American National Standard ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013

ANSI/AAMI/ISO 13408-1:2008/(R)2011
Aseptic processing of health care products Part 1:
General requirements

Amendment 1





Developed by
Association for the Advancement of Medical Instrumentation

Approved 27 March 2013 by:
Ameri can National Standards Institute, Inc.



Abstract: Corrects spelling errors; clarifies a definition note; and replaces terms used in Table 1
and Table 2.
Keywords: sterilization, aseptic


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2013 by the Association for the Advancement of Medical Instrumentation

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Contents Page
Committee representation......................................................................................................................... iv
Background on AAMI adoption of ISO 13408-1:2008 Amd 1 ................................................................. vi
Foreword .................................................................................................................................................... vii
Amendment ................................................................................................................................................. 1
iv 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013
Committee representation
Associ ation for the Advancement of Medical Instrumentation

Steril ization Standards Committee
The adoption of ISO 13408-1:2008/Amendment 1 as an American National Standard was initiated by the AAMI
ST/WG 9, Aseptic Processing Working Group. The AAMI Aseptic Processing Working Group also functions as a U.S.
Technical Advisory Group to the relevant work in the International Organization for Standardization (ISO). U.S.
representatives from the AAMI Aseptic Processing Working Group (U.S. Sub-TAG for ISO/TC 198/WG 9) played an
active part in developing the ISO standard.
At the time this document was published, the AAMI Aseptic Processing Working Group had the following
members:
Cochairs: Thomas J . Arista, FDA/CDRH
Robert P Tomaselli, J ohnson & J ohnson
Members: Thomas J . Arista, FDA/CDRH
Charles Cogdill, Covidien
Steven J . Elliot, NAMSA
Kimbrell Darnell, CR Bard
Susan Elwell, Medtronic Inc. WHQ Campus
Gordon M. Ely, WuXi AppTec Inc
Rosanna Fardo, RN BSN CIC CHSP, Department of Veterans Affairs
Robert Fry, Baxter Healthcare Corporation
Naomi Gamm, St J ude Medical Inc.
Deborah A. Havlik, Hospira Worldwide Inc.
Rachel Hill, CareFusion
Roland C. Kippenhan, Medivators Inc.
J ames P. Kulla, BS MS, LexaMed Ltd
Carol M. Lampe, J M Hansen & Associates
Daniel S. Larrimore, Alcon Laboratories Inc.
Christine Loshbaugh, Edwards LifeSciences
Lisa N. Macdonald, Becton Dickinson & Company
Tonya M. Morris, BS, Nelson Laboratories Inc.
J anet M. Prust, 3M Healthcare
Manuel Saavedra, J r., Kimberly-Clark Corporation
David SIlor, Zimmer Inc.
Robert P Tomaselli, J ohnson & J ohnson
Alternates: David J . Brodersen, Covidien
Trabue D. Bryans, WuXi AppTec Inc.
J onathan Bull, Becton Dickinson & Company
Alyce Dobie, Bausch & Lomb
David A. Dominguez, CareFusion
J oyce M. Hansen, J ohnson & J ohnson
Suzanne Leung, 3M Healthcare
J eff Martin, Alcon Laboratories Inc.
Elaine S. Mayhall, PhD, FDA/CDRH
Terry Mistalski, Medivators Inc.
Emily Mitzel, MS, Nelson Laboratories Inc.
Robert R. Reich, BS MS, LexaMed Ltd
Tyrone S Rouse, Kimberly-Clark Corporation
Mike Sadowski, Baxter Healthcare Corporation
Dennis L. Wildes, St J ude Medical Inc.
Cheryl Work, Becton Dickinson & Company

NOTE--Participation by federal agency representatives in the development of this document does not constitute
endorsement by the federal government or any of its agencies.

