The document outlines the regulatory framework for clinical trials in India, specifically focusing on Schedule Y, which guides the permission process for importing and manufacturing new drugs and conducting clinical trials. It highlights the roles of the Drugs Controller General of India (DCGI), the organizational structure, and the requirements for clinical trial applications, including ethics committee approvals and classifications of trials. Additionally, the document discusses proposed changes made to Schedule Y from its 1985 version to the amended 2005 version, emphasizing the need for stringent protocols and monitoring post-marketing for drug safety.

1. SCHEDULE Y
( AMENDED VERSION
2005)
Prepared By Kamalakar Ambati

2. LEARNING OBJECTIVES
 Regulatory Framework of India
 Organization
 Important sections of Schedule Y
 Appendices
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3. INDIAN REGULATORY
PROCESSES & LAWS
 The Main regulatory laws operating in India are the Drug and
Cosmetics Act (1940) and the Drugs and Cosmetics Rules (1945).
 The Act and Rules are binding on allopathic and other systems of
medicine and regulate imports, manufacture, distribution, and sale
of drugs in India.
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4. ORGANIZATION
The New Drug Regulatory Process come under the
purview of the Drugs Controller General of India
(DCGI), who is the head of the Central Drugs
Standard Control Organization (CDSCO), located in
New Delhi.
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5. REGULATORY FRAMEWORK
OF INDIA
Ministry of Chem & Ministry of Health Ministry of Sci & Ministry of
Fertilizers Tech Enviro
Health Secretary
DBT
NPPA DGHS Department of Additional
National Director General of Biotechnology Secretary
Pharmaceutical Health Services
Pricing Authority GEAC
DCGI Genetic
Drug Controller Engineering
Pricing General of India Approval
Regulations Committee
CDL/CDTL
Gov. Drug Testing
Laboratories 5
State Drug Regulatory Authority :FDA By Kamalakar Ambati
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6.  The DCGI is supported by various bodies, such as the Indian Council of
Medical Research (ICMR) and Department of Biotechnology (DBT) in the
evaluation of specific therapies or clinical trials.
 The ICMR, for example, provides expert advice in evaluation of Phase I
trials or clinical trials relevant to national priorities, eg, malaria, AIDS
etc.
 There are also committees, such as Drugs Consultative Committee and
Drugs Technical Advisory Board, which support the DCGI in assessing
new drug applications.
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7. REGULATORY FRAMEWORK
 DGFT( Directorate General of Foreign Trade ( Ministry of
Commerce and Industry)
 Responsible for Export of Biological Samples
out of the country for analysis
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8. SCHEDULE Y
 Requirements and guidelines for permission to
import and/ or manufacture of new drugs for sale
or to undertake clinical trials.
 Earlier version 1985. Amended in 2005, another
amendment due now.
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9. Proposed Changes ( 1985 vs 2005)
• Clinical trials – definition, conduct
 Responsibilities of Ethics Committee (EC),
Investigator and Sponsor
Formats for critical documents
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10. Clinical Trials
Definition of Phases I – IV
Concurrent Phase II-III 03 5
24 Aug
Central lab and trial samples
 Classification of Fixed Dose Combinations
for clinical studies
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11. STRUCTURE & CONTENTS
 The 2005 version of Schedule Y has three major
sections and 11 appendices.
1. Application for Permission
2. Clinical Trial
3. Studies in Special populations
 11 Appendices
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12. Application for Permission
This section covers the information on data required for clinical
trial application (CTA) and refers to relevant appendices for
documents/ data to be submitted.
Application to import or manufacture new drugs for
sale or to undertake CT shall be made in Form 44.
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13. IMPORT LICENSE
 Application to import drugs for use in clinical trials must be submitted at
the same time as the regulatory approval application.
 The application, submitted on Form 12 of the D & C Rules, should give a
detailed calculation of the quantity of drugs required for the study and
from which country the drugs are to be imported.
 The drug licensing authority, the DCGI issues a “Test License” ( “T
License”) on Form 11 of the Drugs and Cosmetic Rules for the import of
drugs.
 T License is obtained along with the permission for the clinical trial.
 Hence, it is not allowed to import a drug without DCGI approval and T
License.
 A T License is valid for one year
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14. CLASSIFICATION
 Clinical trials are now classified into two categories
– A and B –
 Category A comprising clinical trials for which a protocol
has already been approved in specific regulated countries
such as the US, the UK, Australia, Canada and Japan. Average
of 20 applications per month Time for approval: two to four
weeks.
 All other applications fall under Category B. India and
developing countries/market locations
Time taken estimated eight to six to sixteen weeks.
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15.  For a new drug substance discovered in
India, the sponsor can initiate a Phase I
clinical trial.
 However, for new drug substances
discovered outside India, Phase I data
from other countries are required to be
submitted along with the application.
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16.  The DCGI may grant permission to repeat
Phase I and/or to conduct Phase II trials
and subsequent Phase III concurrently with
other global trials for that drug.
 Phase III trials mandatory for obtaining
permission to market the drug in India.
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17. Clinical Trial
This section includes
1. DCGI and EC approvals for initiating trial, investigator
qualifications and site details, central laboratory details,
protocol amendments,
2. Responsibilities of sponsors,
3. Responsibilities of investigators
4. Informed consent process
5. Responsibilities of Ethics Committee
6. Definitions and objectives of different phases of trials( I, II,
III and IV).
 Earlier Schedule Y did not have such
clear cut sections… 17
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18. EC APPROVAL
 Applications for regulatory and ethics committee approval
of a protocol may be submitted simultaneously.
