This document provides guidelines for conducting clinical trials and importing or manufacturing new drugs for sale according to Schedule Y of the Drugs and Cosmetics Act of 1940 in India. It outlines the application process and required data to be submitted, including chemical/pharmaceutical information, pre-clinical toxicology and pharmacology studies in animals, protocols for human clinical trials through various phases, and post-marketing surveillance requirements. Ethics committee approval and informed consent of participants are necessary. Manufacturers must establish the drug's quality, safety, and efficacy primarily through clinical trials conducted in India.

1. BY
PRAGNYA,(M.pharm)
PHARMACOLOGY(Iyr),GPRCP

2. Schedule Y of DRUG & COSMETICS ACT 1940 detailed
the requirements and guidelines
•Import/manufacture of New DRuGs for sale
•For conducting a “CliNiCal tRial”

3. 122E - NEW DRUG
Not been used in country under label
Approved but now proposed to be marketed with
modified /new claims indications dosage form , route of
administration.

4. Application for permission to import NEW DRUG.
(a) No new drug shall be imported, except under, and in
accordance with, the permission granted by the Licensing
Authority.
(b) An application for the grant of permission to import a
new drug shall be made in Form 44 to the Licensing
Authority, accompanied by a fee of
Rs 50, 000.

5. DATA TO BE SUBMITTED ALONG WITH
THE APPLICATION FORM 44
Chemical &Pharmaceutical Info
Animal Pharmacology –
1)Specific Pharmacological Actions
Dose response rel
ED50 s
2)General Pharmacological Actions

6. Animal Toxicology Data
Systemic toxicity studies - Single Dose Toxicity
Repeated Dose Toxicity
Male fertility studies
Female reproduction and developmental studies
Local toxicity - Dermal Toxicity , Vaginal Toxicity, rectal
Toxicity ,Ocular Toxicity
Allergenicity
Genotoxicity
carcinogenicity

7. HUMAN CLINICAL PHARMACOLOGY
DATA
Human / Clinical pharmacology (Phase I)
• Maximum tolerated dose
• PK –ADME
• PD
• Early measurement of drug activity
 Therapeutic exploratory trials (Phase II)
To determine dose and regimen
Therapeutic confirmatory trials (Phase III)
Confirmation of therapeutic benefits
“For new drug substances discovered in India ,
clinical trials are required to be carried out in India
right from phase I and data should be submitted”

8. FOR NEW DRUG SUBSTANCES DISCOVERED IN
COUNTRIES OTHER THAN INDIA
 After submission of phase I data generated outside India
to the licensing authority, permission may be granted to
repeat phase I trials and/or to conduct phase II trials and
subsequently phase III trials concurrently with other global
trials for that drug.
 PHASE III trials are required to be conducted in India
before permission to market the drug in India is granted

9. Permission to carry out these trials shall be given in
stages
Study report should be certified by the principal
investigator
Regulatory Status In Other Countries
The Full Prescribing Information should be submitted

10. Complete Testing Protocol/S For Quality Control Testing
together with a Complete Impurity Profile And Release
Specifications
For drugs indicated in life threatening / serious
diseases/ diseases of special references to Indian health
scenario , toxicological and clinical data requirements
may be abbreviated ,deffered , ommitted as deemed
appropriate by the licensing authority .

11.  Clinical Trial is a systematic study of new drug(s) in
human subject(s) to generate data for discovering and/or
verifying the clinical, pharmacological(including
pharmacodynamic and pharmacokinetic) and/or adverse
effects with the objective of determining safety and/or
efficacy of the new drug

12. • LICENSING AUTHORITY
• ETHICS COMMITTEE
• INVESTIGATOR
• SPONSOR
SUBJECT
Approval from ethics committee
Approval from licensing authority under rule 21(b)

13. Ethics Committee
Should have atleast 7 members-chairperson,
member & secretary
For review of each protocol the quorum of EC should be at
least 5 members with the following representations:
(a) Basic Medical Scientists (Preferably One Pharmacologist).
(B) Clinicians
(C) Legal Expert
(D) Social Scientist / Representative Of Non-governmental
Voluntary Agency /Philosopher / Ethicist / Theologian Or A
Similar Person
(E) Lay Person From The Community.

