Updated Checklist(1)

8/11/2019 Updated Checklist(1)

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1. A P PLIC A TIONS FOR INV E STIG A TIO N A L NEW DR U GS (IN D s )(Reference: Append! I "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )

0 D"c$+ens re$red " 2e s$2+ed S*$s

'es N"1 App%c*"n f"r (per+ss"n f"r +*n$f*c$re 3+p"r 3c%nc*% r*% &

p$rp"se s#"$%d 2e c%e*r%4 +en"ned)

5 N*+e "f #e *pp%c*n

6 N*+e "f #e Ne7 Dr$

*. C"+p"s"n "f #e Ne7 Dr$

2. D"s*e F"r+

c. Pr"p"sed ndc*"n f"r #e Ne7 Dr$

App%c*"n n F"r+ c"+p%ee n *%% respec d$%4 sned *nd s*+ped

24 *$#"r8ed pers"n "f #e fr+

/ Tre*s$r4 C#*%%*n "f INR /9,999 (f"r P#*se I) "r INR 5/,999 (f"r

P#*se II 3 III)

C"p4 "f ;*%d +*n$f*c$rn %cense n F"r+ 5/35.

- S"$rce "f 2$%< dr$.

19. C#e+c*% *nd P#*r+*ce$c*% Inf"r+*"n

19.1 Inf"r+*"n "n *c;e nredens

10.1.1 Drug information (Generic name, Chemical name, or INN)

19.5 P#4sc"c#e+c*% D**10.2.1 Chemical name and structure, Empirical formula, olecular

!eight.

10.2.2 "h#sical properties$% Description, &olu'ilit#, otation, "artitioncoefficient, Dissociation constant.

19.6 An*%4c*% D**$% Elemental anal#sis, ass spectrum, N spectra, Ispectra, * spectra, "ol#morphic identification.

19. C"+p%ee +"n"r*p# specfc*"n nc%$dn$% Identification,Identit#+uantification of purities, Enantiomeric purit#, -ssa#.

19./ V*%d*"ns$% -ssa# method, Impurit# estimation method, esidualsolent+other olatile impurities (/*I) estimation method.

19.= S*2%es S$des (for details refer -ppendi I of &chedule )$% 3inalrelease specification, eference standard characteri4ation, aterial safet#data sheet

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19.> D** "n F"r+$%*"n:? Dosage form, Composition, aster manufacturingformula, Details of the formulation (Including inactie ingredients),Inprocess ualit# control chec5, 3inished product specification, Ecipientcompati'ilit# stud#, *alidation of anal#tical method.

Comparatie ealuation !ith international 'rand(s) or approed Indian'rands, if applica'le$% "ac5 presentation, Dissolution, -ssa#, Impurities,Content uniformit#, p6, 3orce degradation stud#, &ta'ilit# ealuation inmar5et intended pac5 at proposed storage conditions, "ac5ingspecifications, "rocess alidation.

11 An+*% P#*r+*c"%"4 (as per -ppendi I* of schedule ):

11.1 &ummar#

11.5 &pecific pharmacological actions

11.6 General "harmacological actions

11. 3ollo!%up and supplemental safet# "harmacolog# &tudies

11./ "harmaco5inetics$ a'sorption, distri'ution, meta'olism, ecretion

15 An+*% "!c"%"4 d** (as per -ppendi III of schedule )$

15.1 Gener*% Aspecs

15.5. S4se+c T"!c4 S$des,

15.6 @*%e Fer%4 S$d4

15. Fe+*%e Repr"d$c"n *nd De;e%"p+en*% T"!c4 S$des (for alldrugs proposed to 'e studied or used in !omen of child 'earing age)

15./ L"c*% "!c4 (as applica'le)

12.7.1 Der+*% "!c4(for products meant for topical (dermal) application)

12.7.2 Oc$%*r "!c4(for products meant for ocular instillation)

12.7.8. In#*%*"n "!c4(conducted !ith the formulation proposed to 'e used iainhalation route)

12.7.9 V*n*% "!c4(for products meant for topical application to aginal mucosa)

12.7.7 P#""*%%er4 "r der+*% p#"""!c4(reuired if the drug or a meta'olite is related to an agentcausing photosensitiit# or the nature of action suggests such apotential)

12.7.: Rec*% "%er*nce es(3or all preparations meant for rectal administration)

