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CDSCO

Biological Division
Presentation By:

S.P. Shani
Deputy Drugs Controller
(I)





Introduction:
Drugs fall under the Concurrent list
of the Constitution

Drugs regulated under the
Drugs and Cosmetics Act 1940
Drugs and Cosmetics Rules 1945

The Act is a Federal Act, enforced by
both Federal and State Govts.

Implementing Authorities
Federal Govt:
Ministry of Health & Family Welfare
Directorate General of Health Services
Central Drugs Standard Control Organization
(CDSCO)

State Govts:
State Drug Licensing Authorities, under Department of
Health of respective State Govts.

Objective:
To ensure availability of safe, efficacious and
quality Drugs, Cosmetics and Medical Devices

Preamble:
To regulate Manufacture, Sale, Distribution and
Import of
Drugs
Cosmetics
Biologicals
Medical Devices
Veterinary Drugs

CDSCO:
The Central Drugs Standard Control
Organization (CDSCO) is headed by the
Drugs Controller General (India).

It is the Central Authority for discharging
functions assigned to the Central
Government under the Drugs and Cosmetics
Act, 1940 and Rules, 1945.
Functions
CDSCO
Approval of new drugs and clinical trials
Import Registration and Licensing
Licensing of Blood Banks, LVPs, Vaccines, r-DNA
products & some Medical Devices
Amendment to D &C Act and Rules
Banning of drugs and cosmetics
Grant of Test License, Personal License, NOCs for Export
Testing of Drugs
Functions
State Licensing Authorities
Licensing of Manufacturing Site for Drugs including API and
Finished Formulation
Licensing of Establishment for sale or distribution of Drugs
Approval of Drug Testing Laboratories
Monitoring of Quality of Drugs and Cosmetics marketed in the
country
Investigation and prosecution in respect of contravention of
legal provision
Recall of sub-standard drugs
Mumbai
New Delhi
Chennai
North Zone (Ghaziabad)
Kolkata
.
West Zone (Mumbai)
South Zone (Chennai)
East Zone (Kolkata)
CDSCO, HQ
CDSCO Geographical Location Zonal /Sub ZonalOffices
Hyderabad
Ahmedabad
Port Offices/Airports : 13
Laboratories : 6
28 States
7 Union Territories
Zone (Ahmedabad)
Zone (Hyderabad)
Proposed Zonal/Sub Zonal Offices (2) :
Guwahati, Indore,

Sub Zone (Bangaluru)
Bangaluru
Ghaziabad
Sub Zone (Chandigarh)
Chandigarh
Jammu
Sub Zone (Jammu) and (Goa)
Goa
Drug Testing Laboratories
Central Laboratories: 6 (including CDL Kolkata)

State Labs: 26

Vaccines: CDL, Kasauli (NCL)

r-DNA and Diagnostic kits: NIB, Noida



Drugs Controller General (I)
HEAD QUARTER
SUB ZONAL
OFFICE (4)
ZONAL
OFFICE (6)
LABORATORY
(6)
PORT OFFICE
(13)
New Drugs
Clinical Trials
Imports
Biological
Medical
Devices
Export
QC
Pharmco.Vig
Legal etc

GMP Audits
Enforcement
Draw drug
Samples

GMP Audits
Coordination
with States
Import
Export
Testing of
Drugs
Validation of
Test protocols

Central Drugs Standard Control Organization


DDC(I) (Technical Head)
(Mr. S.P Shani)
ADC(I)
(Mrs.Swati Srivastava)
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DDC(I) (AEFI Head)
(Mrs. Annam Vishala)
ADC(I)
(Somnath Basu)
ADC(I)
(Dr. I.S. Hura)
ORGANOGRAM OF BIOLOGICAL DIVISION
(Dr. G.N. Singh)
Drugs Controller General (I)
Drugs Inspectors:
1. V. Rajappan
2. S. John Gerard
3. P. Dhinesh Pandian
4. Arvind Hiwale
5. Nisha Sankhwar
6. Manish Singhal
7. Saurabh Garg
8. Amol Kandekar
9. Sourabh Mittal
10. Rakesh Negi
11. Devendra Nath
Date:
ADC(I)
(Jayant G.Khedkar)
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Activities undertaken in Biological Division
1. New Drug Approvals Biologicals.
2. Post Approval Changes
3. Registration and Import permission of
Biologicals.
4. Licensing Activity - Form 28 D and Form 28
E (Blood Products).
5. Issuance of Test License.
Types of Biological Products
1. Recombinant DNA Products.
2. Bacterial Vaccine.
3. Viral Vaccine.
4. Combination Vaccine.
5. Veterinary Vaccine.
6. Blood Products.
7. Stem Cells.
8. AEFI Data.
9. Post Approval Changes (Compulsory for
biological products only).

