Amended Schedule Y

Dr Arun D Bhatt
MD (Med) FICP (Ind)
Member Faculty of Pharmaceutical
Medicine (Royal College UK)
President
ClinInvent Research India Pvt Ltd

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 Changes in Schedule Wh(Y)?

§ Schedule Y 1988 relevant to

predominantly generic industry
§ GCP trials since 1995, and arrival of
IPR regime in 2005
§ Integration of India in global clinical
development
§ Legal support to GCP guidelines
§ Improvements in quality of clinical
trials
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 Amended SCHEDULE Y

Regulations and Guidelines for

permission for development (pre-
clinical and/or clinical), import and
manufacture of New Drugs for
Marketing in India

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 Significant Changes

§ Clinical trials – definition, conduct

§ Responsibilities of Ethics Committee
(EC), Investigator and Sponsor
§ Formats for critical documents

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 Definition of Clinical Trial

“Clinical trial” means 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”.

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 Clinical Trials

§ Definition of Phases I – IV
§ Concurrent Phase II-III
§ Central lab and trial samples
§ Compliance to GCP / GLP
§ Flexibility in data requirements for
new drugs for life threatening /
serious conditions or disease of
relevance to India
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 Clinical Trials :
Special Studies
§ Clinical trials required if the indication is
relevant to special population e.g.
pediatrics, geriatrics, pregnancy
§ EC for paediatric trials to include
members knowledgeable about paediatric,
ethical, clinical and psychosocial issues
§ Mature minors and adolescents to sign an
assent form
§ Other – Post-marketing surveillance,
BA/BE

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 Responsibility of Sponsor

§ Quality assurance to ensure compliance

to GCP guidelines of CDSCO
§ Submission of status report at prescribed
periodicity; reasons for premature
termination to be communicated
§ Serious adverse event to be
communicated promptly (within 14
calendar days) to DCGI and other
investigators
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 Responsibilities of Investigator

§ Responsible for conduct of trial according

to protocol and GCP
§ Compliance as per undertaking format
(Indian version of FDA form 1572)
§ Medical care for AEs
§ SAE reporting to
§ Sponsor within 24 hrs
§ EC within 7 days
§ Informed consent
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 Responsibilities of EC

§ Safeguard rights, safety, wellbeing of

subjects
§ Special care for vulnerable subjects
§ Ongoing review
§ Reason’s for revoking approval and
information to investigator /
regulatory authority

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 Ethics Committee

§ EC approval of protocol / informed

consent form (ICF) and notification
to DCGI prior to initiation
§ Approval for sites without EC by
institutional / independent EC
§ EC approval of protocol amendments
and notification to DCGI

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 Appendices

§ I Data to be submitted along with the application to conduct

clinical trials / import / manufacture of new drugs for
marketing in the country
§ I-a Data required to be submitted by an applicant for grant
of permission to import and / or manufacture a new drug
already approved in the country
§ II Structure, Contents And Format For Clinical Study
Reports
§ III Animal Toxicology (Non-clinical Toxicity Studies)
§ IV Animal Pharmacology

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 Appendices
§ I Data for submission for application to conduct
clinical trials / import / manufacture of new drugs
for marketing in the country
§ I-a Data for submission for application for grant
of permission to import and / or manufacture a
new drug already approved in the country.
§ II Structure, Contents And Format For Clinical
Study Reports
§ III Animal Toxicology (Non-clinical Toxicity
Studies)
§ IV Animal Pharmacology
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 Appendices
§ V Informed Consent
§ VI Fixed Dose Combinations (FDCs)
§ VII Undertaking by Investigator
§ VIII Ethics Committee
§ IX Stability Testing Of New Drugs
§ X Contents Of The Proposed Protocol For
Clinical Trial
§ XI Data Elements For Reporting Serious Adverse
Events Occurring In A Clinical Trial

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 Appendix II
Format For Clinical Study Reports

1. Title page
2. Synopsis
3. Statement of Compliance to GCP
4. Abbreviations
5. Table of contents
6. Ethics committee
7. Study team

