VACCINES
REGULATIONS IN
INDIA,EUROPEAN
UNION & US

DEPARTMENT OF DRUG REGULATORY AFFAIRS
www.DuloMix.com

Silver Spring,
Maryland, United
States Amsterdam,

Netherlands

New Delhi

CONTENTS :-

1.INTRODUCTION

2.VACCINE REGULATION
IN INDIA

3.VACCINE REGULATION
IN USA

4.VACCINE REGULATION
N EUROPE

INDIAN VACCINE
REGULATIONS BY

CDSCO

CONTENTS

01. OBJECTIVES 02. BIOLOGICAL
PRODUCTS:

PHASE-I & PHASE- II
CLINICAL TRIAL

03. BIOLOGICAL 04. OTHER
PRODUCTS: REQUIREMENTS
Phase-III (SCHEDULE Y):
CLINICAL
TRIAL

Guidance For Industry

Submission of Clinical
Trial Application for
Evaluating Safety
and Efficacy

OBJECTIVES:-
– This Guidance has been developed in conformity with

Drugs and Cosmetics and Rules there under and GCP
Guidelines of India for the purpose of submission of
Clinical Trial application.

– The clinical trial Sponsor is required to submit
application (Form 44) for the purpose of conducting

vaccine

clinical trial in India and submit documents as per
Schedule Y of D & C Act.

– The Sponsor is also responsible for implementing
and maintaining Quality Assurance system to ensure
that the clinical trial is conducted and data generated,
documented and reported in compliance with the
Protocol and Good Clinical Practice www.DuloMix.com

OBJECTIVES:-

– Sponsors are required to submit a Status report on the clinical trial to the
Licensing Authority at the prescribed periodicity.

– In case of studies Prematurely discontinued for any reason including lack of
commercial interest in pursuing the new drug application, a summary report
should be submitted within 3 months.

– a brief description of the study, the number of patients exposed to the drug,
dose and duration of exposure, details of adverse dr-ug reactions, if any, and the
reason for discontinuation of the study.

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OBJECTIVES:-

– Any expected serious adverse event (SAE) occurring during a
clinical trial should be communicated promptly (with in 14 calendar
days)by the Sponsor to the Licensing Authority and to the other
Investigator(s) participating in the study.

– The manufacturer / sponsor have to submit application on Form
44 for permission of Clinical Trial under the provisions of Drugs
and Cosmetic Act 1940 and Rules 1945.

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BIOLOGICAL PRODUCTS:

PHASE-I & PHASE- II CLINICAL TRIAL

* TABLE OF CONTENT

Section A GENERAL INFORMATION

Section B CHEMISTRY MANUFACTURING
CONTROL

Section C NONCLINICAL DATA

Section D PROPOSED PHASE-I / II
STUDIES

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SECTION A
GENERAL INFORMATION

1. Introduction 2. Administrative 3. Manufacturing
about Company Headquarters Facilities

Brief description about Provide address of
Provide address of

company company
company

Headquarters Headquarters

4. Regulatory permissions/approvals

a. No objection certificate for Form-29 as
issued by Central License Approving
Authority.

b. Form 29 as issued by State Licensing
Authority.

c. Permission – to conduct toxicology
permission (For r-DNA products)

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SECTION B
CHEMISTRY MANUFACTURING CONTROL

1. Product Description
A brief description of the drug and the therapeutic class to which it belongs.
1.1 Name of the product
1.2 Generic name / INN name
1.3 Route of administration
1.4 Dosage of strength
1.5 Qualitative and Quantitative Composition

2. Product Development
2.1 Strain details
Name and source (if any)
Incase of products derived form r-DNA technology, the following details
shall also be furnished.
2.1.1. Clone development (for recombinant products)
o Details on source Nucleic acid
-Nucleic acid sequence
o Vector(s)
-Details about vector, please enclose the map of the vector gene
o Host(s) that carrying the vector(s)/ target gene(s) www.DuloMix.com

● 3. Information on Drug Substance

● 3.1 Production of Drug substance
● 3.1.1 Raw materials

– List of raw materials
– Specification & test methods of raw materials
-Human or animal origin (If any) and its TSE / BSE compliance.

● 3.1.2 Description of Manufacturing Process and Process Control
● 3.1.3 Process flow chart

– Operations flow sheet
● 3.1.4 In process control steps & intermediates

Include process control step at each stage of Drug substance
● 3.2 Characterization of Drug substance

3.2.1 Physicochemical Characterization
3.2.2 Biological characterization

● 3.3 Control of Drug substance
3.3.1 Specification
3.3.2 Analytical procedures and validation / standardization studies
(Data expected to be submitted for recombinant products however not for
biological like Vaccines etc.)

