1. LATAM Latin America Registration Requirements and Harmonization Efforts April 2011 DIA RA SIAC AprilApril

2. Drug Registration Requirements in Latin America  Unique requirements by region  Interactions with Authorities  Proposal for harmonization from Multi-National Company CMC Experts  Regional Awareness Sessions  Credits for Contributors

3. Brazil  Moving faster with vary regulations in progress – NCE´s, Branded generics and Generics with harmonized CMC requirements – New guidelines for API´s site inspections – Braille label – Biosimilars – Biotech products – Technical variations – Biologic stability test  More sophisticated but slower registration cycle time (with same resources)  Bilateral agreement with USA

4. Mexico  New regulation for Biotech products and Biosimilars  Braille label in pharma products in progress  New Decree to simplify procedures  E- submissions initiative  Establishment of GMP standard for API´s during 2011  Recognition of registrations in USA and Canada (Medical devises in force)

5.  New legislation requiring more CMC data for registration  GMP site inspections as new requirement (no expertise within BOH)  All pharmaceutical products must use pharmacopoeia specifications  EU Pharmacopeia is acceptable  Literal application of the requirements with no space for criteria  Countries must be registered in Peru Peru

6. Ecuador  New Regulation in place  Escalation of requirements from 2011 onwards including the items listed below Too many wet-ink signatures in CMC documents – Every Drug product Stability page must be signed by the QP – Additional CMC data for registration – Requirements for legalized documents  Positive side – Acceptance for alternative source – ICH alignment for stability studies

7.  Requirements for Biosimilars  GMP. Increase minimal standard in alignment with WHO reports  GMP inspections in India and China Chile

8. Argentina  GMP Inspection for vaccine sites (no reference concept)  GMP inspection for pharma products of sites outside Annex I countires  Regulation under review for Biotech products.  SUPAC is in force in Argentina for post-approval variations  Typical approval is a range of 8-12 months

9.  GMP site inspections.  New initiative to differentiate pharma and biological products in registration  Recently batch released for vaccines implemented  Confirmation testing is required. Colombia

10.  New regulation on pharmacovigilance  Implementing batch release of vaccines  Post approval registration requirements Venezuela

11. Interaction with Authorities Public consultation Workshops Technical committees Industry Conferences Trading Associations Meetings to present NCE´s Appointments to discuss particular issues Company alone PANDRH Expert Working Groups LARKIT (PhRMA) Pan- American Network

12. Interaction with Authorities Interact & Incorporate Brazil Argentina Chile Interact & difficult to incorporate Peru Ecuador Central America Colombia Venezuela Uruguay Difficult to Interact & to Incorporate Mexico Caribbean

13. Global harmonization efforts and benefits Stability Studies Harmonization  Guideline ICH Q1(R2) “Stability Studies for New Drug Substances and Products  ICH principles adopted by other organizations / regulators  European Medicines Agency (EMA) for existing drug substances: CPMP Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished  WHO technical report 953, Annex 2, Stability testing of active pharmaceutical ingredients and finished pharmaceutical products (2009) Benefits  To have a single registration documentation package for medicinal products in Latin America region  To eliminate unnecessary delay in the global development of new medicines whilst maintaining safeguards on quality, safety and efficacy  To remove redundancy and duplication of work in the development and review process  To reduce the cost of research and development, which has a significant impact on the rising cost of healthcare, and allow patients faster access to safe and efficacious new medicinal products of high quality

14. Current situation Global harmonization achieved a significant success in a relatively short period of time Scientific consensus between the industry and regulators. Commitment of the regulatory agencies to implement guidelines and recommendations However when registering products globally, companies still face challenges  Countries have local stability requirements which hinder global submissions  Local shelf-life confirmatory stability requirements  Non science based specific testing requirements  Testing for parameters which do not change on stability  Specific formatting requirements (e.g. “wet” signatures on all stability sheets)  Other product related data/local requirements (batch related data for excipients, standard deviation for each time point, provision of chromatograms, requirement of product made with different APPI batch per strength, number of batches per strength /presentation for matrixing and bracketing)  Harmonized stability requirements do not apply to post-approval changes (PAC), necessitating companies to consult the widely varied, country-or region-specific guidelines  Readiness and acceptance of more recent innovative/alternative stability approaches (such as statistical approaches), which are not included in the current guidelines

15. LAFG Recommendations  It is suggested that ICH/WHO recommendations be considered in the region.  Adoption of these harmonized guideline in lieu of local stability requirements would allow patients faster access to safe and efficacious new medicinal products of high quality.  Have global scientific stability requirements will lead to a greater mutual acceptance of development data.

16. Regional Opportunities  April 2011 DIA Panama Meeting  May 2011 PhRMA Conference in Brazil  May 2011 ISPE Local Meeting Argentina  Nov 2011 GMP Meeting Puerto Rico

17. Contributors Regional Requirements/Interaction Opportunity with Authorities Slides  Dr. Marisela Poot, VP Regulatory Affairs LA & Mexico, GlaxoSmithKline LA White Paper Authoring and Presentation  Bekki Komas, Director, CMC Advocacy and Regulatory Intelligence, GlaxoSmithKline  Maria Guazzaroni Jacobs, Director Global Quality Strategy, Pfizer Inc  Greg Gallegos, Pharma Technical Regulatory Affairs, Genetech  Sara Abelaira, CMC Documentation Manager, Boehringer Ingelheim  Marta Cicconi Vidal, R&D Director, Boehringer Ingelheim