7 Musculoskeletal
Muscle weakness and vertebral compression fractures (infants only).
6.2.8 Neurological
Headache (adults only), vertigo (adults only), subdural hematoma, intracranial hemorrhage
(adults only), and reversible brain shrinkage (usually secondary to hypertension) (infants only).
6.3 Possible Additional Steroidogenic Effects
Based on steroidogenic effects of H.P. Acthar Gel certain adverse events may be expected due to
the pharmacological effects of corticosteroids. The adverse events that may occur but have not
been reported for H.P. Acthar Gel are:
6.3.1 Dermatologic
Impaired wound healing, abscess, petechiae and ecchymoses, and suppression of skin test
reactions.
6.3.2 Endocrine
Menstrual irregularities.
Page 10
6.3.3 Metabolic
Negative nitrogen balance due to protein catabolism.
6.3.4 Musculoskeletal
Loss of muscle mass and aseptic necrosis of femoral and humeral heads.
6.3.5 Neurological
Increased intracranial pressure with papilledema, (pseudo-tumor cerebri) usually after treatment,
and subdural effusion.
6.3.6 Ophthalmic
Exophthalmos.
7 DRUG INTERACTIONS
Formal drug-drug interaction studies have not been performed.
H.P. Acthar Gel may accentuate the electrolyte loss associated with diuretic therapy.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Class C: H.P. Acthar Gel has been shown to have an embryocidal effect. There are no
adequate and well-controlled studies in pregnant women. H.P. Acthar Gel should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.3 Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in
human milk and because of the potential for serious adverse reactions in nursing infants from
H.P. Acthar Gel, when treating a nursing mother, a decision should be made whether to
discontinue nursing or to discontinue the drug, considering the risk and benefit to the mother.
8.4 Pediatric Use

H.P. Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and
children less than 2 years of age. Both serious and other adverse reactions in this population are
discussed in Warnings and Adverse Reactions in Infants and Children Under 2 Years of Age
[see Sections 5 and 6.1.1].
The efficacy of H.P. Acthar Gel for the treatment of infantile spasms in infants and children less
than 2 years of age was evaluated in a randomized, single blinded (video EEG interpreter
Page 11
blinded) clinical trial and an additional active control supportive trial [see Clinical Studies (14)].
A responding patient was defined as having both complete cessation of spasms and elimination
of hypsarrhythmia.
Safety in the pediatric population for infantile spasms was evaluated by retrospective chart
reviews and data from non-sponsor conducted clinical trials [see Adverse Reactions (6.1.1)].
While the types of adverse reactions seen in infants and children under 2 years of age treated for
infantile spasms are similar to those seen in older patients, their frequency and severity may be
different due to the very young age of the infant, the underlying disorder, the duration of therapy
and the dosage regimen. Effects on growth are of particular concern [see Warnings and
Precautions (5.12)]. Serious adverse reactions observed in adults may also occur in children
[see Warnings and Precautions (5)].
10 OVERDOSAGE
While chronic exposure to H.P. Acthar Gel at high doses can be associated with a variety of
potential serious adverse effects, it is not expected that a single high dose, or even several large
doses, has the potential for serious adverse effects compared to a standard dose. There have been
no reports of death or acute overdose symptoms from H.P. Acthar Gel in clinical studies or in the
published literature.
The intramuscular route of administration makes it unlikely that an inadvertent acute overdose
will occur. The typical daily dose of H.P. Acthar Gel to treat an infant that has a BSA of 0.4 m2
would be 60 U/day. Using the 1-cc syringe supplied with H.P. Acthar Gel, the maximum amount
that can be injected is 80 U/injection, which is a well-tolerated single dose.
11 DESCRIPTION
H.P. Acthar Gel is a highly puriÞed sterile preparation of the adrenocorticotropic hormone in
16% gelatin to provide a prolonged release after intramuscular or subcutaneous injection. Also
contains 0.5% phenol, not more than 0.1% cysteine (added), sodium hydroxide and/or acetic acid
to adjust pH and water for injection.
ACTH is a 39 amino acid peptide with the following chemical formula:
H- Ser- Tyr- Ser- Met- Glu- His- Phe- Arg- Trp- Gly-
1 2 3 4 5 6 7 8 9 10
Lys- Pro- Val- Gly- Lys- Lys- Arg- Arg- Pro- Val-
11 12 13 14 15 16 17 18 19 20
Lys- Val- Try- Pro- Asp- Gly- Ala- Glu- Asp- Gln-
21 22 23 24 25 26 27 28 29 30
Leu- Ala- Glu- Ala- Phe- Pro- Leu- Glu- Phe- OH
31 32 33 34 35 36 37 38 39
Page 12
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanism of action of H.P. Acthar Gel in the treatment of infantile spasms is unknown.
H.P. Acthar Gel and endogenous ACTH stimulate the adrenal cortex to secrete cortisol,
corticosterone, aldosterone, and a number of weakly androgenic substances. Prolonged
administration of large doses of H.P. Acthar Gel induces hyperplasia and hypertrophy of the
adrenal cortex and continuous high output of cortisol, corticosterone and weak androgens. The
release of endogenous ACTH is under the influence of the nervous system via the regulatory
hormone released from the hypothalamus and by a negative corticosteroid feedback mechanism.
Elevated plasma cortisol suppresses ACTH release.
H.P. Acthar Gel is also reported to bind to melanocortin receptors.
The trophic effects of endogenous ACTH and H.P. Acthar Gel on the adrenal cortex are not well
understood beyond the fact that they appear to be mediated by cyclic AMP.
ACTH rapidly disappears from the circulation following its intravenous administration; in
people, the plasma half-life is about 15 minutes. The pharmacokinetics of H.P. Acthar Gel have
not been adequately characterized.
The maximal effects of a trophic hormone on a target organ are achieved when optimal amounts
of hormone are acting continuously. Thus, a Þxed dose of H.P. Acthar Gel will demonstrate a
linear increase in adrenocortical secretion with increasing duration for the infusion.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Adequate and well-controlled studies have not been done in animals. Human use has not been
associated with an increase in malignant disease. [see Warnings and Precautions (5.14) and Use
in Specific Populations (8.1)].
14 CLINICAL STUDIES
The effectiveness of H.P. Acthar Gel as a treatment for infantile spasms was demonstrated in a
single blinded (video EEG interpreter blinded) clinical trial in which patients were randomized to
receive either a 2 week course of treatment with H.P. Acthar Gel (75 U/m2 intramuscular twice
daily) or prednisone (1 mg/kg by mouth twice daily). The primary outcome was a comparison of
the number of patients in each group who were treatment responders, defined as a patient having
complete suppression of both clinical spasms and hypsarrhythmia on a full sleep cycle video
EEG performed 2 weeks following treatment initiation, rated by an investigator blinded to
treatment. Thirteen of 15 patients (86.7%) responded to Acthar Gel as compared to 4 of 14
Page 13
patients (28.6%) given prednisone (p<0.002). The 2-week treatment was followed by a 2-week
period of taper. Nonresponders to the prednisone treatment were eligible to receive H.P. Acthar
Gel treatment. Seven of 8 patients (87.5%) responded to H.P Acthar Gel after not responding to
prednisone. Similarly, the 2 nonresponder patients from the H.P. Acthar Gel treatment were
eligible to receive treatment with prednisone. One of the 2 patients (50%) responded to the
prednisone treatment after not responding to Acthar.
A supportive single-blind, randomized clinical trial comparing high-dose, long-duration

treatment (150 U/m2 once daily for 3 weeks, n=30) of H.P. Acthar Gel with low-dose, short-
duration treatment (20 U once daily for 2 weeks, n=29) for the treatment of infantile spasms was
also evaluated in infants and children less than 2 years of age. Nonresponders (defined as in the
previously described study) in the low-dose group received a dose escalation at 2 weeks to 30 U
once daily. Nominal statistical superiority of the high dose treatment, as compared to the low
dose treatment, was observed for cessation of spasms but not for the resolution of
hypsarrhythmia.
16 HOW SUPPLIED / STORAGE AND HANDLING
H.P. Acthar Gel (repository corticotropin injection) is supplied as 5 mL multi-dose vial (63004-
7731-1) containing 80 USP Units per mL. H.P. Acthar Gel (repository corticotropin injection)
should be warmed to room temperature before using. Do not over pressurize the vial prior to
withdrawing the product.
Store H.P. Acthar Gel (repository corticotropin injection) under refrigeration between 2°-8°C
(36°-46°F). Product is stable for the period indicated on the label when stored under the
conditions described.
17 PATIENT COUNSELING INFORMATION
Caretakers of patients with infantile spasms should be informed of the availability of a

