CENTRAL DRUG STANDARD CONTROL ORGANISATION (CDSCO)

CONTENTS

• INTRODUCTION
• ORGANISATION CHART OF CDSCO

• FUNCTION OF CDSCO
GUIDELINES

• BA/ BE
• BIOLOGICALS
• CLINICAL TRIAL

• COSMETICS

• DRUGS
• MEDICAL DEVICE

• COMMITTEES

• STATE LICENSING AUTHORITY

• SUGAM
• REFRENCES.
AIM: - The Drugs & Cosmetics Act,1940 and rules 1945 have entrusted various responsibilities
to central & state regulators for regulation of drugs & cosmetics. It envisages uniform
implementation of the provisions of the Act & Rules made thereunder for ensuring the safety,
rights, and well-being of the patients by regulating the drugs and cosmetics. CDSCO is constantly
thriving to bring out transparency, accountability, and uniformity in its services in order to ensure
the safety, efficacy, and quality of the medical product manufactured, imported, and distributed
in the country.

ROLE: -
Under the Drugs and Cosmetics Act, CDSCO is responsible for approval of Drugs, Conduct of
Clinical Trials, laying down the standards for Drugs, control over the quality of imported drugs in
the country, and coordination of the activities of State Drug Control Organizations by providing
expert advice with a view of bringing about the uniformity in the enforcement of the Drugs and
Cosmetics Act.
https://cdsco.gov.in/opencms/opencms/en/Home/

Vision: - To protect and promote health in India.

Mission: - To safeguard and enhance public health by assuring the Safety, efficacy and quality of
drugs, cosmetics and medical device.

ORGANISATION CHART OF CDSCO

ROLES: - HEADQUARTES
Regulatory control over the import of drugs, approval of new drugs and clinical trials,
meetings of Drugs Consultative Committee (DCC) and Drugs Technical Advisory Board (DTAB),
approval of certain licenses as Central License Approving Authority is exercised by the CDSCO
headquarters

ZONAL OFFICE: - https://cdsco.gov.in/opencms/opencms/en/Zonal-office/

SUB ZONAL OFFICE: - https://cdsco.gov.in/opencms/opencms/en/subzonaloffice/

Table no: - 1 BA/ BE

SR NO GUIDELINES RELEASE CONTENT

DATE
 1 Updated list of BA-BE study center & 2021-Aug-02 It contains the list of
bio-analytical laboratories dt. registration no. name and
Alerts
10.06.2021 under New CT RULE 2019 address of the firm
clinical facility,
bioanalytical laboratory,
and its validity.

2 Guidance document for approval of 2014-Jan-04 It contains the various

ba/be noc for export purpose as per application for new drugs,
schedule y & test license in form 11 of export, form no 12 form no
drugs and cosmetics rules, 1945 44

3 Module for online processing of 2021-Oct-01 Notice to stakeholders

applications for registration of BA BE regarding Sugam portal
Public
study centers (CT-08)
notice

4 Submission of Post Approval Changes 2021-Sep-29 User manual

Applications through SUGAM Portal

Table no: - 2 BIOLOGICALS (VACCINES)

SR NO GUIDELINES RELEASE DATE CONTENT

1 COVID-19 vaccines 2021-Sep-14 It contains the list of
Public notice approved for Restricted vaccines,
Use in Emergency Date of approval, age
Situation in the country group,
ROA, storage.
2 SOP Guidance for import 2021-May-04 Guidelines for private
of vaccine by the private /government sector
sector or any person for import rules of
covid vaccine.
3 Post approval Guidance for Industry for 2020-Jan-03 Guidance for the
changes Post approval changes in industry for levels
biological products 1,2,3, changes.
Quality safety and
Efficacy Documents
 4 Manufacture Manufacturing Permission 2021-Sep-14 It contains the name
and facility of Human Vaccines from of the firm, molecule
year 2009 to 2021 till date approved, its
indication,
permission no
5 Import and Import Permission of 2021-Sep-14 It contains the name
registration Human Vaccine from year of the firm,
2009 to 2021(till date) formulation, its
indication,
permission no

Table no: - 3 CLINICAL TRIAL

SR NO GUIDELINES RELEASE DATE CONTENT

1 Notice regarding 2020-Mar-30 Responsibilities of
public notice conduct on clinical sponsor for conduct of
trial in the present clinical trials
situation due to the
outbreak of COVID-
19
2 Draft Guidance for 2017-Feb-17 Guidelines for
Industry on industry.
Requirement of
Chemical &
Pharmaceutical
Information Including
Stability Study Data
Before Approval of
Clinical Trials / BE
Studies
3 G.S.R.227(E) 19 2018-Feb-09 Contents of proposed
Gazette notifications March 2019 protocols
For conducting
clinical trials.

4 Ethical committee Notice regarding 2018-Aug-01 Notice to the

Ethics committee stakeholders for e
registration through registration.
SUGAM portal
Table no: - 4 COSMETICS

SR NO GUIDELINES RELEASE CONTENT

DATE
1 Cancellation of two 2021-Jun-25 General News of the
News Cosmetics Registration cancellation of the
Certificate of M/s Stiefel license.
India Pvt Ltd
2 Submission of 2021-Aug-10 Cosmetics rules
Public notice notarized/apostilled GSR NO 763 E
documents for Import and 2020
Registration of cosmetics in Import,
view of COVID-19 manufacturing
during pandemic.
3 Inviting Public comments, 2021-Jul-26 Guideline for
as steps are being taken by stakeholders for
CDSCO to regulate the conducting skin
products like skin patches patch test
which are being used as
cosmetic
4 Notice regarding 2021-Jan-19 D&C rules for
FAQ/Guidance Document cosmetics.
for grant/retention of
registration
certificate/license for
import or manufacture of
cosmetics in India under the
Cosmetics Rules 2020
5 G.S.R 3609(E) 2017-Nov-14 List of amendments.
Gazette notification

Table no: - 5 DRUGS

SR NO GUIDELINES RELEASE CONTENT

DATE
1 New drug_advisory_commitee 2018-Feb-09 NDAC to advise
DCGI for
 regulatory
approval of new
drugs and
clinical trial
2 Procedure to be followed for 2021-Aug-27 List of 31 FDC
News regularisation of FDCs declared as AS Mentioned in
rational in respect of 249 FDCs by annuxure A.
the DTAB which were licensed to
manufacture and market by SLA
without prior approval from
DCG(I)
3 2019.01.11_S.O. 180(E) to 2019-Jan-11 prohibition of
S.O.259(E)_Prohibition of certain FDC of
FDCs appeared in the list of 294 Glucosamine +
FDCs, under Section 26A Calcium
Carbonate
considered as
irrational, which
appeared in the
list of 294 FDCs;
4 Manufacturing and marketing of 2021-Sep-01 For symptomatic
FDC of Tolperisone HCL 150mg + treatment of
Paracetamol IP 500mg tablet post-stroke
spasticity with
pain in adults
only.
5 New Drugs and Clinical Trials 2019-Mar-20 It includes rules,
Gazette Rules 2019 G.S.R. 227(E) regulations,
notification chapters for a
new drug.

