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Transfer Validation
RequirementsMorning Session #2
Robert Beall, PMP
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Introduction
2 Condential
Robert Beall
2
Transfer ExperienceSolids Transfer Engineer for Otimi!ation in "ort $meri%a &OP'"$( )*2 Produ%t transfersManaged Euroe to +S$ "$ rodu%t transfers for * blo%-buster rodu%t lines.
/ead of 'nternational transfers bet0een 1erman, +S and 'ndia for 33 distribution )4rodu%ts/ead of 5ife6C%le rodu%t transfer for arenteral manufa%turing 78 rodu%ts.Solids Transfer Manager for animal /ealt%are rodu%ts 9 *2 rodu%tsMedi%al e:i%e Transfer Consultant 9 8 rodu%tsBiologi%al rodu%t transfer leader 9 8 rodu%ts
Hometown: Syracuse, NYHome: Providence, RIami!y: "#nt$er %Son&, 'aren%(au)$ter&, *a!vin %Son&Ho++ies: Sai!in), Trave!, !ympic
-ei)$t!iftin)Education: RIT .S / En)ineerin)P'P
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0)enda
1 Condential
5ife%%le Validation Requirements
). Regulator Standards
2. Stage ) 9 e:eloment
*. Stage 2 6 Validation
8. Stage * 9 5ife%%le
1
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5ife%%le Validation Requirements
+S Regulator Standards for ValidationSo!id ra! (ose 3 .io!o)ica! Prod4 'edica! (evice
2)).);; &a(2)).));&b(2)).)7; &b(2)).)7< &a,d(
2)).48 &b(2)).)4; &e(
'SO )*84CBER>CVM ?an 2;)) Pro%ess Validation 1eneral Prin%ilesand Pra%ti%es.
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0udience 5uic6.enc$mar6in) Po!! 78
How many of you have read the 2011 FDAGuidance on Process Validation?
Yes or o
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Process Improvement9
"randpas *ar
7
uture"rand6id
s *ar
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Guidance Evolutionfrom 1987 to 2011
1987 !in"le #rotocol a##roach
!tatic event$ disconnected
% &atch re'uirement almoste(#licit
)ore deli&erately #rescri#tive
!im#ly a confirmation
*riticality is &inary +yes or no,
-t is what it is Final re#ort .um#s toconclusions
2011
% #hased a##roach
/ifecycle evolution$ sustaina&le o lon"er a ma"ic run num&er
is&ased decisionmain"
3m#hasi4es u# front learnin"
*riticality is a continuum
Greater clarity of e(#ectations Allowin" the final re#ort to
5return6 to #rocess desi"nallows for learnin"
7
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Borro0ed from 1ra%e E. M%"all
4
"oodp!annin),expectedresu!t
Poor design,lanning, ro%essandunderstanding
Learning Progression
Poor, minimal design
P@ %e%-list
eAer%ise 0> littleunderstanding
+neAlained :ariation,
Produ%t and ro%essroblems, Pro%ess not in%ontrol. 'a;or
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0pproac$ to Process >a!idation
Process validation involves a series of activities
tain" #lace over the lifecycleof the #roduct and
#rocess8 9he "uidance descri&es the #rocess
validation activities in three stages8
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0udience 5uic6.enc$mar6in) Po!! 72
Does the Process Validation Guidance onlya##ly to Product or Device manufacturin"?
Y3! or :?
);
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Process >a!idation Sta)es
Sta)e 8Pro%essesign
Sta)e 2Pro%ess
@uali%ation
Sta)e 1Continued
Pro%ess
Veri%ation
Buildingand
%aturing
ro%ess-no0ledg
e
Establising a %ontrolstrateg
esign offa%ilit andquali%atio
n ofutilities D
equiment&'@>O@>P@(
Pro%essPerforman%
e
@uali%ation &PP@(
'mlement %ontrol
strateg
)2
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0udience 5uic6.enc$mar6in) Po!! 71
How many have a life cycle a##roachdocumented at their facilities?
Yes or o
)*
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0udience 5uic6.enc$mar6in) Po!! 7
How many .ust have what we reco"ni4e asa Phase 2 a##roach?
Yes or o
)8
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0udience 5uic6.enc$mar6in) Po!! 7?