Medication Guide, and they should be instructed to read the Medication Guide prior to
administering H.P Acthar Gel. Patients should be instructed to take H.P. Acthar Gel only as
prescribed. They should not stop treatment suddenly unless instructed by their physician to do so.
Patients, their caregivers and families should be advised as to the importance of the need for
careful monitoring while on and during titration from H.P. Acthar Gel treatment and the
importance of not missing and scheduled doctor’s appointments.
Patients, their caregivers and families should be advised that if the patient develops an infection
or fever they should contact their physician. They should be educated that a fever may not
necessarily be present during infection. The patient should also try to limit contact with other
people with infections to minimize the risk of infection while taking H.P. Acthar Gel. [see
Warnings and Precautions (5.1) and Adverse Reactions (6.1.1)]
Patients, their caregivers and families should be advised that if the patient experiences an
increase in blood pressure they should contact their physician. [see Warnings and Precautions
(5.3) and Adverse Reactions (6.1.1)]
Page 14
Patients, their caregivers and families should be advised that if the patient or the caregiver
notices blood or a change in color of the patient’s stool they should contact their physician. [see
Warnings and Precautions (5.6)].
Caregivers and families of infants and children treated with H.P. Acthar Gel should be informed
that the patient may show signs of irritability and sleep disturbances. These effects are reversible
once H.P. Acthar Gel therapy is stopped. [see Warnings and Precautions (5.7) and Adverse
Reactions (6.1.1)].
Patients, their caregivers and families should be advised that changes in appetite, most often
leading to weight gain, are seen with H.P. Acthar Gel therapy, becoming more frequent as the
dose or treatment period increases. These effects are reversible once H.P. Acthar Gel therapy is
stopped. [see Warnings and Precautions (5.12) and Adverse Reactions (6.1.1].
Patients, their caregivers and families should be advised that the patient may be monitored for
signs of adrenal insufficiency such as weakness, fatigue, lethargy, anorexia, weight loss,
hypotension, abdominal pain or hyperpigmentation (adults only) after treatment has stopped.
Since the recovery of the adrenal gland varies from days to months, patients may need to be
protected from the stress of trauma or surgery by the use of corticosteroids during the period of
stress. [see Warnings and Precautions (5.2)].
Patients should be advised not to be vaccinated with live or live attenuated vaccines during
treatment with H.P. Acthar Gel. Additionally, other immunization procedures in patients or in
family members who will be in contact with the patient should be undertaken with caution while
the patient is taking H.P. Acthar Gel. [see Warnings and Precautions (5.4)].
Patients, their caregivers and families should be advised that prolonged use of H.P. Acthar Gel in
children may result in Cushing’s syndrome and associated adverse reactions, may inhibit skeletal
growth, and may cause osteoporosis and decreased bone density. If prolonged use is necessary,
H.P. Acthar Gel should be given intermittently along with careful observation. [see Warnings
and Precautions (5.2), (5.12), and (5.13) and Adverse Reactions (6.1.1)].
Patients, their caregivers and families should be informed that H.P. Acthar may mask symptoms
of other diseases/disorders without altering the course of the other disease/disorder. The patient
will need to be monitored carefully during and for a period following discontinuation of therapy
for signs of infection, abnormal cardiac function, hypertension, hyperglycemia, change in body
weight, and fecal blood loss. [see Warnings and Precautions (5.5)].
In the treatment of Infantile Spasms, other types of seizures may occur because some patients
with infantile spasms progress to other forms of seizures (for example, Lennox-Gastaut
Syndrome). Additionally the spasms sometimes mask other seizures and once the spasms
resolve after treatment with H.P. Acthar gel, the other seizures may become visible. Parents and
caregivers should inform their physician of any new onset of seizures so that appropriate
management can then be instituted. [see Adverse Reactions (6.1.1)].
Page 15
H.P. Acthar® Gel

(repository corticotropin injection)
Manufactured for Questcor Pharmaceuticals, Inc.

3260 Whipple Road
Union City, CA 94587 USA
phone (800) 411-3065
(510) 400-0700
fax (510) 400-0799
PL065/Rev. 02 No. 1350

Issued: 10/2010
Page 16

RESEARCH
APPLICATION NUMBER:
022432Orig1s000
SUMMARY REVIEW

MEMORANDUM
DATE: April 5, 2010
FROM: Russell Katz, M.D.

Director
Division of Neurology Products/HFD-120
TO: File, NDA 22-432
SUBJECT: Action Memo for NDA 22-432, for the use of H.P. Acthar Gel
(repository corticotrophin injection) in the treatment of Infantile Spasms (IS)
NDA 8-372/S-039, for the use of H.P. Acthar Gel (repository corticotrophin
injection) in the treatment of Infantile Spasms (IS), was submitted by Questcor
Pharmaceuticals, Inc., on 6/16/06 to the Division of Metabolism and
Endocrinology Products. Though not approved for the treatment of IS (Acthar
Gel was approved in 1952 and has been approved subsequently for numerous
indications), Acthar Gel has been the treatment of choice for IS for many years.
The supplement consisted of a meta-analysis of published clinical trials, and the
Agency issued a Not Approvable (NA) letter on 5/10/07, citing numerous
deficiencies, including the lack of a bridge between this specific product and the
products used in the various published studies.
Subsequent to the NA letter, the company and the Division of Neurology

Products (DNP) entered into discussions about how this indication could be
pursued. The sponsor had not conducted any trials of its own, and, in brief, we
determined that the sponsor should attempt to obtain primary data for several
trials published in the archival literature that, potentially, could provide substantial
evidence of effectiveness for Acthar Gel for IS. The sponsor obtained data from
three of these studies, as well as safety data from various sources. With these
data, the sponsor has submitted a response to the CR letter on 12/10/09. This
submission was considered a Type 6 NDA, and was given the new number, NDA
22-432.
The application has been reviewed by Dr. Philip Sheridan, medical officer, Drs.
Quynh-Van Tran and Sharon Watson, Division of Drug Marketing, Advertising,
and Communications, Mary Dempsey and Sharon Mills, Division of Risk
Management, Dr. Jialu Zhang, statistician, Dr. Ju-Ping Lai, Office of Clinical
Pharmacology, Dr. Martha Heimann, chemist, and Dr. Norman Hershkowitz,
neurology team leader. In addition, this application was the subject of a meeting
of the Peripheral and Central Nervous Systems Advisory Committee (PCNS AC)
on 5/6/10.
The review team recommends that the application be approved. In this memo, I
1
will briefly describe the relevant safety and effectiveness data, and offer the
rationale for the division’s action.
Effectiveness
As noted above, the sponsor has submitted data from three controlled studies
that they believe provide substantial evidence of effectiveness for Acthar Gel as
a treatment for IS.
Study 01
This was a single blind, parallel group study in which patients with IS were
randomized to receive either ACTH 150 Units/meter2/day given as a 75
Unit/meter2 dose twice a day or prednisone 2 mg/kg/day (in a 1 mg/kg BID
regimen) for 2 weeks. Each treatment was tapered to 0 over the subsequent 2
weeks. This study was performed by Dr. Baram in 1996.
The primary outcome was based on a video EEG performed at 2 weeks; the
video EEG was to be for 24 hours, but in all cases was to be at least 4 hours (to
include a full sleep-wake cycle). An Overall Success was defined as a patient
who experienced no spasms and elimination of hypsarrythmia, the characteristic
EEG pattern in these patients. The investigator did not pre-specify primary or
secondary outcomes; the outcome described here was chosen by the sponsor
and represents the widely accepted definition of clinical success by the expert
community. Seizure frequency was also monitored and recorded by the patient’s
caregiver during the 2 weeks of the study.
The treating physician was not blinded to treatment assignment, but the video-
EEGs were read by a blinded rater.
Results
A total of 15 patients were randomized to receive ACTH, and 14 were

randomized to receive prednisone. About 86% of each group had symptomatic
IS and about 14% had cryptogenic IS. The mean age was about 5-7 months old.
A total of 13/15 (87%) of ACTH patients were classified as an Overall Success

compared to 4/14 (29%) of prednisone patients (p=0.0025, according to Dr.
Zhang). An examination of the proportion of patients who met criteria for an
EEG response revealed 13/15 (87%) ACTH patients compared to 4/14 (29%)
prednisone patients (p=0.0025), and 14/15 (93%) of ACTH patients and 4/14
(29%) of prednisone patients met clinical success criteria (p=0.0005).
2
According to the sponsor, of the 13 patients who originally responded to ACTH, 2

relapsed. Of the 11 remaining infants who had responded, 3 had no recurrence
(though they were only followed for a month), and 8 were reported to have had
no recurrences, after having been followed for at least 6 months (mean 17
months). Presumably, recurrences were based on caretaker reports.
Study 05
This study compared a high dose of ACTH to a low dose.
In this study (performed by Dr. Hrachovy in 1994), patients received ACTH at

150 Units/meter2 (HD) given once a day or ACTH 20 Units/day (LD), both given
IM. The HD was given for 3 weeks, followed by a 9 week taper, and the LD was
given for 2 weeks followed by a 2 week taper.
As in Study 01, the primary outcome was complete cessation of spasms and
complete resolution of the EEG pattern on video EEG. In the HD group, the
video EEG was performed at Week 12, after the taper period. In the LD group,
the video EEG was performed at the end of the initial 2 week treatment period. If
patients did not respond in the HD group, they were treated with prednisone, 2
mg/kg/day for 4-6 weeks, and then followed in a “routine clinical manner”. If
patients in the LD group did not respond at 2 weeks, their ACTH dose was
increased to 30 Units/day for an additional 4 weeks, and then tapered over a 2
week period.
Results
A total of 59 patients were randomized to treatment (the current sponsor was

able to obtain original data for 58).
A total of 30 patients were randomized to HD and 29 to LD. Four (4) HD patients

did not complete the study, compared to 5 LD patients. The sponsor analyzed
the following populations:
Modified intent-to-treat (mITT): Patients who received at least one dose of drug
and had adequate data to assess the overall response.
Intent-to-treat: All patients randomized.
Spasms Population: All patients with “sufficient” data to evaluate the complete
spasm response. Presumably, “sufficient” data meant any data collected on this
outcome; there need not have been EEG data to be included in this population.
Completed Patients: All patients who completed the study in the opinion of the
investigator
3
The following outcomes were assessed:
Overall Response: Any patient who had complete cessation of spasms and
resolution of the EEG at any time during the study
Spasm Control Response: Any patient who had completed cessation of spasms
at any time during the study. This included all patients with cessation of spasms
during treatment or follow-up as assessed by clinical observation or parental
report.
Hypsarrhythmic EEG Pattern Response: Any patient who had resolution of the
EEG pattern at any time during the study.
The median age was 6.7 months old.
The following table displays the results of the various outcomes in the several
populations.
Pop. Treatment Overall Response Spasm Control EEG Response
mITT HD 15/24 (63%) 19/24 (79%) 16/24 (67%)