Table no: -6 COMMITTEES

DCC Drug consultative committee To advise the central, state, and DTAB on any
matter tending to secure uniformity throughout
in administration of act
DTAB Drug technical advisory To advise the central, state, Govt. on technical
board matters.
 SEC SUBJECT EXPERT Evaluate the applications of clinical trial and
COMMITTEE new drugs for their safety and efficacy of
products
IND Investigational new drug To detail the data that provide documentation
application that it is indeed reasonable to proceed with
certain human trails with drugs
APEX -- Monitor clinical trial
TECHNICAL -- Technical committee meetings.

DTAB: -

DCC

It consists of two representatives nominated by central government and one nominee of each of
the state. The committee meet when required by the central government and is empowered to
regulate its own procedure.
STATE LICIENCING AUTHORITY

FUNCTIONS
1.Licensing of drugs manufacturing and sales establishments
2. Licensing of drug testing laboratories
3. Approval of drug formulation for manufacture.

4. Monitoring of quality of drugs and cosmetics, manufacture by respective state units and those
marketed in the state.

5.Investigation and prosecution in respect of contravention of legal provisions

6. Administrative actions

7. pre- and post-licencing inspection

8.Recall of sub- standard drugs.

SUGAM

An online licensing portal of CDSCO has been implemented in January 2016 and has been named
SUGAM file application for various services like applications submissions, processing and grant
of permission for quick.
SUGAM BENEFITS

• Applicants can apply for license under the import and registration division to CDSCO
• Track the status of the application

• Answer back to raised queries

• Applicants can also upload essential documents for registration, import license and other
related activities

SUGAM CHALLENGES

• There is no provision to upload files greater than 10 Mb file size

• Documents need to be split as per each report generally companies have information in one
single report. for example, biocompatibility used to be one topic earlier now it needs to be
split into cytotoxicity testing, acute toxicity, etc.……….

• There is no provision to upload multiple different files for one heading companies can only
combine them as one pdf giving the possibility of information getting misplaced.

TYPES OF LICENCE CAN APPLY THROUGH SUGAM PORTEL

Table no 8.1: Purpose of Registration& Documents Required

 Purpose of Registration Document Requirement Forms Available
Cosmetics Registration ID Proof Details, Power of Form 42
Attorney, Corporate Address
Proof
Ethics Committee Registration ID Proof Details, Power of Ethics Committee Registration
Attorney, Corporate Address
Proof
Formulation R&D ID Proof Details, Power of Form44, Form12
Organization Attorney
Import of drugs/Medical ID Proof Details, Power of Form 40
Devices/Test License Attorney, Corporate Address Form 8
Proof and Manufacturing
License or Wholesale Licenses
(Form 20B & Form 21B
BA/BE Approved Sites ID Proof Details, Power of Form 44
Attorney, Corporate Address
Proof

Table no: - 8.2 Application Submission for Import & Registration

Purpose of Application Type of Application Form Number
Application for grant of the Registration Fresh, Endorsement & Form 40/41
Certificate (RC) for drugs Re-registration
Application for grant of Import License for Fresh, Endorsement & Form 8/10
Drugs against approved RC Re-registration
Application for grant of the Registration Fresh, Endorsement & Form 42/43
Certificate (RC) for Cosmetics Re-registration

Rules, regulations, guidelines and standards for regulatory filing of

Drugs and Cosmetics, Medical Devices, Biologicals, Food &
Nutraceuticals, Herbals
1. Drugs and Cosmetics

1.0 New drug:

 Demonstration of safety and efficacy of the drug product for use in humans is essential
before the drug product can be approved for import or manufacturing and marketing in the
country. The Rules 122A, 122B, 122 DAB, 122DAC, 122 DD and 122E of Drugs and
Cosmetics Rules and Appendix I- XII of Schedule Y, describe the information/data required
for approval of clinical trial and/or to import or manufacture of new drug for marketing in the
country.
Rules

Rules Content Explanation

Rule 18 Prohibition of manufacture and sale of

certain drugs and cosmetics
Rule 18A Disclosure of the name of the Every person, not being the
manufacturer, etc. manufacturer of a drug or cosmetic or
his agent for the distribution thereof,
shall, if so required, disclose to the
Inspector the name, address and other
particulars of the person from whom
he acquired the drug or cosmetic.
Rule 18B Maintenance of records and furnishing Every person holding a licence under
of information- clause (c) of section 18 shall keep and
maintain such records, registers and
other documents as may be prescribed
and shall furnish to any officer or
authority exercising any power or
discharging any function under this
Act such information as is required by
such officer or authority for carrying
out the purposes of this Act.

Rule 21 A drug already approved by the For certain claims, which is now
Licensing Authority. proposed to be marketed with modified
or new claims, namely, indications,
dosage, dosage form (including
sustained release dosage form) and
route of administration.
A new drug shall continue to be
considered as new drug for a period of
four years from the date of its first
approval.
Rule 22 Powers of Inspectors Subject to the provisions of section 23
and of any rules made by the Central
Government in this behalf, an
Inspector may, within the local limits
of the area for which he is appointed
(a) inspect—
(i) any premises wherein any drug
or cosmetic is being manufactured
and the means employed for
standardizing and testing the drug
or cosmetic
(ii) any premises wherein any
drug or cosmetic is being sold, or
stocked or exhibited or offered for
sale, or distributed.

(b) take samples of any drug or

cosmetic-
(i) which is being manufactured or
being sold or is stocked or exhibited or
offered for sale, or is being distributed
(ii) from any person who is in the
course of conveying, delivering or
preparing to deliver such drug or
cosmetic to a purchaser

Rule 26A Power of Central Government to

prohibit manufacture, etc., of drug and
cosmetic in public interest
Rule 26B Powers of Central Government to
regulate or restrict, manufacture, etc.,
of drug in public interest.
Rule 27 Penalty for manufacture, sale, etc., of
drugs in contravention
Rule 27A Penalty for manufacture, sale, etc., of
cosmetics in contravention
Rule 122A Application for permission to import
new drug
Rule 122B Application for approval to
manufacture new drug
Rule 122D Permission to import or manufacture
fixed dose combination An application for permission to
import or manufacture fixed dose
combination of two or more drugs as
defined in clause (c) of rule 122-E
shall be made to the Licensing
 Authority as defined in clause (b) of
Rule 21 in Form 44, accompanied by a
fee of fifteen thousand rupees and
shall be accompanied by such
information and data as is required in
Appendix VI of Schedule Y.

Rule Mandatory requirement of permission

122DA from DCG (I) for conduct of clinical
trial of new drug
Rule Provision for examination of serious Provision for debarment of the
122DAB adverse event (SAE) of injury and applicant in case of failure to pay
death and payment of compensation in compensation
clinical trial related cases.
Rule Conditions of permission for conduct of Provision for debarment of applicant
122DAC clinical trial which includes mandatory and investigator in case of non-
requirement to follow Good Clinical compliance
Practice (GCP) guidelines, guidelines
and requirements specified in Schedule
Y of Drugs and Cosmetics Rules and
other applicable regulations.
Rule Suspension or cancellation of If the importer or manufacturer under
122DB Permission/Approval this Part fails to comply with any of
the conditions of the permission or
approval, the Licensing Authority
may, after giving an opportunity to
show cause why such an order should
not be passed, by an order in writing
stating the reasons therefor, suspend or
cancel it.

