2-4 ICH Overview

7/21/2019 2-4 ICH Overview

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Satish Mallya January 20-22, 20101 |

2-4 ICH Quality Guidances:an overview

PQP Assessment Training

January 18-21, 212

Satish Mallya

January 18-21, 2012




ICH T!"ics

#ta$ility - Q1A % Q1&

Analytical 'alidati!n % Q2

Im"urities % Q(A - Q(C )Q(* % c!nce"t "a"er+

Parmac!"!eias % Q4A - Q4 )and anne.es+

Quality !/ i!tecn!l!gical Pr!ducts % Q0A % Q0

#"eci/icati!ns % QA % Q

G!!d 3anu/acturing Practice % Q

Parmaceutical *e5el!"ment % Q8

Quality 6is7 3anagement - Q

Parmaceutical Quality #ystem % Q1

*e5el!"ment and 3anu/acturing !/ *rug #u$stances % Q11

January 18-21, 2012




&!cus

Stability - Q1A, B, C, D, E & F

Validation of Analytical Methods – Q2!1"

#$%'ities – Q(A, B & C

S%ecifications – Q)A Che$ical Sbstances" & Q)B& Q)B

Biotechnolo*y+Biolo*ical 'odcts"Biotechnolo*y+Biolo*ical 'odcts"

January 18-21, 2012




#ta$ility

Q1A)62+ Stability estin* of .e/ D'* Sbstances and'odcts

Q1 hotostability estin* of .e/ D'* Sbstances and'odcts

Q1C Stability estin* fo' .e/ Dosa*e Fo'$s

Q1*B'ac0etin* and Mat'iin* Desi*ns fo' Stability estin*of .e/ D'* Sbstances and 'odcts

Q1 Ealation of Stability Data

Q1& Stability Data ac0a*e fo' !e*ist'ation A%%lications inCli$atic 3ones ### & #V 9itdra9n % June 2"

January 18-21, 2012




Q1A!2"SAB#4#5 ES#.6 7F

.E8 D!96 S9BSA.CES A.D !7D9CS

*rug #u$stance *rug Pr!duct#tress testing P!t!sta$ility testing

#electi!n !/ $atces #electi!n !/ $atces

C!ntainer cl!sure system C!ntainer cl!sure system

#"eci/icati!n #"eci/icati!n

Testing /reuency Testing /reuency

#t!rage c!nditi!ns #t!rage c!nditi!ns

#ta$ility c!mmitment #ta$ility c!mmitment

5aluati!n 5aluati!n

#tatements;<a$eling #tatements;<a$eling

January 18-21, 2012




#tress Testing;P!t!sta$ility

*rug #u$stance *rug Pr!duct

7ne %'i$a'y batch

Effect of te$%e'at'es in 1:;Cinc'e$ents e<*<, =:;C, ):;C,etc<" aboe that fo' accele'atedtestin*"

Effect of h$idity e<*<, >

?=@!"

7ne %'i$a'y batch

As in #C Q1B

January 18-21, 2012




#electi!n !/ atces


*ata !n at least tree "rimary $atces !/minimum "il!t scale manu/actured $y te samesyntetic r!ute as used /!r "r!ducti!n $atces=

*ata !n at least tree "rimary $atces !/ tedrug "r!duct % t9! "il!t and tird !ne can $esmaller - same /!rmulati!n and "ac7aged in tesame c!ntainer cl!sure system as "r!"!sed/!r mar7eting=

Te manu/acturing "r!cess used /!r "rimary$atces s!uld simulate tat t! $e a""lied t!"r!ducti!n $atces

>ere "!ssi$le, use di//erent $atces !/ tedrug su$stance=

#!uld $e "er/!rmed !n eac indi5idualstrengt and c!ntainer si?e !/ te drug "r!ductunless $rac7eting !r matri.ing is a""lied=

January 18-21, 2012


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C!ntainer Cl!sure #ystem


Stdies to be condcted on the A# %ac0a*ed in a containe'

clos'e syste$ that is identical too' si$lates the %'o%osedco$$e'cial %ac0a*in*

Stdies to be ca''ied ot incontaine' clos'e syste$ identical

to co$$e'cial %ac0a*in* stdiesca''ied ot in othe' %ac0a*in*$ate'ials can be sed ass%%o'tin* info'$ation