2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013 v
At the time this document was published, the AAMI Sterilization Standards Committee had the following members:
Cochairs: Victoria M. Hitchins, PhD, FDA/CDRH
Michael H. Scholla, Ph.D., Dupont Protection Technologies
Members: Christopher Anderson, Boston Scientific Corporation
Trabue D. Bryans, WuXi AppTec Inc.
Peter A. Burke, PhD, Steris Corporation
Nancy Chobin, RN CSPDM, St Barnabas Healthcare System
Charles Cogdill, Covidien
Ramona Conner, RN MSN CNOR, Association of Perioperative Registered Nurses
J acqueline Daley, Sinai Hospital of Baltimore
Kimbrell Darnell, CR Bard
Lisa Foster, Adiuvo QS & SA Consulting
J oel R. Gorski, PhD, NAMSA
J oyce M. Hansen, J ohnson & J ohnson
Deborah A. Havlik, Hospira Worldwide Inc.
Susan G. Klacik, CCSMC FCS ACE, IAHCSMM
Byron J . Lambert, PhD, Abbott Laboratories
Colleen Patricia Landers, RN, Timmins & District Hospital
Reynaldo Lopez, Cardinal Health (MP&S)
Lisa N. Macdonald, Becton Dickinson & Company
J eff Martin, Alcon Laboratories Inc.
Patrick J . McCormick, PhD, Bausch & Lomb Inc.
J anet M. Prust, 3M Healthcare
Nancy Rakiewicz, Moog Medical Devices
Mark Seybold, Baxter Healthcare Corporation
Andrew Sharavara, PhD, Propper Manufacturing Co Inc.
Mark N. Smith, Getinge USA
Martell Kress Winters, BS SM, Nelson Laboratories Inc.
William E. Young
William T. Young, Sterigenics International
Alternates: Lloyd Brown, Covidien
Glenn W. Calvert, Becton Dickinson & Company
Dave Dion, Cardinal Health (MP&S)
Gordon M. Ely, WuXi AppTec Inc.
Thomas J . Frazar, J ohnson & J ohnson
Martha M. Kadas, Sterigenics International
J im Kaiser, Bausch & Lomb Inc.
Natalie Lind, IAHCSMM
Ralph Makinen, Boston Scientific Corporation
Mary S. Mayo, CR Bard
Gerald E. McDonnell, PhD, Steris Corporation
David Ford McGoldrick, BS, Abbott Laboratories
J erry R. Nelson, PhD, Nelson Laboratories Inc.
Patrick Polito, Moog Medical Devices
Karen Polkinghorne, Dupont Protection Technologies
Shaundrea L. Rechsteiner, NAMSA
Mike Sadowski, Baxter Healthcare Corporation
Craig A. Wallace, 3M Healthcare

NOTE--Participation by federal agency representatives in the development of this document does not constitute
endorsement by the federal government or any of its agencies.
vi 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013
Background on AAMI adoption of ISO 13408-1:2008 Amd. 1
As indicated in the foreword to the main body of this document (page vii), the International Organization for
Standardization (ISO) is a worldwide federation of national standards bodies. The United States is one of the ISO
members that took an active role in the development of this standard, which was developed by ISO Technical
Committee 198, Sterilization of health care products, to correct errors; clarify language; and replace terms used in
Table 1 and Table 2 of ISO 13408-1:2008.

U.S. participation in this ISO TC is organized through the AAMI Sterilization Standards Committee which serves as
the U.S. Technical Advisory Group for ISO/TC 198. AAMI ST Working Group 09, Aseptic processing, serves as the
U.S. sub-TAG for the relevant ISO working group and supports the adoption of this amendment.

The U.S. adoption of ANSI/AAMI/ISO 13408-1 Amd 1 was approved by the American National Standards Institute
(ANSI) on 27 March 2013.

AAMI and ANSI procedures require that standards be reviewed and, if necessary, revised every five years to reflect
technological advances that may have occurred since publication.

AAMI (and ANSI) have adopted other ISO standards. See the Glossary of Equivalent Standards for a list of ISO
standards adopted by AAMI which gives the corresponding U.S. designation and the level of equivalency with the
ISO standard.

The concepts incorporated in this standard should not be considered inflexible or static. This standard, like any other,
must be reviewed and updated periodically to assimilate progressive technological developments. To remain relevant,
it must be modified as technological advances are made and as new data come to light.