LD 13/27 (48%) 14/27 (52% 14/27 (52%)
P-value 0.28 0.03 0.27
ITT HD 15/30 (50%) 23/30 (77%) 16/30 (53%)

LD 15/29 (52%) 16/29 (55%) 13/29 (45%)
P-value 0.94 0.07 0.52
Spasm HD 15/28 (54%) 23/28 (82%) 16/28 (57%)

LD 13/27 (48%) 14/27 (52%) 14/27 (52%)
P-value 0.64 0.013 0.66
Completed HD 15/26 (58%) 21/26 (81%) 16/26 (62%)

LD 13/24 (54%) 14/24 (58%) 14/24 (58%)
P-value 0.82 0.08 0.83
4
A total of 3/15 (20%) of HD and 2/13 (15%) of LD patients relapsed (these are
patients who met the Overall response criteria at some point, but later were
noted to have failed these criteria, based on video EEG verification performed
based on caretaker reports of recurrent spasms).
Study 04
This was a double-blind, randomized trial comparing ACTH and prednisone. The
study was performed by Dr. Hrachovy in 1983.
In this study, patients were randomized to receive ACTH 20 Units/day IM and

prednisone placebo or ACTH placebo and prednisone 2 mg/kg/day PO for 2
weeks.
If the patient responded to the drug (same responder definition as in the previous
studies) at 2 weeks, the drug was tapered over 1-2 weeks. These patients were
monitored at 2 and 6 weeks after the end of the taper period. If the patient did
not respond in the first 2 weeks, they continued the original treatment for 4
weeks. If they did not respond during this 4 week period they were switched to
the other drug after a one week washout. If they did respond after the 4 week
period, they had drug tapered over 1-2 weeks.
Results
A total of 24 patients were randomized, 12 to each group.
The median age was 8.2 months. Similar outcomes (Overall Response, Spasm
Response, and EEG Response) were analyzed.
The following table displays the results for the initial phase of the study,
presumably meaning the first 2 weeks.
Treatment Overall Spasm EEG
ACTH 5/12 (42%) 5/12 (42%) 9/12 (75%)

Prednisone 4/12 (33%) 4/12 (33%) 4/12 (33%)
P-value 0.99 0.99 0.99

(for the Overall
Variable)
5
Safety
The sponsor obtained analyzable safety data from 3 sources:
1) A retrospective chart review performed by Partikian and Mitchell (N=84).
2) Another retrospective chart review from 4 clinical sites (N=178).
3) Safety data from Study 05 (N=57).
Together, these sources provide safety data from a total of 319 patients.
Drs. Partikian and Mitchell reviewed charts from all patients treated for IS (in
patient and out-patient) at the Children’s Hospital of Los Angeles (CHLA)
between January 1996 and August 2006. These patients were treated with a
standard protocol: ACTH 150 Units/meter2/day (given as a BID regimen) for 1-2
weeks, followed by a taper of 4-5 weeks.
Patients were evaluated at all visits from 1-3 weeks after treatment initiation, at 4-
8 weeks after treatment initiation, and at 3 months or more after treatment
initiation. Assessments included adverse events reported by caregivers, weight
and blood pressure, medication changes and the development of new seizure
types.
As noted above, a total of 84 patients received initial treatment of ACTH in this

cohort.
As noted by Dr. Sheridan, common adverse events included irritability, increased

appetite, infections, and difficulty sleeping. These were mostly reported during
the first follow-up visit, and decreased as drug was tapered.
Serious adverse events included seizures (not known if this represented new
seizure types or exacerbation of IS), infections, and hospitalizations.
Mean changes in weight of 11%, 18%, and 26% were seen at the first, second,
and third follow-ups, respectively. As Dr. Sheridan notes, it is difficult to know if
this weight gain was related to ACTH or growth of the patient over time.
At baseline, 18% of patients had at least one significant increase in systolic blood
pressure (SBP), compared to 33% at the first follow-up. The percent of patients
who had at least one significant increase in SBP was 21% and 4% at the second
and third visits, respectively.
At baseline, 14% of patients had at least one significant increase in diastolic

blood pressure (DBP), compared to 24%, 11%, and 5% at the first, second, and
third follow-up, respectively.
6
The second study involved retrospective chart review at 4 clinical centers,

covering a period from January 2000 to May 2008. These patients received
ACTH in a range of 135-160 Units/meter2/day in a BID regimen (Questcor
Recommended Dose); > 80 Units/meter2/day but outside the recommended
range, or within the recommended range, but once a day (Other high dose); or
<80 Units/meter2/day (Low dose). Adverse events were assessed at baseline,
subsequent visits, and a final visit (any visit at least 2 weeks after the last dose of
ACTH).
As noted above, data on 178 patients was collected.
A total of 59% of patients had at least one adverse event. In the Recommended
and Other high dose groups, 62% and 64%, respectively, had at least one AE
compared to a rate of 30% in the Low dose group. The most common AEs in the
Recommended dose group were hypertension (18%), irritability (12%) and left
ventricular hypertrophy (8%). In the Other high dose group, Cushingoid
appearance (13%) and increased appetite (11%) were also seen.
A total of 20 patients had at least one Serious AE (SAE). A total of 10 patients

had an SAE of hypertension (most recovered with specific treatment of drug
discontinuation), 5 patients had infections (mostly pneumonia), and there was
one case each of hepatomegaly, fever, respiratory failure, diarrhea, reflux,
convulsion, hypertrophic cardiomyopathy, and renal failure.
There was one death, due to aspiration pneumonia.
Other common adverse events included upper gastrointestinal irritability,

infections, drowsiness, sleep difficulties, fever, and increased secretions.
There were reversible blood pressure increases that returned to baseline with
discontinuation of treatment.
Study 05
This was the study that compared the 150 Units/meter2/day given as a single IM
dose for 3 weeks followed by a 9 week taper compared to a 2 week dose of 20
Units/day or additional treatment for 4 weeks with 30 Units/day in non-
responders.
There were a total of 57 patients in this study; 93% in the high dose and 86% of
the patients in the low dose had at least one adverse event. The most common
adverse events and clinical findings are given below:
7
Event High dose Low dose
Candidiasis 36% 38%

Cushingoid 29% 21%
Otitis media 25% 21%
Irritability 14% 17%
Fever 18% 14%
Acne 21% 10%
Diarrhea 21% 7%
Increased BP 18% 7%
Vomiting 11% 10%
Drowsiness 18% 10%
Sleep difficulties 46% 35%
Increased appetite 50% 24%
Decreased appetite 43% 31%
One child, a 3 month old boy with multiple medical problems, developed
pulmonary edema, respiratory failure, and died of cardiac arrest after several
weeks of treatment (20 Units-40 Units/day).
Serious AEs in the high dose group (N=4 patients) were dehydration, pneumonia,
increased blood pressure, decreased appetite, and skin discoloration.
Four (4) patients (1 high dose, 3 low dose) discontinued treatment due to
adverse events. These events included high blood pressure, skin discoloration,
fever, and otitis media.
Across all 319 patients, 134 were dosed with the Recommended Dose, 133 with
the Other High Dose, and 52 with the Low Dose. Across these dose groups, the
adverse event pattern reflects, of course, the types and incidences of events
seen in the individual studies (see Dr. Sheridan’s review, page 42, which reprints
the sponsor’s table of the common AEs across doses); there is no obvious dose
response for any given adverse event. The most common AEs are infections,
irritability, Cushingoid appearance, and hypertension.
Post-Marketing reports
The sponsor has presented reports of adverse events from the spontaneous
reporting system from 1952 to June 2009. The sponsor identified AEs in patients
treated for IS or in infants between 1-24 months. Of course, we do not have
information on how many patients have been treated for this indication or in this
age group.
There were a total of 76 reports meeting these criteria, with 33 considered

serious. Dr. Sheridan describes these events; they are mostly similar to those
8
events already described.
Advisory Committee Meeting
As noted above, this application was discussed at a meeting of the PCNS AC on