 ECs can grant a conditional approval, i.e. on obtaining
NOC from DCGI, same can be notified to EC and proper
approval can be given the next day
( Earlier Schedule Y mentioned, DCGI permission first and then EC
submission)
 Also, Trial Sites may accept the approval granted to the
protocol by the ethics Committee of another trial site or
the approval granted by an independent ethics committee.
This provision was not there in earlier Schedule Y
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19. PROTOCOL AMENDMENTS
 With a view to further streamlining the protocol review
process, categories have been introduced for protocol
amendments.
Amendments which require notification to the licensing authority but need not
wait for permission
additional investigator sites;
change in investigator with a documented reason why earlier one has
withdrawn( if applicable)
Amended investigator brochure, amended informed consent
Administrative and logistic changes
Minor protocol amendments and additional safety assessments where the
ethics committee has already approved the changes.
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20.  Amendments which require prior
permission of the licensing authority:
 additional patient recruitment;
 major changes in protocol with respect to study design, dose
and treatment options; and
 any change in inclusion or exclusion criteria.
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21. Phases of trials
 The section covers objectives and scope of
Human pharmacology (Phase I),
Therapeutic exploratory trial (Phase II),
Therapeutic confirmatory trial (Phase III)
Post-marketing trials (Phase IV).
Earlier Schedule Y had less emphasis on the
objective and more on the no. of subjects 21
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22. POST MARKETING
SURVEILLANCE
 New Drugs should be closely monitored for their Clinical
safety once they are marketed.
 This includes the requirement for submission of periodic
safety update reports (PSURs), PSUR cycle, template for
PSUR, and the timelines
 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.
 Serious unexpected adverse reactions, must be reported
to LA within 15 days of knowledge of applicant.
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23.  Studies in special populations
This section covers clinical trials in geriatric and
pediatric populations, and in pregnant or
nursing women.
Bioavailability/ Bioequivalence Studies
Still, this area needs to be clearly defined.
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24.  With an objective of bringing uniformity
in trial processes, the new Schedule also
provides formats of critical documents,
eg, informed consent documents, study
reports, EC approvals, reporting of serious
adverse events etc.
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25. SCHEDULE Y1
 Rule 122 DAB. – Registration of clinical
research organization for conducting clinical
trials.
 CRO shall perform functions if it is duly registered, under
the rules, by the Licensing Authority defined in Clause (b)
of Rule 21.
 An application for registration of clinical research
organization shall be made to the said authority
accompanied by the information as required under
Schedule Y-1.
 A registration, unless it is sooner suspended or cancelled,
shall be valid for a period of five years from the date of
issue. 25
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26. REQUIREMENTS AND GUIDELINES FOR REGISTRATION
OF CLINICAL RESEARCH ORGANISATIONS ( CRO)
Scope
 These guidelines cover all organisations, individuals,
institutions and companies that takes the responsibility
of the initiation or management or coordination of a
clinical trial. It does not include clinical trial sites.
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27. Criteria for Registration
(i) The CRO shall be under the charge of a person who is responsible for the
overall activities of the organisation.
(ii) The organisation shall have adequate resources, qualified and trained staff
for oversight of clinical trials.
(iii) The trial related duties and functions transferred to and assumed by the
CRO shall be specified in writing and properly quantified.
(iv) The organisation shall ensure that the trials are adequately monitored and
the trial related responsibilities transferred to it, partially or fully, by the
sponsor are discharged effectively and efficiently.
(v) The organisation shall implement quality assurance and quality control as
per standard operative procedures designed for the purpose. Such SOPs
shall be well documented.
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28. (viii) An undertaking to declare that
(a) We shall comply with the conditions imposed on the registration
certificate along with the adherence to other guidelines like GCP
guidelines and provisions of the Drugs and Cosmetics rules,
1945.
(b) We shall comply with such further requirements, if any, as may
be specified by the Government of India, under the Act and the
rules, made thereunder
.
(c) We shall allow the licensing authority and/or any person
authorised by him in that behalf to enter and inspect the
premises and to examine the process/procedure and documents
in respect of any clinical trial conducted by us for which the
registration certificate has been made. 28
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29. 4. INFORMATION REQUIRED FOR
REGISTRATION
(i) Name and address of the organisation
(ii) Name and address of the proprietors/partners/directors.
(iii) Status of the organisation as legal entity.
(iv) A brief profile of the specific activities/services undertaken by
the organisation including facilities, resources and infrastructure.
(v) An organogram of the organisation including brief CVs of key
personal.
(vi) List of SOPs with salient highlights about specific areas to be
scrutinised.
(vii) Copy of the contract between the sponsor and the
organisation.
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30. SCHEDULE Y1 CONTD…
vi) The organisation should check the accuracy and
completeness of the data/documents and other related
records and ensure that the investigator(s) have maintained
the essential documents required for the conduct of the trial.
(vii) The organisation shall ensure that the investigator(s)
received all documents and trial related supplies needed to
conduct the trial properly.
(viii) The organisation shall have education programmes to help
its investigators to carry out the research studies as per
guidelines applicable to such trials.
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31. RESTRUCTURING FRAMEWORK
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32. CONSTRAINTS
 Regulatory Evaluation Capacity
 Regulatory inspections capacity
 Special Products like Devices, Diagnostics
etc
 No supervision over ECs in India
 Lack of Regulatory Inspections
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33. SYNOPSIS
Clinical trial – rationalization for globalization
Ethics committee – DC for EC
Informed consent – torture of additional signatures
Investigator – overtaken by undertaking
Sponsor – Audit-ory hallucinations of compliance to ICH-
GCP and Indian GCP
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34. REFERENCES
 www.cdsco.nic.in
 www.scheduley.co.in
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