Rule Registration of Ethics Committee No Ethics Committee shall review and

122DD record its approval to a clinical trial
protocol without prior registration
with the Licensing Authority as
defined in clause (b) of Rule21
Rule 122E Definition of new drug
Schedule Y Detailed guidelines and requirements For drugs indicated in life threatening
for conduct of clinical trial and / serious diseases or diseases of special
approval of new drug. relevance to the Indian health
scenario, the toxicological & clinical
data requirements may be abbreviated,
deferred or omitted, as deemed
appropriate by the Licensing Authority
 Good Issued by CDSCO, Directorate General
Clinical of Health Services, Govt. of India
Practice
Guidelines

2.0 Cosmetics rules 2020

Cosmetic is defined under section 3(aaa) of the Drugs and Cosmetics Act, 1940 as, any
article intended to be rubbed, poured, sprinkled or sprayed on, or introduced into, or
otherwise applied to, the human body or any part thereof for cleansing, beautifying,
promoting attractiveness or altering the appearance, and includes any article intended for use
as a component of cosmetic.

Rules Content Explanation

Rule 12 Import of cosmetic (1) No cosmetic shall be imported into India unless the product
has been registered in accordance with these rules by the Central
Licensing Authority or by any officer to whom such powers may
be delegated under sub-rule (1) of rule 5.
(2) An application for registration of a cosmetic product
intended to be imported into India shall be made through the
online portal of the Central Government in Form COS-1 either
by the manufacturer himself or by his authorised agent or the
importer in India or by the subsidiary in India authorised by the
manufacturer.

Rule 13 Grant of import (1) After examination of documents furnished with the
registration application under sub-rule (2) of rule 12 the Central
certificate Licensing Authority may, on being satisfied, grant import
registration certificate in Form COS- 2 or may reject such
application for which reasons shall be recorded in writing
within a period of six months from the date of application.
(2) In case of a new cosmetic, the applicant shall obtain prior
permission in Form COS- 3 as provided in Chapter V from
the Central Licensing Authority before registration of import
of new cosmetic into India.

Rule 14 Validity of import A registration certificate granted under rule 13 shall remain valid in
registration perpetuity, subject to payment of registration certificate retention fee as
certificate specified in the Third Schedule before completion of the period of five
years from the date of its issue, unless, it is suspended or cancelled by
the Licensing Authority.
Rule 15 Fresh application in In case of change in constitution of a registration holder or overseas
case of change in manufacturer, after grant of registration under sub-rule (1) of rule 13, an
constitution application shall be made under sub-rule (2) of rule 12 for grant of fresh
registration within a period of one hundred and eighty days from the
date of such change in constitution
Rule 16 Suspension and
cancellation of
Registration
Certificate
Rule 17 Import of cosmetics
already registered
for import
Rule 18 Prohibition of (1) No cosmetic, the manufacture, sale or distribution of which is
import of certain prohibited in the country of origin, shall be imported under the same
cosmetic- name or under any other name except for the purpose of examination,
test or analysis.
(2) No cosmetics shall be imported unless the ―Use Before or use by
‘‘date shown on the label, wrapper or container of the cosmetic is later
than six months from the date of import.
(3) No cosmetic containing hexachlorophene shall be imported.
Rule 19 Documents to Before any cosmetics are imported, a declaration signed by
be supplied to manufacturer or on behalf of the manufacturer or by importer or
the on behalf of the importer that the cosmetics comply with the
Commissioner provisions of Chapter III of the Act, and the rules made
of Customs. thereunder, shall be supplied to the Commissioner of Customs.

Rule 20 Procedure for

import of cosmetics
Rule 21 Import of cosmetic
for personal use
Rule 22 Import through No cosmetic shall be imported into India except through the points of
points of entry entry as specified in rule 43A of the Drugs and Cosmetics Rules, 1945.
Rule 23 Application for like in case, the original license or loan licence is damaged or lost; a
grant of license or duplicate copy of the licence or loan licence may be requested for from
loan license to the State Licensing Authority on payment of fee as specified in the
manufacture Third Schedule. Application under sub-rule (1) shall be made through
cosmetics for sale or an identified online portal in Form COS-5 for licence or in Form COS-6
for distribution for loan licence accompanied with a fee, as specified in the Third
Schedule along with respective documents as specified in Part II of the
Second Schedule
Rule 24 Manufacture at If cosmetics are manufactured at more than one premises, a separate
more than one application for each of such premises shall be made and a separate
premise license obtained for each such premises.

Rule 27 Grant or refusal of (1) If the Licensing Authority, after such further enquiry, if any, as he
license may consider necessary, is satisfied that the requirements of the rules
 under the Act have been complied with and that the conditions of the
license, loan licence and the rules under the Act shall be observed, he
shall grant a license in Form COS-8 or Form COS-9 as the case may be.
(2) If the Licensing Authority is not so satisfied, he shall reject the
application and shall inform the applicant of the reasons for such
rejection and of the conditions which must be satisfied before a license
can be granted or renewed and shall supply the applicant with a copy of
inspection report
Rule 28 Further application
for licence or loan
licence after
rejection
Rule 31 Inspection for
verification of
compliance
Rule 32 Permission for
import or
manufacture of new
cosmetic
Rule 33 Prohibition of sale
or distribution
Rule 34 Manner of labelling Subject to other provisions of the rules, a cosmetic shall carry on both
the inner and outer labels: (a) the name of the cosmetics, (b) the name
of the manufacturer and complete address of the premises of the
manufacturer where the cosmetic has been manufactured.
Rule 36 Prohibition against
false or misleading
claims.
Rule 37 Labelling of hair
dyes containing
dyes, colours and
pigments.
Rule 39 No cosmetic shall be In case, the cosmetic is not included under the Ninth Schedule, it shall
imported or meet the requirements under these rules and specifications and
manufactured standards applicable to it in the country of origin.
unless it complies
with the
specifications
prescribed under
the Ninth Schedule
Rule 40 Testing of Cosmetic An application from a purchaser for test or analysis of a cosmetic under
from a purchaser section 26 of the Act shall be made to the Government Analyst in Form
COS- 13 and the report of the test or analysis of the cosmetics made on
such application shall be supplied to the applicant in Form COS- 14
Rule 41 Procedure for The Inspector while exercising powers under section 22 of the Act shall
sampling follow the procedure provided in section 23 of the said Act.
 3.0 List of Documents Required for Grant of Registration Certificate for
import of Cosmetics into India
➢ Covering Letter mentioning the purpose of application
➢ Authorisation from the manufacturer (Authorisation including complete product list duly
apostilled and authenticated from the country of origin. All the pages of the authorisation
including product list should be signed by both authorised Indian agent and manufacturer
before authentication.)
➢ Filled in Part-I of Second Schedule D
➢ List of Ingredients along with its percentage contents
➢ Labels of proposed products -In case of cosmetics; where a hazard exists, every inner label
shall clearly indicate adequate directions for safe use, any warning, caution or special
direction required to be observed by the consumer, a statement indicating the names and
quantities of ingredients that are hazardous or poisonous.
➢ Specifications and testing methods
➢ Pack inserts
➢ Manufacturing Licenses/undertaking for no provision of manufacturing license in the
country- Authenticated copy of manufacturing licenses/registration/marketing authorization
in respect of applied products issued by Regulatory Authority from country of origin. In case
there is no provision of manufacturing licenses/marketing authorization in country of origin,
an undertaking for the same from the manufacturer is required to be submitted.
➢ Free Sale Certificate (duly authenticated)
➢ Non-Animal Testing Declaration -No person shall use any animal for testing of cosmetics.
An Undertaking from the manufacturer that the applied cosmetic products to be imported
into the country have not been tested on animals needs to be submitted along with application
in Form COS-1.
➢ Declaration for Heavy Metal and Hexachlorophene content.
➢ Other documents (If any).
➢ Application in Form COS-1
➢ Fee: Original Bharatkosh e-receipt for free paid

