US ANDA Filing Process

7/24/2019 US ANDA Filing Process

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Yongtian Ni

Sino-American Regulatory Consulting AllianceDecember 4, 2011


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TopicsC! an" CTD

ANDA C#ec$list %or CTD an" eCTD %ormat

CTD &o"ules'(D)s ANDA *iling +rocess

Re%usal to Receie ssues

Regulations %or ANDA Submissions


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nternational Con%erence on

!armoniation .C!/C! broug#t toget#er t#e regulatory

aut#orities %rom urope, apan an" t#e nite"States to "iscuss scienti3c an" tec#nicalaspects o% pro"uct registration

C! "eelope" gui"elines %or t#e CommonTec#nical Document %or Registration o%

+#armaceuticals %or !uman se .CTD/


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CTD an" eCTD *ormatNe5 C!-CTD %ormat, pre%erably electronic to

support 6uestion-base" Reie5 .6bR/

+re-assigne" ANDA numbers are issue" only

%or true electronic CTD submissions#ttp788555%"ago8c"er8og"8re9uest:preassigne":ect"#tm


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CTD an" eCTD *ormat&o"ule 1 A"ministratie

- Speci3c %or *DA

- Contains regulatory in%ormation .;etter, Debarment ? *inancial Cert, +atent,>oA, @asis %or Submission, Comparison to R>D,A, @A8@ aier, >abeling/

Note: FDA will soon charge user fee forANDA. Details have not been nalized.


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CTD an" eCTD *ormat&o"ule 2 Summaries

- Contains t#e summaries o% c#emistry an"

bioe9uialence in%ormation- 2; 6uality 'erall Summary .6'S/, 6bR

.2;S an" 2;+/ %or '(D

- 2B Clinical Summary- @ioe9uialence Stu"ies

#ttp788555%"ago8c"er8og"8Summary:

@ioTables:CTD#tm


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CTD an" eCTD *ormat&o"ule ; 6uality .C#emistry/

- Drug Substance

- Drug +ro"uct- +#armaceutical Deelopment

- Regional n%ormation


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CTD an" eCTD *ormat&o"ule 4 Nonclinical Stu"y Reports

- Not re9uire" %or ANDAs


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CTD an" eCTD *ormat&o"ule < Clinical Stu"y Reports

Not re9uire" i% t#ere are no @A8@ stu"ies an"

i% a re9uest %or 5aier o% @A8@ stu"ies 5assubmitte" in &o"ule 1121


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ANDA *iling +rocess


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ANDA C#ec$list %or CTD or eCTD*ormat %or Completeness an"

Acceptability o% an Application%or *iling

#ttp788555%"ago8c"er8og"8an"a:c#ec$listp"%


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ANDA C#ec$listT#is c#ec$list 5as create" to %ollo5 t#e

Compre#ensie T'C !ea"ings an" !ierarc#y %ort#e CTD %ormat

nclusie o% t#e C*R re9uirements %or ANDA 3ling

Consultation 5it# in"ii"ual "iisions o% '(D as5ell as re%erences to t#e multiple gui"ances %orin"ustry 5ere use" in t#e "eelopment o% t#is

c#ec$listSections not liste" on t#e c#ec$list are not

re9uire" %or ANDA 3ling, but may be inclu"e" i%"eeme" necessary %or reie5


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&o"ule 1- A"ministratie112 Signe" an" complete" Application *orm

21C*R;144.a/.2/ *orm ;


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&o"ule 1- A"ministratie12 Coer >etter

'nly re9uire" %or paper submission

A""ress any issues or preiouscommunication 5it# t#e Agency

T'C


See Compre#ensie T'C .!ea"ings ?!ierarc#y/


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&o"ule 1- A"ministratie1;2 *iel" Copy Certi3cation


Re9uires original signature

1;; Debarment Certi3cation-(DA

*irms must "eclare t#at t#ey #ae not an" 5illnot use in any capacity any in"ii"ual t#at #as

been "ebarre" pursuant to Section ;0=.$/.1/an" .2/ o% t#e (DA


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&o"ule 1- A"ministratie1;4 *inancial Certi3cations

@A8@ *inancial Certi3cation .*orm ;4D in t#e lectronic'range @oo$


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&o"ule 1- A"ministratie1;