Definition of New Drug
As per under Rule 122-E New Drug is defined A drug, including
bulk drug substance which has not been used in the country to
any significant extent under the conditions prescribed,
recommended or suggested in the labeling thereof and has not
been recognized as effective and safe by the licensing authority
mentioned under Rule 21 for the proposed claims.

A drug already approved by the Licensing Authority mentioned in
Rule 21 for certain claims , which is now proposed to be marketed
with modified or new claims , namely , indications, dosage,
dosage form ( including sustained release dosage form) and route
of administration.

All vaccines and r-DNA products are New Drugs
vide G.S.R. 45 (E) dated 24/01/2011.

122-A clearance required for imported
vaccines/r-DNA products.

122-B clearance required for Indigenously
manufactured vaccine/r-DNA products.

Regulatory Requirement for Market Authorization of Biological
Products
Drugs and Cosmetics Act & Rules,
1945.

Guidance for Industry
Specific for Biological Products


Regulatory Requirement for Market Authorization of Biological
Products
Legal Provisions for regulation of Clinical Trials
Requirements and Guidelines - Schedule Y
Rule 122 DA
Rule 122 DAA
Definition of New Drugs
Rule 122 DB
Rule 122 E
Definition of Clinical trials
Suspension / Cancellation of permissions
Permission to conduct clinical trial
Technical Review and
Forward the file to
Concern DIs
for validation
Manufacturers
for submission
Submission of application
in CRU After acceptance
By Pre screening officers
And FTS No. generated
Flow of Applications in Biological Division: flow chart in India
Pre-screening
1. Check administrative
2. Check legal document
3. Check fees
1
st
Level
Review
Central Registry
Unit
DDC (I)
ADC (I)
DIs
TDAs
DCG(I)
File signed and
send back to
concerned officer for
issue the letter
Letter send to
CRU for issue
2nd Level
Review
On Site Evaluation
CMC Evaluation
NDAC
Zonal
Hard and Soft
copies
IND
CDL, Kasauli
for Vaccines
State Licensing
Authority (SLA) License
for Counter Signature
License to Manufacture Vaccine (Form 28D): Flow chart in India
1. Check administrative (Grant/
Fresh/ Additional Product/
Dosage Form)
2. Inspection Report
3. Check New Drug Permission
DDC (I)
ADC (I)
DIs
TDAs
Query Letter
CRU
FTS no. allotted
through CRU
DCG (I)
CRU for Dispatch
Approval
Guidance for
Industry (Specific for
Biological Products) published on
CDSCO website : www.cdsco.nic.in
on 4th Dec, 2008
Submission of Clinical Trial
Application for Evaluating Safety
and Efficacy
Requirements for permission of
New Drugs Approval
Post approval changes in
biological products:
Quality safety and Efficacy
Documents
Preparation of the Quality
Information for Drug Submission
for New Drug Approval:
Biotechnological/Biological
Products
Regulation for r-DNA Technology based
Therapeutic proteins - Indian Scenario
The Guidelines on Similar Biologics
was prepared by CDSCO and DBT
laid down the regulatory pathway for
similar biologic claiming to be similar
to an already authorized reference
biologic.

CDSCO is the national regulatory
authority in India that evaluates
safety, efficacy and quality of drugs in
the country.

DBT through Review Committee on
Genetic Manipulation/ Institutional
Biosafety Committee is responsible
for overseeing the development and
preclinical evaluation of recombinant
biologics.





There are three Competent Authorities involved in
approval process namely :
a) Review Committee on Genetic Manipulation
(RCGM)/IBSC under Department of Biotechnology
(DBT), Ministry of Science and Technology.
b) Genetic Engineering Appraisal Committee (GEAC)
under the Ministry of Environment and Forests
(MoEF) and
c) Central Drugs Standard Control Organization
(CDSCO) under Ministry of Health & Family
Welfare

Competent Authorities

Filing of Information as per CTD


Module I: Administration/Legal
Information
Module II: Overall Summaries

Module III: Quality Information
(Chemical, Pharmaceutical
and Biological)
Module IV: Non-Clinical Information
Module V: Clinical Information
For Biological section Comprehensive Information is asked as per
CTD Module:-
MODULE - 1

CTD Format
Module
CTD Format
Section Headings
1
1.1 Comprehensive table of contents (Modules 1 to 5)
1.2 Administrative information
1.2.1 Application in Form 44 and Treasury Challan (fee)
1.2.2 Legal and statutory documents
1.2.2.2 Legal documents pertaining to application (to be notarized):
a) A copy of plant registration / approval certificate issued by
the Ministry of Health / National Regulatory Authority of the
country of origin.
b) A copy of approval, if any, showing the drug is permitted for manufacturing
and/or marketing in the country of origin.
c) A copy of Pharmaceutical Product Certificate (PPC) as per
WHO GMP certification scheme for imported drug products
d) A copy of Free Sale Certificate (FSC) from the country of
origin for imported drug products
e) Certificate of Good Manufacturing Practices of other manufacturers
f) Batch release certificate issued by NRA for imported
products.
MODULE - 1