4.0 DCG(I) approval process for drug substance/ drug product

References: cdsco.gov.in
 2. Medical devices
In India, at present only notified medical devices are regulated as Drugs under the Drugs and
Cosmetics Act 1940 and Rules made thereunder in 1945.
1. Substances used for in vitro diagnosis and surgical dressings, surgical bandages,
surgical staples, surgical sutures, ligatures, blood and blood component collection bag
with or without anticoagulant covered under sub-clause (i)
2. Substances including mechanical contraceptives (condoms, intrauterine devices, tubal
rings), disinfectants and insecticides notified under sub-clause (ii)
3. devices notified from time to time under sub-clause (iv), of clause (b) of section 3 of
the Drugs and Cosmetics Act, 1940
4. lists of Devices
1. Disposable Hypodermic Syringes
2. Disposable Hypodermic Needles
3. Disposable Perfusion Sets
4. In vitro Diagnostic Devices for HIV
5. Cardiac Stents
6. Bone Cements
7. Heart Valves
8. Orthopedic Implants
Classification of medical devices:

Medical devices under the MDR 2017 are classified on the basis of parameters specified in part 1
of the first schedule,

1. CLASS A (low risk)

2. CLASS B (low moderate risk)
3. CLASS C (moderate high risk)
4. CLASS D (high risk)

• In-Vitro diagnostic medical devices are classified on the basis of part Il of first schedule,
• Assessment authority as per class of medical devices.
• Class A or class B-state licensing authority
• Class C or class D-central licensing authority
• For class C and class D the inspection will be carried out by Central Licensing Authority
within a period of 60 days from the date of application and Central Licensing Authority
may grant licence if satisfied that the requirements of these rules have been complied
within a period of forty-five days from the date the inspection report has been received.
 • For the import of additional product from different manufacturing site the Indian agent has
to submit fee for additional site as well as for the product and, the import licence will be
issued with fresh validity. In case the importer desires to get endorsed the additional
product then product fees are required to be submitted and the import license will be issued
with the same validity as of the existing license.
• Manufacturing firm is complying with ISO/IEC standards

(i) The medical device shall conform to the standards laid down by the Bureau of
Indian Standards established under section 3 of the Bureau of Indian Standards
Act, 1985 (63 of 1985) or as may be notified by the Ministry of Health and Family
Welfare in the Central Government, from time to time.
(ii) Where no relevant standard of any medical device has been laid down under
subrule (1), such device shall conform to the standard laid down by the
International Organization for Standardization (ISO) or the International Electro
Technical Commission (IEC), or by any other pharmacopeial standards.
(iii) In case of the standards which have not been specified under sub-rule (1) and sub-
rule (2), the device shall conform to the validated manufacturer’s standards.

1. Rules of Medical devices -

Rule 13 (6): certificate of registration for a notified body under MDR 2017
Rule 20(2): Application for grant of license to manufacture for sale or for distribution for class A
or class B medical devices
Rule 20(2): Application for grant of loan license to manufacture for sale or for distribution for
class A or class B medical device
Rule 21(2): Application for grant of license to manufacture for sale or for distribution for class
Cor class D medical device and Application for grant of loan license to manufacture for sale or
for distribution for class C or class D medical device
Rule 26(4): Form in which audit or inspection book shall be maintained
Rule 34(2): Application for issue of import license to import medical device
Rule 36(1): license to import medical device
Rule 31(3): License to manufacture medical device for purpose of clinical investigations, test,
evaluation, examination, demonstration or training
Rule 41(1): Licence to import medical device for purpose of clinical investigations, test,
evaluation, demonstration or training
Rule 43(2): Application for permission to import small quantity of medical device for personal
use
Rule 52(1): Permission to conduct clinical investigation
Rule 67(4): Certificate of test or evaluation by the central medical device testing laboratory
 2. Standards for regulatory filing of medical devices-
➢ An application shall be made to the Central Licensing Authority (CDSCO) for Class C
& D medical devices by the manufacturer, having a valid License to manufacture for
sale or for distribution of notified Medical Devices.
• Covering Letter – The covering letter should clearly specify the intent of the application.
The list of documents that are being submitted (Index with page no’s) as well as any
other important and relevant information may be provided in the covering letter. The
covering letter should be duly signed and stamped by the authorized signatory,
indicating the name & designation of the authorized signatory along with the name and
address of the firm.
• The requisite fees prescribed in second schedule of Medical Devices Rules 2017 for
Certificate to export medical device. The Applicant shall make a payment of 1000 INR
for obtaining Free Sale Certificate for each category of medical device through online
Bharatkosh challan.
• A valid copy of license to manufacture for Sale or for Distribution of Medical Devices
along with approved product list issued by State Licensing Authority or Central
licensing Authority, as the case may be
• Legal undertaking by the manufacturer stating that no action has been initiated against
firm due to adverse events, market complaint and not of Standard Quality (NSQ) report
of any product in India on one hundred rupees non-judicial notarized stamp paper.
• Requirement to obtain a license

References: cdsco website

3. Biologicals
1. Introduction:

Biological products, or biologics, are medical products. Many biologics are made from a
variety of natural sources (human, animal or microorganism). Like drugs, some biologics are
intended to treat diseases and medical conditions. Other biologics are used to prevent or
diagnose diseases. Examples of biological products include
➢ vaccines
➢ blood and blood products for transfusion and/or manufacturing into other products
allergenic extracts, which are used for both diagnosis and treatment (for example, allergy
shots)
➢ human cells and tissues used for transplantation (for example, tendons, ligaments and
bone)
➢ gene therapies
➢ cellular therapies
➢ tests to screen potential blood donors for infectious agents such as HIV
 2. Applicable Regulations and Guidelines:
The Similar Biologics are regulated as per the Drugs and Cosmetics Act, 1940, the Drugs and
Cosmetics Rules, 1945 (as amended from time to time) and Rules for the manufacture, use,
import, export and storage of hazardous microorganisms/ genetically engineered organisms
or cells, 1989 (Rules, 1989) notified under the Environment (Protection) Act, 1986. Various
applicable guidelines are as follows:
• Recombinant DNA Safety Guidelines, 1990.
• Guidelines for generating preclinical and clinical data for rDNA vaccines, diagnostics and
other Biologicals, 1999.
• CDSCO guidance for industry, 2008:
➢ Submission of Clinical Trial Application for Evaluating Safety and Efficacy
➢ Requirement for permission of New Drug Approval
➢ Post approval changes in biological products: Quality, Safety and Efficacy
Documents
➢ Preparation of Quality Information for Drug Submission for New Drug
Approval: Biotechnological/Biological Products
• Guidelines and Handbook for Institutional Biosafety Committees (IBSCs), 2011.
• Guidelines on Similar Biologics: Regulatory Requirements for Marketing authorization in
India 2012.

3. Biological product regulations

Regulations governing market approval of biologic products are published
21 CFR part 600 through part 680.
Part 600: Biological Products: General
Part 601: Licensing
Part 606: cGMP for Blood and Blood Components

Part607: Establishment Registration and Product listing for

Manufacturers of Human Blood and Blood Products.

