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UI!:J)ARTMENTOFIlEALTfiANDIIUMANSERVrCES
POOI>
AN!)DRUGADMINISTRATION
DATE(B)
01'
ISPEC
-04/27/2012
040NorthCentralExpressway,Suite300Dallas.
TX75204
(214)253-5200Fax:(2ll])253-5314Information:www.fda.gov/oc/industry3009499974Blvd,orporation
Su
arland,
TX77478
BioloicalDrugManufacturer
Thisdocumentlistsobservatlonsmade
by
theFDArepresentative(s)duringtheInspectionofyourfacll.ity.Theyareinspectionalobservations,anddonotrepresent
I\.
finalAgencydeterminationregardingyourcompliance.Ifyouhaveanobjectionregardingan,observation,orhaveimplemented,orplantoImplement,correctiveactionInresponsetoanobsorvution,youmaydiscusstheobjectionor
action
withthe
FDA
represontatlvcts)
during
the
inspection
orsubmit
thisinformationto
FDA
atthe
addressabove.
If
youhaveanyquestions,pleasecontactFDAatthephoneDumberIII1daddressabove.
DURINGANINSPECTIONOFYOURFIRMWEOBSgRVEO:
OBSERVATION1
Controlproceduresarenotestablishedwhich
validatethe
performanceofthosemanufacturingprocesses
that
may
be.responsibleforcausingvariabilityinthocharacteristicsofin-processmaterialandthedrugproduct.Specifically,You
have
manufactured
(mesenchymal
stem
cells)MSC's
which
you
have
released
for
distributionatleas.iruesbetween
7/1/11
andto
thepresent,however:
A.You
havenot
performed
a
processvalidationformanufacturing
MSC's
to
assure
batch
uniformity
andintegrity
asrelated
to
eachof
the
followingfinishedproductcharacteristics:viability
of
cells,
the
specifiedcellcount,celltypo,andappearance
ofcells.B.
~rmedwmaanalyscs
onthefinalproductto
assureWJlUJoftb.e
~e
fmalMSC's.
(b)(4)
C.You
have
notverifiedthefinalproductwith
the
finalMSC's.
:(b)(4)
oassurethe
identity
ofthe
cell
typein
.(b)(4)
.You
have
not
performedrmmassay
toverify
th
the
MSC's.B.Youhavenotperformedinstallationqualification,operationalqualification,andperformancequalification
on
thebiological
safety
cabinets,theincubators,
and
thecentrifuges.F.Youhavenotperformedavalidationofyourbankingand
thawing
process
to
assure
viabilityof
MSC's.G.You
have
norequirementforpressuredifferentialbetween
theclean
roomsandtheexteriorroomsto
assurethat
non-controlled
airdoes
notflowinthecleanrooms.H.Youhavenotmonitoredthetemperatureorhumidityoftheprocessingroomswhere
you
manufactured
SEEREVERSE
OF
THISPAGE
JoelMartinez,Investigator,LindaM.Hoover,Investigator
~r'~,/
7'u-.-.:iJI
en?~~
04/27/2012
JNSPECTlONALOBSERVAnONS
PAOElI
or
9PAUIIS
 
-OJ)
2012
Corporation
Blvd,
mesenchymalstemcells(MSC's).Themanufacturer'smanualforstatesthatshouldbeinenvironmentalconditionsof
OBSERVATION2
Proceduresdesignedtopreventmicrobiologicalcontaminationofdrugproductspurportingtobesterilearenotestablished,written,andfollowed.Specifically,
You
havemanufacturedMSC'swhichyoureleasedfordistributionatleas.timesbetween
711111
to
thepresent.TheMSC'sareintendedtobeadministeredtopatientseitherintravenouslyorinjectedintra-articularlyandmustbesterile.Thisinspectionrevealed:
,(b)(4)B.
Youhavenotvalidatedyourasepticgowningprocessinordertopreventmicrobiologicalcontamination.Inadditionthereisnodatatosupportthevalidation/quallflcatlonoftheautoclavecycle,Theautoclaveisusedtosterilizegowningwardrobe(labcoat)andpartsoftheincubators.C.Youhavenotperformedenvironmentalswabbingofyourenvironmentalmonitoringprogram.
