REGULATORY TREND OF PHARMACEUTICALS IN “BRIC”

COUNTRIES Shivam Vashisth M Pharmacy 2nd Year M.D University, Rohtak

Guided By

Professor Dr. Arun Nanda

HOD & Dean, Faculty of Pharmaceutical

Sciences, M.D University, Rohtak

AIM OF RESEARCH WORK

1. Drug Regulatory Framework in BRIC countries.

2. Drug Approval Process in BRIC countries.

3. Patent Regime of Drugs in BRIC countries.

BRIC AS AN EMERGING PHARMACEUTICALS MARKET

BRIC word includes the developing market of Brazil, Russia, India and China. Some recent trends shows the development of BRIC as an emerging market.

BRIC+ Mexico Turkey and South Korea contributed more than half of the global market growth in 2009 and is expected to have a sustained average growth of 40% by 2013. On the other hand global pharmaceutical market showed growth between 2.5-3% in 2009.

BRIC has been growing at a rate of 15-20% for last 5 years and their revenue will be doubled by 2013.

China is the 4th largest world market and is expected to become 3rd largest by 2011.

With GDP of between US$2-4 trillion in 2008, Brazil, Russia, and India are each expected to add US$5-15 billion to the pharmaceutical market through 2013.

India is the 4th largest generic pharmaceutical market in the world and is consistently achieving a growth rate of 9% over the last 5 years.

BRIC market is expected to have a growth rate of 12-14% in 2010 and 12-14% per annum over the following five years.

REASONS FOR THE EMERGENCE OF “BRIC” MARKET

Decline in the growth rate of the developed pharmaceutical market in developed nations .

Decline in R & D productivity.

Availability of patient population in emerging markets.

R & D resources availability.

Changing regulatory and investment environment for the research.

INDIAN DRUG REGULATORY FRAMEWORK Health is in the concurrent list of Indian constitution. In India drugs are regulated both at central and state level At the central level CDSCO(Central Drug Standard Control organization) under the Ministry of Health and Family Welfare is responsible for approving new drug, clinical trials, and licensing of drugs. At the state level state drug regulatory authorities issues licences to manufacture approved drugs and to monitor the quality of drugs along with CDSCO. In India the regulation of drug, medical devices, biological and r-DNA products is distributed within various ministries.

CENTRAL DRUG STANDARD CONTROL ORGANIZATION CDSCO under the aegis of Ministry of Health & Family

Welfare have the duty of regulating and ensuring the quality of medicines and pharmaceuticals under the Drugs & Cosmetic Act.

The DCGI (Drug Controller, India) is the main personality of CDSCO responsible for approving new drugs, clinical trials, Licensing and to ensure quality, safety and efficacy of pharmaceuticals in India.

CDSCO is organized in to various Headquarters'’, Zonal Offices “, Sub zonal Offices “, Port Offices”, and Laboratory.

MAJOR LAWS RESPONSIBLE FOR DRUG REGULATION

D&C ACT,1940 and Rules 1945

DRUG PRICE CONTROL

ORDER ACT, 1995

DRUGS AND MAGIC

REMEDIES ACT, 1954

THE MEDICINAL &

TOILET PREPARATION

S ACT,1955

THE PHARMACY

ACT.1948

MAIN SCEDULES TO THE DRUGS AND COSMETIC ACT, 1940 & RULES

1945

SCHEDULE-A

SCHEDULE-C&C1

SCHEDULE-G and H

SCHEDULE-M

SCHEDULE-Y

RULES GOVERNING REGISTRATION OF DRUGS IN INDIA

RULE 122A PERMISSION TO IMPORT A NEW DRUG

RULE 122B PERMISSION TO MANUFACTURE A NEW DRUG

RULE 122 D PERMISSION TO IMPORT OR MANUFACTURE A FDC’s’

RULE 122DA PERMISSION TO CONDUCT CLINICAL TRIALS FOR NEW DRUG

RULE 122E DEFINITION OF NEW DRUG

NEW DRUG DEFINFITION (122E)

NOT USED IN THE COUNTRY.

APPROVED DRUG - 1. NEW CLAIMS (Indications, Dosage, Dosage form, Route)

2. FDCs ( New or Modified) ALL VACCINES SHALL BE CONSIDERED AS NEW DRUG AS

SPECIFIED BY LICENSING AUTHORITY.

NOTE:- A NEW DRUG IS CONSIDERED NEW FOR THE PERIOD OF 4 YEARS FROM THE DATE OF ITS FIRST APPROVAL OR ITS INCLUSION IN THE INDIAN PHARMACOPOEIA.

APPLICATION FOR PERMISSION TO CONDUCT CLINICAL TRIALS

A Sponsor needs to file an IND application (Form-44) with the CDSCO to get permission to conduct clinical trials. The same Form-44 can be used to import or manufacture a new drug. An INDs contents described in Schedule-Y are similar to those of a submission to USFDA or EMEA. IND mainly includes Chemical and pharmaceutical information Animal pharmacology data Animal toxicology data Regulatory status in other countries, if available Proposed phase-1 and phase-2 studies

INVESTIGATIONAL NEW DRUG APPLICATION

TYPES OF IND APPLICATION IN INDIA

CATEGORY-AThese includes clinical trials

whose protocols have been approved by USA, UK, Switzerland, EMEA, Japan, Australia, Canada, Germany, South Africa.

These are also known as Abbreviated INDs.

Category-A applications are approved within 3-4 weeks of filling.

CATEGORY-BAll other clinical trials not

Covered under category-A will fall under Category-B, and will be reviewed normally defined earlier.