Part 610: General Biological Products Standards

Part 640: Additional Standards for Blood and Blood products

Part 600: Additional Standards for Diagnostic Substances for Laboratory Tests

4. Biologics license application

 A request for permission to introduce, or deliver for introduction of commerce. a biologic
product into interstate
• Form FDA 356h (cover sheet)
• Applicant information
• Product/ manufacturing information
• Pre- clinical studies
• Clinical studies
• Labelling

5. Provision related to biologicals product

• Part X of D & C Rules is related to provisions for biological and special products
• Proper name of schedule ‘C’ product shall appear on label as specified in schedule
F or if veterinary as specified in schedule F (1) or British pharmacopoeia
(veterinary) or as approved by licensing authority
• Product shall be filled and sealed in previously sterilized glass container if not
sterilized terminally.
• Multi-dose containers should contain preservative.
• Labeling: in addition to particulars specified under schedule F or F (1), a substance
specified in schedule ‘C’ shall bear following particulars on label
1. where a drug is imported, the number of licences under which it is imported
2. a statement of the potency in units
3. The date of expiry shall be in terms of month and year
4. the date of manufacture of the particular batch
5. the nature and the percentage proportion of preservative used
6. the precaution necessary for preserving the properties

6. Standards for regulatory filing of biologicals-

REGULATION: - The ‘similar biologicals’ are regulated under the D & C act 1940, the
Drugs and cosmetics rules 1945 for the manufacture, use, import, export and storage of
harmful microorganism or genetically engineered organism or cells, rules 1989 notified
under the environment (protection act)

Stage Agency involved Application Approval

Manufacturing State FDA/CDSCO Form 30 Form 29

licence for test
analysis and
examination
Preclinical studies RCGM Form C3 Form C4
permission
 Submission of RCGM Form C5 Form C6
preclinical study
report
Clinical trial CDSCO Form 44 Permission letter

Manufacturing and CDSCO Form 44 Form 45/46(finished

marketing product)
permission
Form 46 A (bulk product)

Manufacturing State FDA/ CDSCO Form 27D Form 28 D

licence
Registration and CDSCO Form 40/ Form Form 41 /Form 10
import licence B

References: cdsco website

4. Food & Nutraceuticals

1. Regulation Registration of Dietary supplement in India:

➢ In India the registration of Nutraceutical is required for the marketing of the product in
Indian market.
➢ The FSS act (2006) gives the procedure for the registration of the Nutraceutical products, but
there is no standard format is available for the purpose.

➢ FSSAI issued the Food safety and standard rules, 2011 in May of 2011.This rule gives the
regulations for licensing and registration of food products, food business, packaging and
labelling methods, standards for food products and additives used in the food product.

➢ The FSS rules are implemented in the country from August 5, 2011.This opens up the single
legislation with competent authorities to govern the sale, manufacture and distribution of the
products within the country

2. Filing for food and nutraceuticals-

Guidance Document For filing and processing of the FSSAI license application for the
products covered under Food Safety and Standards (Health Supplements, Nutraceuticals,
Food for Special Dietary Purpose, Food for Special Medical Purpose, Functional Food, and
Novel Food) Regulations, 2016.
1)The products covered under the said regulation shall be listed under Food Product Category 13.3,
13.4, 13.5, 13.6
2)Identify the category of product as per the above regulation.
a. Health Supplements - Food Product Category 13.6
b. Nutraceuticals - Food Product Category 13.6
c. Food for Special Dietary Uses - Food Product Category 13.4, 13.5, as per
ingredients/intended use
d. Food for Special Medical Purposes other than infants- Food Product Category 13.3, 13.4 as
per ingredients / intended use
e. Food with added Probiotic Ingredients - Food Product Category 13.6
f. Food with added Prebiotic Ingredients - Food Product Category 13.6
g. Specialty Food containing plant/botanical ingredients with a safe history of usage - Food
Product Category 13.6
3) Mention a Common/Generic name of the product in the application in the case of Health
Supplements and Nutraceuticals and mention the specific name of the product in the remaining
categories.
4) Mention the list of the ingredients along with FSSR according to the selected category of
product.
5) Food Business Operator may also refer Food Product Identity Verification System (FPIVS –
Url: https://fssai.gov.in/fpivs) to get help on the permitted ingredients, 2016
6. Re-labellers shall ensure that their third-party manufacturers have valid FSSAI licenses for
manufacturing the same product. Designated Officers while scrutinizing the licensing applications
for the food products covered under Food Safety and Standards (Health Supplements,
Nutraceuticals, Food for Special Dietary Purpose, Food for Special Medical Purpose, Functional
Food and Novel Food) Regulations, 2016 shall ensure that the listed ingredients of the product are
as per relevant Schedule mentioned in the said regulations. Designated Officers shall also refer to
direction dated 07th January 2020 on Recommended Dietary Allowance (RDA) for products
containing vitamins, minerals, and amino acids.

3. Documents required for FSSAI registration of Health supplements,

Nutraceuticals, and Novel foods: -
• Blueprint/layout plan of the processing unit showing the dimensions in meters/square
meters and operation-wise area allocation (mandatory for manufacturing and processing
units only).
• List of Directors with full address and contact details (mandatory for companies only).
• Name and List of Equipment and Machinery along with the number, installed capacity, and
horsepower used.
 • Analysis report (Chemical & Bacteriological) of water to be used as an ingredient in food
from a recognized/ public health laboratory to confirm the potable.
• Upload Production unit photograph
• Photo I.D and address proof issued by the Government authority of Proprietor / Partner /
Director(s) / Authorized Signatory.
• Proof of possession of premises. (Sale deed/ Rent agreement/ Electricity bill, etc.).
• Partnership Deed/Self Declaration for Proprietorship/Memorandum & Articles of
Association towards the constitution of the firm.
• Form IX: Nomination of Persons by a Company along with the Board Resolution.
• Category of the product as per Food Safety and Standards (Health Supplements,
Nutraceuticals, Food for Special Dietary Use, Food for Special Medical Purpose,
Functional Food and Novel Food) Regulations, 2016 and List of Ingredients

4. Regulations:
I. Food Safety and Standards Regulations
1. Licensing and Registration of Food Businesses regulations, 2011
2. Food Products Standards and Food Additives Regulation, 2011
3. Prohibition and Restriction of Sales Regulation, 2011
4. Packaging and Labelling Regulation, 2011
5. Contaminants, Toxins and Residues Regulation, 2011
6. Laboratory and Sampling Analysis Regulation, 2011
7. Health Supplements, Nutraceuticals, Food for Special Dietary Use, Food for
Special Medical Purpose, Functional Food and Novel Food) Regulations, 2016
8. Food Recall Procedure Regulation, 2017
9. Import Regulation, 2017
10. Approval for Non-Specific Food and Food Ingredients) Regulation, 2017
11. Packaging Regulation, 2018
12. Safe food and balanced diets for children in school Regulations, 2020
13. Labelling and Display Regulations, 2020
II. Food Safety and Standards Authority of India Regulations, 2011
1. Food Safety and Standards Authority of India (Transaction of Business at its
Meetings) Regulations, 2010
2. Food Safety and Standards Authority of India (Procedure for Transaction of
Business of the Central Advisory Committee) Regulations, 2010
3. Food Safety and Standards Authority of India (Transaction of Business and
Procedure for the Scientific Committee and Scientific Panel) Regulations, 2016