January 18-21, 2012


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#"eci/icati!n

*rug #u$stance *rug Pr!duct #tudies t! include attri$utes

susce"ti$le t! cange duringst!rage and 9ic can in/luenceuality, sa/ety and e//icacy:- Pysical

- Cemical- 3icr!$i!l!gical

#tudies t! include attri$utessusce"ti$le t! cange duringst!rage and 9ic can in/luenceuality, sa/ety and e//icacy:- Pysical

- cemical,- micr!$i!l!gical,- "reser5ati5e c!ntent- /uncti!nality tests )e=g= 9it

deli5ery systems+

'alidated analytical met!ds t! $eem"l!yed

'alidated analytical met!ds t! $eem"l!yed

June 21January 18-21, 2012




Testing &reuency


&!r API 9it "r!"!sed re-test "eri!d;sel/-li/e!/ at least 12 m!nts: 5ery ( m!nts !5er/irst year, e5ery m!nts !5er ne.t 12 m!ntsand annually terea/ter=

&!r &PP 9it "r!"!sed re-test "eri!d;sel/-li/e!/ at least 12 m!nts: 5ery ( m!nts !5er/irst year, e5ery m!nts !5er ne.t 12 m!ntsand annually terea/ter=

Accelerated c!nditi!n: 3inimum !/ ( time"!ints, including initial and /inal time "!ints)e=g= , ( @ m!nts+

Accelerated c!nditi!n: 3inimum !/ ( time"!ints, including initial and /inal time "!ints)e=g= , ( @ m!nts+

Intermediate c!nditi!n )due t! signi/icantcange under accelerated c!nditi!n+: studydesign s!uld include 4 time "!ints )e=g= , ,

and 12 m!nts

Intermediate c!nditi!n )due t! signi/icantcange under accelerated c!nditi!n+: studydesign s!uld include 4 time "!ints )e=g= , ,

and 12 m!nts+

3atri.ing !r rac7eting may $e a""lied





#t!rage C!nditi!ns

6ene'al Case *rug #u$stance *rug Pr!duct

#tudy #t!rage

C!nditi!ns

3inimum

"eri!d

c!5ered $y

data at

su$missi!n

#tudy #t!rage

C!nditi!ns

3inimum

"eri!d

c!5ered $y

data at

su$missi!n

<!ng term 20 C⁰ 2 C; B⁰

0B6H !r

( C⁰ 2 C ;0B⁰

0B6H

12 m!nts <!ng term 20 C⁰ 2 C ;B⁰

0B6H !r

( C⁰ 2 C ;0B⁰

0B6H

12 m!nts

Intermediate ( C⁰ 2 C ;0B⁰

0B6H

m!nts Intermediate ( C⁰ 2 C ;0B⁰

0B6H

m!nts

Accelerated 4 C⁰ 2 C ;0B⁰

0B6H

m!nts Accelerated 4 C⁰ 2 C ;0B⁰

0B6H

m!nts







#t!rage C!nditi!ns

Sto'a*e in f'eee'

Sto'a*e belo/ - 2: C Case by case basis⁰


#tudy #t!rage

C!nditi!ns

3inimum

"eri!d c!5ered

$y data atsu$missi!n

#tudy #t!rage

C!nditi!ns

3inimum

"eri!d c!5ered

$y data atsu$missi!n

<!ng

term

- 2 C⁰ 0 C⁰ 12m!nts <!ng

term

- 2 C⁰ 0 C⁰ 12m!nts





#t!rage C!nditi!ns % *rug Pr!duct

Se$i-%e'$eable containe's Stdy Sto'a*e Conditions Mini$$ %e'iod

coe'ed by data at

sb$ission

<!ng term 20 C⁰

2 C;4B⁰

0B 6H !r ( C⁰ 2 C;(0B⁰ 0B 6H 12 m!nts

Intermediate ( C⁰ 2 C;0B⁰ 0B 6H m!nts

Accelerated 4 C⁰ 2 C;⁰ 3T 20B 6H m!nts





#igni/icant Cange

*rug #u$stance *rug Pr!duct*e/ined as /ailure t! meets"eci/icati!ns

-D0B cange in assay /r!m te initialresults

-Any degradati!n "r!duct e.ceedingits acce"tance criteri!n

-&ailure t! meet acce"tance criteria/!r a""earance, "ysical attri$utesand /uncti!nality tests

