8ackground

Manufactur|ng Iac|||ty: Llquld ln[ecLlons

Manufactur|ng 1echno|ogy: AsepLlc
Comm|ss|oned: 2001
Iac|||ty Approva| (USIDA): 03/2006
Commerc|a| 8x. Mfg: 06/2006
rob|em: vlslble parLlculaLes M1 (llmlL <1)
Act|on: 1horough and deLalled lnvesLlgaLlon
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8ackground
Invest|gat|on Cb[ect|ve
1o |dent|fy ] |mp|ement:
naLure of Lhe parLlculaLe conLamlnanL
Mechanlsm of Lhe parLlculaLe conLamlnaLlon
lmprovemenL ln Lhe vlsual lnspecLlon process
and lnspecLlon sLandards
ApproprlaLe correcLlve and prevenLlve acLlons
L
k|sk Assessment
Ser|ous
oLenLlal llfe LhreaLenlng healLh hazard
veln lrrlLaLlon, phleblLls.
Local Llssue lnfarcLlon, severe pulmonary
dysfuncLlon.
Cccluslon of caplllarles and arLerles.
AnalaphylacLlc shock and deaLh.
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Invest|gat|on
Cb[ect|ve
!"# % &'()*+,-). /-,0)+, (,)11-.2 3)44'&3-5* 1&)6+3,-).
1opmost pr|or|ty
7),'.,-5* 0'5*,0 0585&6
Invest|gat|on team
7&)6+3,-).9 :-3&);-)*)2<9 =# % >.2-.''&-.2
1eam funct|on
7*5. -.?'(,-25,-).9 !"#9 "#7#9 % "#7# 4).-,)&-.2 ,0&)+20
3*)(' /)&@-.2 % A&'B+'., 4'',-.2(
Invest|gat|on
C.-,-5,'6 -. D3,E FGGH
N
keso|ut|on Strategy
I|ve-po|nt approach (|n order of pr|or|ty),
V|sua| |nspect|on process
I5J 7&)3'(( &'?-'/9 I;J 7&)3'(( 3515;-*-,< -41&)?'4'.,
Ident|f|cat|on of contam|nant
I5J K5,+&'L 305&53,'&-(,-3(9 3)41)(-,-).9 I;J M)+&3'
Ident|f|cat|on of product contam|nat|on mechan|sm
I5J N)/ OOO9 I;J P0< OOOO
CAA
I5J C6'.,-A-35,-).9 I;J C41*'4'.,5,-).
Mon|tor|ng CAA
I5J #6'B+53<9 I;J >AA-353<
O
V|sua| Inspect|on rocess
P
V|sua| Inspect|on rocess
Q
Machlne
L|ght Source
(normal Lo olarlzed)
V|a| Sp|nn|ng
(40 Lo 100)
rocess
Inspect|on 2k
(100 Lo 200)
I Contro|s
(ACL - ???)
CperaLor
Inspector
(CuallflcaLlon SLandards)
ke-qua||f|cat|on
(new CuallflcaLlon
SLandards)
Implementation of the CAPAs resulted in:
SlgnlflcanL lmprovemenL ln Lhe vlsual lnspecLlon
process capablllLy
lncreased confldence and assurance ln reduclng Lhe
probablllLy of conLamlnaLed vlals ln Lhe good
lnspecLed vlals
LllmlnaLlng / reduclng poLenLlal rlsk Lo Lhe paLlenL
healLh
RS
V|sua| Inspect|on rocess
RR
Ident|f|cat|on of Contam|nant
Methodo|ogy:
ConLamlnaLed producL & suspecL M collecLed for lnvesLlgaLlon
Lxamlned by sLereo llghL mlcroscopy (Clympus SZ61, Clympus uk
LLd, Mlddx) Shape, slze & naLure of any characLerlsLlc feaLures
hoLographed (!vC 3-CCu Camera no. 2, CpLlvlslon, CsseLL, W
?ork)
ConLamlnanL lsolaLed washed and examlned furLher by sLereo
llghL mlcroscopy & Lhen under mlcroscope by LransmlLLed llghL
mlcroscopy (olyvar, Lelca LLd., Cambrldge)
1yplcal reglons recorded (Zelss Axloplan, lmaglng AssoclaLes LLd.,
1hame)
R!
Ident|f|cat|on of Contam|nant
RK
Ident|f|cat|on of Contam|nant
RL
Ident|f|cat|on of the Mechan|sm of
Contam|nat|on
V|a| f||||ng |so|ator des|gn:
LnvlronmenL: Closed , conflned, hlgh alrflow & low
humldlLy
arLlcle reLalnlng PLA fllLers: lnsLalled ln Lhe alr
lnleL(s) and ouLleL(s)
Alr lnslde Lhe lsolaLor: 1urbulenL & 100
(re)clrculaLed
Q'(-2. 305&53,'&-(,-3( *-4-, ,0' 3515;-*-,< )A
15&,-3+*5,' &'4)?5*9 -A ,&511'6 /-,0-. ,0' -()*5,)&
'.?-&).4'.,
RM
Ident|f|cat|on of the Mechan|sm of
Contam|nat|on
RN
Ident|f|cat|on of the Mechan|sm of
Contam|nat|on
V|a| f||||ng |so|ator des|gn resu|ts |n:
CeneraLlng sLaLlc-aLLracLed parLlcles
1he charged parLlcles geL aLLracLed or comblned
wlLh Lhe surfaces LhaL cannoL dlsslpaLe Lhelr sLaLlc
charges (lnsulaLors e.g. rubber sLoppers, gloves,
vlals, plasLlc parLs eLc.) Lhls phenomenon was
observed under black light
ConLamlnaLed surfaces resulL ln Lransferrlng
parLlculaLe conLamlnaLlon wlLhln Lhe producL
RO
Ident|f|cat|on of the Mechan|sm of
Contam|nat|on
RP
Ident|f|cat|on & Imp|ementat|on
of CAA
Strategy:
8educLlon of parLlculaLe load wlLhln Lhe lsolaLor
I5J C41&)?-.2 ,0' -()*5,)& 3*'5.-.2 1&)3'(( 1)(, 3*'5.-.2 &-.(' /-,0
PRC9 I;J M'*'3,-). )A ;',,'& 45,'&-5* A)& /-1'( /-1'( 305.2'6 A&)4
"*5(( SGG ,) "*5(( S
ulscharglng Lhe charged parLlcles: uslng alr-lonlzer
(alr knlfe) wlLhln Lhe vlal fllllng lsolaLor
RQ
Ident|f|cat|on & Imp|ementat|on
of CAA
!S
Ident|f|cat|on & Imp|ementat|on
of CAA
!R
Ident|f|cat|on & Imp|ementat|on
of CAA
!!
Mon|tor|ng CAA Adequacy &
Lff|cacy
ost |mp|ementat|on:
LffecLlveness of each CAA monlLored
kl = vlslble parLlculaLe maLLer ln producL baLch
1rends closely monlLored
Course correcLed lmmedlaLely, lf lmprovemenLs noL
vlslble
rocess capablllLy esLabllshed & yleld llmlLs revlsed
accordlngly
!K
Mon|tor|ng CAA Adequacy &
Lff|cacy
!L
Summary
roblem: CrlLlcal, poLenLlal healLh hazard, hlgh rlsk
raLlng
rlorlLy: 1opmosL
1eam: MulLl-dlsclpllnary, focused, planned, loglcal &
sclenLlflc Lhlnklng / approach ln lnvesLlgaLlon
LffecLlve CAA monlLorlng sLraLegy
1eamwork = Success
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