National Drug Authority Its Structure and ActivitiesSeminar on Clinical Trials: The Heart of Medical Science on 4th November, 2008 at Assocham House, New Delhi By Dr. Surinder Singh Drugs Controller General (India) CDSCO, Directorate General of Health Services, Ministry of Health & Family Welfare, Govt. of India, New Delhi www.cdsco.nic.in

CD SCO

Drug Regulatory System Health is in concurrent list of Indian constitution It is governed by both Centre and State Governments

1

Legal Enactments to Regulate Import, Manufacture & Sale of DrugsDrugs and Cosmetics Act, 1940Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954

Drugs and Cosmetics Rules, 1945 made under the Act

Drug Price Control Order (DPCO), 1995

The overall objective of a Drug Regulatory Authority (DRA) is to ensure that medicinal products are of acceptable quality, safety and efficacy, are manufactured and distributed in ways which ensure their quality until they reach the patient/consumer, and their commercial promotion is accurate.

2

C DSCODrugs Controller General (I)HEAD QUARTER ZONAL OFFICE (4) SUB ZONAL OFFICE (2) PORT OFFICE (7) LABORATORY (6)

New Drugs CLAA Imports DTAB/ DCC

GMP Audits Coordinations with States

GMP Audits Coordinations with States

Import Export

Testing of drug Samples Validation of Test protocol

STRUCTURE AT STATE LEVELSTATE DRUGS CONTROL ORGANISATION

DRUGS CONTROLLER/ COMMISSIONERDEPUTY DRUGS CONTROLLER

DRUGS TESTING LABORATOTY

GOVT. ANALYST

DRUGS INSPECTOR

ANALYST

SUPPORTING STAFF

SUPPORTING STAFF

Total No. of Drugs Inspectors Total No. of Drugs Manufacturers Total No. of Sales Premises

: : :

~1000 ~10000 ~ 500000

3

Functions of CDSCOApproval of new drugs and clinical trials

Import Registration and LicensingLicensing 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 of State Licensing AuthoritiesLicensing 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

4

Approval of Clinical Trials, Import, & Manufacture of New DrugsRequirements and Guidelines - Schedule Y Rule 122 A Rule 122 B Rule 122 DA Rule 122 E Permission to import new drug Permission to manufacture new drug Definition of Clinical trials Definition of New Drugs* New substance having therapeutic indication Modified or new claims, new route of administration for already approved drug Fixed Dose Combination

Approval of INDIND Applicant CDSCO HQ

Examination by New Drug Division

Detailed Review by IND Committee Timeline Phase I 90 days Phase II 45 days Phase III 60 days

Approval

Recommendation to DCG(I)

5

Import, Registration and LicensingMfg sites and Products are required to be Registered Issue of Import License in Form 10 / 10A

Rules 21 to 30 Schedule DI & DII Timeline

Rules related to grant of Registration Certificate and Import License Information required for registration of Mfg site and Product Registration Certificate(RC) and Import License - Valid for 3 years

For RC: As per D& C Rules, 9 Months ,However in practice, 2 months For Import License2 -3 weeks

As per Rule 24A (5), there is provision to inspect overseas manufacturing site for which manufacturer has to pay 5000 USD

Requirements For Import and Registration Registration of overseas Manufacturing site and Drugs Registration Certificate issued in form 41 by the Licensing Authority Import License issued in Form 10 or 10A

6

Central Licensing*CLAA Approval and Grant of LicenseLicense Prepared by State Licensing Authority

Manufacturer

STATE LICENSING AUTHORITY

Joint Inspection by State and Central Inspectors

Examination of Report

*

For Biologicals, Large volume parenterals (LVP), Blood bank and blood products & Some Medical Devices

Global Clinical Trials

Permission is required from CDSCO for conducting global clinical trials in the country Phase I for New Drug substance developed outside India is not permitted So far, approx. 500 permissions have been granted since 2003

7

National Pharmacovigilance Programme

CDSCO

NPAC

ZPC RPCN N N N N N N N E S E S E S E S E S S E S E S E S E S E W W W W W

PPC

NPAC = National Pharmacovigilance Advisory Committee, ZRP = Zonal Pharmacovigilance Centre, RPC = Regional Pharmacovigilance Centre, PPC = Peripheral Pharmacovigilance Centre

Proposal to Create CDA Setting up of autonomous Central Drugs Authority (CDA) of global standards under the Ministry of Health & FW. To introduce a system of centralized licensing for manufacture of drugs Bill has already been introduced in the Parliament

8

Proposed Structure of CDACentral Drug Administration Drugs Controller General

Office - 1

Office - 2

Office - 3

Regulatory Affairs and Enforcement

New Drugs & Clinical Trials Enforcement Biologicals & Biotechnology products

Organizational services

Division for Import

Training & Services

Pharmacovigilance

Quality control

Medical Devices and Diagnostics

Legal and Consumer Affairs

Collaborations With Health Canada, US FDA, Brazil, South Africa to strengthen Functioning in several areas including monitoring drugs for adverse reactions, regulating medical devices, clinical practices and biological drugs

9

Clinical Trial Inspection Inspection of clinical trial sites is an important tool to ensure subject protection and integrity of data. To develop knowledge and skill in inspecting clinical trial sites, implementing GCP inspection programme, CDSCO has collaborated with US FDA.

Clinical Trial Inspection The first USFDA-CDSCO collaborative GCP inspection workshops conducted in September 2008. Next advanced workshop planned in May 2009. Each workshops will be followed by series of regional workshops across the country.

10

Expansion of Organization Shifted to the state of the art FDA Bhawan Aggressive approach in filling up vacant posts and creating new vacancies Contractual staff hired for smooth functioning of the organization

Image Upliftment of CDSCO Corporate culture Professional approach Moral boost Modulating work culture Strict timelines Interactive workshops Sending staff abroad

11

TimelinesApproval Export NOC Dual use, Rule 37 & Neutral code Additional indication etc. Form 10 Test License First response to New Drug FDC first response Endorsement of additional products on registration Registration

Time Frame2 Weeks 3 Weeks 4 Weeks 4 Weeks 4 Weeks 6 Weeks 6 Weeks 8 Weeks 12 weeks

12

13

14

15

16

17

18

19

20

21

22

23

24