How many have a develo#ed Phase %#ro"ram in #lace?
Yes or o
)Conrm
Stage 2Pro%ess @uali%ation
&P5(
esign ofa%ilities D
@uali%ation of
Equimentand +tilities
Pro%ess
Performan%e@uali%atio
n &PP5(
,istrib
ut
e
Stage 3
Continued
Process
Verification
istribute
C#anges
C#anges
Ref: Grace E. McNally F! "Guide #eader$ Se%t &'( )*&* )7
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-$at does t$is mean9
/ifecycle a##roach ; #roduct conce#tionthrou"h commerciali4ation
Focusing exclusively on qualification effortswithout also understanding the manufacturing
process and associated variations may not leadto adequate assurance of quality8
FDA Guideline !ection --ariation (etected
Sc$ematic of Sta)es%Conrm
Stage 2Pro%ess @uali%ation
&P5(
esign ofa%ilities D
@uali%ation of
Equimentand +tilities
Pro%ess
Performan%e@uali%atio
n &PP5(
,istrib
ut
e
Stage 3
Continued
Process
Verification
istribute
C#anges
C#anges
Ref: Grace E. McNally F! "Guide #eader$ Se%t &'( )*&* )4
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)
ST$1E )F PROCESSES'1"
9hou"htful #lannin" very early in Develo#ment
!ources of nowled"e #rior to !ta"e 1
o Previous e(#erience with similar #rocesses +e8"8 #latform
#rocess,
o Product and #rocess understandin" from clinical and #re
clinical activities
o Analytical characteri4ation
o Pu&lished literature
o 3n"ineerin" !tudies=&atches
o *linical )anufacturin"
Process develo#ment and characteri4ation studies
nowled"e +!ta"e 1 ; Process Desi"n,
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2;
ST$1E )F PROCESSES'1"
3arly !ta"e 1 ; Process Develo#ment
o 3sta&lish 9ar"et Product Profile and uality 9ar"et Product
Profile +9PP, ; /ivin" Documents
o -dentify *ritical uality Attri&utes +*As,
o Define the )anufacturin" Process /ate !ta"e 1 ; Process *haracteri4ation
!cale u#$ 9ech 9ransfer and !et Desi"n !#ace
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2)
ST$1E )F PROCESSES'1"
9his is done at the initiation of !ta"e 1
Periodically u#dated to incor#orate any new data that may have &een
"enerated durin" develo#ment
Addresses relevant characteristics that include@
o -ntended use in a clinical settin"
o Dru" su&stance 'uality attri&utes a##ro#riate to the dru" dosa"eform &ein" develo#ed +e8"8 #hysical$ chemical and &iolo"ical
#ro#erties,
o Dru" #roduct 'uality attri&utes for the intended mareted #roduct
+e8"8 #urity=im#urities$ sta&ility$ sterility$ #hysical and chemical
#ro#erties,
o Pharmacoinetic characteristics +e8"8 dissolution$ aerodynamic
#erformance,
o 3(ci#ient and com#onent 'uality attri&utes$ dru" ;e(ci#ient
com#ati&ility$ and dru" container com#ati&ility that affect the
#rocess a&ility$ sta&ility or &iolo"ical effect of the dru" #roduct
uality 9ar"et Product Profile +9PP,
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ST$1E )F PROCESSES'1"
Does not include +this is contained in the 9PP,
o Dosa"e forms and stren"ths
o *ontraindications
o arnin"s and Precautions
o Adverse eactionso Dru" interactions
o A&use and de#endence
o overdose
uality 9ar"et Product Profile +9PP,
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2*
ST$1E )F PROCESSES'1"
Physical$ chemical$ &iolo"ical or micro&iolo"ical #ro#erties orcharacteristics that should &e within an a##ro#riate limit$ ran"e
or distri&ution to ensure the desired #roduct 'uality
*As are :9 synonymous with s#ecifications
!everal *As may &e detected &y a sin"le test method
*As with corres#ondin" *riticality is Assessment and desiredconfidence
*As are su&.ect to chan"e in the early sta"es of #roduct
develo#ment +ris mana"ement should allow for an evolution of
#roduct and #rocess nowled"e
*As for commercial #roducts should &e defined #rior to
initiation of !ta"e 2 activities
*ritical uality Attri&utes +*As,
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28
ST$1E )F PROCESSES'1"