-&ailure t! meet acce"tance criteria/!r "H

-&ailure t! meet acce"tance criteria/!r diss!luti!n !/ 12 d!sage units

January 18-21, 2012




5aluati!n


#tatistical analysis n!t necessary i/data e.i$its little !r n! degradati!nand 5aria$ility

#tatistical analysis n!t necessary i/data e.i$its little !r n! degradati!nand 5aria$ility

<imited e.tra"!lati!n !/ real time data

"ermitted 9it Eusti/icati!n

<imited e.tra"!lati!n !/ real time data

"ermitted 9it Eusti/icati!n





Q1B 77SAB#4#5 ES#.6 7F

E8 D!96 S9BSA.CES A.D !7D9CS

'oides 2 o%tions fo' so'ces of li*ht – arti/icial dayligt /lu!rescent lam" c!m$ining 5isi$le and ultra5i!let

)F'+ !ut"uts, .en!n, !r metal alide lam" – sam"le s!uld $e e."!sed t! $!t te c!!l 9ite /lu!rescent and near

ultra5i!let lam"

est on A# fi'st – if not %hotosensitie then no f'the' testin* is'ei'ed

#f A# is %hotosensitie then testin* to be contined on asa%%'o%'iate" – Tests !n te e."!sed drug "r!duct !utside !/ te immediate "ac7 – Tests !n te drug "r!duct in te immediate "ac7

– Tests !n te drug "r!duct in te mar7eting "ac7

8he'e a%%'o%'iate, i$%act of li*ht d'in* $anfact'in*

January 18-21, 2012




Q1C

Anne. t! Q1A )62+

Additional *idance on line etensions

!edced 'ei'e$ents at ti$e of filin* ) $onths

accele'ated and ) $onths lon* te'$

January 18-21, 2012




Q1* - rac7eting

January 18-21, 2012




Q1* - 3atri.ing

January 18-21, 2012




Q1* - 3atri.ing

January 18-21, 2012




Q1

EVA49A#7. 7F SAB#4#5 DAA

'oides 'eco$$endations fo' at !, !ef'i*e'ated andF'eee' sto'a*es"

– t'eatin* stability data

– Etendin* 'e-test %e'iod o' shelf-life beyond %e'iod coe'ed by

lon*-te'$ data

– Statistical a%%'oaches to analysis of stability data

'o*'ession

– Sta't /ith data nde' accele'ated condition

– hen assess data nde' inte'$ediate condition, if a%%'o%'iate – Finally ealate t'ends and a'iability of the lon*-te'$ data

January 18-21, 2012




utc!mes

When there is no significant change under accelerated conditions (RT)Long-term and accelerated data showinglittle or no change over time and little orno variability

6etest "eri!d !r sel/ li/e can $e u" t!t9ice, $ut 3T 12 m!nts $ey!nd te"eri!d c!5ered $y l!ng-term data

Long-term or accelerated data showingchange over time and/or variability

*ata n!t amena$le t! statistical analysis,$ut rele5ant su""!rting data "r!5ided:6etest "eri!d !r sel/ li/e can $e u" t!1=0 times, $ut 3T m!nts $ey!nd te"eri!d c!5ered $y l!ng-term data

I/ a statistical analysis is "er/!rmed:6etest "eri!d !r sel/ li/e !/ u" t! t9ice,$ut n!t m!re tan 12 m!nts $ey!nd te

"eri!d c!5ered $y l!ng-term data

January 18-21, 2012




utc!mes

When there is significant change under accelerated conditions(RT) but no significant change at intermediate condition

*ata n!t amena$le t! statistical analysis

6etest "eri!d !r sel/ li/e can $e u" t! ( m!nts $ey!nd te "eri!d c!5ered

$y l!ng-term data i/ $ac7ed $y rele5ant d!cumentati!n

I/ statistical analysis is "er/!rmed

6etest "eri!d !r sel/ li/e can $e u" t! 1=0 times, $ut 3T m!nts $ey!nd

te "eri!d c!5ered $y l!ng-term data 9en $ac7ed $y statistical analysis

and rele5ant su""!rting data

January 18-21, 2012




Q2)61+VA4#DA#7. 7F A.A45#CA4 !7CED9!ES

*e/ines 5alidati!n caracteristics: – Accuracy – Precisi!n

• Repeatability• nter!e"iate #re$isi%n

– #"eci/icity – *etecti!n <imit

– Quantitati!n <imit – <inearity – 6ange

6!$ustness t! $e c!nsidered at a""r!"riate stage !/ de5el!"ment !/ teanalytical met!d