15.= Gen""!c4

15.> A%%erenc434persens;4

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15. C*rcn"enc4(Carcinogenicit# studies should 'e performed for all drugs that areepected to 'e clinicall# used for more than : months as !ell as fordrugs used freuentl# in an intermittent manner in the treatmentof chronic or recurrent conditions. 6o!eer, completed rodentcarcinogenicit# studies are not needed in adance of the conduct oflarge scale clinical trials, unless there is a special concern for thepatient population)

Rep"rs "f f"%%"7n "!c4 s$des s#"$%d 2e s$2+ed *%"n 7#c%nc*% r*% *pp%c*"ns "f dfferen P#*ses f"r INDs:

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F"r P#*se I C%nc*% Tr*%s

stemic ;oicit# studies

(i) &ingle dose toicit# studies

(ii) Dose anging &tudies

(iii) epeat%dose s#stemic toicit# studies of appropriate duration tosupport the duration of proposed human eposure.

ale fertilit# stud#

In%itro genotoicit# tests

eleant local toicit# studies !ith proposed route of clinical application

(duration depending on proposed length of clinical eposure)

-llergenicit#+6#persensitiit# tests (!hen there is a cause for concern orfor parenteral drugs, including dermal application)

"hoto%allerg# or dermal photo%toicit# test (if the drug or a meta'olite isrelated to an agent causing photosensitiit# or the nature of action

suggests such a potential)F"r P#*se II C%nc*% Tr*%s

"roide a summar# of all the non%clinical safet# data (listed a'oe)alread# su'mitted !hile o'taining the permissions for "hase I trial, !ithappropriate references.

In case of an application for directl# starting a "hase II trial % complete

details of the non%clinical safet# data needed for o'taining the permissionfor "hase I trial, as per the list proided a'oe must 'e su'mitted.

epeat%dose s#stemic toicit# studies of appropriate duration to support

the duration of proposed human eposure In%itro and In%io genotoicit# tests.

&egment II reproductie+deelopmental toicit# stud# (if female patientsof child 'earing age are going to 'e inoled)

F"r P#*se III C%nc*% Tr*%s

"roide a summar# of all the non%clinical safet# data (listed a'oe)

alread# su'mitted !hile o'taining the permissions for "hase I and IItrials, !ith appropriate references.

In case of an application for directl# initiating a "hase III trial % complete

details of the non%clinical safet# data needed for o'taining thepermissions for "hase I and II trials, as per the list proided a'oe must'e proided.

epeat%dose s#stemic toicit# studies of appropriate duration to supportthe duration of proposed human eposure

eproductie+deelopmental toicit# studies

In%itro and In%io genotoicit# tests.

&egment I (if female patients of child 'earing age are going to 'einoled), and

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!here there are indications of possi'le aderse effects on foetaldeelopment).

Carcinogenicit# studies (!hen there is a cause for concern or !hen thedrug is to 'e used for more than : months).

16 $+*n 3 C%nc*% p#*r+*c"%"4 (P#*se I) nc%$dn s$++*r4 "f #e s$d4*nd rep"rs16.1 &ummar#

16.5 &pecific "harmacological effects

16.6 General "harmacological effects

16. "harmaco5inetics, a'sorption, distri'ution, meta'olism, ecretion

16./ "harmacod#namics + earl# measurement of drug actiit#

1 T#er*pe$c e!p%"r*"r4 r*%s (P#*se II)

1.1 &ummar#

1.5 &tud# report(s) as gien in -ppendi II

1/ T#er*pe$c c"nfr+*"r4 r*%s (P#*se III)

1/.1 &ummar#

1/.5 Indiidual stud# reports !ith listing of sites and Inestigators.

1= Spec*% S$des

1=.1 &ummar#

1=.5


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59. STR U CT U RE, C O NTEN T S A ND FO R @ A T FOR CLIN IC A L T R I A L P ROTOCOL

(Reference: Append!? B "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )


'es N"

1. ;itle "age

2. ;a'le of Contents

8. &tud# /'@ectie(s) (primar# as !ell as secondar#) and their logicalrelation to the stud# design.

9. &tud# Design

7. &tud# "opulation

:. &u'@ect Eligi'ilit# % Inclusion Criteria and Eclusion Criteria

=. &tud# -ssessments

A. &tud# ;reatment

B. -derse Eents

10. Ethical Considerations

11. &tud# onitoring and &uperision


18. Inestigational "roduct anagement

19. Data -nal#sis

17. nderta5ing '# the Inestigator as per -ppendi *II of &chedule $%(Ethics Committee should 'e of same area !here the site is located and details of

the committee should 'e mentioned).

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1:. Inf"r+ed C"nsen D"c$+ens:? "atient Information &heet ("I&) +Informed consent form (IC3) as per reised -ppendi * of &chedule including the follo!ing clauses.