References: www.fssai.gov.in

5. HERBALS
1. Introduction:
➢ Herbal medicines/drugs are plant-derived materials with therapeutic and different health
benefits for human, which are acquired or captured from the plants and their parts.
➢ In India herbal medicines are used in Ayurveda, Siddha, and Unani and Homeopathic
system of medicines.
➢ Research councils (ICMR and CSIR), department of AYUSH (Ayurveda, yoga &
naturopathy, Unani, Siddha and homeopathy) & Drugs and Cosmetics act 1940 and rules
1945 regulates herbal medicines in India.
➢ Schedule T of D&C act provides the GMP requirements to be carried for the manufacture
of herbal drugs.
➢ Part XVI-A(rule 158(B))-provides guidelines for issue of license with respect to
Ayurveda, siddha and Unani drugs.
➢ As per Rule 3 a of Drugs and Cosmetics Act, 1940 "Ayurvedic, Siddha or Unani drug"
includes all medicines intended for internal or external use for in the diagnosis, treatment,
mitigation or prevention of disease or disorder in human beings or animals, and
manufactured exclusively in accordance with the formulae described in, the authoritative
books of [Ayurveda, Siddha, Unani Tibb systems of medicine], specified in the First
Schedule.

2. Regulatory requirements for approval of herbal medicines in India

➢ Every state government appoints a licensing authority to approve ASU drugs.
➢ To seek a licence to manufacture the drugs, Form 24-D is to be filled and submitted to
the authority. License is issued in form 25-D.
➢ The General Guidelines for Safety/Toxicity Evaluation of Ayurvedic Formulations is to
be followed to apply and acquire a licence to manufacture a drug are based on the
ingredients used in the medicine.
➢ When it comes to the approval process, Ayurvedic, Siddha and Unani text based
classical drugs are divided in three categories:
1. If the applicant seeks to use the drug to treat the same disease as
mentioned in the text,
2. Wants to alter the dosage
3. Wants to treat another ailment.
➢ For the first two kinds of applications, no safety study or proof of effectiveness are
required. For the last one, no safety study is needed, but a proof of effectiveness and
published literature on the drug has to be submitted.

3. Patent or Proprietary Drugs under section 3(h): The Act defines patented or
proprietary Ayurveda, Siddha, and Unani medicines as those which contain ingredients
mentioned in the formulae of the respective authoritative books, and does not include a
medicine administered by parenteral route (through injections, syringes, catheters).
For approval, patent or proprietary medicines (PPM) have two categories: • medicines that
have ingredients listed in classical texts and
 Those that have ingredients listed in the Drugs and Cosmetic Rules, 1945, which is
essentially a list of "poisonous substances under the Ayurvedic (including Siddha) and Unani
Systems of Medicine".
For the first category, no safety study is required but published literature and proof of
effectiveness based on pilot study should be provided, according to General Guidelines for
Clinical Evaluation of Ayurvedic Interventions.
For the second category a safety study, published literature and proof of effectiveness all are
required. "For such substances, 'Caution: to be taken under medical supervision' is to be
conspicuously labelled on the container.
➢ For drugs that are listed in the recognized texts, there's no need for trials because the
ingredients are already approved.
➢ Unless it is new formulations clinical trial not necessary
➢ Medicine approved by individual state authorities a throughout the country
➢ There are two types of licenses: state and central. If a firm wants to manufacture a and
sell in a particular state, then a state licence is enough, which also falls under the Union
AYUSH Ministry. And, if they want to sell in other states or on an online platform, then a
central licence is required too.
➢ All clinical trials for Ayurvedic drugs, can be registered on the Clinical Trials Registry-
India (CTRI)
➢ According to the general guidelines for clinical evaluation of ayurvedic intervention the
preliminary/ pilot studies, preclinical assessment of safety and toxicity, quality assurance
and standardization of trial drugs must be documented before a clinical trial undertaken

REFERENCES: Ayush website

DOSSIER (Format and contents of Regulatory dossier filing): -

➢ Pharmaceutical Dossier is defined as the collection of detailed documents containing
information about a particular drug which is to be extensively attached on the dossier for
grant of Regulatory Approval in any country.
➢ By this a licensed Product is registered or approved for manufacturing, marketing, use,
distribution or sale in the field.
➢ Its commonly called as Marketing Authorization Application (MAA) for European Union
and New Drug Application (NDA) for United Nation.
➢ Dossier is required to prepare as per the internationally accepted format i.e. CTD & ACTD
so as to reduce the time and extra working for registration of a drug product in multiple
countries
➢ ICH has bought up the internationally acceptable format i.e. Common Technical Dossier
CTD. All the main regulatory bodies i.e. USA, EU and Japan for submission and accepting
the documents complies with the ICH guideline and dossier is as per the format mentioned
in ICH M4.
ACDT Format
➢ ASEAN Countries (Association of Southeast Asian Nations) namely Indonesia,
Malaysia, Philippines, Singapore, Thailand, Brunei Darussalam, Vietnam, Laos,
Myanmar and Cambodia follow ACTD (Asian Common Technical Dossier) format.
➢ ACTD Format comprise of four parts namely
1. Part I: Table of Content, Administrative Information and Prescribing
Information
2. Part II: Quality Document
3. Part III: Nonclinical Document
4. Part IV: Clinical Document
• For compilation of Dossier in ACTD format it’s important to compile the documents as per
the requirement of ASEAN Guideline and format for registration of pharmaceutical product
in their respective countries/ region.

PART I
➢ This contains the table of content of the entire ACTD format to provide the initial
information of the documents compiled in the dossier.
➢ It contains the Administrative Information which require specific documents in details along
with the Application for registration of Product such as Certificate of Pharmaceutical
Product, Free Sale Certificate, Letter of Authorization, Company certifications and
Prescribing Information.
➢ It is not compulsory to contain the same documents for registering the Product in Part I as
the entire ASEAN Market its region specific.
➢ A general introduction of the pharmaceutical product, including its pharmacologic class and
mode of action shall be included
PART II
➢ It contains the brief documentation of the Quality Part, this is further divided into three
sections
I. SECTION A - Table of Content,
II. SECTION B - Quality Overall Summary, and
III. SECTION C - Body of Data i.e., Quality Part
i. Drug Substance (S)
ii. Drug Product (P)

❖ Drug Substance (S)