#ystem suita$ility test "arameters t! $e esta$lised /!r a "articular"r!cedure de"ending !n te ty"e !/ "r!cedure $eing 5alidated -Parmac!"!eias t! $e c!nsulted /!r additi!nal in/!rmati!n

January 18-21, 2012




'A<I*ATI CHA6ACT6I#TIC#

'alidati!ncaracteristics

I* Im"urities

Quant= limit

Assay

Accuracy

Precisi!n

6e"eati$ility

Int=Precisi!n

#"eci/icity

<*

<Q

<inearity

6ange

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

January 18-21, 2012

Q(




Q(

#$%'ities

#$%'ities in .e/ D'* Sbstances Q3A(R2): Defines thresholdsfor reporting, identification and qualification of impurities in DS

#$%'ities in .e/ D'* 'odcts Q3(R2): Defines thresholds for

reporting, identification and qualification of impurities in D

6ideline fo' !esidal Solents Q3! !=" Classifies 'esidal

solents by 'is0 assess$ent

– Class 1 s!l5ents: s!l5ents t! $e a5!ided

– Class 2 s!l5ents: s!l5ents t! $e limited

– Class ( s!l5ents: s!l5ents 9it l!9 t!.ic "!tential

6ideline fo' Metal #$%'ities Q3D (!oncept paper " #ul$ 2%%&)

January 18-21, 2012




Q(A!2"C4ASS#F#CA#7. 7F #M9!##ES

7'*anic #$%'ities – #tarting materials – y-"r!ducts – Intermediates – *egradati!n "r!ducts – 6eagents, ligands, catalysts

#no'*anic #$%'ities – 6eagents, ligands, catalysts – Hea5y metals !r !ter residual metals – In!rganic salts – ter materials )e=g=, /ilter aids, carc!al+

!esidal Solents

January 18-21, 2012




Q(A)62+Definitions

Quali/icati!n Te "r!cess !/ acuiring and e5aluating data tatesta$lises te $i!l!gical sa/ety !/ an indi5idual im"urity !r a gi5enim"urity "r!/ile at te le5el)s+ s"eci/ied=

6e"!rting Tres!ld: A limit a$!5e )D+ 9ic an im"urity s!uld $ere"!rted<

#"eci/ied Im"urity An im"urity tat is indi5idually listed and limited 9it a

s"eci/ic acce"tance criteri!n in te ne9 drug su$stance s"eci/icati!n= As"eci/ied im"urity can $e eiter identi/ied !r unidenti/ied=

Fnidenti/ied Im"urity An im"urity /!r 9ic a structural caracterisati!nas n!t $een acie5ed and tat is de/ined s!lely $y ualitati5e analytical"r!"erties )e=g=, cr!mat!gra"ic retenti!n time+

Fns"eci/ied im"urity An im"urity tat is limited $y a general acce"tancecriteri!n, $ut n!t indi5idually listed 9it its !9n s"eci/ic acce"tancecriteri!n, in te ne9 drug su$stance s"eci/icati!n

January 18-21, 2012




Q(A)62+

January 18-21, 2012




Q(A)62+

January 18-21, 2012




Q()62+

January 18-21, 2012




Q()62+

January 18-21, 2012




Q(C)60+

Pr!5ides 2 !"ti!ns /!r descri$ing limits !/ Class 2 #!l5ents

'ption : As %e' the table %'oided - calclated sin* D# of 1: * andthe calclation - – C!ncentrati!n )""m+ 1 . Permitted *aily ."!sure )P*+; *!se