5/6/10.
The Committee concluded by a vote of 22 Yes and 1 No that the sponsor had
submitted substantial evidence of effectiveness for Acthar gel as a treatment for
Infantile Spasms, although they agreed that there was no evidence that the
treatment prevented other seizure types or other clinical sequelae.
They also voted (16 Yes, 7 No) that the effect was shown to have been
“sustained”, although there was considerable sentiment for the view that the
specific duration of effect was not well characterized.
When asked if they felt that the adverse effects were predictable, easily
recognized, manageable, and reversible upon discontinuation, a slight majority
voted no (10 Yes, 12 No); however, they voted overwhelmingly (20 Yes, 1 No, 2
Abstain) that the sponsor had submitted sufficient evidence of safety to support
approval.
Discussion
The sponsor has submitted data from three controlled trials that they believe
provide substantial evidence of effectiveness for Acthar Gel as a treatment for
patients with IS. In addition, they have provided safety data from 319 patients
treated with Acthar Gel, under various treatment conditions, with 134 treated at
the recommended dose (75 Units/meter2/day BID), and another 135 treated at
doses close to that, but given once a day.
The data that the sponsor has provided differ considerably from that typically
submitted in an NDA. As noted earlier, none of the studies were commissioned
or conducted by the sponsor, and detailed protocols, and, in particular, detailed
statistical plans for the analyses of these studies, did not exist. The sponsor has
presented the results of these studies in a uniform way; that is, the primary
outcome in each trial (Overall Response) was taken to be the same, and
mirrored the expectations of the expert community regarding an effective
treatment for IS; namely, complete cessation of spasms and normalization of the
typical EEG pattern. The sponsor presents one of the studies, Study 01, as the
“pivotal” study, one of the studies, Study 05, as a “supportive” study, and Study
04 as an “additional” study.
Although Study 01 did not, apparently, have a detailed statistical plan, the results
showed a clear statistically significant superiority to prednisone not only on the
overall response, but on the individual components (EEG and spasms). This
9
result occurred with a total sample size of only 29 patients. This result has been
confirmed by the Agency’s statistician, based on her review of the primary data
that the sponsor obtained from the investigator.
The results of Study 05 are more difficult to interpret. There were no differences
between the Overall Response Rates in the high and low dose groups (and the
treatment paradigms were different in the two groups), and the only (nominally)
statistically significant differences were seen in the Spasm Control variable, with
nominal p-values varying between 0.01 and 0.08, depending upon the population
analyzed.
The third study, Study 04, was of a complicated design, making interpretation
difficult. In any event, no differences were seen between the two treatment
groups (ACTH and prednisone).
Study 01 lends itself to a fairly straightforward interpretation, but this seems not
to be the case for the other two studies. Dr. Sheridan does point out that the
response rates, though basically not different between the treatment groups in
these 2 latter studies, do seem to be greater than published estimates of the
placebo response rates (he cites a placebo response rate of about 5% for a
study by Appleton, et al., a study previously relied upon, to some extent, by the
Agency when we considered the approval of Sabril for IS). However, it is fair to
say that the interpretation of an active control trial that does not demonstrate a
difference between treatments (the case for these latter two studies) is
problematic, at best.
The Food, Drug, and Cosmetic Act requires that the Agency find that a sponsor
has submitted substantial evidence of effectiveness (in addition to adequate
safety) in order to approve a New Drug Application. Substantial evidence of
effectiveness is defined as data from adequate and well-controlled clinical
investigations (typically interpreted to mean more than one such trial) or data
from a single such trial and confirmatory evidence (neither the circumstances
under which this latter standard should apply nor what constitutes “confirmatory
evidence” is defined in the Act). As a general matter, this latter standard is
applied in the setting of a serious or life-threatening condition in which a second
trial is essentially impossible to perform (for any of a number of reasons), and a
wide variety of evidence can be considered “confirmatory” (e.g., a very low p-
value, multiple sub-groups and or study sites strongly positive, multiple outcomes
strongly positive, etc.). However, whether to apply this latter standard to any
given data set, and what constitutes confirmatory evidence, are issues that need
to be considered on a case by case basis.
As described above, the PCNS AC clearly concluded that the sponsor had
provided substantial evidence of effectiveness. The review team agrees, as do I.
10
I believe that the sponsor has met the statutory standard of substantial evidence
of effectiveness based on having submitted a single adequate and well-controlled
trial and confirmatory evidence. Study 01, though small, produced clear and
convincing evidence of effectiveness on an outcome widely considered by the
community of experts to be a clinically important measure of the utility of a
treatment of IS (indeed, one could consider such a strong finding of effectiveness
from such a small study as further evidence of the robustness of the result). The
fact that, in this study, ACTH was clearly superior to an “active” control (albeit,
admittedly, one not known from previous trials to be effective), and that one
component (EEG) of the primary outcome was an objective measure of spasm
control, further support the conclusion. The additional studies, though not being
interpretable by themselves as being “positive”, do, in my view, suggest an effect
of the drug (especially Study 04, which, as noted by Dr. Sheridan, produced
treatment responses far greater than those seen in patients treated with placebo
in at least one other study).
With regard to the question of effectiveness, there is another important question

that needs to be addressed.
ACTH has been the standard of care for patients with IS for many years. The
typical treatment course consists of a short (e.g., two weeks) period of treatment,
followed by a tapering period. If patients experience a recurrence of spasms,
another short course is often given. It has long been considered that such short
courses are all that is necessary to control the spasms after the treatment is
discontinued. The controlled trial data establishing effectiveness did not
systematically address the persistence (i.e., duration) of effectiveness of a single
course of therapy; follow-up of patients in Study 01 suggested a lack of
recurrence of spasms out to several months in at least some patients (they
assert that 2/13 patients who originally responded had recurrence of spasms),
but the duration of follow-up was very variable, and recurrences were not
systematically looked for. Further, the studies did not examine the effects of a
second treatment course. The sponsor has submitted literature to attempt to
address the question of whether or not a second treatment course is useful in
treating recurrences, but these data do not provide useful guidance about
treatment of recurrences. The review team agrees that labeling should be silent
on the utility of treating recurrences.
The sponsor has also submitted safety data of the sort that is not typically
contained in an NDA. Specifically, a typical NDA contains complete reports of a
cohort of patients prospectively followed forward in time. This permits a
complete (or near complete) accounting of the experience of all patients started
on a particular treatment (e.g., how many patients discontinued, what all of the
adverse events were, etc.). That is not the case here.
As described, much of the data presented has been obtained from a

retrospective review of charts of patients treated with ACTH at various institutions
11
over the course of several years. The data were not collected for the purpose of
establishing the safety of the treatment, as would be the case in typical company-
sponsored drug trials. However, the adverse events described are, for the most
part, those known to be associated with treatment with ACTH, and there were no
unexpected or significant adverse events that would, in my view, preclude
approval. As noted above, the AC overwhelmingly agreed. Several committee
members did, however, note the potential seriousness of adrenal insufficiency,
and the necessity for caregivers to be made aware of the clinical presentation of
this potential event should it occur during discontinuation of the drug (the
committee also felt that caregivers should be made aware that discontinuing
treatment abruptly carries significant risk and danger).
As noted above, H.P. Acthar Gel has been approved for many years, and current
approved labeling includes numerous (>50) approved indications. With this
action, labeling will be brought into conformance with current labeling
requirements, and the sponsor has agreed to remove numerous of the previously
included indications.
The sponsor has also proposed a Risk Evaluation and Mitigation Strategy
(REMS), consisting of a Medication Guide. The Medication Guide will discuss
only the IS indication, because infants are particularly at risk for several serious
adverse events, and IS will be the only approved indication for infants.
For the reasons given above, then, I will issue with attached Approval letter, with
attached labeling to which the sponsor has agreed.
Russell Katz, M.D.
12
Appears This Way on Original
13
---------------------------------------------------------------------------------------------------------
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
RUSSELL G KATZ
10/15/2010


RESEARCH
APPLICATION NUMBER:
022432Orig1s000
CROSS DISCIPLINE TEAM LEADER REVIEW

Cross Discipline Team Leader Review
Cross-Discipline Team Leader Review

Date 9/27/10
From Norman Hershkowitz, MD, PhD
Subject Cross-Discipline Team Leader Review
NDA/BLA # 22432 (000)
Supplement#
Applicant Questcor Pharmaceuticals
Date of Submission 9/30/10
PDUFA Goal Date 9/11/10
Proprietary Name / H.P. Acthar Gel (repository corticotropin injection)