In
additionairflowpatternunderneaththebiologicalsafetycabinet.manufacturetheMSC's.biologicalsafetycabinets
8S
partofnotbeenperformedtoassure
IIIl
adequateThebiologicalsafetycabinetsareusedtoasepticallyD.Environmentaltestresultsofthecleanroom,blosafetycabinets,andgowningareashowtheisolationofmicroorganismsastheresultoftheuseofsettlingplates.Someofthemicrobiologicalcountsdocumentedarebeyond
the
establishedspecifications.Thereisnodatatoshowthatthemicroorganismsisolatedhavebeenidentifiedorinvestigated.
OBSERVATION
3
Writtenrecordsarenotmadeofinvestigationsintothefailureofabatchoranyofitscomponentstomeetspecifications.Specifically.AfailureInvestigationwasnotperformedforthefollowingoutofspecificationresults
Wld/OT
failurestodeterminetheunderlyingreasonorsourceofthefailure:
JoelMartinez,Investigator~,LindaM.Hoover,Investigator~~
EEREVERSE
OF
THISPAGE
04/27/2012
JIOltM
I'D"
413
 
DEPARTMENt'OFHEALTHAN})HUMANSEltVlCES
roon
ANDDRUGADMINISTRAnON
DIS
4040
NorthExpressway,Suite300
3009499974TO:
David
G.
Eller"
CEO
andPresident
AR~
CelltexTherapeuticsCorporation
12621
CITY.8TA
TE.
Z
Sugarland,
TX77~70
Manufacturer
A.
initialandrepeattestingforsterility;MSC'sfailedinitialsterlllty
B.Ed
Edotoxintest
records
show
the
following
MSC's
uni_,failediniti1etesting:
on12-20-11on12-7-U
I.•
td
,
"
on11-10-11.
.T
ti
(b)(4)-
(b)(4)
C.Environmental
Testing:BacterJa
and
Fungl
testresul~e
been
exceededfortheB~(BiosafetyCabinet-
Clean
Room.GowningArea,
_(CleanRoo._CCleanRoom.
and
BSCUEBioSafety
Cabinet-Clcsn
RoomIlBSC-M
(BlosafetyCabinet-Manufacturing),
BSC-Q(BiosafetyCabinet-Quality
Control),
ClcanRoorrii
Inadditionthereisnowrittenprocedureforconductingfailureinvestigations.
OBSERVATION4
Drug
productproduction
and
controlrecords,
arenot
reviewed
bythe
qualitycontrolunit
to
determine
compliancewithallestablished,approvedwrittenproceduresbeforeabatchisreleasedordistributed.
Specifically,
YoumanufacturedMSCswhichyoureleasedfordistributionat
least.imes
between711111tothepresent.However,youhavenotreviewed
allmanufacturing
rccordsJGIIGJ__
test
records,
endotoxintest
records,orsterility
testrecords
prior
totherelease
for
distribution
of
the
m()senchym~MSC's)
that
youmanufactured
as
evidenced
y
the
following:A.~Theinspectorsignaturelineonthe
manufacturing
recorddated10-20-
11is
blank,however,accordingto
the
outgoing
logthe
MSC'swere
released
forintravenous
infusion
on10-21-11.B.~Theinspector
signature
lineonthemanufacturing
record
dated7-26-11isblank,however,accordingtothe
outgoing
log
the
MSC'swerereleased
tor
intravenous
(IV)
infusionon
10-11-11.C.~Theinspectorsignaturelineonthemanufacturingrecorddated10-6-11
is
blank,
however,
accordingto
the
outgoing
logthe
MSC's
werereleasedfor
intravenous
(lV)
infusion
on
10-7-11.
SEEREVERSE
OF
THISPAGE
04/27/2012
DI\
e
I88U
JoelMartinez,Investigator..
:1'M·
LindaM.Hoover,Investigator
'/IJIH+--
FORMPlJA03
Ot/OI)
fNSPECTIONAl.ODSERVATIONS
OBVIOUSIlIlmONOOSOUITEI
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