Coordinators :

1. Bioequivalence, data exclusivity and genericdrugsAn analysisfrom the cases of India and Brazil Coordinators : Fabienne Orsi (IRD-SE4S, Marseille) and Claudia Chamas (Fiocruz, Rio de Janeiro) Research Team : Amit Ray (Jawaharlal Nehru University, New Delhi), Christine Noiville, Olivier Le Queré, Jean-René Binet (Centre de recherche « droit sciences et techniques », CNRS, Paris), Roberto Reis (Fiocruz)

2. Bioequivalence and Data Exclusivity What is at stake • Since the 80’s in Northern countries : To obtain a marketing approval of a generic version of a product already registered (without patent protection or with patent already expired), the generic producer only needs to demonstrate bioequivalence and bioavailability tests. • The drug regulatory agency uses the initial dossier generated by the original producer to establish safety and effectiveness and to avoid redoing all the clinical tests. • The key condition of cheaper generics availability • But data exclusivity legislation forbids regulatory authorities to rely upon clinical data submitted by originator companies to register a generic product (for 10 years in the EU, 5 in the US). • This oblige generic producers to repeat clinical trials  High cost and time or to wait until the expiration of DE period (in addition to patent expiration if it exists)

3. Challenges in southern countries Bioequivalencenowat the heart of the international quality standard for GenericDrugs : ie WHO prequalification program for ARVs and other « essential drugs » • Bioequivalenceactivityis a veritableindustrywhichrequires: • Specificcompetenciesand specific infrastructures • few capabilitiesin southern countries (high concentration in India) • Access to clinical data submitted by originatorcompanies to regulatoryauthorities. • Strong pressure on Southern countries by the US and the UE to recognizedata exclusivity

4. Research Objectives • To studybioequivalencecapacity building : • In Indiaas country of reference and as largest supplier of genericdrugs (especially for HIV/AIDS) • In Brazil: How the shift from « similar » to genericdrugs has been organized • To analyse the diffusion/enforcementprocess of data exclusivity(as TRIPS+) • Mainlythrough the study of Free Trade Agreements • More specifically : in depthstudy of EU-India FTA currentlyundernegociation

5. Method and expected results • Method : qualitative studies conducted mainly through semi-structured interviews • Expected results, from Indian and Brazilian cases studies • To understand how the bioequivalence activity works, what are the main conditions of its development in developing countries • To underdand how data exclusivity regimen works independently or in interfercence with the patent system and flexibilities • To determine if and how data exclusivity can really hinder access to drugs in developing countries

6. Constructionofinfrastructureand expertise in bioequivalence in Brazil Legislation Anvisa (Law 9782, January 1999) Generic law (Law 9.787, February 1999) Resolution 391 (1999)  Resolution RDC 10 (2001)  Resolution RDC 135 (2003)  Resolution RDC 16 (2007) Approves the Technical Regulation for Generic Drugs. Resolutions 41 (2000) and 103 (2003) Set criteria for acceptance of units that perform tests for Pharmaceutical Equivalence, Bioavailability and Bioequivalence of drugs Inspection Coordination Centers of pharmaceutical equivalence and bioequivalence – CIBIO

7. Constructionofinfrastructureand expertise in bioequivalence in Brazil In 2002 was also developed the Productivity System of Centres in Brazil Resolution RE 1170 (2006) - Guide for evidence of bioequivalence studies - Certified Centers (2000 20 bioequivalence centers certified) (2010 27 in Brazil, 25 internationals) 2 national and 6 international centres in certification process) Anvisa. List of certified centers. http://www.anvisa.gov.br/reblas/Bioequivalence/centers/national/certificados.htm http://www.anvisa.gov.br/reblas/Bioequivalence/centers/international/certificados.htm

8. Case Studies Profile of Bioequivalence / Bioavailability Internalization Process Fonte: COBIO/GESEF/GGMED

9. Number of Pharmaceutical Equivalence Studies Fonte: Adapted from SINEB, Anvisa 2010

10. Patent Registry Patent expiration Market Standard situation (NCE) 1st Scenario Data Exclusivity Patent Registry Patent expiration Market Possible interference (TRIPS flexibility - CL) 2nd Scenario Data Exclusivity Patent Registry Patent expiration Market 3er Scenario 2nd indication Second or further medical indications Data Exclusivity Data Exclusivity

11. The Situation in Brazil There is no provision of data exclusivity under the Brazilian Legal Structure, but it can be noticed, the existence of constant movement over an inclusion of TRIPS-plus clauses in the Brazilian juridical framework. Some questions still need to be addressed and agreed to build up consensus to respond to future pressures, such as: How many drugs would have the data exclusivity as main mechanism of intellectual protection? What would be the influence of data exclusivity over the price of medication? Which would be the effect of the presence of a legislation in data exclusivity over the Brazilian generic industry?