validation what is the new guidance

7/21/2019 Validation What is the New Guidance

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VALIDATION

What is the new guidance?



What is a Compliance Policy

Guide? !plain "DA policy on #egulato#y issues

CG$P #egulations and application commitments%

Ad&ise the 'eld sta( on "DA)s standa#dsand p#ocedu#es to *e applied whendete#mining indust#y compliance

CPGs may come +#om a #e,uest +o# anad&iso#y opinion- +#om a petition +#omoutside the Agency- o# +#om a pe#cei&edneed +o# a policy cla#i'cation *y "DApe#sonnel%



The .ig Disclaime# It #ep#esents the "DA/s cu##ent thin0ing

on the topic%

It does not c#eate o# con+e# any #ights+o# o# on any pe#son and does notope#ate to *ind "DA o# the pu*lic%

An alte#nati&e app#oach may *e used i+such app#oach satis'es the#e,ui#ements o+ the applica*le statuteand #egulations%



P#ocess Validation1e,ui#ements +o# D#ugP#oducts and APIs 2u*3ect toP#e4$a#0et App#o&alCPG 567%877



.ac0g#ound The CPG co&e#s

CD19C.19CV$ p#oducts

2te#ile and Nonste#ile p#ocesses The CPG does not add#ess methods

and cont#ols designed to ensu#ep#oduct ste#ility :e%g% aseptic 'll

&alidation; Does not co&e# .LAs o# #ecom*inant

p#otein d#ug p#oducts



A#eas o+ inte#est Con+o#mance *atch

Validation *e+o#e PAI

Validation *e+o#e comme#cialdist#i*ution

P#ocess analytical technology

API p#ocess &alidation



When is p#ocess &alidation

e!pected? Not necessa#y *e+o#e an NDA is

app#o&ed Although many p#e+e# to &alidate the

manu+actu#ing p#ocess prior to thep#eapp#o&al inspection% 1educe time to ma#0et Gain additional p#ocess in+o#mation

It is necessa#y *e+o#e comme#cialdist#i*ution



Why Validate? <uality *y design- *uilt in

Can)t inspect ,uality in

Demonst#ate cont#ol o+ p#ocess

Good science

Good *usiness It)s the law



P#ocess Validation and the

Law Dosage "o#ms

1e,ui#ed *y CG$P1s :=88%877>

=88%887; n+o#ced as G$P unde# the "DC Act

:@78:a;:=;:*;;

APIs n+o#ced as G$P unde# the "DC Act

:@78:a;:=;:*;;



Validated P#ocess P#o&ides a high le&el o+ scienti'c

assu#ance to #elia*ly p#oduce

accepta*le p#oduct sing #ational e!pe#imental design

&aluation o+ data

"#om de&elopment to comme#cialphase



What is e!pected? .e+o#e comme#cial dist#i*ution

*egins- a manu+actu#e# is e!pected

to ha&e accumulated enough dataand 0nowledge a*out thecomme#cial p#oduction p#ocess to

suppo#t post4app#o&al p#oductdist#i*ution%



The#e is a new te#mBB Con+o#mance .atch

P#epa#ed to demonst#ate that-unde# no#mal conditions andde'ned #anges o+ ope#ating

pa#amete#s- the comme#cial scalep#ocess appea#s to ma0eaccepta*le p#oduct%



Con+o#mance .atches "o#me#ly 0nown as &alidation *atches NDAs may *e app#o&ed p#io# to

