1. EXPERTSEU/US Marketing Authorization:Coordinating a Two Continent-Strategy

2. The European Uniono 1 continento 27 Countrieso 23 Languageso 4,325,675 kmo 497,198,740inhabitantsContinent 3. European Union:o EU Marketing Access/Authorizationo One Approval Access to 27 Member Stateso What do you need ? 4. European Union:o CE Mark Safety + Performanceo ISO 13485 Quality Standardo Technical File / Contentso Notified Bodyo Authorized Representative 5. European Union:o Timelines to Market Authorizationo Actual Placing on the Market 6. European Union:o Contents CE Mark Technical Fileo EU Clinical Data for CE Mark and FDASubmissions 7. European Union:o Device Classification based on indicationo Exit Strategies and Milestoneso CE Mark, Patient Numbers, FU timelines 8. European Union:o Notified Body Selection / Registered with EUCommissiono Pre-meeting Notified Bodieso Determine Fast Track NB reviewso Determine milestones (CE Mark / Patient FU)o Literature Review-Equivalence 9. European Union:o Prototypeo Determine Strategyo What is available? More important: What is notavailable (yet)o Take into consideration: Languages Cultural differenceso Fastest Route to Marketing Authorizationo LIMIT Sites / IndicationsCase Study: 10. EU/US Marketing Authorization:o Define Two Continent Marketing Strategyo Testing done in accordance with ISO Standardso Clinical Protocol to cover Two Continents inline with Notified Body and FDAo Site Selection/Qualification for FDA-experienced Sites 11. EU/US Marketing Authorization:o Animal Testing safety considerations Device placement Acute tissue effects Chronic Tissue effects Gross pathology and histological response 12. EU/US Marketing Authorization:o Coordinating the Strategies: Why? Save $$ More efficient use of resources Faster realization of revenue Avoid redundancy 13. United States:o Quality System and Manufacturing Information Controls and procedures To ensure consistency in product To ensure ongoing review of product/system To ensure management commitment To ensure investigation of defects and correctiveactiono 21 CFR 820 and ISO 13485 14. United States:o Manufacturing and QS Complexity of Manufacturing Process requiring validation Outside testing requirement Number of design iterationso Manufacturing documents and validationreports can be used for US and EUo ISO 13485 and the QSR are similar, not identical 15. EU/US Marketing Authorization:Coordinating a Two Continent-Strategyo Human Clinical Datao First-in-human Clinical Experience Longest duration follow-up datao Pivotal Study Results Demonstrate Safety and Effectiveness or SE Sufficient sample size for statistical support 16. EU/US Marketing Authorization:Coordinating a Two Continent-Strategyo Clinical Study Focus: Safety and Efficacyo Class II Devices and Non-invasive Class III Single phase is usually adequateo Class III Devices Two phase approach often required Pilot phase 20-50 subjects with 6 month Pivotal phase 100-1000 subjects with significant long termfollow-up (multi-year) in a controlled, comparative design 17. EU/US Marketing Authorization:Coordinating a Two Continent-Strategyo Study Duration = TIME Study duration is critical path item Delays market release and revenue Quarterly monitoring Data management Investigators over-estimate their subject volume 18. EU/US Marketing Authorization:Coordinating a Two Continent-Strategyo Investigator / Sites Payments In the US, sites and IRBs are commanding more inpayments Competition for Investigators in studies Institutions are often a party to the contracts andcharge overheado EU experience can often suffice for US feasibilityrequirements 19. EU/US Marketing Authorization:Coordinating a Two Continent-Strategyo First, understand totality of the requirements In Europe In the US 20. Section DividerTHANK YOU FOR YOUR ATTENTION