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NC clusiityNC clusiity- only eclusiity t#at bloc$ssubmission o% ANDAs %or a perio" o% < years%rom t#e "ate o% approal o% t#e 3rst approe"NDA % an ANDA contains a +E certi3cation toa liste" patent coering t#e NDA %or 5#ic# anNC applies, t#en t#e application may besubmitte" one year prior to t#e epiration o%t#e NC eclusiity


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&o"ule 1- A"ministratie141 >etters o% Aut#oriation

Allo5s *DA to reie5 t#e re%erence" D&*

- Type .A+/- Type .CC/

- S Agent >oA must be submitte" by all 3rmsresi"ing outsi"e o% S S Agent is grante"

aut#ority by t#e D&* #ol"er to act as aninterme"iary bet5een *DA an" t#e applicant


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&o"ule 1- A"ministratie11211 @asis %or Submission&ust inclu"e name o% R>D as "esignate" by

t#e 'range @oo$nclu"e t#e NDA number on t#e @asis %or

submission% utiliing an approe" Suitability +etition as

@asis o% Submission, t#e applicant mustproi"e a copy o% t#e approal letter %or t#eSuitability +etition 21 C*R ;14;


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&o"ule 1-A"ministratie11211 @asis %or Submission .Cont)"/

;14122 ANDAs t#at rely upon an R>D t#at is

no longer mar$ete"An application may be 3le" pen"ing t#eoutcome o% t#e Agency)s "etermination t#at a"rug pro"uct 5as remoe" %rom t#e mar$et %or

reasons ot#er t#an sa%ety or eFcacy T#ispetition must be submitte" un"er 102


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&o"ule 1- A"ministratie11212 Comparison @et5een (eneric Drug

an" R>D-


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&o"ule 1- A"ministratie11214 nironmental Analysis

*irms s#oul" submit a statement t#at t#ey arein compliance 5it# all %e"eral, state an" localenironmental la5s

Categorical eclusion un"er 2


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&o"ule 1- A"ministratie1121< Re9uest %or aier o% n-Eio @A

Stu"ies

*or certain "rug pro"ucts, t#e in io @A8@ o%t#e "rug pro"uct may be sel%-ei"ent an"meets one o% t#e criteria "e3ne" in 21C*R;2022.b/.1/


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&o"ule 1- A"ministratie1141 Dra%t >abeling+ropose" "ra%t labeling .electronic %ormat/H

inclu"ing S+>S I S container labeling 5it# "iJerences

annotate" an" eplaine"

lectronic submission re9uirements

ANDAs submitte" a%ter une K, 2004 arere9uire" to proi"e t#eir labeling in electronic%ormat


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&o"ule 1- A"ministratie114; >iste" Drug >abeling .R>D/

S I S >abeling o% +ac$age an" +atient nsert

5it# all "iJerences annotate" an" eplaine"1 R>D label an" 1 R>D container label


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&o"ule 2- Summaries2; 6uality 'erall Summary

6'S s#oul" inclu"e suFcient in%ormation

%rom eac# section in &o"ule ; to proi"e t#ereie5er an oerie5 o% t#e application

C#emistry8@io Diision re9uests submissionin +D* an" &S %ormat

&o"el 6'S an" &o"el @io Summary Tablesaailable in '(D 5ebsite


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&o"ule 2- Summaries2B Clinical Summary .@ioe9uialence/

Summary o% results o% @A8@ stu"ies

@ioe9uialence Diision re9uest submission in+D* an" &S %ormat


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&o"ule ;- 6uality;2S1 (eneral n%ormation .Drug

Substance/

NomenclatureStructure

(eneral +roperties


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&o"ule ;- 6uality;2S2 &anu%acture .Drug Substance/

Name an" %ull a""ress o% %acilities

.Summary table o% all %acilities- contacts,a""resses, p#one8%a numbers, C*N L, etc/

*unction or Responsibility

Type D&* No %or A+

M D&* %or A+ must be stampe" receie" byAgency prior to submission o% an ANDA t#atrelies upon sai" D&*


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&o"ule ;- 6uality;2S4 Control o% Drug SubstanceSpeci3cations

Test +roce"uresEali"ationSpectra an" c#romatogramsSample statement in accor" 5it# 21 C*R