completion o+ the initial con+o#mance*atch phase o+ p#ocess &alidation

The manu+actu#e o+ the initialcon+o#mance *atches should *e

success+ully completed p#io# tocomme#cial dist#i*ution



Inspection o+ &alidation

acti&ities du#ing a PAI PAI team will assess any &alidation

acti&ities whethe# completed o# not

A withhold #ecommendation will *e made i+ <uestiona*le integ#ity

Demonst#ate that the p#ocess is not unde#cont#ol

"i#m has not committed to ma0ing app#op#iatechanges

I+ de'ciencies +ound in al#eady app#o&edp#oduct &alidations




acti&ities 4 4 post4app#o&al Co&e# within 8st yea# o+ manu+actu#e

at comme#cial scale i+

It is the '#st d#ug p#oduced at the site The#e we#e p#e&ious p#o*lems &alidating

a simila# p#ocess +o# anothe# p#oduct

,uipment9p#ocess is su*stantially

di(e#ent +#om e!istinge,uipment9p#ocesses

Inhe#ently &a#ia*le9comple! ope#ations




acti&ities 4 4 post4app#o&al I+ a '#m has a good &alidation

histo#y with simila#

p#oducts9p#ocesses P#ocess &alidation p#otocol #epo#t

may *e sent to Dist#ict oce +o#

e&aluation



Inspection o+ &alidationacti&ities 4 4 post4app#o&al

I+ signi'cant de'ciencies in&alidation e(o#ts a#e +oundE Initial con+o#mance *atch phase not

completed P#otocol not +ollowed o# inade,uate Data shows p#ocess not in cont#ol

And p#oduct has *een dist#i*utedE 1ecommend #egulato#y action



Completion o+con+o#mance *atches p#io#to dist#i*ution It is e!pected +o# most p#oducts

$ay not *e needed +o# ce#tainp#oducts O#phan d#ugs

1adiopha#maceuticals



Completion o+con+o#mance *atches p#io#to dist#i*ution I+ p#oduct dist#i*ution is to *e

concu##ent with #elease o+

con+o#mance *atches- "DA will assess .asis +o# 3usti'cation

P#otocol9plan a&aila*le data to &e#i+ycont#ols p#io# to #elease> e&entual p#ocess

&alidation Post dist#i*ution monito#ing +o# p#o*lems



P#ocess analyticaltechnology

"o# manu+actu#ing p#ocesses thatuse PAT- it may not *e necessa#y

+o# a '#m to manu+actu#e multiplecon+o#mance *atches p#io# to initialdist#i*ution%

This will *e decided on a case *ycase *asis *y "DA depending onhow and the e!tent PAT is used%



API)s used in othe# al#eadyapp#o&ed d#ug p#oducts

P#ocess &alidation is e!pected p#io#to app#o&al o+ the application i+ the

API is al#eady *eing used inanothe# d#ug p#oduct and is made*y essentially the same

p#ocess9scale Con+o#mance *atches will *e

#e&iewed



API)s N$s o# newp#ocess

Not ha&ing completed p#ocess &alidation andinitial con+o#mance *atches will not delayapp#o&al o+ the NDA

"DA will audit and assess any a&aila*le p#ocess&alidation p#otocols- acti&ities- data- andin+o#mation whethe# o# not completed

A withhold #ecommendation will *e made i+ anycompleted API &alidation e(o#ts include data o+,uestiona*le integ#ity o# demonst#ate that theAPI p#ocess is not unde# cont#ol and the '#m hasnot committed to ma0ing app#op#iate changes%



APIs .iotech

2ome *iotech NDAs #e,ui#e&alidation in+o#mation to *e

su*mitted as pa#t o+ the C$Csection%



De'ciencies in othe#&alidated API p#ocesses

I+ p#ocess &alidation acti&ities a#e de'cient +o#an API p#ocess simila# to that o+ the API unde#inspection and +o# which a wa#ning lette# o#

othe# #egulato#y action will *e p#oposed- awithhold #ecommendation +o# the dosage +o#mwill *e made%

A withhold #ecommendation will *e made i+ theAPI '#m has not esta*lished o# is not +ollowing

an ade,uate initial con+o#mance *atch &alidationplan9p#otocol o# when the p#ocess is not unde#cont#ol as demonst#ated *y #epeated *atch+ailu#es due to manu+actu#ing p#ocess &a#ia*ility%



2o What Is New?

:nothing #eallyEE

Win0- win0Nudge- nudgeBB;



2o What Is $issing?

validation what is the new guidance

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