Established (USAN) names
Dosage forms / Strength Injection Solution: 5 mL multi-dose vial containing 80
(b) (4)
USP Units per mL
Proposed Indication(s) 1. Infantile Spasms
Recommended: (Approval vs. Approvable vs. Not Approvable vs.
Complete Response)
1. Introduction
Acthar gel was originally approved in 1952, prior to the period of time when the FDA was
required to demonstrate substantial benefit. Later DESI review permitted a number of
indications including use for adrenalcorticol function testing and the treatment of a number of
disorders for which steroids were also indicted (e.g. rheumatic disorders, collagen disease,
dermatologic disorders, etc. The administrative responsibility for this NDA is that of DMEP.
However, a later efficacy supplements (1979), adding the treatment of acute exacerbation of
multiple sclerosis, was reviewed by review by this division (DNDP).
The present application’s history begins with an efficacy supplement submitted for review to
DMEP in 2006 for the treatment of Infantile Spasms (IS). This application was reviewed by
(b) (4)
that division but was not approved
. Following the complete response a
decision was made to transfer the supplement to DNP. It is noteworthy that there has been no
industry Sponsored planned perspective controlled trials. The evidence for efficacy is based
upon published trials performed by independent investigators. A type C meeting was held
with the Sponsor and DNP on 11/5/07, regarding their response to the CR letter, and the
following recommendations were made: 1) source efficacy data should be provided from the 5
published, randomized control studies where Acthar was evaluated for the treatment of
patients with IS along with an independent analyses of this data (Askalan et al. 20031, Baram
1
Askalan R, Mackay M, Brian J, Otsubo H, McDermott C, Bryson S, et al. Prospective preliminary analysis of
the development of autism and epilepsy in children with infantile spasms. J Child Neurol. 2003 Mar;18(3):165-
170.
Page 1 of 12 1
1996 et al.2; Dreifuss et al. 19863; Hrachovy et al. 19944; Hrachovy et al. 19835); 2) source
safety data should be obtained and analyzed from hospitals that had treated patients in the last
10 years; 3) enough safety data on IS patients treated with Acthar should be provided to define
the safety profile and to assert that the benefit outweighs the risk. Subsequent to this the
Sponsor attempted to obtain data from all 5 studies, but because studies were performed some
time ago, data were not available for 2 studies. Data were obtained for the Hrachovy et al.
(1983) Hrachovy et al. (1994) Baram et al. (1996) and studies, the latter study likely being the
most important one.
2. Background
Infantile Spasms (IS) is a syndrome that develops in children younger then 2 years old and is
associated with frequent recurrent seizures (or spasms) and marked EEG abnormalities. The
disease is frequently associated with delayed development, permanent cognitive impairment
and the occurrence of other seizure types upon maturation. Death may also occurs. The long
term prognosis of infantile spasms is bleak. Fewer than 5% of patients are
neurodevelopmentally normal. While there are no definitive data that treatment of the spasms
will improve long term neurologic prognosis, there are limited data suggesting that this is the
case. The prevalence of IS is approximately 0.25 and 0.42 per 1000 live births per year. There
is presently only one drug labeled for the treatment of IS, Sabril, which was recently approved.
A number of other drugs, most notable Acthar Gel and Valproic Acid are used off label.
Indeed Acthar Gel has been used for decades and is generally considered, by the pediatric
Neurology community, as the treatment of choice.
3. CMC/Device
Dr. Heimann, the chemistry reviewer, recommended approval without post-approval
commitments or requirements.
4. Nonclinical Pharmacology/Toxicology
No new information.
2
Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH)
versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996;97:375-379.
3
Dreifuss F, Farwell J, Holmes G, Joseph C, Lockman L, Madsen JA, et al. Infantile spasms. Comparative trial of
nitrazepam and corticotropin. Arch Neurol. 1986 Nov;43(11):1107-1110.
4
Hrachovy RA, Frost JD Jr, Glaze DG. High-dose, long-duration versus low-dose, short duration corticotropin
therapy for infantile spasms. J Pediatr. 1994 May;124(5 Pt 1):803- 806.
5
Hrachovy RA, Frost JD, Jr, Kellaway P, Zion TE. Double-blind study of ACTH vs prednisone therapy in
infantile spasms. J Pediatr. 1983;103(4):641-655.
Page 2 of 12 2
5. Clinical Pharmacology/Biopharmaceutics
6.
The Sposnor has provided additional new information on the PK of Acthar Gel in pateints with
IS. This informtion has been included in the label as per the clinical pharmacology labeling
review.
7. Clinical Microbiology
The product is already marketed and there is no new additional comments.
8. Clinical/Statistical- Efficacy
Philip Sheridan, MD (Medical reviewer) and Jialu Zang, PhD (Statistical reviewer) performed
the efficacy review.
Studies provided by the Sponsor to support “substantial evidence” for efficacy consisted of
published investigative reports of Baram et al. (1996; also refered to as study 01), Hrachovy et
al. and (1983; also referred to as study 04) Hrachovy et al. (1994; also refered to as study 05),
previously noted. Data from the publications as well as original data was obtained by the
Sponsor to prepare study reports provided to the FDA. The Sponsor considers 01 a pivotal
trial and 05 as supportive. An additional study, 04, is also described in this application.
Study 01
This was a prospective, randomized, single-blind (blinded to the video-EEG reader), controlled
study that compared intramuscular Acthar 150 U/m2/day (divided as 75 U/m2/bid)
administered for a two week period to oral prednisone at 2 mg/kg/day (divided as 1 mg/kg/bid)
admistered for a 2 week period. Both cohorts 2 week treatment period was followed by a 2
week taper on the same medications. After the 2-week period a video-EEG was performed.
The recording was to include at least one sleep wake cycle. The goal was to obtain a 24 hour
recording, but some were as short as 4 hours. The primary endpoint required cessation of both
the EEG and clinical expression of this disorder: i.e. both hypsarrhythmia and spasms,
respectively. A seizure diary was also kept by the family/guardian. Dr Sheridan makes two
important comments regarding the study design. First he notes that while this is a single blind
study, it may be considered tantamount to a double blind study as it is unlikely that the use of
intramuscular versus oral treatment would alter EEG and clinical behavior of the infant.
Second, he notes that the primary endpoint is considered the “gold standard’ for studies in IS.
I agree with both points.
A total of 29 patients were randomized. There was a similar percent of symptomatic and
cryptogenic patients in both treatment groups (e.g. 14.3 % and 13.3 % cryptogenic in the
Page 3 of 12 3
prednisone and Acthar Gel groups, respectively). This is particularly important considering
the difference in prognosis of these two groups. The Acthar Gel group had a higher number of
female patients (73.4% vs. 42.9%). Prednisone treated patients tended to me slightly older
then those of Acthar gel patients (a median of 7.0 vs. 5.0 months).
The following table presents the data from the study. The primary outcome of the absence of
hypsarrhythmia and clinical spasm during the video EEG is denoted by “Overall Control.”
Data on clinical and EEG outcomes are also presented in the two additional columns. Data in
other studies (see below) are presented in a similar fashion.
Treatment Overall Spasm Hypsarrhythmia

Control Control Control
Acthar Gel 13/15 (87%) 14/15 (93%) 13/15 (87%)
Prednisone 4/14 (28.6%) 4/14 (28.6%) 4/14 (29%)
p-value 0.015 0.0003 0.0015
Analysis of the primary endpoint indicated that Acthar Gel was superior to prednisone. Thus,
the response rate for Acthar Gel was 86.7% (13/15) as compared to that of prednisone at
28.6% (4/14,). This was statistically significant, with a p-value of 0.0015 (Chi-square).
Adjustment for age still resulted in a significant difference. Examination of spasm alone or
hypsarrhythmia alone revealed statistical superiority of Acthar Gel to prednisone. As noted
above there was some degree of disparity between male and female populations in both
treatment groups . The statistical reviewer noted because of the small number of patients in
the overall study that it was hard to determine how sex factored into the final results.
The FDA statistical analysis reproduced that of the Sponsor. In addition the statistical
reviewer noted that it would be more appropriate to use a Fisher’s exact test. This analysis
was performed and was found to reveal a similar similar significant outcome.
Boutt The Medical and Statistical Reviewer conclude that this trial demonstrates superiority of
Acthar Gel to prednisone regimen. I agree.
Study 05
This prospective, randomized, single-blind study compared high-dose, long-duration to low-

dose short-duration treatment with Acthar Gel. The Acthar high-dose regimen consisted of
Acthar given at a dose of 150 U/m2/day as a single (150 U/m2/QD) intramuscular dose for 3
weeks followed by a 9-week taper; the Acthar low-dose regimen consisted of Acthar 20 U/day
(20 U/QD) as a single intramuscular dose for 2 weeks followed by a 2-week taper in
responders or a dose escalation to 30 U/QD IM in non-responders.
The primary endpoint was complete cessation of both spasms and hypsarrhythmia (overall) at
the time of measurement. Secondary endpoints include cessation of hypsarrhythmia alone or
cessation of spasm at any time during the study. The time of measurement was unbalanced in
Page 4 of 12 4
that in the high dose group this was performed following the complete titration from drug (12
weeks after its initiation) and in the low dose group this was performed 2 weeks after the
initial treatment was initiated. A total of 30 patients were randomized to high dose and 29 to
low dose groups.
Two populations of analysis were identified for analysis: 1) the ITT population (all
randomized patients, n=59); in this case a worst case scenario was assumed for patients with
missing data (n=9), 2) an mITT population (all patients randomized for which there was at
least one single post treatment measurement of efficacy, n=51).
Except for the low dose group having disproportionally percent low percent of females (29.6%
vs. 50%) the demographics were balanced across treatment groups. Of note, similar percent of
cryptogenic and symptomatic patients were studied in each treatment group.
The following table presents primary and secondary endpoints in the two principal analyzed
populations. None of the primary endpoint analyses showed statistical significant difference
between high and low dose groups, although there was a nominal trend for a greater response
the mITT population. Secondary endpoints also appeared to show a similar trend of greater
control in the high dose groups. Other sub-divided populations were examined which showed
a similar trend. As per the statistics reviewer , the study was inconclusive.
Population Treatment Overall Spasm Hypsarrhythmia