-. &tatement descri'ing the financial compensation and medicalmanagement as under$%a) In the eent of an in@ur# occurring to the clinical trial su'@ects,

such su'@ects shall 'e proided free medical management aslong as reuired.

') In the eent of a trial related in@ur# or death, the sponsor or hisrepresentatie, !hosoeer has o'tained permission fromlicensing authorit# for conduct of clinical stud# shall proidefinancial compensation for the in@ur# or death.


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22. Details of the contract entered '# the sponsor !ith theinestigator+institutions !ith regard to financial support, amount of fees,honorarium, pa#ments in 5ind etc. to 'e paid to the inestigator.In case no contract has #et 'een entered !ith an# Inestigator +Institution, plan for financial support, fees, honorarium, and pa#ments in5ind etc. to 'e paid to the inestigator.

51. STRUCTURE, CONTENTS AND FOR @ AT F OR CLINIC AL S TUD ' REP ORTS

(Reference: Append!? II "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )


'es N"

1. ;itle "age

5. &tud# nopsis

6. &tatement of compliance !ith the HGuidelines for Clinical ;rials on"harmaceutical "roducts in India

. ?ist of -''reiations and Definitions

/. ;a'le of contents

=. Cop# of Ethics Committee approal

>. &tud# ;eam

. Introduction

-.&tud# /'@ectie

19. Inestigational "lan

11. ;rial &u'@ects

15. Efficac# ealuation

16. &afet# Ealuation

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1. Discussion and oerall Conclusion

1/. ?ist of eferences

N"e:1. -ll items mentioned a'oe ma# not 'e applica'le to all drugs. ;he items not releant to aparticular ne! drug should 'e mar5ed !ith Not -pplica'le (N-)F.

2. In case the application is for clinical trial permission $%

(a) adeuate chemical and pharmaceutical information should 'e proided to ensure the

proper identit#, purit#, ualit# strength of the inestigational product, the amount of

information needed ma# ar# !ith the "hase of clinical trials, proposed duration of trials,

dosage forms and the amount of information other!ise aaila'le

(') In case of applications for protocol amendments of alread# approed studies, applicants

should su'mit cop# of approal of protocol, amended ne! protocol, summari4ed list of all

the ne! changes incorporated along!ith @ustification + reasons for the change.

(c) E#cs C"++ee Appr";*%: Ethical approal should 'e o'tained from Ethics

Committee located in the same area !here the clinical trial site is located.

(d) ;he proposed clinical trial stud# centers should 'e geographicall# distri'uted in the

countr# and should also include clinical sites !hich hae their o!n Institutional Ethics

Committee.

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5. C EC LIS T FOR A C CE P T A ILIT ' O F A P PLIC A TION PER T A N I NG TO

G R A N T OF PER @ IS SIO N TO I @ P ORT OR @ A N U F A C T U R E NEW

DR U GS G O I NG TO E INT R ODU C ED FOR TE FIRST T I @ E I N T E

COUN T R' FOR S A LE OR TO U N DER T A E CLIN IC A L TR I A LS

(Reference: Append! I "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )


'es N"1 App%c*"n f"r (per+ss"n f"r +*n$f*c$re 3+p"r3c%nc*% r*% &

p$rp"se s#"$%d 2e c%e*r%4 +en"ned)

5 N*+e "f #e *pp%c*n

6 N*+e "f #e Ne7 Dr$

*. C"+p"s"n "f #e Ne7 Dr$

2. D"s*e F"r+

c. Pr"p"sed ndc*"n f"r #e Ne7 Dr$

App%c*"n n F"r+ c"+p%ee n *%% respec d$%4 sned *nd s*+ped

24 *$#"r8ed pers"n "f #e fr+

/ Tre*s$r4 C#*%%*n "f INR /9,999 (f"r P#*se I) "r INR 5/,999 (f"r

P#*se II 3 III)

C"p4 "f ;*%d +*n$f*c$rn %cense n F"r+ 5/35 *%"n 7# c"p4 "f

- S"$rce "f 2$%< dr$.

19. C#e+c*% *nd P#*r+*ce$c*% Inf"r+*"n

19.1 Inf"r+*"n "n *c;e nredens

10.1.1 Drug information (Generic name, Chemical name, or INN)

19.5 P#4sc"c#e+c*% D**

10.2.1 Chemical name and structure, Empirical formula, olecular!eight.

10.2.2 "h#sical properties$% Description, &olu'ilit#, otation, "artitioncoefficient, Dissociation constant.

