Bringing Medical Devices to the Market Paths and Pitfalls

1. Bringing Medical Devices to the MarketPaths and Pitfalls By Daniel R. Matlis and David J. Lennard February 21st, 2007

2. Agenda • Business Issues Facing The Device Industry • FDA Requirements For Medical Devices • Medical Device Submission Vehicles • Same Or Novel? • Design Changes: Knowing When To Stop • Discussion

3. About the Speakers David J. Lennard • 30 years experience in Life-Sciences • 25 years with Johnson & Johnson • Worked in project management, manufacturing, product/process development, clinical research, medical device reporting, product liability, regulatory affairs and quality assurance and compliance • Holds two U.S. Patents Daniel R. Matlis • 16 Years Experience in Life-Sciences • Involved in projects spanning R&D, Manufacturing, Regulatory Compliance, Business Development Sales, Marketing and Information Technology. • Governance, Risk Management and Compliance • Computer System and Software Compliance

4. Business Issues FacingtheDevice Industry

5. Business Issues • Market Factors • Reimbursement • Intellectual Property • Manufacturing Factors • Import / Export Laws • 40% of approved device firms manufacture abroad • Sales, Marketing and Licensing • Better to be first than Best • Know your buyer • Know your competition • Regulatory Factors • Device Development • Studies conducted world-wide • Post Marketing Vigilance is a world-wide network • Application formats are becoming harmonized • Inspectional Methods are converging

6. FDA RequirementsforMedical Devices

7. FDA’s Role in Technology and Innovation

8. Regulatory Process Differences

9. Patchwork of Regulatory Requirements • Food and Drug Administration • Safety • Effectiveness • Clinical utility • Hospital and Clinical Laboratory • FDA • Health Care Financing Administration (HCFA) • Clinical Laboratory Improvement Amendments (CLIA) • Mammography Quality Standards Act (MQSA) • Other Authorities • Federal Communications Commission (wireless, telemetry) • Nuclear Regulatory Commission (Nuclear radiation) • Rinse and Repeat for every country you plan to market in

10. The Basic Regulatory Requirements • Manufacturers of medical devices distributed in the U.S. must comply with: • Premarket Notification 510(k), unless exempt, or Premarket Approval (PMA), • Establishment registration on form FDA-2891 • Medical Device Listing on form FDA-2892 • Quality System Regulation (QSR) • Labeling Requirements • Medical Device Reporting (MDR)

11. Pre-Approval • 510(k) Submission Components • Medical Device User Fee Cover Sheet • CDRH Premarket Review Submission Cover Sheet (voluntary) • 510(k) Cover Letter • Executive Summary • Indications for Use Statement • 510(k) Summary or 510(k) Statement • Truthful and Accuracy Statement • Class III Summary and Certification (if Applicable) • Financial Certification or Disclosure Statement • Device Description • Substantial Equivalence • Labeling • Sterilization and Shelf Life • Biocompatibility • Software (if Applicable) • Electromagnetic Compatibility and Electrical Safety (if Applicable) • Performance Testing

12. Post-Approval • Quality System Regulation 21 CFR Part 820 • Regulates methods used in & facilities and controls used for: • Designing • Purchasing • Manufacturing • Packaging • Labeling • Storing • Installing • Servicing • Manufacturing facilities undergo FDA inspections to assure compliance with the QSR

13. Risk-based Inspections QSR Patient Safety Quality (Patient) Factors Processes Inspection Risk No Correlation RISK  RISK  Traditional Inspection Approach Patient Safety QSR Processes Inspection Risk Quality (Patient) Factors RISK  RISK  High Correlation Risk Based Inspection Approach

14. Medical Device Submission Vehicles

15. No Guarantees • Even if you do all the right things, there are no guarantees • FDA is “people” • Target submission to facilitate review • Focus your energies on meeting requirements, not working around them

16. Who Decides Device Classification? • FDA established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels. • 868 Anesthesiology870 Cardiovascular862 Clinical Chemistry and Clinical Toxicology872 Dental874 Ear, Nose, and Throat876 Gastroenterology and Urology878 General and Plastic Surgery880 General Hospital and Personal Use864 Hematology and Pathology866 Immunology and Microbiology882 Neurology884 Obstetrical and Gynecological886 Ophthalmic888 Orthopedic890 Physical Medicine892 Radiology

17. Class I: less stringent classification • 47% of medical devices fall under this category • Subject to general controls • Premarket Notification 510(k), unless exempt • 74% of the Class I devices are exempt from the premarket notification process • Establishment registration • Device Registration & Listing • Quality System (QS) regulation (Good Manufacturing Practices –GMP’s) • Labeling requirements • Misbranding

18. Class I Device • Root canal post • Dental floss • Tongue depressor • Surgeons glove

19. Class II: Need to meet performance standards • 43% of medical devices fall under this category • In addition to general controls Class II require: • post-market surveillance

20. Class II Devices • Oxygen mask • Powered wheelchair • Skull clamp • Ultrasonic imager

21. Class III Devices • 10% of medical devices fall under this category • Class III are those devices for which there is not enough information to show that general controls and performance standards would ensure their safety and effectiveness these include: • devices implanted in the body • life supporting or sustaining devices

22. Class III Devices • Intraocular lens • Heart valve • Infant radiant warmer • Ventricular bypass device • Blood cell separator • Pacemaker

23. Same or Novel

24. Same or Novel • The 510(k) paradox • Proving Equivalency • Different but not too different • If you goal is to run a business • Let the pendulum swing to approvable • Then iterate for improvements • Systems Approach to bringing device to market • Involve all the key stake holder from the beginning

25. Dealing with Design ChangesKnowing when to Stop

26. Knowing When to Stop • Drawing the line in the sand • Don’t wait for perfect! • Safe and effective • Be strict on setting release date goals

27. Key Points • Be familiar with the 510(k) regulations • Check for CDRH Guidance Documents: • Administrative • Device Specific • General Scientific Concerns • Software • EMC • Material Safety • Submission Checklists • Consider FDA-recognized consensus standards

28. Boston Scientific Expands Recall of Troubled Stent Boston Scientific Stent Recall Grows to 96K Units FDA won't expand recall of stents FDA Is Reviewing Reports of Trouble With Taxus Stent FDA Temperature up over Cordis Boston Scientific's Older Stents Draw Scrutiny of FDA Don’t look for Shortcuts Drug-coated stents may face additional FDA scrutiny

29. Discussion • Contact Information David J. Lennard • email: dlennard@axendia.com • phone: (215) 262-3582 Daniel R. Matlis • email: dmatlis@axendia.com • phone: (215) 262-8037 • website: www.axendia.com • Journal: http://LS-Panorama.axendia.com