Response Control Control
mITT High Dose 15/24 (63%) 19/24 (79%) 16/24 (67%)
Low Dose 13/27 (48%) 14/27 (52%) 14/27 (52%)
p-value 0.28 0.03 0.27
ITT High Dose 15/30 (50%) 23/30 (77%) 16/30 (53%)
Low Dose 15/29 (52%) 16/29 (55%) 13/29 (45%)
p-value 0.94 0.07 0.52
The Sponsor concludes that this at least supports the use of Acthar Gel. Dr Sheridan suggests
that the reason that obvious superiority was not demonstrated in the high over the low dose
group may be related to an adeqaute cortisol response. Thus, he notes that the high dose was
given once a day and that the twice daily dosing, as in study 01, may increase the endogenous
cortisol more efficiently.
Study 04
This was a randomized, controlled, double-blind, double-dummy study that compared Acthar
at a dose of 20 to 30 U/day administered as a single daily intramuscular dose (20 to 30 U/QD)
(Acthar low-dose) to a single oral prednisone (2 mg/kg/day). Patients received Acthar 20
U/QD IM and a prednisone placebo PO or prednisone 2 mg/kg/day PO and an Acthar placebo
IM, for 2 weeks. Patients were accessed for a response (cessation of spasms and
hypsarrhythmia) after 2 weeks of therapy and:
Page 5 of 12 5
• If the patient responded to the initial 2 weeks of treatment they were tapered for a 1
to 2 week period and monitored for continued response at 2 and 6 weeks after the
discontinuation of treatment. If patients spasms returned at the 2 week period they
were changed to the alternative medication or the original medication was continued
for an additional 4 weeks after which they underwent a 2 week taper.
• If there was no response after the initial 2 weeks of treatment (or the additional 4
weeks of treatment with the original drug, see first bullet) patients were started on the
alternative treatment following a one week washout period.
The primary endpoint was considered complete cessation of hypsarrhythmia and spasms
(overall control) as determined by a video-EEG performed following the initial 2-weeks of
therapy. Secondary endpoints included in the analysis included EEG changes in non-
responders and changes in mental and developmental status.
A total of 24 patients were randomized to the study with 12 in each group.
The following table presents the results for the primary (overall) and some secondary
endpoints . Although there was a trend toward an effect in all measures, none reached
statistical significance. The statistical reviewer was able to reproduce the Sponsor’s
conclusions. The Sponsor notes that the level of a statistically significant effect may result
from the study being underpowered and the low dose of ACTH. Dr Sheridan also notes that
the response rate for both treatments are suggestive of an effect of both as the control rates are
greater then what is usually historically observed.
Treatment Overall Spasm Hypsarrhythmia

Control Control
Acthar Gel 5/12 (42%) 5/12 (42%) 9/12 (75%)
Prednisone 4/12 (33%) 4/12 (33%) 4/12 (33%)
p-value 0.99 0.99 0.99
Discussion on substantial Proof of Efficacy
These data consist of only one positive study. Although small, this study exhibited a rather
large statistically significant effect, when compared to a presumed positive control. This study
was considered by both the medical and statistical reviewer as an adeqaute positive study.
Both additional studies, which also utilized presumed active controls, while not positive, did
trend in the direction of an effect in the majority of measures. As to why an effect was not
apparent is a matter of speculation. The Sponsor notes there may be inadequate power (study
04) or inadequate dosage regimens (study 05). The fact that all studies used active controls
was a likely contributor to the difficulty in designing studies that provide adeqaute power.
Considering the severity of this disease, this reviewer believes that an active control study
design or an adjunctive design would be the only ethical design for such a study. The Sponsor
Page 6 of 12 6
also notes that although some studies did not demonstrate statistical significance, in two
studies the response rates are above that which is historically anticipated. Also noted by Dr
Sheridan is the fact that many of similar dosages across studies exhibited similar treatment
effects. Such arguments are not unreasonable but lack the rigor usually required by the FDA
for approval of an indication. This may also be considered against the background of the fact
that Acthar Gel has been used for decades by pediatric Neurologists to control infantile spasms
and is generally considered as the treatment of choice. The FDA requires substantial evidence
of proof before we approve an indication. This is usually interpreted as two positive studies
on efficacy, but under certain conditions one strong study and additional supportive data may
be used. Because the issue of approval was not readily obvious the agency, a Advisory
Committee was convened, whose makeup consisted of a number of expert pediatric
epileptologists.
Of note, the data presented by the Sponsor contains no careful examination of dose-response,
comparison of different dose regimen or the utility of retreatment in the case of treatment
failure or remission. On face, cross study comparison would suggest that the best dose was
obtained with the dose regimen examined in study 01, however there was no single in study
comparison of regimens in a single study. The dose utilized in study 01 will therefore be
proposed.
Of importance , while this reviewer believes that the Sponsor appears to have demonstrated
that Acthar Gel suppresses infantile spasms there is no demonstration that this treatment
improves the long term outcome (e.g. loss of developmental milestones) of this disorder.
As will be described below, the Advisory Committee decided that there was adeqaute data to
conclude that the requirement of substantial evidence was fulfilled.
Additional Analysis Relapse Rate and Retreatment
The Sponsor was asked, during the review process, to provide additional data that would
address relapse rate and the utility of additional Acthar Gel treatments.
The Sponsor submitted information on relapse rates observed from published studies. These
are presented in the form of a table, which is reproduced below. Note that the Baram 96,
Hrachovy 94, and Hrachovy 83 studies in the table correspond to Studies 01, 05, and 04,
respectively, which are discussed in this review.
Page 7 of 12 7
One conclusion made by the Sponsor , based upon this analysis, is that the Baram dose
exhibited the lowest relapse rate (15%). Dr. Sheridan notes this conclusion is not definitive as
follow-up periods during the study differ. I agree and would add, that other treatments may be
occurring during this period, and that these other treatments may also affect relapse rate. I do
not believe that this information should be included in the label as it is highly speculative.
There also does not appear to be any definitive data on retreatment. The Sponsor concludes
that retreatment with Acthar Gel after a recurrence should be a decision made by the physician
and parent. Dr Sheridan and I agree. I do not believe that there is adeqaute information on
this issue to include in the label.
9. Safety
As Acthar Gel is presently marketed, safety information is already contained in the label.
Much of the information described in label is similar to that for glucocorticosteroids. (e.g.
immune suppression, ophthalmological effects, metabolic effects etc.). Indeed, DMEP
assisted of drugs in the labeling review and changes initiated by them was to harmonize the
label with information contained of the class of glucocorticosteroids. The Sponsor has
provided additional data for safety in IS patients.
Clinical Studies safety Data
Young children with IS may be considered a particularly vulnerable population. The Sponsor
was asked to obtain additional safety information. To provide this information the Sponsor
obtained safety information from 3 principal sources: 1) Retrospective chart review for
patients from one treatment center (Children’s Hospital of Los Angeles), which was also the
Page 8 of 12 8
subject of a publication (Partikian and Mitchell 20076) with some patients having presumably
participated in the Baram study (study 01), this is referred to as study CSR 222017-02 (n=84),
2) A retrospective review of charts for infants treated with Acthar Gel at four treatment centers
(n=178), this is referred to as study CSR QSC007-ACT-002, 3) Safety data from the two
studies published by Hrachovy and Colleagues, which are described in the efficacy section
above.
The database includes a total of 319 patients who receive Acthar Gel. The database included
patients exposed to different dosages including those similar to the pivotal trial 01 (dose
range within the range 135 to 160 U/m2/day, n= 134,), higher then pivotal trial doses
( 80 U/m2/day, n=133) and doses lower <80 U/m2/day, n=52) then the pivotal trials.
Demographic profile of the patients adequately covered the intended population to be treated.
Although a majority of patients had symptomatic IS (59%) there were a number with
cryptogenic IS (39%).
Three deaths were reported. Two were a result of pneumonia thought to possible be
the result of the ACTH treatment. The third death appears to be complicated by the patients
general neurologic status (microcephaly). This patient was admitted to the hospital with
severe respiratory symptoms and was said to have died from “respiratory failure and cardiac
arrest.” The possibility of infections, probably contributed by this drugs immunosuppressive
effect, will be clearly noted in the Warnings and Precautions section of the label.
Serious adverse events occuring in greater in 3 patients or greater (> 0.9% of patients)
included convulsions (20.1%), infections (5.0%), hypertension (3.8%), and pyrexia (1.9%).
Other notable events occurring in 1 to 2 patients included aspiration pneumonia, osteoporotic
fracture, irritability, cardiac hypertrophy and diarrhea/hemorrhage. These are consistent with
what is known about steroid toxicity and will be appropriately labeled.
Data on drug discontinuation were very limited. Thus, it was unclear at times as to whether
the discontinuations were planned or due to noncompliance or an adverse effect. When
present, however, the reasons for discontinuation were consistent with the reported serious
adverse events.
Treatment emergent adverse event occurring in >2%of patients included Cushing’s, diarrhea,
vomiting, irritability, pyrexia, infections, weight gain, convulsions, acne, rash and
hypertension. The convulsions are likely part of the disease process. Because these data do
not consist of placebo controlled trials it is difficult to absolutely determine causality, but
many of these adverse events are known as common adverse events associated with ACTH
and steroids and will be noted in the label.
In general, there was a trend for a greater incidence of adverse events with higher doses.
6
Partikian A, Mitchell WG. Major adverse events associated with treatment of infantile spasms. J Child Neurol.
2007 Dec;22(12):1360-1366.
Page 9 of 12 9
Post-Marketing Safety Information
The Sponsor provided an analysis of postmarketing safety reports in young children treated for
IS. The Sponsor identified eight deaths. At least 4 of these were related to respiratory
infections. The other 4 appeared to be related to the patients underlying disease, although in
one case of ACTH related metabolic acidosis was thought to exacerbate that condition. The
Sponsor identified 76 serious adverse event reports. The most common and notable events
were similar to those identified in the above studies and/or are already described in the label.
These include the following that were reported in 3 or more patients: Cushing’s syndrome,
fever lethargy, sepsis, dehydration, hyperkalemia, metabolic acidosis, seizure, irritability,
pneumocystis carni pneumonia, rash and hypertension. Again, these events are generally
described in label to some degree. For example although pneumocystis carni pneumonia is not
specifically noted, susceptibility to infection is and although acidosis is not mentioned acidosis
may be associated with adrenal hypo-function related to steroid withdrawal (Addison’s),
which is noted in the label.
10. Advisory Committee Meeting