14. Responsibilities of the Ethics Committee
• Reviews and accords its approval to a trial protocol
• To protect the rights, safety and well being of all vulnerable
subjects participating in the study
• An ongoing review of the trials for which they review the
protocol(s).
• Revokes its approval accorded to a trial protocol

15. INVESTIGATORS
Study not to begin until EC / DCGI approval
Adherence to protocol
Personal supervision
Report of ADE to sponsor
Understanding of investigator’s brochure
Maintenance of records and availability for
audits / sponsor inspection / EC and DCGI

16. SPONSOR
• Responsible for implementing and maintaining quality
assurance systems
• Data generated, documented and reported in compliance
with the protocol and good clinical practice (GCP) guidelines
issued by the “CDSCO”, “DIRECTORATE GENERAL OF
HEALTH SERVICES”, “GOI” as well as with all applicable
statutory provisions
• Submit a status report
• Discontinued – 3 months
• Serious adverse event (SAE)-14 days

17. INFORMED CONSENT TO PARTICIPANT
That the study involves research and explanation of the
purpose of the research
Duration
Procedures to be followed
Reasonably foreseeable risks or discomforts
Trial treatment schedule
Statement that participation is voluntary, that the subject can
withdraw from the study at any time and that refusal to
participate will not involve any penalty or loss of benefits to
which the subject is otherwise entitled

18. MULTI-NATIONAL CLINICAL DEVELOPMENT:
 The number of sites & the patients as well as the
justification for undertaking such trials in India shall
be provided to the licensing authority.
For new drugs approved outside India, Phase III
studies need to be carried out primarily to generate
evidence of efficacy and safety of the drug in Indian
patients when used as recommended in the
prescribing information.

19. STUDIES IN SPECIAL POPULATIONS
Information supporting the use of the drug in Geriatrics ,
Paediatrics
Pregnant or
Nursing women
children & patients with renal or other organ systems failure,
and those on specific concomitant medication is required to
be submitted if relevant to the clinical profile of the drug and
its anticipated usage pattern.

20. POST MARKETING SURVEILLANCE
PSUR :-
New drugs should be closely monitored for their clinical safety submission of
PSURs in order to-
Report all the relevant new information (patient exposure)
Summarize the market authorization status in different countries and
any significant variations related to safety
Indicate whether changes should be made to product information
PSURs shall be submitted every 6 months for the first two years after
approval
For subsequent two years – the PSURs need to be submitted
Annually
PSURs due for a period must be submitted within 30 calendar days of
the last day of the reporting period.

21. SPECIAL STUDIES:
BIOAVAILABILITY / BIOEQUIVALENCE STUDIES
For drugs approved elsewhere in the world:
Data regarding the BE with reference formulation should be
submitted whereever applicable
Data on the extent of systemic absorption may be required
for formulations other than those designed for systemic
absorption
Data on effect of food on absorption
Data on Dissolution studies (oral dosage forms)

22. Dissolution and bioavailability data submitted with
the new drug application must provide information
that
 Assures bioequivalence
 Establishes bioavailability and dosage correlations
between the formulation(s) sought to be marketed
and those used for clinical trials during clinical
development of the product

23. FIXED DOSE
COMBINATIONS
1st group
New drug
2nd group
Already approved
/marketed but
combined for the first
time
4th group
Active ingredients
combination
becomes
necessary
3rd group
Already approved or
marketed as FDC but now
changed the ratio or make a
new claim

24. APPENDIX -I
Data To Be Submitted Along With The Application To
Conduct Clinical Trials / Import / Manufacture Of
New Drugs For Marketing In The Country.
Chemical and pharmaceutical information
Physicochemical Data
Analytical Data
Complete monograph specification
Validations
Material safety data
Regulatory status in other countries
Samples and Testing Protocol/s

25. Appendix II FORMAT FOR CLINICAL
STUDY REPORTS
Title Page
Study Synopsis
List of Abbreviations and Definitions
Study Team
Introduction
Study objective
Investigational Plan
Trial Subjects
Safety Evaluation

26. Appendix III : Animal Toxicology (non-clinical
toxicity)
Systemic toxicity studies - Single Dose Toxicity
Repeated Dose Toxicity
Male fertility studies
Female reproduction and developmental studies
Local toxicity - Dermal Toxicity , Vaginal Toxicity,rectal
Toxicity ,Ocular Toxicity
Allergenicity
Genotoxicity
carcinogenecity

27. Route of administration Duration of proposed
human administration
Human Phase(s) for
which study is proposed
to be conducted
Long term toxicity
requirements
Oral or Parenteral or
Transdermal
Single dose or several
doses in one day,
Upto 1wk
I,II,III 2sp,2wk
> 1 wk but upto 2wk I,II,III 2sp;4wk
> 2 wk but upto 4wk I,II,III 2sp;12wk
Over 1mo
I,II,III 2sp;24wk
Inhalation (general
anaesthetics, aerosols)
Upto 2 wk I,II,III 2sp;1mo; (Exposure
time 3h/d, 5d/wk)
Upto 4wk I,II,III 2sp;12wk, (Exposure
time 6h/d, 5d/wk)
> 1 4wk I,II,III 2sp;24wk, (Exposure
time 6h/d, 5d/wk)
Single dose toxicity studies DATA