;14


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&o"ule ;- 6uality;2+1 Description an" Composition o%t#e Drug +ro"uct

nit composition

nactie ingre"ients an" amounts ascompare" to (


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Components an" Composition o%

t#e Drug +ro"uctnactie ingre"ients not preiously approe"

or #ig#er t#an preiously approe" .&ostprealent RTR issue/

'(D 5ill not consi"er (RAS8(RA statusconclusie ei"enceH use in %oo" pro"ucts 5illnot persua"e *DA to allo5 its use in "rugpro"ucts

ception cipients7 c#anges in preseratie,buJer or antioi"ant7 ;144.a/./.iii/

Note t#at p! a"Gusters in parenterals are noteception ecipients


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&o"ule ;- 6uality;2+2 +#armaceutical DeelopmentS#oul" contain in%ormation on t#e

"eelopment stu"ies con"ucte" to establis#t#at t#e "osage %orm, %ormulation,manu%acturing process, container closuresystem, microbiological attributes an" usageinstructions are appropriate %or t#e purposespeci3e" in t#e application

See (ui"ance %or n"ustry 6K


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&o"ule ;- 6uality;2+; &anu%acture .Drug +ro"uct/Name an" %ull a""ress o% manu%acturers,

contract labs, contacts an" speci3c %unctions

All 3rms per%orming any testing, pac$aging,steriliation, etc o% DS or D+ must be D)e" sot#at a re9uest may be initiate" %or inspection

c(&+ certi3cation 5it# signature*DA inspection in%ormation


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&o"ule ;- 6uality;2+;2 @atc# *ormula .Drug +ro"uct/>ist o% all components o% t#e "osage %orm to

be use" in t#e manu%acturing process,amounts on a per batc# basis, inclu"ingoerages an" a re%erence to t#eir 9ualitystan"ar"s


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&o"ule ;- 6uality;2+;; Description o% &anu%acturing +rocessan" +rocess Controls .Drug +ro"uct/

*lo5 Diagram s#o5ing t#e process steps an"5#ere materials enter t#e process

@lan$ &aster +ro"uction @atc# Recor"s

- &aimum pro"uction scale-up o% 10 t#e

t#eoretical yiel" o% t#e e#ibit batc# may bere9ueste"


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&o"ule ;- 6uality;2+;; Description o% &anu%acturing+rocess an" +rocess Controls .Cont)"/Reprocessing Statement

- *orms s#oul" certi%y t#at it "oes not utiliereprocessing proce"ures in t#emanu%acturing o% t#e "rug pro"uct % t#e3rm "oes 5is# to reprocess t#e "rug

pro"uct, t#ey 5ill submit a +rior ApproalSupplement to t#e Agency "escribing t#eprocess Release o% t#e reprocesse"pro"uct 5ill be 5it##el" until t#e +AS isapproe" by t#e Agency


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&o"ule ;- 6uality;2+;4 Controls o% Critical Steps an"nterme"iates .Drug +ro"uct/

All critical process controls an" t#eirassociate" numeric ranges, limits, oracceptance criteria s#oul" be i"enti3e" an"

Gusti3e" an" a brie% "escription o% t#e testproi"e"


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&o"ule ;- 6uality;2+;< +rocess Eali"ation an"8or aluation.Drug +ro"uct/Description, "ocumentation, an" results o%

t#e ali"ation an"8or ealuation s#oul" beproi"e" %or critical steps or critical assaysuse" in t#e manu%acturing process

- &icrobiological steriliation ali"ation-

*ilter Eali"ation&ust #ae complete 3lter ali"ation presentupon submission o% an ANDA, t#is in%ormationmay not be submitte" at a later "ate


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&o"ule ;- 6uality;2+4 Controls o% cipients .nactiengre"ients/

"enti%y source o% supplier %or all inactieingre"ients .tabular %ormat/

CoA

;2+41 Speci3cationsTesting Speci3cations


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&o"ule ;- 6uality;2+42 Analytical +roce"uresTest proce"ures s#oul" be proi"e", 5#en

appropriate

;2+4; Eali"ation o% Analytical +roce"ures

Normally not nee"e" %or ecipients

S#oul" be submitte" in special circumstances.ie, c#aracteristic o% ecipient is critical topro"uct 9uality/