The Peripheral and Central Nervous System Drugs Advisory Committee
Advisory panel was convened on May 6, 2010. This panel consisted of the division’s core
members and a number of experts in pediatric epilepsy.
The Committee voted overwhelmingly (22 yes and 1 no) that the sponsor presented substantial
evidence of effectiveness for Acthar Gel as a treatment for patients with Infantile Spasms (IS). The
committee agreed in a consensus that effectiveness was expressed as cessation of spasms and
amelioration of the EEG, but not in the prevention of other seizure types or improvement in
long-term developmental outcome. A majority of committee members voted that the effect of
Acthar Gel was sustained (16 yes and 7 No). Amongst those who voted against a sustained effect, there
was an expression that what was meant by a sustained effect was ambiguous.
The Committee was asked to vote as to whether the serious adverse events were predictable, easily
recognized, manageable, and reversible upon drug discontinuation. A slight majority voted against this
(yes 10,no 12). Those who voted yes based their decision on 50 years of experience of the use of
Acthar Gel in the treatment of IS. Those who voted no based their decision on the limitations of data
provided by the Sponsor in the application (e.g. small database and retrospective analysis). Despite the
latter vote the Committee overwhelmingly voted that the sponsor had submitted sufficient evidence of
the safety of Acthar Gel at an effective dosing regimen (20 yes, 1 no, 2 abstain). The committee,
however, believed that patients should be closely monitored and that post-marketing surveillance is
needed.
Some on the committee suggested that the sponsor may wish to better study maintenance of effect and
alternative dosing regimens in the future. Also the committee noted that labeling should very clearly
describe adverse events including infections , adrenal insufficiency and elevated blood pressure. The
committee also recommended that good physician and patient education was crucial in the safe use of
this drug. The Sponsor noted that Acthar Gel was distributed through specialty pharmacies. Some
speakers thought that this may make a registry easy, which can then collect data on the use of the drug.
Page 10 of 12 10
There was some recommendations, however, that the FDA should not make it to complicated for
physicians to use Acthar Gel.
Although the committee discussed the potential of additional studies the recruitment and the execution
of such studies may be difficult considering the small number of patients suffering this disorder and the
fact that the presently recommended dose of Acthar Gel is the only dosage that has demonstrated
efficacy and is the dosage recommended by the American Academy of Neurology and the Child
Neurology Society. The division does believe that additional patient education should be performed
and believes that this can be accomplished with a MedGuide based REMS. A single issue indication
(IS) MedGuide has been requested. The argument for a single indication, rather then multiple
indications, MedGuide was expressed in a Memo (9/10/10) by this reviewer. The argument,
transcribed from that memo, is as follows:
“One of the most worrisome side effects of ACTH is the lowering of immunologic resistance. As a
child’s immature immune system is already considered compromised, as a result of its immaturity7, the
additional immuno–suppressive effect of ACTH is thought to add an additional risk to this population.
It is also noteworthy that while it is generally difficult to identify whether a child at this very young
age is infected, the cognitive/behavioral deficits associated with Infantile Spasms make it even more
difficult2. Moreover, Acthar Gel may suppress normal signs of infection such as fever. Thus, parents
would have to be educated to these facts and highly vigilant for any potential signs of infection that
may be limited to changes in behavior (e.g. decreased responsiveness or feeding). Moreover, parents of
children must also be educated and advised to monitor other symptoms of Acthar Gel toxicity (e.g.
post treatment adrenal insufficiency). The parents must also be educated as to the importance of
adequate follow up for their children so that other potential serious adverse events (hypertension) can
be monitored.”
11. Pediatrics
The present study examined and labeled the pediatric population (< 2 years of age) for which
IS is known to occur. IS essentially does not occur in older children. This is an orphan
indication, and as such does not require a PERC commitment.
12. Other Relevant Regulatory Issues

Dr Sheridan reviewed the Financial Disclosure Forms in his review and determined there was no conflict.
7
Rudolph’s Pediatrics – 21st Ed. (2003), Chapter 13 by Julie A. Jaskiewicz “Fever Without Localizing Signs In
Infants And Children.”
Page 11 of 12 11
DMEP determined , upon the initial review of this application at filling, that a DSI audit was
unnecessary.
The application was initially submitted as a 505(b)(2) application, but was reclassified as a
505(b)(1) based upon the fact that, while studies were published, the Sponsor acquired the
right to use these studies and provide the division with their own final study report as a
response to the complete response.
13. Labeling
The labeling review was a joint effort by this division and that of DMEP. It included a
conversion to the PLR format and removal of a number of DESI indications, which was
negotiated with the Sponsor.
14. Recommendations/Risk Benefit Assessment

Recommended Regulatory Action: Approval.
Risk Benefit Assessment: There was a general consensus from myself, the review team and the
Advisory Committee that approval of Acthar Gel provided an adeqaute risk-benefit. While the
treatment with Acthar Gel is not without serious consequences, these may be dealt with by
adeqaute patient education (e.g. in the form of a MedGuide) a
Recommendation for Postmarketing Risk Management Activities: The division recommends a

MedGuide so as to better educate parents and guardians of children on the risks of ACTH use.
Recommendation for other Postmarketing Study Commitment: None. For a discussion on this
the reader is referred to the section on the Advisory committee.
Page 12 of 12 12
---------------------------------------------------------------------------------------------------------
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
NORMAN HERSHKOWITZ
09/27/2010

MEMORANDUM DEPARTMENT OF HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE
FOOD AND DRUG ADMINISTRATION
CENTER FOR DRUG EVALUATION AND RESEARCH
DATE: August 8, 2008
SUBJECT: Creating Type 6 NDA
NDA 08-372/S-039 was submitted to and reviewed by the Division of Metabolic and Endocrine
Products. However, it should have been reviewed by the Division of Neurology Products as a
type 6 NDA because the indication is for infantile spasms.
Therefore, sNDA 08-372/S-039 has been converted to the new NDA 22-432 for the 2nd cycle.

---------------------------------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed electronically and
this page is the manifestation of the electronic signature.
---------------------------------------------------------------------------------------------------------------------
/s/
---------------------
Susan B. Daugherty
8/8/2008 02:45:50 PM
CSO


































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RESEARCH
APPLICATION NUMBER:
022432Orig1s000
APPROVAL LETTER


NDA 022432
NDA APPROVAL

3260 Whipple Road
Union City, CA 94587
Dear Dr. Bigora:
Please refer to your New Drug Application (NDA) dated June 16, 2006, received June 23, 2006,
submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for H.P. Acthar®
Gel (repository corticotropin) Injection.
We acknowledge receipt of your amendments dated December 10, 2009, and January 19, April
1, 22, and 28, June 8, and August 10, 2010.
The December 10, 2009, submission constituted a complete response to our May 10, 2007,
action letter.
This new drug application provides for the use of H.P. Acthar® Gel (repository corticotropin) to
treat infantile spasms.
We have completed our review of this application, as amended, and it is approved, effective on
the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
prescribing information. This waiver applies to all future supplements containing revised
labeling unless we notify you otherwise.
CONTENT OF LABELING
As soon as possible, but no later than 14 days from the date of this letter, submit, via the FDA
automated drug registration and listing system (eLIST), the content of labeling
[21 CFR 314.50(l)] in structured product labeling (SPL) format, as described at
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
identical to the enclosed labeling (text for the package insert and Medication Guide).
Information on submitting SPL files using eLIST may be found in the guidance for industry
titled “SPL Standard for Content of Labeling Technical Qs and As” at

NDA 022432
Page 2
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM072392.pdf.
The SPL will be accessible via publicly available labeling repositories.
We request that the labeling approved today be available on your website within 10 days of
receipt of this letter.
Submit final printed carton and container labels that are identical to the enclosed carton and
immediate container labels, except with the revisions listed below, as soon as they are available,
but no more than 30 days after they are printed.
1. Because H.P. Acthar Gel is a multiple-dose injectable product, the strength per total
volume should be the primary and prominent expression on the principle display panel,
followed in close proximity by the strength per mL enclosed by parenthesis per USP
standards. Please revise the strength expression on all labels and labeling to read as
follows:
400 USP units/5 mL

(80 USP units/mL)
2. Relocate the strength expression immediately following the established name

presentation in all labels and labeling.
Please submit these labels electronically according to the guidance for industry titled “Providing
Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications
and Related Submissions Using the eCTD Specifications (June 2008).” Alternatively, you may
submit 12 paper copies, with 6 of the copies individually mounted on heavy-weight paper or
similar material. For administrative purposes, designate this submission “Final Printed Carton
and Container Labels for approved NDA 022432.” Approval of this submission by FDA is
not required before the labeling is used.
Marketing the product with FPL that is not identical to the approved labeling text may render the
product misbranded and an unapproved new drug.
REQUIRED PEDIATRIC ASSESSMENTS
Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
administration are required to contain an assessment of the safety and effectiveness of the
product for the claimed indication(s) in pediatric patients unless this requirement is waived,
deferred, or inapplicable.
Because this drug product for this indication has an orphan drug designation, you are exempt

