View
226
Download
0
Category
Preview:
Citation preview
8/11/2019 Updated Checklist(1)
1/17
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
1
8/11/2019 Updated Checklist(1)
2/17
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$%*r "!c4(for products meant for ocular instillation)
12.7.8. In#*%*"n "!c4(conducted !ith the formulation proposed to 'e used iainhalation route)
12.7.9 V*n*% "!c4(for products meant for topical application to aginal mucosa)
12.7.7 P#""*%%er4 "r der+*% p#"""!c4(reuired if the drug or a meta'olite is related to an agentcausing photosensitiit# or the nature of action suggests such apotential)
12.7.: Rec*% "%er*nce es(3or all preparations meant for rectal administration)
15.= Gen""!c4
15.> A%%erenc434persens;4
2
8/11/2019 Updated Checklist(1)
3/17
15. C*rcn"enc4(Carcinogenicit# studies should 'e performed for all drugs that areepected to 'e clinicall# used for more than : months as !ell as fordrugs used freuentl# in an intermittent manner in the treatmentof chronic or recurrent conditions. 6o!eer, completed rodentcarcinogenicit# studies are not needed in adance of the conduct oflarge scale clinical trials, unless there is a special concern for thepatient population)
Rep"rs "f f"%%"7n "!c4 s$des s#"$%d 2e s$2+ed *%"n 7#c%nc*% r*% *pp%c*"ns "f dfferen P#*ses f"r INDs:
3
8/11/2019 Updated Checklist(1)
4/17
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
4
8/11/2019 Updated Checklist(1)
5/17
!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$des
1=.1 &ummar#
1=.5
8/11/2019 Updated Checklist(1)
6/17
59. STR U CT U RE, C O NTEN T S A ND FO R @ A T FOR CLIN IC A L T R I A L P ROTOCOL
(Reference: Append!? B "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )
0 D"c$+ens re$red " 2e s$2+ed S*$s
'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
12. &tud# onitoring and &uperision
18. Inestigational "roduct anagement
19. Data -nal#sis
17. nderta5ing '# the Inestigator as per -ppendi *II of &chedule $%(Ethics Committee should 'e of same area !here the site is located and details of
the committee should 'e mentioned).
6
8/11/2019 Updated Checklist(1)
7/17
1:. Inf"r+ed C"nsen D"c$+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$%a) In the eent of an in@ur# occurring to the clinical trial su'@ects,
such su'@ects shall 'e proided free medical management aslong as reuired.
') In the eent of a trial related in@ur# or death, the sponsor or hisrepresentatie, !hosoeer has o'tained permission fromlicensing authorit# for conduct of clinical stud# shall proidefinancial compensation for the in@ur# or death.
8/11/2019 Updated Checklist(1)
8/17
22. Details of the contract entered '# the sponsor !ith theinestigator+institutions !ith regard to financial support, amount of fees,honorarium, pa#ments in 5ind etc. to 'e paid to the inestigator.In case no contract has #et 'een entered !ith an# Inestigator +Institution, plan for financial support, fees, honorarium, and pa#ments in5ind etc. to 'e paid to the inestigator.
51. STRUCTURE, CONTENTS AND FOR @ AT F OR CLINIC AL S TUD ' REP ORTS
(Reference: Append!? II "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )
0 D"c$+ens re$red " 2e s$2+ed S*$s
'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
8
8/11/2019 Updated Checklist(1)
9/17
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 $%
(a) adeuate chemical and pharmaceutical information should 'e proided to ensure the
proper identit#, purit#, ualit# strength of the inestigational product, the amount of
information needed ma# ar# !ith the "hase of clinical trials, proposed duration of trials,
dosage forms and the amount of information other!ise aaila'le
(') In case of applications for protocol amendments of alread# approed studies, applicants
should su'mit cop# of approal of protocol, amended ne! protocol, summari4ed list of all
the ne! changes incorporated along!ith @ustification + reasons for the change.
(c) E#cs C"++ee Appr";*%: Ethical approal should 'e o'tained from Ethics
Committee located in the same area !here the clinical trial site is located.
(d) ;he proposed clinical trial stud# centers should 'e geographicall# distri'uted in the
countr# and should also include clinical sites !hich hae their o!n Institutional Ethics
Committee.
9
8/11/2019 Updated Checklist(1)
10/17
5. C EC LIS T FOR A C CE P T A ILIT ' O F A P PLIC A TION PER T A N I NG TO
G R A N T OF PER @ IS SIO N TO I @ P ORT OR @ A N U F A C T U R E NEW
DR U GS G O I NG TO E INT R ODU C ED FOR TE FIRST T I @ E I N T E
COUN T R' FOR S A LE OR TO U N DER T A E CLIN IC A L TR I A LS
(Reference: Append! I "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )
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"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
8/11/2019 Updated Checklist(1)
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
11
8/11/2019 Updated Checklist(1)
12/17
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$des
1=.1 &ummar#
1=.5
8/11/2019 Updated Checklist(1)
13/17
1- S*+p%es *nd Tesn Pr""c"%3s
1-.1 &les of pure drug su'stance and finished product (an euialent of70 clinical doses, or more num'er of clinical doses if prescri'ed '# the?icensing -uthorit#), !ith testing protocols, full impurit# profile andrelease specifications.) (;o 'e su'mitted to the la'orator# as directed '#the ?icensing -uthorit#)
59 Pr"p"sed Dr*f spec+en "f #e %*2e% *nd c*r"n. ;he drafts of la'eland carton tets should compl# !ith proisions of ules B: and B=.
51 If the stud# drug is intended to 'e imported for the purposes ofeamination, test or anal#sis, the application for import of small uantities ofdrugs for such purpose should also 'e made in 3orm 12.
13
8/11/2019 Updated Checklist(1)
14/17
55. STRUCTURE, CONTENTS AND FOR@AT FOR CLINICAL TRIAL PROTOCOL
(Reference: Append! ? B "f Sc#ed$%e & ' " Dr$s *nd C"s+ecs R$%es, 1-/ )
0 D"c$+ens re$red " 2e s$2+ed S*$s
'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
12. &tud# onitoring and &uperision
18. Inestigational "roduct anagement
19. Data -nal#sis
17. nderta5ing '# the Inestigator as per -ppendi *II of &chedule $%
(Ethics Committee should 'e of same area !here the site is located and detailsof the committee should 'e mentioned).
14
8/11/2019 Updated Checklist(1)
15/17
1:. Inf"r+ed C"nsen D"c$+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-
8/11/2019 Updated Checklist(1)
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 $nder*
8/11/2019 Updated Checklist(1)
17/17
15. Efficac# ealuation
16. &afet# Ealuation
1. Discussion and oerall Conclusion
1/. ?ist of eferences
N"e:
1. -ll items mentioned a'oe ma# not 'e applica'le to all drugs. ;he items notreleant to a particular ne! drug should 'e mar5ed !ith Not -pplica'le (N-)F.
5. -pplication for 'oth 'ul5 as !ell as formulation is reuired to 'e su'mitted.
"roposal for grant of permission to manufacture onl# 'ul5 drug !ill 'econsidered after approal of itKs formulation.
6. In case the application is for clinical trial permission$
*. -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.
%%%%%%%%%%%%%%%%%%%%%%%%%
17
Recommended