CTD Format
Module
CTD Format
Section Headings
1.2.2.3 A copy of Site Master File
1.2.2.4 Certificate of Analysis from Central Drug Laboratory (India) of three
consecutive batches.
1.2.2.5 Product Permission Document (PPD)
1.2.3 Coordinates related to the application
1.2.4 General information on drug product in including Summary of product
characteristics, Product Labeling etc
1.2.5 Summary protocol of batch production and control
1.2.6 List of countries where MA or import permission for the said drug
product is pending and the date of pendency.
1.2.7 List of countries where the drug product has been licensed and
summary of approval conditions.
1.2.8 List of countries where the drug product is patented.
1.2.9 Domestic price of the drug followed in the countries of origin in INR.
1.2.10 A A brief profile of the manufacturers research activity
1.2.11 A brief profile of the manufacturers business activity in domestic as
well as global market.
1.2.12 Information about the expert(s)/ Information regarding involvement of
experts, if any
1.2.13 Environmental risk assessment
MODULE - 2

Introduction
Quality overall summary
Overview of non-clinical studies
Non-clinical Summary
Overview of clinical studies
Clinical summary
MODULE - 3

Quality Information (Chemical, Pharmaceutical and
Biological)
Strain details
Name and source (if any)
In case of products derived from r-DNA technology,
the following details shall also be furnished
Clone development (for recombinant products)
Details on source Nucleic acid
Nucleic acid sequence
MODULE 3

Vector(s)
Details about vector, please enclose the map of the
vector gene
Host(s) that carrying the vector(s)/ target gene(s)

Substrate details (For cell culture based products)
Details of name and source of substrate

Master seed and Working seed details
MODULE 3

Drug substance(s): Information must be submitted
for each drug substance in the product.
General information, starting materials and raw
materials
Manufacturing process for drug substance
Characterization of drug substance
Quality control of drug substance
Reference standards
Container closure system
Stability of drug substance
Drug product



Description and composition of drug product
Pharmaceutical development
Manufacture of drug product
Control of excipients (adjuvant, preservative, stabilizers and
others)
Control of drug product
Reference standards of materials
Container closure system
stability of drug product
Appendix
Details of equipment and facilities for production of drug
product: master formula, batch record and set release
documentation in respect of consistency batches
Safety evaluation of adventitious agents

MODULE 3

MODULE - 4

Non-Clinical Reports

Reports on studies
Pharmacology
Pharmacokinetics
Toxicology
General toxicology
Special toxicology (Studies of genotoxicity and carcinogenicity)
Toxicity of new substances used in formulation (new adjuvant,
stabilizers, additives)
Appendix III
Animal Toxicity
Non Clinical Toxicity studies

Appendix III of Schedule Y {Animal Toxicity (Non Clinical
Toxicity studies)}
Systemic Toxicity studies
Single and repeated dose toxicity studies

Male fertility study
Female reproduction and developmental toxicity studies
Female fertility study
Treratogenicity study
Preinatal study

Local Toxicity
Allergenicity / Hyper sensitivity
Genotoxicity
Carcinogenicity

MODULE - 4

Animal Pharmacology
Specific Pharmacological action

General Pharmacological Action
Follow-up and supplemental safety Pharmacology study
Timing of safety Pharmacology studies in relation to clinical
development
Prior to First administration in humans
During clinical development
Before applying the marketing approval

MODULE - 4

MODULE - 5

Clinical Reports

Reports of clinical studies
Phase I studies
Phase II studies
Phase III studies
Bridging Studies
Phase IV studies and / or Pharmacovigilance Plan if required
Non-inferiority studies (for combined vaccines, or approved
vaccines prepared by new manufacturers)
Case Report Forms and Individual Patient Listings
Appendices of Schedule Y

Appendix V of Schedule Y - Informed Consent
Appendix VII of Schedule Y - Undertaking by the Investigator
Appendix VIII of Schedule Y - Ethics Committee
Ethics Committee should be registered as per Rule 122 DD of
Drugs & Cosmetics Rules 1945 under GSR No. 75 (E) dated 08
th

Feb, 2013
Appendix IX of Schedule Y - Stability Testing of the New Drug
Appendix X of Schedule Y - Content of proposed protocol for
conducting clinical trials
Appendix XI of schedule Y - Data elements for reporting
Serious Adverse Events occurring in a clinical trial



Detailed Guidelines for conducting
Inspection of clinical trial sites and
Sponsor/CRO are already available at
CDSCO website (www.cdsco.nic.in)
Covers the inspection of Ethics
Committees



Clinical Trials
Thank You