Transfer Validation Requirements

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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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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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How many have a life cycle a##roachdocumented at their facilities?

Yes or o

)*


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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;


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)


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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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*


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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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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)( 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

Transfer Validation Requirements

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