Drugs Approving Authorities

8/12/2019 Drugs Approving Authorities

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CDSCOBiological Division

Presentation By:

S.P. Shani

Deputy Drugs Controller(I)


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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.


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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.


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Objective:To ensure availability of safe, efficacious and

quality Drugs, Cosmetics and Medical Devices

Preamble:

To regulate Manufacture, Sale, Distribution andImport of

Drugs

Cosmetics

Biologicals

Medical Devices

Veterinary Drugs


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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.


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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


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Mumbai

New Delhi

Chennai

North Zone (Ghaziabad)

Kolkata

.

West Zone (Mumbai)

South Zone (Chennai)

East Zone (Kolkata)

CDSCO, HQ

CDSCOGeographical 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


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Drug Testing Laboratories

Central Laboratories: 6 (including CDL Kolkata)

State Labs: 26

Vaccines: CDL, Kasauli (NCL)

r-DNA and Diagnostic kits: NIB, Noida


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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

ExportQC

Pharmco.Vig

Legal etc

GMP AuditsEnforcement

Draw drug

Samples

GMP AuditsCoordination

with States

ImportExport

Testing ofDrugs

Validation of

Test protocols

Central Drugs Standard Control Organization


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BIOLOGIC L

DIVISION


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BIOLOGIC L

DIVISION

DDC(I) (Technical Head)

(Mr. S.P Shani)

ADC(I)(Mrs.Swati Srivastava)

Veterinaryvaccine

DI(Ankur)

PSUR,AEFI,PMS,

coordinationwith

immunizationDivision,&

complainthandling

DI(Ravindra)

ClinicalTrialInspection

DI(Shraddha)&DI(Ankur)

ApprovalofVaccine

(MA+CT)Viral

DI(Yogesh)

Form28D

DI(Rajesh),&

DI(Minakshi)

Form-29,TestLicenseand

ExportNOC

DI(Rajesh)

PostApprovalChanges

DI(Vinod)&

DI(Chandrashekar)

ApprovalofVaccine

(MA+CT)Bacterial

DI(Rajesh)

Drugs Controller General (India)

(Dr. G. N. Singh)

Rule37,ImportRegistration

DI(Shashipaul)&

DI(Manish)

DDC(I) (QA Head)

(Dr. K. Bangarurajan)

ADC (I)

(Rubina Bose)

Zones / Sub zonesHeads

Zones/Subzones

GMPInspectorate

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 . DhineshPandian

4. Arvind H iwale

5. Nisha Sankhwar

6. Manish Singhal

7. Saurabh Garg

8. Amol Kandekar

9. Sourabh Mittal

10. RakeshNegi11. DevendraNath

Date:

ADC(I)(Jayant G.Khedkar)

Approvalofr-DNA

products(MA+CT)

DI(Shraddha)&DI

(Chandrashekar)

StemCells

DI(Shraddha)


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Activities undertaken in Biological Division

1. New Drug ApprovalsBiologicals.

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.


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Types of Biological Products1. 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 forbiological products only).


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Definition of New Drug

As per under Rule 122-E New Drug is defined Adrug, including

bulk drug substance which has not been used in the country toany significant extent under the conditions prescribed,recommended or suggested in the labeling thereof and has notbeen recognized as effective and safe by the licensing authoritymentioned under Rule 21 for the proposed claims.

A drug already approved by the Licensing Authority mentioned inRule 21 for certain claims , which is now proposed to be marketedwith modified or new claims , namely , indications, dosage,dosage form ( including sustained release dosage form) and routeof administration.

R l t R i t f M k t A th i ti f Bi l i l


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All vaccines and r-DNA products are New Drugsvide 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

R l t R i t f M k t A th i ti f Bi l i l


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Drugs and Cosmetics Act & Rules,

1945.

Guidance for Industry

Specific for Biological Products

Regulatory Requirement for Market Authorization of Biological

Products


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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


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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 administrative2. Check legal document

3. Check fees

1stLevel

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 issue2nd Level

Review

On Site Evaluation

CMC Evaluation

NDAC

Zonal

Hard and Soft

copies

IND

CDL, Kasauli

for Vaccines


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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 CRUDCG (I)

CRU for Dispatch

Approval


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Guidance for

Industry (Specific forBiological 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
http://www.cdsco.nic.in/http://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_5/CDSCO-GuidanceForIndustry-3%20PAC.pdfhttp://www.cdsco.nic.in/


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Regulation for r-DNA Technology based

Therapeutic proteins - Indian Scenario

The Guidelines on Similar Biologics

was prepared by CDSCO and DBTlaid down the regulatory pathway forsimilar biologic claiming to be similarto an already authorized referencebiologic.

CDSCO is the national regulatoryauthority in India that evaluatessafety, efficacy and quality of drugs inthe country.

DBT through Review Committee onGenetic Manipulation/ InstitutionalBiosafety Committee is responsiblefor overseeing the development andpreclinical evaluation of recombinantbiologics.

C t t A th iti


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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


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Filing of Information as per CTD

Module I: Administration/LegalInformation

Module II: Overall Summaries

Module III: Quality Information(Chemical, Pharmaceuticaland Biological)

Module IV: Non-Clinical Information

Module V: Clinical Information

For Biological section Comprehensive Information is asked as per

CTD Module:-

MODULE 1


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MODULE - 1CTDFormat

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 thecountry 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


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MODULE - 1CTDFormat

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 threeconsecutive 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 drugproduct 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


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MODULE - 2

Introduction

Quality overall summary

Overview of non-clinical studies

Non-clinical Summary

Overview of clinical studies

Clinical summary

MODULE 3


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MODULE - 3

Qual i ty Info rmation (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


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MODULE3

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


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MODULE3

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

MODULE 3


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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

MODULE3

MODULE 4


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MODULE - 4

Non-Cl inical Repo rts

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

MODULE 4


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AppendixIII of Schedule Y {Animal Toxicity (Non ClinicalToxicity 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

MODULE 4


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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


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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


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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

Clinical Trials


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Detailed Guidelines for conductingInspection 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
http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/http://www.cdsco.nic.in/


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Thank You