– P* is gi5en in terms !/ mg;day and d!se is gi5en in g;day=

f *D is more than % g use option 2

#!l5ent P* )mg;day+ C!ncentrati!nlimit )""m+

Acet!nitrile

Cl!r!$en?ene

4=1

(=

41

(

January 18-21, 2012




.am"le /!r "ti!n 2

!"tion # It is n!t c!nsidered necessary /!r eac c!m"!nent !/ te drug "r!duct t!c!m"ly 9it te limits gi5en in "ti!n 1= Te P* in terms !/ mg;day can $e used9it te 7n!9n ma.imum daily d!se and euati!n )$oncentration (""m) % &''' *+/ *ose+ t! determine te c!ncentrati!n !/ residual s!l5ent all!9ed in drug"r!duct

.am"le: P* !/ acet!nitrile is 4=1mg;day

$om"onent ,mount in formulation ,cetonitrile content *aily

e"osure

*rug su$stance =( g 8 ""m =24 mg

.ci"ient 1 = g 4 ""m =( mg

.ci"ient 2 (=8 g 8 ""m (=4 mg

*rug Pr!duct 0= g 28 ""m (=4 mg The sum of the amounts of solvent "er day should be less than that given by the

*+

January 18-21, 2012




QA

Add'esses as%ects sch as

– Peri!dic !r s7i" testing

– 6elease 5s sel/-li/e criteria

– In-"r!cess tests

– *esign and de5el!"ment c!nsiderati!ns

– <imited data a5aila$le at /iling – Parametric release

– Alternati5e "r!cedures

– Parmac!"!eial tests and acce"tance criteria

– 5!l5ing tecn!l!gies

– Im"act !/ drug su$stance !n drug "r!duct s"eci/icati!ns – 6e/erence standard

January 18-21, 2012

QA




QA

*ecisi!n Trees

1 % sta$lising acce"tance criteria /!r s"eci/ied im"urity In *# 2 % sta$lising acce"tance criteria /!r degradati!n "r!duct in *P

( % sta$lising acce"tance criteria /!r P#* in *#

4 % In5estigating need t! set acce"tance criteria /!r "!lym!r"ism in *#and *P

0 % sta$lising I*, Assay and enanti!meric im"urity "r!cedures /!rciral *# and ciral *# in *P

% 3icr!$i!l!gical Quality Attri$utes !/ *# and .ci"ients

% #etting acce"tance criteria /!r *P diss!luti!n

8 % 3icr!$i!l!gical Quality Attri$utes !/ n!n sterile *P

January 18-21, 2012




Peri!dic !r #7i" Testing

Shold be stified<

May be a%%lied to ce'tain tests only e<*< 'esidal

solents and $ic'obiolo*ical test fo' solid o'al %'odcts"

!eco$$end that it shold be a%%lied %ost a%%'oal

Batch to batch 'etestin* to be 'esto'ed in the eent of

fail'e

January 18-21, 2012




Desi*n and Deelo%$ent Conside'ations

#t $ay be %ossible to %'o%ose ecldin* o' 'e%lacin*ce'tain tests based on e%e'ience and data acc$lated

– micr!$i!l!gical testing /!r drug su$stances and s!lid

d!sage /!rms 9ic a5e $een s!9n during de5el!"ment

n!t t! su""!rt micr!$ial 5ia$ility !r gr!9t )*ecisi!n Trees

and 8+ – e.tracta$les /r!m "r!duct c!ntainers 9ere it as $een

re"r!duci$ly s!9n tat eiter n! e.tracta$les are /!und in

te drug "r!duct !r te le5els meet acce"ted standards /!r

sa/ety

January 18-21 2012January 18-21, 2012




Desi*n and Deelo%$ent Conside'ations

– "article si?e testing may $e "er/!rmed as an in-"r!cesstest, !r may $e "er/!rmed as a release test, de"ending !n

its rele5ance t! "r!duct "er/!rmance

– diss!luti!n testing /!r immediate release s!lid !ral drug

"r!ducts made /r!m igly 9ater s!lu$le drug su$stances

may $e re"laced $y disintegrati!n testing, i/ tese"r!ducts a5e $een dem!nstrated during de5el!"ment t!

a5e c!nsistently ra"id drug release caracteristics

)*ecisi!n Tree + )!nly acce"ted in e.ce"ti!nal

circumstances and all c!nditi!ns must $e met including

su$stantial de5el!"ment data+

January 18-21, 2012



Documents

2-4 ICH Overview