Overview of FDA Regulation of Devices & Diagnostics

1. Overview of FDA Regulation of Devices & Diagnostics LARTA NIH-CAP Program Webinar February 2008 Michael A. Swit, Esq.Vice President

2. Standard Disclaimers • Views expressed here are solely mine and do not reflect those of my firm or any of its clients. • This presentation supports an oral briefing and may not be relied upon solely on its own to reach any conclusion of law or fact.

3. Regulatory Overview • Food and Drug Administration is the sole federal agency regulating safety and effectiveness for medical devices • Medical devices first regulated by FDA in 1938 • 1976 -- Major reform of regulations occurred in Device Amendments

4. Statutory Overview • Safe Medical Devices Act of 1990 (SMDA) • Problems with the “76” amendments; left a lot of leeway for industry to work around the more stringent requirements of the amendments • SMDA initiated more market entry “Gatekeeper” functions, enforcement and compliance, safety and post-marketing surveillance • Resulted in Quality System Regulation (QSR)

5. Statutory Overview • Medical Device Amendment of 1992 -- “tweaking of the law” • FDAMA -- Food and Drug Modernization Act of 1997 -- key theme -- FDA’s mission includes timely review and approval of beneficial new products • MDUFMA– 2002 -- User Fees and additional tweaks (e.g., combination products)

6. What is a Medical Device? • Section 201(h) of the FDCA defines a device as: … an instrument, apparatus implement, contrivance, implant, in vitro reagent, or other similar or related article, including components, parts or accessories which are; (1) Recognized in the National Formulary, or US Pharmacopeia (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease (3) intended to affect the structure or any function of the body and which does not achieve its primary intended purposes through chemical action within or on the body and which is not dependent upon being metabolizedfor the achievement of its primary intended purposes

7. Device Classification • Risk based • Class I -- includes devices with the lowest risk, subject to general controls –e.g., labeling, listing, QSRs, etc. • Class II -- includes devices for which general controls are insufficient to assure safety and effectiveness -- mandatory performance standards

8. Device Classification … • Class III -- devices with the greatest risk and insufficient information exists to assure safety and efficacy • generally require a PMA submission • “Post amendment” Class III devices considered substantially equivalent to pre-amendment devices may be marketed through the 510(k) process until FDA specifies PMA requirement • New technology – automatically into Class III, regardless of risk

9. Ways to Market a Medical Device • Premarket Approval (PMA) – for Class III devices • FDA has 180 days to review the PMA and make a determination of safety and effectiveness • Usually requires clinical studies • “510(k)” or “Premarket Notification” – for most Class II and some Class I devices • notify FDA 90 days prior to introducing a device into the US market • Must show “substantial equivalence” to a “predicate” device • General Controls – if PMA or 510k not required, go to market

10. Investigational Device Exemption (“IDE”) • Needed to conduct clinical studies of devices in most instances (there are exceptions) • Three basic types • Feasibility Study -- evaluate safety • Pilot Study -- effectiveness and optimization of clinical protocol • Pivotal Study -- expanded study with finished device and intended population

11. IDE … • Institutional Review Board (IRB) must review and approve IDE • IRB must make determination of significant risk vs non-significant risk device • Significant risk device -- one that presents a potential risk to the health, safety, or welfare of a human study subject. Includes devices used in supporting or sustaining human life or substantial importance in preventing impairment

12. IDE … • Examples of significant risk devices: • Implantable devices • CPR devices • Extended wear contact lenses • Injectable collagen • Intrauterine devices

13. IDE … • Examples of non-significant risk devices: • Daily-wear contact lenses • General hospital catheters • MRIs within FDA specified parameters • Limited classes of wound dressing Listing of significant and non-significant risk devices is available in “FDA Guidance for Institutional Review Boards and Clinical Investigators”

14. Premarket Approval Application (“PMA”) • Standard of Approval – • “…valid scientific evidence …there is reasonable assurance that the device is safe and effective…” • “Valid scientific evidence is evidence from well-controlled investigations …that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use…” • Two approaches to filing a PMA – • Traditional PMA • Full and complete filing in first instance • Initially reviewed by FDA scientist and experts to determine whether file is “administratively complete” and meets the requirements of 21 CFR Part 814, PMA is then officially filed

15. PMA … • Modular Approach • Sponsor is responsible for PMA “shell” -- outline of basic sections for PMA • Mechanism for interaction of sponsor with agency reviewers • Breaks the PMA into well-delineated components, stages or “modules” • Module reports filed when testing and analysis of particular module is complete