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● -3.6 Stability data

3.6.1 Write-up for stability study Program
3.6.2 Specification and Test Methods: Stability study
3.6.3 Accelerated Stability Data (3 months) on pilot scale batches
3.6.4 Real time Stability Data (3 months) on pilot scale batches

● 4. Information on Drug Product

4.1 Description & composition
4.2 Components of Drug product
4.3 Manufacturing process
– Description of facility where clinical trial material will be manufactured.
4.6 Equipment and Premises: Details of equipments , instruments etc involved

in manufacturing for testing of product).
4.7 Control of Excipients
-4.7.3 Excipients human or animal origin (If any) and its TSE / BSE compliance

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4.8 Control of Drug Product

4.8.1Specifications
Final product specifications should be included in detail with reference to the pertaining
compendia.
Non-pharmacopeial tests must also be included.

4.8.2 Analytical procedures

Describe in detail test methods followed in the analysis of the final product. Include detailed
pharmacopeial references when appropriate.

4.8.3 Certificate of analysis (Pilot scale batches)

4.10. Container closure system
4.10.1 Packaging Materials: Specifications and Test methods
4.10.2 Art work – Packaging material (label, primary carton, secondary
carton and Pack Insert.

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4.11 Stability data
4.11.1 Write-up for stability study Program
4.11.2 Specification and Test Methods: Stability study
4.11.3 Accelerated Stability Data (3 months) on pilot scale batches
4.11.4 Real time Stability Data (3 months) on pilot scale batches

SECTION C
NONCLINICAL DATA

(Compliance as per Schedule Y )

References:
1. Schedule – Y, Amendment version 2005, Drugs and Cosmetics Rules, 1945

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4.1 Table of contents of the Module

4.2 Reports on studies

4.2.1 Pharmacology
4.2.1.1 Pharmacodynamic studies (immunogenicity of product)
4.2.1.2 Pharmacodynamic studies of adjuvant (if applicable)
4.2.2 Pharmacokinetics
4.2.2.1 Pharmacokinetic studies (in case of new adjuvant, new modes of

administration)
4.2.3 Toxicology
4.2.3.1 General toxicology – information on:

Design of study and justification of animal model
Animal species used, age and size of groups
Dose, mode of administration and control groups.

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SECTION D
PROPOSED PHASE-I/II STUDIES
(Compliance as per Schedule Y)

1. Protocol for Phase-I / II studies

References:
1. Schedule – Y, Amendment version 2005, Drugs and Cosmetics Rules,
1945.
2. GCP guidelines published by CDSCO, DGHS, Govt. of India.
3. Ethical Guidelines for Biomedical Research on Human Subjects published
by Indian Council of Medical Research, New Delhi.

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BIOLOGICAL PRODUCTS:

PHASE-III CLINICAL TRIAL

* TABLE OF CONTENT

Section A SECTION A GENERAL
INFORMATION

Section B CHEMISTRY
MANUFACTURING CONTROL

Section C NONCLINICAL DATA

Section D PROPOSED PHASE-III STUDIES

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SECTION B
CHEMISTRY MANUFACTURING

Module 3 CONTROL

Quality Information (Chemical, Pharmaceutical and Biological)

3.2.S.1 -General information, starting materials and raw materials
3.2.S.1.1 – Trade and/or non-proprietary name(s)
3.2.S.1.2 – Structural &Molecular Formula and Relative Molecular Weight
3.2.S.1.3 – Description and characterization of drug substance
3.2.S.1.4 – General Description And History of starting material
3.2.S.1.4.1 -Strain
3.2.S.1.5 – General description of raw material.
3.2.S.1.6 -Analytical certificates signed
3.2.S.2.3 -Flow diagram of manufacturing process.
3.2.S.2.7 Description of inactivation or detoxification process
3.2.S.2.8 Description of purification process

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3.2.S.2.9- Description of conjugation process
3.2.S.2.10- Stabilization of drug substance
3.2.S.2.11 -Reprocessing
3.2.S.2.12 -Filling procedure for the drug substance, in-process controls
3.2.S.2.13 -Selection and justification of critical steps
3.2.S.2.14- Description of batch identification system
3.2.S.3- Characterization of drug substance
3.2.S.3.1 – Physicochemical Characterization
3.2.S.3.2 – Biological Characterization
3.2.S.4 – Quality control of drug substance
3.2.S.5 – Reference standards
3.2.S.6 – Container closure system
3.2.S.7 -Stability of drug substance
3.2.S.7.3 -Storage and shipping conditions of drug substance