Most phase-1 clinical trials are reviewed as Category-B applications.

Category-B applications are approved with in 8-12 weeks.

CLINICAL TRIAL REQUIREMENTSFor new drugs discovered in India, clinical trials should be carried

out right from Phase-1 to Phase-3.

Phase-1 trials are not allowed for the new drugs discovered in other countries untill of special relevance to health in India.

The data related to safety and efficacy of the drug can be accepted from other countries if the drug is applicable in treating serious diseases.

For drugs indicated in life threatening/serious diseases or disease of special relevance to the Indian health scenario, the toxicological and clinical data requirements may be abbreviated, deferred or omitted.

REGULATION & APPROVAL OF CLINICAL TRIALS

No new drug clinical trial can be carried out without the permission of the DCGI, and the approval obtained from the respective ethics committee(s). Trial sites and the protocol must be approved by independent ethics committee (s). Important regulations are- • SCHEDULE-Y, Ammended Version 2005.• GCP Guidelines as per CDSCO.• ICMR Guidelines , 2006. (Revised)• GLP Guidelines as per CDSCO.• BIOAVAILABILTY & BIOEQUIVALANCE Guidance.• National Pharmacovigilance Programme, 2004.

PHASES OF CLINICAL TRIALS PHASE-1 TRIALS (Human Pharmacology)- To determine safety and tolerability of a drug. Common objectives are to determine MTD, ADME and MOA of the drug.

PHASE-2 TRIALS (Therapeutic Explanatory Trials)- To determine the effectiveness and safety of the drug for a particular indication.

PHASE-3 TRIALS (Therapeutic Confirmatory Trials)- To confirm the therapeutic benefits of the drug. The results must support the prescribing information. PHASE-4 TRIALS (Post Marketing Trials)- To compare the risk and benefits of the drug in wider population after the approval of the drug.

CONTENTS OF REGISTRATION DOSSIER IN INDIA

- Introduction- Chemical and Pharmaceutical Information- Animal Pharmacology- Animal Toxicology- Human/Clinical Pharmacology (Phase I)-Therapeutic Exploratory Trials (Phase II)- Therapeutic Confirmatory Trials (Phase III)- Special Studies- Regulatory Status in Other Countries- Prescribing Information- Samples and Testing Protocols

CTD IN INDIAThe New Drug Application can be submitted as per

international guidelines in form of ICH Common Technical

Document as shown below-

• Module-1 Administrative and Prescribing information

• Module-2 Summary of Module-1,2 and 3

• Module-3 Quality section

• Module-4 Non-Clinical study Report

• Module-5 Clinical Study Report

Patent on pharmaceuticals• Patent Act,1970• Generic Industry

Process

Patent• Patent Amendment,

2005• To comply with TRIPS

Product

Patent

Data Protection

FIVE YEARS

FOR NME

HIV/ AIDS Public Interest

Undisclosed Data

Patent+ Data protection up to 20 years

REFERENCESSreeharan.N, Sykes.A.K. Pharmaceutical medicine in the Emerging Markets In: John P.Griffin, editor. The Textbook of Pharmaceutical Medicine. 6th ed. London: A John Wiley & BMJI Publication. 2009. P. 641-55 (cited 2010 Aug10). Available from: URL: http://pharma-books. blogspot.com /2010 / 02 /textbook-of-pharmaceutical-medicine.html.

CDSCO (cited 2010 Aug 2). Available from: URL: http://cdsco.nic.in/

Drugs and Cosmetic Act, 1940 and Rules, 1945. www.cdsco.nic.in/html/ Drugs & Cosmetic Act.pdf (cited 2010 Sept 11).

Schedule Y, CDSCO, Ministry of Health and Family Welfare, January 2005 (cited 2010 Oct 4) Available from website www.cdsco.nic.in.

REFERENCESIndian Patent Amendment Act, 2005, Ministry Laws and Justice. (cited 2010 Oct 14) Available from:URL: www.patentoffice .nic.in /ipr/ patent/ patent_ 2005.pdf.

Dr. Surinder Singh, DCGI, India.”National Drug Authorities-Its Structure and Activities”. Seminar on Clinical Trials: The Heart of Medical Science on 4th November, 2008 at Assocham House, New Delhi. Available from: URL:http://www.scribd. com/doc/20538766/Dr-Surinder-Singh-1 (cited 2010 Sept 18).

Guidance for Industry on Preparation of Common Technical Document for Import/ Manufacture and Marketing Approval of New Drugs for Human Use (New Drug Application-NDA). Published on 2010 Oct 28 by CDSCO. Available from: URL: http://cdsco.nic.in/CTD_Guidance%20-Final.pdf (cited 2010 Dec 10).

REFERENCESRam.P. “India s New “TRIPS-Compliant” Patent Regime between Drug Patents and the Right to Health”. Chicago-Kent Journal of Intellectual Property. 2006 (cited 2010 Oct 22). Available from: URL: ip.kentlaw.edu/.../5%20Chi-Kent %20 J%20 Intell %20 Prop %20195.pdf.

Satwant Reddy Committee. “Report on Steps to be taken by Government of India in the context of Data Provisions of Article 39.3 of TRIPS Agreement”. 2007 5 30 (cited 2010 Oct 20). Available from: URL: chemicals.nic.in/DPBooklet.pdf.

Requirements for Patent Law and Practice (cited 2010 Aug 30). Available from: URL: http://www.indiaip.com/india/patents/filling/Filling.htm.

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ATTENTION