16. PMA -- Changes • Amendments: used to revise existing information, prior to approval • Supplement: changes that affect safety or effectiveness of the existing device such as intended use, labeling, packaging, sterilization • May require new clinical studies

17. 510(k) • Device is substantially equivalentif in comparison to predicate device, the new device has: • same intended use as predicate • same technological characteristics as predicate • if new device has different technological characteristics: • they do not raise new questions of safety and effectiveness; and • sponsor demonstrates that new device is as safe and effective as predicate

18. 510(k) & Substantial Equivalence • Substantial equivalence (“SE”) does not mean new device and predicate must be identical • SE -- established relative to intended use, design, energy used or delivered, materials, safety, performance, effectiveness, labeling, biocompatibility, standards and other applicable characteristics • Clinical studies -- about 10% of 510(k) need to show SE

19. 510(k) … • Who is required to submit -- • domestic manufactures introducing device to US markets • specification developers introducing device to US markets • repackers or relabelers who make a labeling change, or whose operations significantly affect device • foreign manufactures/exporters or US representatives offoreign /exporters introducing a device to US market

20. Types of 510(k) • Three types of 510(k) developed under “510(k) Paradigm” • Special 510(k) • Limited to certain circumstances and must contain a “Declaration of Conformity” with design control requirements • FDA intends to process special 510(k)s within 30 days of DCO receipt

21. Types of 510(k) … • Abbreviated 510(k)- manufacturer may choose if one of the following apply: • Guidance document exist • A special control has been established • FDA has recognized a relevant consensus standard • If relying on either a guidance document or special controls, manufacturer must provide a summary that describes adherence to such documents during development and testing of the device. • If relying on an FDA recognized standard, manufacturer must include “Declaration of Conformity” to the recognized standard • About 400 standards to which submitter can declare conformity

22. Types of 510(k) … • Traditional 510(k) -- No specific 510(k) form but there is an FDA suggested format • Steps to preparing a Traditional 510(k) • Find a predicate • If applicable use Guidance Documents • Prepare and format all contents • Assemble 510(k) • For more detailed information on preparing a Traditional 510(k) -- http://www.fda.gov/cdrh/devadvice/3143.html

23. Quality System Regulation • Instituted because Good Manufacturing Practices did not address “original design of device” • Needed pre-production design controls • New authority given to FDA to require manufacturers to have documented and validated design controls for the production of new devices

24. User Fees • First authorized in 2002 under the Medical Device User Fee and Modernization Act (MDUFMA) • Reauthorized through FY 2012 by Food & Drug Administration Amendments Act (“FDAAA”) • PMA -- $185,000 • PMA-Supp: $27,750 • 510(k) -- $3,404

25. Quality System Regulation • Places focus on post-marketing as well as pre-marketing activities • Prior to QSR going into effect, 44% of quality problems during a 6-year period attributed to design related defects

26. Quality System Inspection Technique • QSIT -- focuses on four major QS subsystems: • Management Controls • Design Controls • Corrective and Preventive Actions (CAPA) • Production and Process Controls • For more information and guidance on Quality System Regulation: http://www.fda.gov/cdrh/comp/gmp.html

27. Federal Device Hierarchy

28. Resources • Code of Federal Regulations (“CFR”) -- 21 Parts 800 to 1299 – Key provisions: • 801 – Labeling • 803 – Medical Device Reporting (“MDR”) • 807 – Registration, Listing, and 510(k) • 812 – IDE • 814 – PMA • 820 – QSR • 822 – Postmarket Surveillance • 860 – Classifications • FDA Website -- http://www.fda.gov/cdrh/devadvice

29. Questions? Call, e-mail, fax or write: Michael A. Swit, Esq. Vice President, Life Sciences THE WEINBERG GROUP INC. 336 North Coast Hwy. 101 Suite C Encinitas, CA 92024 Phone 760.633.3343 Fax 760.454.2979 Cell 760.815.4762 michael.swit@weinberggroup.com www.weinberggroup.com

30. About your speaker… Michael A. Swit, Esq., is a Vice President at THE WEINBERG GROUP, where he develops and ensures the execution of a broad array of regulatory and other services to clients, both directly and through outside counsel. His expertise includes product development strategies, compliance and enforcement initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and clinical research efforts for drug, biologic, device, IVD, and other life sciences companies, as well as those in the food and dietary supplement industries. Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience includes serving for three and a half years as corporate vice president, general counsel and secretary of Par Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius.Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.

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