1. Laura Gomes Castanheira ANVISA- Brazil Implementation of bioequivalent medicines regulation

2. 2 Summary -History from 2009 - 2013 -Regulations -Challenges -Positive and negative results

3. 3 History - before 1999 Innovator or Similar medicines brand name No generics License granted using similarity approach (same active ingredient and pharmaceutical dosage form of innovator drug) Technical information: production, QC, stability, packaging In vivo studies not necessary

4. 4 History - 1999 Law 9782 – Creates Anvisa Law 9787 – Creates Generic Drugs in Brazil Resolution 391/99 – ANVISA - first regulation for generic drugs -Pharmaceutical equivalence and bioequivalence for all generics

5. 5 History 2000 - 2003 2000 - Resolution 41/00 - criteria for Bioequivalence CROs habilitation and creation of Generic Drugs General Office 2001 - Bioequivalence Coordination was created, CROs inspections 2003 - Resolution 133/03 - Pharmaceutical equivalence and bioequivalence study mandatory; Resolution 899 - analytical methodology validation; Resolution 897- biowaive; Resolution 134/03 - BE studies for drugs already in the market; risk based approach

6. 6 2006 - Resolution 1170 - Guideline for bioequivalence studies 2008 - Electronic information System - SINEB CRO production, electronic submission of BE reports, volunteers national database 2009 - Normative Instruction 12 - Guideline for controlled released sprays and aerosols 2011 - Resolution 37 - Biowaive Pharmaceutical form, dosages biowaive, biowaive based on BCS 2012 - Resolution 27- Bio analytical methodology validation 2013 - CROs certification system revision History 2006 - 2013

7. 7 Current Regulations RDC 41/2003 - Habilitation RDC 103/2003 - Certification RE 894/2003 - BE protocol elaboration guideline RE 895/2003 - BE report elaboration guideline RE 898/2003 - Statistical part planning and execution guideline RE 1170/2006 - BE guideline RE 37/2011 - Biowaive RDC 27/2012 - Bioanalytical methodology validation

8. 8 Challenges Reference medicine CROS - national and international Biowaive

9. 9 Positive and negative points Shortage Number of therapeutic equivalents Impact on public purchase Access

10. 10 Thank you!