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

BIOLOGICAL DIVISION

BIOLOGICAL DIVISION

DDC(I) (Technical Head)

(Mr. S.P Shani)

ADC(I) (Mrs.Swati Srivastava)

Vet

erin

ary

va

ccin

e

DI

(An

ku

r)

PS

UR

, A

EF

I, P

MS

,

coo

rdin

ati

on

wit

h

imm

un

iza

tio

n D

ivis

ion

, &

com

pla

int

ha

nd

lin

gD

I (

Rav

ind

ra)

Cli

nic

al T

ria

l In

spec

tio

n

DI

(Sh

rad

dh

a) &

DI

(An

ku

r)

Ap

pro

va

l o

f V

acc

ine

(MA

+C

T)

Vir

al

DI

(Yo

ges

h)

Fo

rm 2

8D

DI

(Raj

esh

), &

DI

(Min

aksh

i)

Fo

rm-2

9, T

est

Lic

ense

an

d

Ex

po

rt N

OC

DI

(Raj

esh

)

Po

st A

pp

rov

al

Ch

an

ges

DI

(Vin

od

) &

DI

(Ch

and

rash

ekar

)

Ap

pro

va

l o

f V

acc

ine

(MA

+C

T)

Ba

cter

ial

DI

(Raj

esh)

Drugs Controller General (India)

(Dr. G. N. Singh)

Ru

le 3

7,

Imp

ort

Reg

istr

ati

on

DI

(Sh

ash

ip

aul)

&

DI

(Man

ish

)

DDC(I) (QA Head)

(Dr. K. Bangarurajan)

ADC (I)

(Rubina Bose)

Zones / Sub zonesHeads

Zon

es / S

ub

zon

es

GM

P I

nsp

ecto

rate

Technical Data Associate (1 Nos.)Technical Data Associates (11 Nos)

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)

Ap

pro

va

l o

f r-

DN

A

pro

du

cts

(MA

+C

T)

DI

(Sh

rad

dh

a) &

DI

(Ch

and

rash

ekar

)

Ste

m C

ells

DI

(Sh

rad

dh

a)

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 DI’s

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

1st Level

Review

Central Registry

Unit

DDC (I)

ADC (I)

DI’s

TDA’s

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)

DI’s

TDA’s

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 manufacturer’s research activity

1.2.11 A brief profile of the manufacturer’s 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 08th

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