Suggestions for improving this standard are invited. Comments and suggested revisions should be sent to Standards
Department, AAMI, 4301 N. Fairfax Dr., Ste. 301, Arlington, VA 22203-1633.
NOTEBeginning with the foreword on page vii, this American National Standard is identical to ISO 13408-1:2008
Amd. 1.
2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013 vii
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national
standards bodies (ISO member bodies). The work of preparing International Standards is
normally carried out through ISO technical committees. Each member body interested in a
subject for which a technical committee has been established has the right to be represented on
that committee. International organizations, governmental and non-governmental, in liaison with
ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical
Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives,
Part 2.
The main task of technical committees is to prepare International Standards. Draft International
Standards adopted by the technical committees are circulated to the member bodies for voting.
Publication as an International Standard requires approval by at least 75 % of the member
bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the
subject of patent rights. ISO shall not be held responsible for identifying any or all such patent
rights.
Amendment 1 to ISO 13408-1:2008 was prepared by Technical Committee ISO/TC 198,
Sterilization of health care products.
viii 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013

2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013 1
American National Standard ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013
Aseptic processing of health care products Part 1: General
requirements
Page xi, Introduction
In the second paragraph, replace the second sentence with the following:
ISO/TC 198 has prepared standards for terminal sterilization of health care products by
irradiation (ISO 11137 series), by moist heat (ISO 17665 series), by dry heat (ISO 20857),
by ethylene oxide (ISO 11135) and by liquid chemical sterilants (ISO 14160).

Page vii, Introduction
At the end of the last sentence of the penultimate paragraph, add the word "component" so that
it reads:
"... of which process simulation studies are an essential component."

Page 1, Normative references
Delete the following reference:
ISO 9001, Quality management systems Requirements

Page 2, Normative references
Delete footnote 1 and renumber footnote 2 accordingly.

Page 3, 3.7
Delete the following:
[ISO 13408-6:2005, definition 3.1]

Page 4, 3.14
Correct the spelling of the term to read "depyrogenation".
2 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013
Page 5, 3.24
Replace the note with the following:
NOTE The required grade of cleanliness of the indirect support zone depends on the aseptic
processing technologies and activities performed.

Page 7, 4.1.1
In the first sentence, replace "over all activities affecting aseptic processing" with "over all
activities affecting aseptic processing (e.g. ISO 9001 and/or ISO 13485)".
Delete the second sentence.

Page 8, 4.3.2
Replace the text with the following:
The accuracy and tolerance of all measuring instruments shall be adequate for the
parameters to be measured.

Page 9, 5.2.1.2
At the end of the subclause, insert the following note:
NOTEAssessment of risk to condone poor or improper practice during aseptic processing is not
appropriate.

Page 10, 5.2.4.4
Replace item a) with the following:
a) microbiological quality of the product at defined stages during the manufacturing process,
alert and action levels shall be established;

Page 11, 6.1.2
Replace the second sentence of the note with the following:
Where highly potent, cytotoxic or radioactive health care products are to be processed, protection of
personnel and the environment is considered an ancillary element of aseptic processing design.

2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013 3
Page 40, Table 1, fifth column
In the first, third and fifth rows, replace "restart validation" with "repeat initial performance
qualification" to be in line with the title of Table 1.

Page 36, Table 2, fourth column
In the first, third and fifth rows, replace "revalidation" with "repeat initial performance
qualification" to be in line with the title of Table 1.

Page 36, 11.1
Replace the text of 11.1 (excluding the notes) with the following:
Where a test for sterility is required for aseptically-filled products, then this testing shall be
conducted for each batch of product. The pharmacopoeia test for sterility is used when the
method is applicable. Where there is no specific method in the pharmacopoeia that is
applicable to a particular product, then the manufacturer of the product shall specify the
method to be used.
Replace NOTE 2 with the following:
NOTE 2 In certain jurisdictions approval of a non-pharmacopoeia test for sterility is required by the
relevant competent authorities.

Page 41, 11.2.2
Replace "from positive units using tests for sterility" with "from positive units during tests for
sterility".
In the note, replace "from positive units using tests for sterility can be found in the
pharmacopoeias" with "from positive units during tests for sterility can be found in the
pharmacopoeias".
4 2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013
Page 42, Figure A.1
Replace Figure A.1 with the following:

Key

indirect support zone

direct support zone outside APA

critical processing zone

direct support zone

indirect support zone +grade A air flushing
Figure A.1 Example of an aseptic process divided into unit operations

2013 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO 13408-1:2008/(R)2011/A1:2013 5
Page 45, Table D.1
In footnote b, replace "EU GMP Guide, Annex 1:2003 (drafted revision 2005)" with "EU GMP
Guide, Annex 1:2009".

Page 49, Bibliography
Insert the following new reference:
[2] ISO 9001, Quality management systems Requirements
Renumber subsequent references accordingly.
Replace Reference [16] with the following:
[16] EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and
Veterinary Use (GMP), Volume 4 Annex 1:2009 Manufacture of Sterile Medicinal
Products