28. Local Toxicity Studies data
Route of
administration
Duration of
proposed human
administration
Human Phase(s) for
which study is
proposed to be
conducted
Long term toxicity
requirements
Dermal Upto 2 wk I,II 1sp;4wk
III 2sp;4wk
> 2 wk I,II,III 2sp;12wk
Ocular or Otic or
Nasal
Upto 2 wk I,II 1sp;4wk
III
2sp;4wk
> 2 wk I,II,III 2sp;12wk
Vaginal or Rectal Upto 2 wk I,II 1sp;4wk
III 2sp;4wk
> 2 wk I,II,III 2sp;12wk

29. Repeated-dose Toxicity Studies
Data
14-28 days 84-182 days
Group Rodent (Rat) Non-rodent
(Dog or Monkey)
Rodent (Rat) Non-rodent
(Dog or Monkey)
M F M F M F M F
Control 6-10 6-10 2-3 2-3 15-30 15-30 4-6 4-6
Low dose 6-10 6-10 2-3 2-3 15-30 15-30 4-6 4-6
Intermediat
e dose
6-10 6-10 2-3 2-3 15-30 15-30 4-6 4-6
High dose 6-10 6-10 2-3 2-3 15-30 15-30 4-6 4-6

30. LABORATORY PARAMETERS TO BE
INCLUDED IN TOXICITY STUDIES.
1. Haematological
parameters
2. Urinalysis Parameters
3. Blood Biochemical
Parameters
4. Gross and Microscopic
Pathology
 Haemoglobin,haematocrit,
blood PICTURE
Colour, appearance,
albumin, bilirubin
Proteins ,cholestrol. urea
Ca,P,K
Brain,spinalcord,spleen,
trachea,lungs,pancreas

31. Appendix IV : Animal Pharmacology
SPECIFIC PHARMACOLOGICAL ACTION
GENERAL PHARMACOLOGY
( CVS ,CNS ,RESPIRATORY)
SAFETY PHARMACOLOGY

32. Appendix V : INFORMED CONSENT
Format of informed consent form for Subjects
participating in a clinical trial
Informed Consent form to participate in a clinical trial
Study Title:
Study Number:
Subject’s Initials: _______________ Subject’s
Name:_______________
Date of Birth / Age: _________________

33. Signature (or Thumb impression) of the Subject/Legally Acceptable
Representative:_____________
Date: _____/_____/______
Signatory’s Name: ______________________________________________________
Signature of the Investigator: ____________________________ Date:
_____/_____/______
Study Investigator’s Name: __________________________________________________
Signature of the Witness
______________________ Date:_____/_____/_______
Name of the Witness: _______________________________________________________

34. Appendix VI
FIXED DOSE COMBINATIONS (FDCs)
Appendix VII
UNDERTAKING BY THE INVESTIGATOR
Appendix VIII
ETHICS COMMITTEE

35. Format for Approval of Ethics Committee
a. Trial Protocol( including protocol amendments), dated____________
Version no (s).__________
b. Patient Information Sheet and Informed Consent Form
c. Investigator’s Brochure, dated_________, Version no.________
d. Proposed methods for patient accrual including advertisement (s) etc.
proposed to be used for the purpose.
e. Principal Investigator’s current CV.
f. Insurance Policy / Compensation for participation and for serious
adverse events occurring during the study participation.
g. Investigator’s Agreement with the Sponsor.

36. Appendix IX : Stability Testing Of New Drugs
Storage conditions and the length of studies
Photostability on at least one primary batch of the drug
The susceptibility of the drug substance to hydrolysis across a
wide range of ph values when in solution or suspension

37. Appendix X
CONTENTS OF THE PROPOSED PROTOCOL FOR
CONDUCTING CLINICAL TRIALS
 Title Page
 Table of Contents
 Background and
Introduction
• a. Preclinical
experience
• b. Clinical experience
• C. Study rationale
 Study Design
 Subject Eligibility
 a. Inclusion Criteria
 b. Exclusion Criteria

38. Cont…..
 Study Treatment
 Adverse Events
 Ethical Considerations
 Study Monitoring And Supervision
 Investigational Product Management
 Data Analysis

39. APPENDIX XI
Data Elements for reporting serious adverse
events occuring in a clinical trial
1. Patient Details
2. Suspected Drug(s) & Its complete information
3. Details of Suspected Adverse Drug Reaction(s)
 Start date (and time) of onset of reaction
 Stop date (and time) or duration of reaction
 Dechallenge and rechallenge information
4. Outcome
5.Details about the Investigator

40. REFERENCES
http://cdsco.nic.in/html/schedule-y%20(amended
%20version-2005)%20original.htm
http://202.54.104.237/intranet/eip/legislation/uploads
/SCHEDULE-Y.pdf