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3.2.P – Drug product
3.2.P.1 – Description and composition of drug product
3.2.P.2 – Pharmaceutical development
3.2.P.2.3 – Justification of final qualitative/quantitative formula.
3.2.P.3 – Manufacture of drug product.
3.2.P.3.6 – Description of batch identification system.
3.2.P.4 – Control of excipients (adjuvant, preservative, stabilizers
and others).
3.2.P.5 – Control of drug product
3.2.P.6 – Reference standards of materials
3.2.P.7- Container closure system
3.2.P.8 – Stability of drug product
3.2.P.8.4 – Description of procedures to guarantee cold chain.
3.2.A Appendix
3.2.A.2 Safety evaluation of adventitious agents.

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OTHER REQUIREMENTS
(SCHEDULE Y):

Part 1: Contents of the proposed protocol for conducting
Clinical Trials

1. Title Page:

a. Full title of the clinical study.
b. Protocol/Study number and protocol version number with date.
c. The IND name/number of the investigational drug.
d. Complete name and address of the sponsor and contract research
organization, if any.
e. List of the Investigators who are conducting the study, their
respective institutional affiliations and site locations.
f. Name(s) of clinical laboratories and other departments and/or
facilities participating in the study.

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2. Table of contents:-

A complete Table of Contents including a list of all Appendices
1. Background and Introduction
a. Pre-clinical experience
b. Clinical experience- Relevant information regarding
pharmacological, toxicological and other biological properties of
the drug/biological/medical device and previous efficacy and
safety experience should be described.

2. Study Rationale- Describe Background information relevant to study
design and protocol methodology.

3. Study Objective:-

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4. Study Design:

a. Overview of the Study Design: Including a description of the
type of study (i.e. double-blind, multi-centre , placebo controlled, etc.)
b. Flow chart
c. Method of Procedure

5. Study Population- The number of subjects.

6. Subject Eligibility- A) Inclusion & Exclusion Criteria

7. Study Assessments-

Discontinued Subjects :- State how drop-outs would be managed and if they
would be replaced.
Describes how Protocol violations will be treated including conditions
where the study will be terminated for non-compliance with the
protocol. www.DuloMix.com

9. Study Treatment
a. Dosing schedule (dose, frequency and duration). Describe the

administration of placebos and/or dummy medications.
b. Study drug supplies and administration : who is going to provide

the study medications & Details of the product stability, storage
requirements and dispensing requirements.

c. Rules for changing the dose or stopping the study drug should be
provided.

d. Possible drug interactions.
e. drugs that are permitted during the study and the conditions under

which they may be used & the drugs that a subject is not allowed to use.
f. description of the blinding procedure.
g. circumstances in which un-blinding may be done and the

mechanism to be used.

10. Adverse Events
-Procedures used to evaluate an adverse event.

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11.Ethical Considerations:-

a. Risk/benefit assessment.
b. Ethics Committee review and communications.
c. Informed consent process.
d. Statement of subject confidentiality.

12.Study Monitoring and Supervision:-

A description of study monitoring policies and procedure should be
provided.
Case Record Form(CRF):- completion requirements, including
who gets which copies of the forms and any specifics required in
filling out the forms CRF correction requirements, including who
is authorized to make corrections on the CRF and how queries
about study data are handled and how errors, if any, are to be
corrected should be stated. www.DuloMix.com

13.Investigational Product Management-
a. Give Investigational product description and packaging.
b. precise dosing
c. Method of packaging, labeling
d. Assigning of Subject identification code numbering system.
e. Storage conditions.
f. Investigational product accountability: Describe instructions for
the receipt, storage, dispensation, and return of the investigational products.
h. policy and procedure for handling unused investigational products.

14.Data Analysis-

Provide details of the statistical approach to be followed
including sample size
Statistical Analysis: Give complete details of how the results will
be analyzed and reported.

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– Describe the level of significance, statistical tests to be used, and the
method used for missing data, method of evaluation of the data for
treatment failures, non-compliance, and subject withdrawals.

15.Undertaking by the Investigator-
– (as per the Appendix VII of Schedule Y)

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REFERENCE

● Guidance for Industry© Central Drugs Standard
Control Organization Ministry of Health Govt. of India.
(Accessed On 08 June 2022)

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THANK
YOU