➢ Drug Substance is denoted by letter ‘S’.
➢ In this section we’ll compile the complete documents w.r.t to the quality of the API
which includes General Information of the API Manufacturer, Characterization of the
 API, Specifications, Analytical Method Validation, Stability and Studies of the Container
in which the Drug Substance are packed.
• For registration of Product in ASEAN Market we require the BP, USP, EP grade DMF
(Drug Master File) with further mentioned information.
General Information

a. Nomenclature- IUPAC Name, Registry number of chemical abstract service (CAS) and
Chemical Name.
b. Structural Details- structure, stereochemistry, molecular formula, relative molecular.
c. General Properties- All the Physiological properties of the drug
Manufacture
a. Manufacturer(s) – Manufacturers detail i.e. Name, address, city, country of the
manufacturer, details of Corporate Head Office, Manufacturing Facilities and Authorized
Person.
b. Description of Manufacturing Process and Process Controls - flow diagram of
synthetic Process. identification and justification of reprocessing.
c. Control of Materials – list and quality control of materials used in the manufacturing.
d. Controls of Critical Steps and Intermediates - All critical steps along with their test,
acceptance criteria should be justified with proper references and experimental data.
e. Process Validation and/or Evaluation Process - Validation shall be carried out to study
the results, analysis and conclusion of the executed batches. The validation should be
cross-referenced and justified.
f. Manufacturing Process Development Manufacturing – Carried out for new drug
substance. The process should be evaluated and justified. Non-clinical and clinical
studies in other modules should be included.
Characterizations
a. Elucidation of Structure and Characteristic - All the physio-chemical characteristics
of Drug Substance shall be provided in the DMF with justification to support the
structure of Drug Substance.
b. Impurities - Information on impurities should be provided as per ICH guidelines: Q3A,
Q3C, Q5C, Q6A and Q6B.
Control of Drug Substance
a. Specification - Detailed specification and indication of drug substance either is
purchased based on specification with a certificate of analysis, or tested by applicant.
 b. Analytical Procedures – Method should be justified using the compendia method or, if
method is used out of compendia the adequate information shall be provided from the
supplier.
c. Validation of Analytical Procedures – Validation ensures that analytical procedure is
same as mentions in Official Monographs.
d. Batch Analyses – It is to be performed for the Three Batches as per the pre-approved
Specifications and the Testing Procedures. The COA of the Batch Analysis shall be
performed which ensures that the results.
e. Justification of Specification – This is required for In-House specifications.
Reference Standards or Materials
Quality information of Reference standard or material used for testing of substance should be
provided.
a. Container Closure System - A complete description with compendial methods i.e.
required for testing if not then complete validations shall be provided.
b. Stability - Stability studies are conducted for 3 consecutive batches on two conditions i.e.
Long Term (As per ICH and WHO it is for 24, 36 and even 48 months based on the
stability of the finished product) and Accelerated Condition (only 06 months). The types
of studies conducted, protocols used, and the results of the studies should be summarized.
❖ Drug Product (P)
Drug Product is denoted by the word ‘P’
Compilation of complete documents of the Drug Product part w.r.t to the quality of the
Finished Product
Description and Composition
a. Description of the dosage - list of all components of the dosage form, and their amount,
function, reference to their quality standards, diluent(s) and type of container and closure
used.
Pharmaceutical Development
a. Information on Development Studies – Information and development data with
supportive data related to non-clinical is been included
Component of Drug Product
Active Ingredients/ Excipients - compatibility and key physicochemical characteristics which
influences the performance need to be mentioned.

Finished Product
Formulation Development- in vitro studies (e.g. dissolution) or in vivo studies (e.g.,
bioequivalence) should be discussed.
Overages - overages described in Item P 1 should be justified.
 b. Physicochemical and biological Properties
c. Manufacturing Process Development - selection and optimization of the manufacturing
process (Item P 3.2) should be explained.
d. Container Closure System - suitability of the container is explained.
e. Microbiological Attributes – microbiological limit testing and selection and
effectiveness of anti-microbial preservatives.
f. Compatibility

Manufacture
a. Batch formula - The formula with name and quantities of all ingredients, actual
quantities, Overage, total number of dosage unit per batch must be stated.
b. Manufacturing process and process control- all required data should be provided.
c. Controls of Critical Steps and Intermediates – This should be monitor, ensured for
uniformity and recorded
d. Process Validation and/or Evaluation
Control of Excipient
a. Specification
b. Analytical Procedures
c. Excipients of Human and Animal Origin
d. Novel Excipients
e. Control of finished Product
f. Specification
g. Analytical Procedure
h. Validation of Analytical Procedure
i. Batch analysis
j. Characterization of Impurities
k. Justification of Specification
l. Reference Standards or Material
Container closure system
Product Stability
a. Stability Summary and Conclusion - All criteria under ICH Guidelines are acceptable
with the exception of real time storage conditions which should be 30°C, 75% RH.
b. Post-approval stability protocol and stability commitment
c. Stability
Product Interchangeability - The Multisource Pharmaceutical Products shall be conformed
with the same appropriate standards. The type of studies conducted, shall be justified according
to BCS(Biopharmaceutical classification) .
PART III
It contains the Non-Clinical Documents having four sections namely:
I. SECTION A - Table of content
 II. SECTION B - Non clinical Overview
III. SECTION C - Tabulated summaries of the Pharmacological, Pharmacokinetics and
Toxicological data,
IV. SECTION D - Nonclinical Study Report of Pharmacology, Pharmacokinetics and
Toxicology data.

PART IV
It contains the Clinical Studies having Six Sections namely:
I. SECTION A - Table of Content
II. SECTION B - comprises of complete Clinical Overview
III. SECTION C - Summary of Biopharmaceutics and Associated Analytical Methods,
Clinical Pharmacology Studies, Clinical Efficacy, Clinical Safety and Synopses of
Individual Studies,
IV. SCETION D - tabular listing of all clinical studies
V. SECTION E - contains the Clinical Study Reports
VI. SECTION F - contains the list of Key References

CTD format
➢ CTD Format was introduced by three regulatory Bodies i.e. United Nation, Japan and
Europe to assemble all the Quality, Safety and Efficacy of the drug under a single for
format known as Common Technical Dossier.
➢ For Industries it works as a good Format because it has eliminated the need to reformat
the information for submission to the different ICH regulatory authorities.
➢ CTD Format comprise of Five Modules namely:
Module 1: Administrative Information and Prescribing Information
Module 2: Common Technical Document Summaries
Module 3: Quality
Module 4: Nonclinical Study Reports
Module 5: Clinical Study Reports

Module 1
➢ Module 1 is for administrative information and prescribing information.
➢ This part contains documents that are specific to WHO and each region/ country as per the
requirement. So, it should contain required documents.

Module 2
➢ This part shall contain the general information of the drug Product, its pharmaceutical and
clinical use, its mode of action, its pharmacological class, therapeutic category of the product
in short, the overall view of the drug product.
➢ General introduction shall not exceed more than one page.
(The organization of these summaries is described in Guidelines for ICH M4, M4Q and M4S)

Quality Overall Summary (QOS)

➢ This section contains the summary of the overall quality part of the dossier which contains
summary of the Active Moiety present in the Drug Product and studies done on Drug
Product, required for preparation and compilation of dossier.
➢ QOS (Quality Overall summary) shall discuss the critical parameters of the product
➢ The QOS should not exceed more than 40 pages.
(QOS broadly follows the structure of the data included in Module 3)

Nonclinical Overview
➢ The reason behind preparation of Non-Clinical Writing and Tabulated Summaries is to give
the information and criticality about pharmacology, pharmacokinetics, and toxicology
aspects of Medicinal product in animals.