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&o"ule ;- 6uality;2+44 usti3cation o% Speci3cationsApplicant)s CoA

+#arm8To stu"ies 5#en appropriate to Gusti%yt#e sa%ety o% an inactie ingre"ient

( "atabase, compen"ial, etc


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&o"ule ;- 6uality;2+< Controls o% Drug +ro"uct;2+


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&o"ule ;- 6uality;2+


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&o"ule ;- 6uality;2+B Container Closure System1 Summary o% CC System .i% ne5 resin,

proi"e "ata/

2 Components Speci3cation .inclu"ingngineering Dra5ing/ an" Test Data

; +ac$aging Con3guration an" Sies

4 Container Closure testing


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&o"ule ;- 6uality;2+K Stability;2+K1 Stability Summary an" Conclusion

Stability +rotocol+ropose" epiration "ating perio"

- Tentatie 24 mont# epiration "ate base"upon ; mont#s o% accelerate" stability


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&o"ule ;- 6uality;2+K2 +ost-approal Stability +rotocol an"Stability Commitment*irm must commit to placing 3rst ;

pro"uction lots as pac$age" in t#e largestan" smallest container on long term stabilityac# year t#erea%ter, a minimum o% one lot

pac$age" in t#e largest an" smallest

container 5ill be a""e" to long term stability*irm must report t#e stability "ata as it

becomes aailable .perio"ic reports/


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&o"ule ;- 6uality

;2+K; Stability DataMData %rom 4 timepoints s#oul" be submitte"- 0, 1, 2,

an" ; mont#s; mont#s o% accelerate" stability con"ucte" per C!

61A, een i% pro"uct %ails un"er stresse" con"itionsRS@ 5ill 3le an ANDA 5it# %ailing accelerate" stabilitybut may not 3le an ANDA i% only unstresse" stability isproi"e"*irm can brac$et interme"iate pac$age sies an" only

per%orm stability on largest an" smallest pac$age siesi% same CC system is use" %or multiple pac$age sies@atc# number must be t#e same as t#e e#ibit batc#

M*DA soon 5ill re9uire 12 mont#s RT "ata an" = mont#sAccelerate"8nterme"iate "ata %or t#ree lots %or eac# +ac$age con3guration


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&o"ule ;- 6uality;2RRegional n%ormation;2RDrug Substance

ecute" @atc# Recor"s .i% aailable/Comparability +rotocols .optional/

-use" to "emonstrate t#e lac$ o% a"erseeJect %or speci3e" types o% post-approal

manu%acturing c#anges&et#o"s Eali"ation +ac$age


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&o"ule ;- 6uality;2RDrug +ro"uctecute" @atc# Recor"s

- +arenteral pro"ucts7

&ust pac$age a minimum o% 10 o% t#ee#ibit bul$ sie in eac# ial sie propose" %ormar$etingH scale-up base" upon actualpac$age" amounts

- +roi"e reconciliation "etailing t#e "ispositiono% all "osage units


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&o"ule ;- 6uality;2R Drug +ro"uct .Cont)"/n%ormation on Components

&anu%acturer n%ormation*unction o% Contract *acilities .Steriliation,etc/CoAComparability +rotocols

- use" to "emonstrate t#e lac$ o% a"erseeJect %or speci3e" types o% post-approalmanu%acturing c#anges&et#o"s Eali"ation +ac$age


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Certi3cation to Accompany Drug, @iological+ro"uct,

an" Deice Applications or SubmissionsT#e recently enacte" S +ublic >a5 110-K


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Re%usal to Receie ssuesncomplete @ stu"iesNo "issolution "ata

D&* not present or receie" by Agency by t#estampe" ANDA receipt "ate

&issing or incomplete stability "ata

No patent certi3cations

&issing Citien)s +etition or Suitability +etition


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Re%usal to Receie ssues

.Cont)"/nactie ngre"ients

&aster pro"uction batc# recor"s not in accor"5it# 10 scale-up

No in%ormation "emonstrating t#at "iJerencesin inactie ingre"ients "o not impact sa%etyan" eFcacy


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Regulations %or ANDA

submissions21 C*R

US ANDA Filing Process

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