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 Appendix II
Format For Clinical Study Reports

8. Introduction
9. Objective
10. Plan
11. Subjects
12. Efficacy
13. Safety
14. Discussion
15. List of References
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Appendices for Clinical Study Reports

a. Protocol and amendments

b. Specimen of Case Record Form
c. Investigators’ name(s) with contact addresses, phone, email etc.
d. Patient data listings
e. List of trial participants treated with investigational product
f. Discontinued participants
g. Protocol deviations
h. CRFs of cases involving death and life threatening adverse
event cases
i. Publications from the trial
j. Important publications referenced in the study
k. Audit certificate, if available
l. Investigator’s certificate that he/she has read the report and that
the report accurately describes the conduct and the results of
the study.

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 Appendix V Essential
Elements of Informed Consent
§ Trial involves research
§ Purpose
§ Trial treatments and randomization
§ Trial procedures
§ Risk
§ Benefit
§ Alternative treatments
§ Compensation / treatment for injury
§ Subject’s responsibilities
§ Experimental aspects
§ Any payment
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 Appendix V Essential
Elements of Informed Consent
§Confidentiality
§New information
§Voluntary participation
§Person/s to contact
Ø for study information
Ø rights of subject
Ø if study related injury
§Reasons for termination
§Duration of study
§Number of subjects
§Any other pertinent information
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 Appendix V
Format Of Informed Consent Form
§Study Title: Study Number:
§Subject’s Initials: Subject’s Name: Date of Birth / Age:
§ Consent Statements with initials in [ ]
§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:

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 Appendix VII
Undertaking By The Investigator
1. Full name, address and title of the Principal Investigator (or
Investigator(s) when there is no Principal Investigator)
2. Name and address of the medical college, hospital or other facility
where the clinical trial will be conducted: Education, training &
experience that qualify the Investigator for the clinical trial (Attach
details including Medical Council registration number, and / or any
other statement(s) of qualification(s))
3. Name and address of all clinical laboratory facilities to be used in
the study.
4. Name and address of the Ethics Committee that is responsible for
approval and continuing review of the study.
5. Names of the other members of the research team (Co- or sub-
Investigators) who will be assisting the Investigator in the conduct
of the investigation (s).
6. Protocol Title and Study number (if any) of the clinical trial to be
conducted by the Investigator
8. Signature with Date
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 Appendix VII.7
Commitments by The Investigator
i. Study not to begin until EC / DCGI approval
ii. Adherence to protocol
iii. Personal supervision
iv. Ensure requirements of IC and EC review
v. Report of AE to sponsor
vi. Understanding of investigator’s brochure
vii. Ensure that all associates, colleagues and
employees suitably qualified and experienced
and aware of their obligations

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 Commitments by Investigator

viii.Maintenance of records and availability for

audits / sponsor inspection / EC and DCGI ;
Cooperation in audits
ix. Report to EC promptly about changes and
unanticipated problems
x. Report all unexpected serious adverse events to
the Sponsor in 24 hrs and EC within 7 days
xi. Confidentiality of data and patients
xii. Compliance with all other obligations of clinical
investigators

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 Appendix VIII
Ethics Committee

§ No of members at least 7 members

§ Chairperson from outside the
institution)
§ Other members a mix of
medical/non-medical, scientific and
non-scientific persons, including lay
public

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 Quorum for EC

At least 5 members with the following

representations:
a) basic medical scientists (preferably one
b) pharmacologist).
c) clinicians
d) legal expert
e) social scientist / representative of non-
governmental voluntary agency / philosopher /
ethicist / theologian or a similar person
f) lay person from the community.

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 Documents for Review by Ethics
Committee

a. Trial Protocol( including protocol amendments), date

version
b. Patient Information Sheet and Informed Consent Form
(including updates if any) in English and/or vernacular
language.
c. Investigator’s Brochure, date, version
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.
h. Investigator’s Undertaking (Appendix VII).

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GCP - A Shared Responsibility

Sponsor
Investigator
Regulatory
Authority
Ethics
Committee
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