NDA 022432
Page 3
from this requirement.
RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
Section 505-1 of the FDCA authorizes FDA to require the submission of a risk evaluation and
mitigation strategy (REMS), if FDA determines that such a strategy is necessary to ensure that
the benefits of the drug outweigh the risks [section 505-1(a)]. The details of the REMS
requirements were outlined in our REMS notification letter dated September 27, 2010.
H.P. Acthar Gel (repository corticotrophin) was approved on April 29, 1952, for multiple
indications. The label was later expanded to include multiple sclerosis (MS) in 1972. We are
now adding the indication of infantile spasms in pediatric patients. The known risks of
infections and blood pressure elevation in MS patients have also been identified as risks in the
pediatric population based on clinical trial data. Additionally, the risk of adrenal insufficiency
seen in other patient populations is an important potential serious adverse event in the pediatric
population. The extension of the indication to pediatrics changes the risk benefit profile of H.P.
Acthar Gel (repository corticotrophin) and is considered to be “new safety information” as
defined in section 505-1(b)(3) of the FDCA.
Your proposed REMS, submitted on September 28, 2010, and appended to this letter, is
approved. The REMS consists of a Medication Guide and timetable for submission of
assessments of the REMS.
The REMS assessment plan should include, but is not limited to, the following:
An evaluation of patients’ understanding of the serious risks of H.P. Acthar® Gel (repository
corticotropin).
Assessments of an approved REMS must also include, under section 505-1(g)(3)(B) and (C),
information on the status of any postapproval study or clinical trial required under section 505(o)
or otherwise undertaken to investigate a safety issue. With respect to any such postapproval
study, you must include the status of such study, including whether any difficulties completing
the study have been encountered. With respect to any such postapproval clinical trial, you must
include the status of such clinical trial, including whether enrollment has begun, the number of
participants enrolled, the expected completion date, whether any difficulties completing the
clinical trial have been encountered, and registration information with respect to requirements
under subsections (i) and (j) of section 402 of the Public Health Service Act. You can satisfy
these requirements in your REMS assessments by referring to relevant information included in
the most recent annual report required under section 506B and 21 CFR 314.81(b)(2)(vii) and
including any material or significant updates to the status information since the annual report was
prepared. Failure to comply with the REMS assessments provisions in section 505-1(g) could
result in enforcement action.
We remind you that in addition to the assessments submitted according to the timetable included
in the approved REMS, you must submit a REMS assessment and may propose a modification to
the approved REMS when you submit a supplemental application for a new indication for use as
described in section 505-1(g)(2)(A) of FDCA.

NDA 022432
Page 4
If you currently distribute or plan to distribute an authorized generic product under this NDA,
you will also need to submit a REMS, REMS supporting document, and any required appended
documents for that authorized generic, to this NDA. In other words, you must submit a complete
proposed REMS that relates only to the authorized generic product. Review and approval of the
REMS is required before you may market your product.
Prominently identify the submission containing the REMS assessments or proposed

modifications with the following wording in bold capital letters at the top of the first page of the
submission as appropriate:
NDA 008372 REMS ASSESSMENT
NEW SUPPLEMENT FOR NDA 008372

PROPOSED REMS MODIFICATION
REMS ASSESSMENT
NEW SUPPLEMENT (NEW INDICATION FOR USE)

FOR NDA 008372
REMS ASSESSMENT
PROPOSED REMS MODIFICATION (if included)
If you do not submit electronically, please send 5 copies of REMS-related submissions.
PROMOTIONAL MATERIALS
You may request advisory comments on proposed introductory advertising and promotional
labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
proposed materials in draft or mock-up form with annotated references, and the package insert
to:

Division of Drug Marketing, Advertising, and Communications
5901-B Ammendale Road
Beltsville, MD 20705-1266
As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
information about submission of promotional materials to the Division of Drug Marketing,
Advertising, and Communications (DDMAC), see
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.

NDA 022432
Page 5
LETTERS TO HEALTH CARE PROFESSIONALS
If you decide to issue a letter communicating important safety-related information about this
drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
24 hours prior to issuing the letter, an electronic copy of the letter to this NDA to the following
address:
MedWatch Program
Office of Special Health Issues
10903 New Hampshire Ave
Building 32, Mail Stop 5353
Silver Spring, MD 20993
(21 CFR 314.80 and 314.81).
All 15-day alert reports, periodic (including quarterly) adverse drug experience reports, field
alerts, annual reports, supplements, and other submissions should be addressed to the original
NDA 008372 for this drug product, not to this NDA. In the future, do not make submissions to
this NDA except for the final printed labeling requested above.
If you have any questions, call Susan Daugherty, Regulatory Project Manager, at
(301) 796-0878.
Sincerely,
Russell Katz, M.D.

Director
ENCLOSURES:
Content of Labeling
REMS

---------------------------------------------------------------------------------------------------------
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
RUSSELL G KATZ
10/15/2010













Health Care Financing Administration
Center for Medicaid and State Operations
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5018.2

POLICY AND PROCEDURES
Office of Pharmaceutical Quality
NDA Classification Codes

Table of Contents

PURPOSE ..............................................................................1
BACKGROUND ...................................................................1
POLICY .................................................................................1
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RESPONSIBILITIES ...........................................................7
REFERENCES ......................................................................9
DEFINITIONS ......................................................................9
EFFECTIVE DATE ............................................................10
CHANGE CONTROL TABLE..........................................10

PURPOSE
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Type 1 — New Molecular Entity

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Type 6 — New Indication or Claim, Same Applicant

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RESPONSIBILITIES
Office of New Drugs (OND) Review Division Project Management Staff will:

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Office of Pharmaceutical Quality (OPQ) Regulatory Business Process Manager will:

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CERTIFICATE OF SERVICE
I certify that on June 2, 2020, the foregoing was electronically filed through
this Court’s CM/ECF system, which will send a notice of filing to all registered
users.
I further certify that the foregoing was served by email on:
Joshua M. Salzman
Attorney, Civil Appellate Staff
U.S Department of Justice
950 Pennsylvania Ave., NW
Joshua.M.Salzman@usdoj.gov
Counsel for Defendants-Appellees

(Page 442 of Total)

Mallinckrodt Appeal Dated 06.02.20

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USCA Case #20-5154 Document #1845229 Filed: 06/02/2020 Page 1 of 34

ORAL ARGUMENT NOT YET SCHEDULED

United States Court of Appeals

SEEMA VERMA, in her official capacity as ADMINISTRATOR, CENTERS

On Appeal from the United States District Court

EMERGENCY MOTION FOR INJUNCTION PENDING APPEAL

Counsel for Mallinckrodt ARD LLC

CERTIFICATE OF PARTIES, RULINGS, AND RELATED CASES

Pursuant to Circuit Rule 28.1(a)(1), Mallinckrodt ARD LLC certifies that:

1. The following are parties in this Court:

a. Plaintiff-Appellant: Mallinckrodt ARD LLC

b. Defendant-Appellees: Seema Verma, in her official capacity as

2. For purposes of Federal Rule of Appellate Procedure 26.1 and Circuit

Rule 26.1, Mallinckrodt ARD LLC states that it is a biopharmaceutical company.

Mallinckrodt ARD LLC is a wholly owned subsidiary of Mallinckrodt plc, a

publicly traded company.

B. RULINGS UNDER REVIEW

Mallinckrodt ARD LLC is appealing two rulings: The District Court’s

judgment and denying Mallinckrodt’s motion for summary judgment, Mallinckrodt

on May 29, 2020. Dkts. 46, 47.

defined in Circuit Rule 28(a)(1)(C).

/s/ Catherine E. Stetson

Counsel for Mallinckrodt ARD LLC

CERTIFICATE AS TO PARTIES, RULINGS, AND RELATED CASES ..........i

TABLE OF AUTHORITIES ...............................................................................v

Statutory and Regulatory Framework.............................................................4

Acthar’s Approval Under NDA 022432, And CMS’s Change In

Procedural History .........................................................................................8

I. MALLINCKRODT PRESENTS A SUBSTANTIAL

A. The District Court Ignored the Key Statutory

B. The District Court Failed To Address The Argument

C. The District Court Overlooked CMS’s Inconsistent

D. The District Court Shortchanged Core Fair-Notice

II. MALLINCKRODT WILL SUFFER IRREPARABLE HARM

III. GRANTING PRELIMINARY INJUNCTIVE RELIEF

IV. DEFENDANTS WILL NOT BE SUBSTANTIALLY

General Elec. Co. v. EPA,

Ipsen Biopharms., Inc. v. Azar,

National Med. Care, Inc. v. Shalala,

Retail, Wholesale and Dep’t Store Union, AFL-CIO v. NLRB,

Reuters Ltd. v. FCC,

Washington Metro. Area Transit Comm’n v. Holiday Tours, Inc.,

Winter v. Natural Res. Def. Council, Inc.,

Wisconsin Gas Co. v. FERC,

21 U.S.C. § 331(d) ..................................................................................................4

21 U.S.C. § 355(a) ..................................................................................................4

21 U.S.C. § 355(b) ..................................................................................................4

42 U.S.C. § 1396r-8(b) ..................................................................................... 4, 20

42 U.S.C. § 1396r-8(c) ............................................................................................5

42 U.S.C. § 1396r-8(c)(2)(A) ........................................................................... 5, 10

42 U.S.C. § 1396r-8(c)(2)(B) ......................................................................... 12, 13

42 U.S.C. § 1396r-8(d) ................................................................................... 20, 22

* 42 U.S.C. § 1396r-8(k)(7)(iv) ...................................................................... 5,10, 13

* 42 C.F.R. § 447.502..................................................................................... 5,10, 16

81 Fed. Reg. 5170-01, 5192 (Feb. 1, 2016) ....................................................... 5, 16

D.C. Cir. Practice & Internal Proc. R. VIII (B) ......................................................9

ANDA Abbreviated New Drug Application

CMS Centers for Medicare & Medicaid Services

DDR Drug Data Reporting for Medicaid system

FDA U.S. Food and Drug Administration

MDRP Medicaid Drug Rebate Program

NDA New Drug Application

NDC National Drug Code

NDRA National Drug Rebate Agreement