19.6 An*%4c*% D**$% Elemental anal#sis, ass spectrum, N spectra, I

spectra, * spectra, "ol#morphic identification.19. C"+p%ee +"n"r*p# specfc*"n nc%$dn$% Identification,

Identit#+uantification of purities, Enantiomeric purit#, -ssa#.

19./ V*%d*"ns$% -ssa# method, Impurit# estimation method, esidualsolent+other olatile impurities (/*I) estimation method.

19.= S*2%es S$des (for details refer -ppendi I of &chedule )$% 3inalrelease specification, eference standard characteri4ation, aterial safet#data sheet

10


11/17

19.> D** "n F"r+$%*"n:? Dosage form, Composition, aster manufacturingformula, Details of the formulation (Including inactie ingredients),Inprocess ualit# control chec5, 3inished product specification, Ecipientcompati'ilit# stud#, *alidation of anal#tical method.

Comparatie ealuation !ith international 'rand(s) or approed Indian'rands, if applica'le$% "ac5 presentation, Dissolution, -ssa#, Impurities,Content uniformit#, p6, 3orce degradation stud#, &ta'ilit# ealuation inmar5et intended pac5 at proposed storage conditions, "ac5ingspecifications, "rocess alidation.

11 An+*% P#*r+*c"%"4 (as per -ppendi I* of schedule ):

11.1 &ummar#

11.5 &pecific pharmacological actions

11.6 General "harmacological actions

11. 3ollo!%up and supplemental safet# "harmacolog# &tudies

11./ "harmaco5inetics$ a'sorption, distri'ution, meta'olism, ecretion

15 An+*% "!c"%"4 d** (as per -ppendi III of schedule )

15.1 Gener*% Aspecs

15.5. S4se+c T"!c4 S$des,

15.6 @*%e Fer%4 S$d4

15. Fe+*%e Repr"d$c"n *nd De;e%"p+en*% T"!c4 S$des (for alldrugs proposed to 'e studied or used in !omen of child 'earing age)

15./ L"c*% "!c4 (as applica'le)

12.7.1 Der+*% "!c4(for products meant for topical (dermal) application)

12.7.2 Oc$%*r "!c4(for products meant for ocular instillation)

12.7.8. In#*%*"n "!c4(conducted !ith the formulation proposed to 'e used iainhalation route

12.7.9 V*n*% "!c4(for products meant for topical application to aginal mucosa)

12.7.7 P#""*%%er4 "r der+*% p#"""!c4(reuired if the drug or a meta'olite is related to an agentcausing photosensitiit# or the nature of action suggests such apotential)

12.7.: Rec*% "%er*nce es(3or all preparations meant for rectal administration)

15.= Gen""!c4

15.> A%%erenc434persens;4

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15. C*rcn"enc4(Carcinogenicit# studies should 'e performed for all drugs that areepected to 'e clinicall# used for more than : months as !ell as fordrugs used freuentl# in an intermittent manner in the treatmentof chronic or recurrent conditions. 6o!eer, completed rodentcarcinogenicit# studies are not needed in adance of the conduct oflarge scale clinical trials, unless there is a special concern for thepatient population)

16 $+*n 3 C%nc*% p#*r+*c"%"4 (P#*se I) nc%$dn s$++*r4 "f #e s$d4*nd rep"rs16.1 &ummar#

16.5 &pecific "harmacological effects

16.6 General "harmacological effects

16. "harmaco5inetics, a'sorption, distri'ution, meta'olism, ecretion

16./ "harmacod#namics + earl# measurement of drug actiit#

1T#er*pe$c e!p%"r*"r4 r*%s (P#*se II)

1.1 &ummar#

1.5 &tud# report(s) as gien in -ppendi II

1/ T#er*pe$c c"nfr+*"r4 r*%s (P#*se III)

1/.1 &ummar#

1/.5 Indiidual stud# reports !ith listing of sites and Inestigators.

1= Spec*% S$des

1=.1 &ummar#

1=.5


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1- S*+p%es *nd Tesn Pr""c"%3s

1-.1 &amples of pure drug su'stance and finished product (an euialent of70 clinical doses, or more num'er of clinical doses if prescri'ed '# the?icensing -uthorit#), !ith testing protocols, full impurit# profile andrelease specifications.) (;o 'e su'mitted to the la'orator# as directed '#the ?icensing -uthorit#)

59 Pr"p"sed Dr*f spec+en "f #e %*2e% *nd c*r"n. ;he drafts of la'eland carton tets should compl# !ith proisions of ules B: and B=.