Clinical Overview and Clinical Summary

➢ The Clinical Overview is a key document in the CTD dossier
➢ The Clinical Overview is a short document that provides a Critical Assessment of the clinical
data, whereas the Clinical Summary is a longer document that focuses on data summarization
and integration.
➢ The Clinical Overview is divided into six sections: product development rationale,
biopharmaceutics, and clinical pharmacology, efficacy, safety, and risk/benefit conclusions.
➢ Clinical Overview should provide an evaluation of the benefits and risks of the IMP
(Investigational Medicinal Product) based upon clinical studies and risk management.
➢ The Clinical Overview presents the conclusions and implications of the data and it should not
repeat the information presented in the Clinical Summary or elsewhere in the CTD
➢ Appropriate reference should be made to the literature to put the results into context.
➢ The Clinical Overview should present the strengths and limitations of the development
programme and study results, analyse the benefits and risks of the IMP in its intended use,
and describe how the study results support critical parts of the prescribing information.
➢ The Clinical Summary and Clinical Overview provide the supporting information for the
Summary of Product Characteristics (SmPC) or the product label, so it is important these
documents are consistent.
➢ The Clinical Overview should be a relatively short document of approximately 30 pages

Module 3
Quality part contains the detailed information about the Drug Product w.r.t Chemistry,
Manufacturing and control and the detailed studies of the same is to be introduced in the
Dossier which is required for registration of Drug Product in the Regulatory countries.
 • 3.1 Table of Contents of Module 3
• 3.2 Body of Data
• 3.2. S Drug Substance
• 3.2. P Drug Product
• 3.3 Literature Reference
➢ For preparation of Dossier in CTD format and registration of Pharmaceutical Product in
Regulated Market basically the Drug Substance of required grade along with the requirement
of that specific region or country.
Eg. USDMF (United State Drug Master File), EP grade along with the requirement of
EUDMF (European Nation Drug Master File) or CEP certificate is required
➢ CEP (Certificate of suitability) means the drug substance is approved and registered under
European Nation and can be used for the registration of Pharmaceutical Product in EU
Nation.
➢ The Manufacturing process of Drug Product shall be developed in the Research and
Development Department according to the following ICH Guideline which will be key
reference for development or manufacturing of Drug Products for registration of Drug
Product in Regulated Market which are mentioned below:
ICH Q8: Pharmaceutical development
ICHQ9: Quality Risk Management.
ICH Q10: Pharmaceutical Quality System.
ICH Q11: Drug Substance Development and Manufacturing.

Module 4: Non-clinical study reports

This represents the non-Clinical report that is to be included in the Dossier. The main
heading that shall be included in the dossier are:
4.1 Table of contents of Module
4 4.2 Study reports
4.2.1 Pharmacology
4.2.2 Pharmacokinetics
4.2.3 Toxicology
4.3 Literature references used in Module 4.
Module 5: Clinical study reports
➢ This represents the Clinical report that is to be included in the Dossier
➢ Under this module that is Clinical part the report on Biopharmaceutics studies,
Pharmacokinetic and pharmacodynamic studies are to be conducted which assures that the
Drug Product are effective and safe to use.
Difference between CTD & ACTD format
➢ CTD format is a harmonized format for registration of Pharmaceutical product in
Regulatory Countries i.e. EU, US & Japan whereas ACTD format is required for
registration of Drug product in ASEAN Nation (Association for South East Asians
Nation)
➢ CTD Format contain 5 Module whereas ACTD format contains only 4 Parts.
 CLINICAL TRIALS/ INVESTIGATION

Clinical Trial (Clinical Study)

A systematic study of pharmaceutical products on human subjects – (whether patients or non-
patient volunteers) – in order to discover or verify the clinical, pharmacological (including
pharmacodynamics / pharmacokinetics), and / or adverse effects, with the object of determining
their safety and / or efficacy.
• Phases of Clinical Trials: -

1. Phase I - Human/Clinical Pharmacology trials

➢ The objective of phase I of trials is to determine the maximum tolerated dose in humans;
pharmacodynamic effect, pharmacokinetic behaviour and adverse reactions, if any, with
their nature and intensity of the drug as far as possible.
➢ Evaluate safety and identifies whether any side effect is seen
➢ These studies are often carried out in healthy adult volunteers using clinical,
physiological and biochemical observations. At least 2 subjects should be used on each
dose.
➢ 20-80 participants are involved.
➢ Phase I trials are usually carried out by investigators trained in clinical pharmacology and
having the necessary facilities to closely observe and monitor the subjects.
 ➢ These may be carried out at one or two centres.

2. Exploratory trials (Phase II)

➢ In phase II trials a limited number of patients are studied carefully to determine possible
therapeutic uses, effective dose range and further evaluation of safety and
pharmacokinetics.
➢ 100-300 participants are involved.
➢ Normally 10-12 patients should be studied at each dose level.
➢ These studies are usually limited to 3-4 centres and carried out by clinicians specialized
on the concerned therapeutic areas and should having adequate facilities to perform the
necessary investigations for efficacy and safety.

3. Confirmatory trials (Phase III)

➢ The purpose of these trials is to obtain sufficient evidence about the efficacy and safety of
the drug in a larger number of patients, generally in comparison with a standard drug
and/or a placebo as appropriate.
➢ 300-3000 participants are involved.
➢ These trials may be carried out by clinicians in the concerned therapeutic areas, having
facilities appropriate to the protocol.
➢ If the drug is already approved/marketed in other countries, phase III data should
generally be obtained on at least 100 patients distributed over 3-4 centres primarily to
confirm the efficacy and safety
➢ Data on ADRs observed during clinical use of the drug should be reported along with a
report on its efficacy in the prescribed format. The selection of clinicians for such
monitoring and supply of drug to them will need approval of the licensing authority under
Rule 21 of the Act.

4. Phase IV Post Surveillance Studies

➢ Studies performed after marketing of the pharmaceutical product.
➢ Trials in phase IV are carried out on the basis of the product characteristics on which the
marketing authorization was granted in the form of, assessment of therapeutic value,
treatment strategies used and safety profile.
➢ Provide additional information after approval including risk and benefits.
➢ Phase IV studies should use the same scientific and ethical standards as applied in pre-
marketing studies.
➢ After a product has been placed on the market, clinical trials designed to explore new
indications, new methods of administration or new combinations, etc. are considered as
trials for new pharmaceutical products.

• FAQs: -
No. QUESTIONS ANSWERS

1. What is Global Clinical Trial? Global Clinical Trial is a clinical trial conducted for approval
of a new drug worldwide.
2. What is academic trial? “Academic clinical trial” means a clinical trial of a drug
already approved but initiated for a new indication/ route of
administration/ new dose/ new dosage form.

3. What is a randomized trial? Randomized is used to describe a research study that hopes
to compare two or more different treatments or
procedures. Done to avoid biasness

4. What are "blind" or "masked" In a "blinded" or "masked" study, participants do not know
studies? whether they are getting the drug being tested, or whether
they are in the control group. The placebo effect is the
phenomenon of patients feeling better simply because they
think they are receiving a helpful drug or treatment

5. What are "double blind" or The "double-blind" or "double-masked" means that neither
"double masked" studies? the participants, nor the study staff members, know who is
receiving the experimental drug and who is in the control
group.

6. What is an impartial witness? If the trial subject or his/her legally acceptable

representative is unable to read/write an impartial witness
should be present during the entire informed consent
process

7. Where to apply for permission Application for Global Clinical Trial done in Form 44 shall be
of Global Clinical Trial (GCT)? accepted only through Sugam online portal mode and no
offline applications is accepted
8. Form for application for import Form 12, available on online Sugam portal.
of drugs for Global Clinical
Trial?
9. What happens during & after Depending on the results, Sponsor and the Data Safety
the study is over? Monitoring Board (DSMB) then decide whether to stop or
continue testing the new drug or treatment. if it is safe and
if there are any side effects. Clinical Study Report should be
submitted to DCGI in prescribed manner as per Schedule Y
of Appendix II in Drugs and Cosmetics Rules, 1945 further
approval of new drug and marketing authorization