The FDA Landscape AdvaMed September 2008

1. The FDA LandscapeAdvaMed September 2008 Judith K. Meritz meritz@blankrome.com

2. FDA Mission • “The FDA is responsible for protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nations' food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.”

3. FDA Regulatory Authority • Laws Published in United States Code (USC) Federal Food, Drug and Cosmetic Act Public Health Service Act Radiation Safety and Health Act Safe Medical Devices Act • Regulations Comments Published in Code of Federal Regulations

4. FDA Regulatory Authority • Food and Drug Act of 1906. Prohibits shipment of adulterated or misbranded food or drugs in interstate commerce. DEVICES NOT INCLUDED • Food, Drug and Cosmetic Act of 1938. Device adulteration and misbranding prohibited and inspection and rulemaking authority added… (also premarket approval for new drugs) • Radiation Control for Health and Safety Act of 1968 Standards for radiation emitting devices (x-ray)

5. FDA Regulatory Authority • Medical Device Amendments of 1976 Premarket approval devices, GMP’s and Post Market Controls (Registration Listing) (Reporting to FDA of deaths/serious injuries – MDR) • Safe Medical Devices Act of 1990 (SMDA) Substantial equivalence for 510(k) FDA post-market regulation/enforcement Device tracking; civil penalties Reports removals corrections/ recalls User facilities to report deaths, serious injuries and serious illnesses to FDA

6. FDA Regulatory Authority • Food and Drug Administration Modernization Act of 1997 (FDAMA) Streamline Premarket Review Limit device tracking and post-market surveillance requirements • Medical Device User Fee and Modernization Act of 2002 (MDUFMA) • Food and Drug Administration Amendments Act of 2007 (FDAAA)

7. Structure of FDA • FDA part of US Government • Office of the Commissioner • Product Specific Centers Drug Evaluation and Research (CDER) Biologics Evaluation and Research (CBER) Devices and Radiological Health (CDRH) Food Safety and Applied Nutrition (CFSAN) Veterinary Medicine (CVM)

8. Device Basics • Establishment Listing • Device Listing • 510(k) • PMA • Quality System • Labeling Requirements • Medical Device Reporting

9. Definition of Medical Device • An “instrument, apparatus, implement, machine, contrivance, implant, in vivo reagent…including any component, part or accessory” WHICH IS intended for use in the diagnosis or treatment of a disease or condition OR Intended to affect the structure or function of the body AND

10. Definition of Medical Device Which does not achieve any of its primary intended purposes through chemical action within the body AND Which is not dependent on being metabolized for the achievement of any of its primary intended purposes

11. Device Classification • Completed in 1970’s through FDA rulemaking with input from advisory panels • Classification lists are in 21 CFR Part 800 Medical Device Classification

12. Medical Devices Licensed as Biologics or by Drug Center • Some devices proceed through different pathways and are reviewed by CBER not CDRH Generally in vitro diagnostic devices used to test blood supply; some cell and tissue products [test kits to test for blood type or HIV] Devices for blood collection • Devices that are considered biologics

13. Combination Products • Need to determine which product application to submit and which FDA center will have primary review responsibility • Decision based on primary mode of action • Addressed in FDA Intercenter Agreements • Sponsor may submit a “Request for Designation” • FDA Office of Combination Products established in December 2002 • Examples: drug-eluting coronary stent or antibiotic bone cement

14. Paths to Market • Class I devices generally exempt from pre-market clearance by FDA • 510(K) clearance from FDA – show that class II device you want to market is “substantially equivalent” to another marketed device. SE comparison based on intended use, materials, performance. • PMA (Pre-Market Approval application) approved by FDA – show that class III device has reasonable assurance of safety & efficacy. Requires clinical testing data from humans.

15. Who must Register Device Manufacturers Contract Manufacturers Component Manufacturers Accessory Manufacturers Contract Sterilizers Initial Importer Foreign Establishments Repackagers and Relabelers Processors of Single use Devices Registration

16. Registration • Who does not register? • Manufacturers of Raw Materials • Manufacturers of general purpose articles (e.g. chemical reagents) not labeled/ promoted medical use • Licensed health care practitioners who manufacture a device solely for use in practice • Pharmacies that sell or deliver to ultimate user • Wholesale distributors • Carriers (e.g. UPS, FED Ex) • Manufacturers of devices intended solely for research, teaching or analysis and which are not commercially distributed

17. Registration • How and when to Register • FDA forms for initial registration Within 30 days of beginning activity Annual registrations • Electronically • “Official” correspondent designated to register and keep records • “US Agent” for foreign establishments • Prior to exporting devices to U.S. • Within 30 days of charge in ownership, establishment name, official correspondent or address

18. Device Listing Registration • Listing - Must File list of devices company has placed in commercial distribution • Who, What, When • Same entities who register, except: • Contract manufacturers; Contract Sterilizers • Initial importers • FDA forms electronically • List devices when initial registration is completed • Annually between 10/1 and 12/31 • Must update listing