51 If the stud# drug is intended to 'e imported for the purposes ofeamination, test or anal#sis, the application for import of small uantities ofdrugs for such purpose should also 'e made in 3orm 12.

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55. STRUCTURE, CONTENTS AND FOR@AT FOR CLINICAL TRIAL PROTOCOL

(Reference: Append! ? B "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )


'es N"1. ;itle "age

2. ;a'le of Contents

8. &tud# /'@ectie(s) (primar# as !ell as secondar#) and their logicalrelation to the stud# design.

9. &tud# Design

7. &tud# "opulation

:. &u'@ect Eligi'ilit# % Inclusion Criteria and Eclusion Criteria

=. &tud# -ssessments

A. &tud# ;reatment

B. -derse Eents

10. Ethical Considerations



18. Inestigational "roduct anagement

19. Data -nal#sis

17. nderta5ing '# the Inestigator as per -ppendi *II of &chedule $%

(Ethics Committee should 'e of same area !here the site is located and detailsof the committee should 'e mentioned).

14


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1:. Inf"r+ed C"nsen D"c$+ens:? "atient Information &heet ("I&) +Informed consent form (IC3) as per reised -ppendi * of &chedule including the follo!ing clauses.

D. &tatement descri'ing the financial compensation and medicalmanagement as under$%c) In the eent of an in@ur# occurring to the clinical trial su'@ects,

such su'@ects shall 'e proided free medical management aslong as reuired.

d) In the eent of a trial related in@ur# or death, the sponsor or hisrepresentatie, !hosoeer has o'tained permission fromlicensing authorit# for conduct of clinical stud# shall proidefinancial compensation for the in@ur# or death.

E. In serial no. 02 of an -ppendi *, the follo!ing shall 'e included$-ddress of the su'@ect$ualification$/ccupation$ &tudent+&elfemplo#ed+serice+6ouse!ife+/ther.("lease tic5 as appropriate)-nnual income of &u'@ect$Name and -ddress of nominee and his+her relation to the su'@ect.( for the purpose of compensation in case of trial related death )

3. -fter the name of !itness occurring at the end, the follo!ing shall 'einserted$Cop# of the patient information sheet and dul# filled IC3 shall 'ehanded oer to the su'@ect or his+her attendantF

1=. nderta5ing '# the &ponsor+&ponsors representatie+applicant to thelicensing authorit# to proide medical management and compensation in

case of clinical trial related in@ur# or death for !hich su'@ects are entitledto compensation as reuired under rule 122D-


16/17

22. Details of the contract entered '# the sponsor !ith theinestigator+institutions !ith regard to financial support, amount of fees,honorarium, pa#ments in 5ind etc. to 'e paid to the inestigator.In case no contract has #et 'een entered !ith an# Inestigator +Institution, plan for financial support, fees, honorarium, and pa#ments in5ind etc. to 'e paid to the inestigator.

56. Pr""c"% "f "e$;*%ence s$d4 *%"n 7# Inf"r+ed C"nsend"c$+en *nd $nder*


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15. Efficac# ealuation

16. &afet# Ealuation

1. Discussion and oerall Conclusion

1/. ?ist of eferences

N"e:

1. -ll items mentioned a'oe ma# not 'e applica'le to all drugs. ;he items notreleant to a particular ne! drug should 'e mar5ed !ith Not -pplica'le (N-)F.

5. -pplication for 'oth 'ul5 as !ell as formulation is reuired to 'e su'mitted.

"roposal for grant of permission to manufacture onl# 'ul5 drug !ill 'econsidered after approal of itKs formulation.

6. In case the application is for clinical trial permission$

*. -deuate chemical and pharmaceutical information should 'e proided to

ensure the proper identit#, purit#, ualit# strength of the inestigational

product, the amount of information needed ma# ar# !ith the "hase of

clinical trials, proposed duration of trials, dosage forms and the amount of

information other!ise aaila'le.

2. In case of applications for protocol amendments of alread# approed

studies, applicants should su'mit cop# of approal of protocol, amended

ne! protocol, summari4ed list of all the ne! changes incorporated

along !ith @ustification + reasons for the change.

c. Ethics Committee -pproal$ Ethical approal should 'e o'tained fromEthics

Committee located in the same area !here the clinical trial site is located.

d. ;he proposed clinical trial stud# centres should 'e geographicall# distri'uted

in the countr# and should also include clinical sites !hich hae their o!n

Institutional Ethics Committee.

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Updated Checklist(1)