Desi"ned to consistently #rovide a #roduct that will meet its re'uired 'uality
attri&utes Process Descri#tion showin" #rocess in#uts$ out#uts$ yields$ in#rocess tests
and controls$ and #rocess #arameters +set #oints and ran"es, for each unit
o#eration
o Process re'uirements includin" raw materials$ scale and order of
o#erations
o !et #oints and ran"es for #rocess #arameterso -dentification and 'uantity of all material flows +addition$ wastes and
#roduct streams,
o 9estin"$ sam#lin" and in#rocess controls
o Hold times and hold conditions for #roduct and addition solutions
o 3stimated yields and durations
o !i4in" for e'ui#ment includin" chromato"ra#hy columns$ filtration units$
etc8
o !#ecific identification +manufacturer$ #art num&er, for manufacturin" +e8"8
filters, and #roduct com#onents +e8"8 vials$ sto##ers$ etc8,
o :ther information necessary to successfully re#roduce the #rocess
Define the )anufacturin" Process
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2nowin" : and PA +with su##ortive data, can &e used to
assess the severity of #rocess deviations caused &y #arameter
e(cursions
outine monitorin" re'uirements +includin" sam#lin" and testin",
o Data collection and analysis should &e"in in !ta"e 1 and will
&ecome inte"ral #arts of !ta"e 2 and eventually evolves into
!ta"e %
o 38"8@ Flow rates$ tem#eratures$ volumes$ #H$ etc8
*ontrol !trate"y
ST$1E ) PROCESS
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* "o Hes > "oSe%Range
Hes > "o Control Carts Caabilit $ssessment
Pattern$nalsis
$:erage >Standard
de:iation
istributionanalsis
I2 PPI
Ra0MaterialRelease 9
0!6y!atin)0)ents
84 Hes 9MVR6)2*8
Hes 9 +SP)24;
Hes 9Reort);2
"$ .*> ;.8 J 6 "ormal *.; ).8 "o 9 "'Rlannedfor 2;)aria+i!ity 0ssessment
7;
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-$y PP@and not *P@9
PPK: +nde, -ased on #ong er/ Variation
Calculated using o0erall standard de0iation
+ndicates t1e o0erall %erfor/ance of a %rocessincluding s%ecial causes of 0ariation
PP2ca%tures -ot1 it1in4-atc1 and -eteen4-atc1
0ariation
5sually used 1en t1e state of statistical control is
un6non
7)
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72
)( Summar of results2( Conrm Pro%ess Performan%e :alue*( 5ist of CPPs b Ris- Priorit "umber8( Control sstem
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*ommercia! (istri+ution
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78
ST$1E *F CO"T'"+E PROCESSVER''C$T'O"
-ncor#oration of Feed&ac from *PV )onitorin"
Validation *PP and *ABs checed ; A isAssessment is conducted to confirm future state8
/oc validated #arameters
ST$1E *F CO"T'"+E PROCESS
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7eriBcation
Goal ; to continually assure that #rocess remains in astate of control
*ollection and evaluation of data will allow detection of#rocess drift
3valuation should determine whether action must &etaen
:n"oin" #ro"ram to collect and analy4e data must &eesta&lished
!tatisticians can develo# the data collection #lan Omethods
;
EA *ontinuous Process
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>a!idation
An alternative a##roach in which manufacturin"
#rocess #erformance is continuously monitored andevaluated8
-ncomin" materials or com#onents$ in#rocessmaterial and finished #roducts
Verification of attri&utes$ #arameters and end #oints$and assessment of *A and *PP trends
se of tools to su##ort +PA9$ -$ etc8,
)
EA *ontinuous Process
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A *o uous ocess>a!idation
:ther Factors
*om#liance with G)P #rinci#les O re'uirements
Prior develo#ment O manufacturin" nowled"e *om#le(ity of #roduct=manufacturin" #rocess
Process should &e verified on commercialscale&atches #rior to maretin"
2
Is t$ere a conc!usion9
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Is t$ere a conc!usion9
>now your #rocess
nderstand your varia&ility