How does the U.S. FDA Regulate Medical Devices?

1. How does the U.S. FDA Regulate Medical Devices? Carole C. Carey Director CDRH International Staff U.S. FDA Center for Devices and Radiological Health

2. Learning Objectives To have an awareness and basic understanding of the FDA’s legal authority, regulatory framework, principles, and approach in the management and supervision of medical devices & radiation-emitting devices marketed in the U.S.

3. Outline • Who are we? • What, who and why do we regulate? • How do we do it? • What we do • Premarket • Postmarket • Enforcement

4. Departmentof Health & Human Services

5. U.S. Food and Drug Administration • Scientific • Regulatory • Public Health Agency that oversees items accounting for 25 cents of every dollar spent by consumers. • Protect and Promote Public Health. http://www.fda.gov/

6. Center for Food Safety & Nutrition (CFSAN) Food and Cosmetics Center for Drugs & Evaluation Research (CDER) Drugs Center for Biologics & Biologics Research (CBER) Biologics, Vaccines Center for Veterinary Medicine (CVM) Animal Feed and Drugs Center for Devices & Radiological Health (CDRH) Medical devices Radiation- emitting products Combination Products are (drug-device* biologic-device*drug-biologic) NEWLY Established!!FDA Center for Tobacco Products U.S. FDA Centers and Regulated Products

7. Division of Small Manufacturers, International, and Consumer Assistance dsmica@fda.hhs.gov

8. U.S. Medical Device Industry According to the US Census Bureau, there are over 12,000 medical device manufacturing firms in the US.* Employees Per Firm* Smallest Firms * Source: Census Bureau, Number of Firms, Number of Establishments, Employment, and Annual Payroll by Employment Size of the Enterprise for the United States, All Industries 2005 using NAICS codes 339111,339112, 339113, 339114, 339115, 339116, 334517, 334510, 325413 http://www.census.gov/csd/susb/susb05.htm

9. “CDRH protects American citizens go about their daily lives with safety measures in place so that medical devices and radiological products are reasonably safe and effective as intended.” Medical devicesPacemakers, Contact Lenses, Hearing Aids... In-vitro diagnostic devices (lab tests and home use tests) Radiation-Emitting Products Lasers, Microwaves... Combination ProductsDrug eluting stents… FDA CDRH Regulates All Medical Devices in the U.S.

10. Federal Food Drug and Cosmetic Act (FDCA) Medical Device Amendments (MDA) Act ***May 28, 1976*** Radiation Control for Health and SafetyAct of 1968 Authority to protect unnecessary human exposure to radiation from medical and non-medical products in the home, industry. The Code of Federal Regulations (CFR) Title 21 Code of Federal Regulations Parts 800 – 1299medical devices Title 21 of the Code of Federal RegulationsParts 1000 – 1050electronic product radiation Legal Framework: FDA’s Authority

11. Regulatory Approach • Base degree of control on risk • Weigh probable benefit vs. risk to determine safety and effectiveness • Use valid scientific evidence • Consider least burdensome means • Provide “reasonable assurance”

12. 1. Three Tier Classification Scheme • “Medical devices are classified into 3 classes and regulated according to their complexity and degree of risk to the public health.” 1976 Medical Device Amendments Act • Two pathways to market • Show as safe and as effective as device on the market on May 28, 1976; (510k) or premarket notification. • Prove device is safe and effective; (PMA) or premarket approval • Good manufacturing Practices

13. Examples of Device Classes Medical Device Classes: Class I General Controls Most exempt from premarket submission Class II Special Controls Premarket Notification [510(k)] Class III Require Premarket Approval [PMA]

14. 862 Clinical chemistry and clinical toxicology 864 Hematology and pathology 866 Immunology and microbiology 868 Anesthesiology 870 Cardiovascular 872 Dental 874 Ear, nose and throat 876 Gastroenterology & urology devices 878 General and plastic surgery 880 General hospital and personal use 882 Neurological 884 Obstetrical and gynecological 886 Ophthalmic 888 Orthopedic 890 Physical medicine 892 Radiology Sixteen Device Specialty Categories21 CFR (part 800-1299) Medical Device Definition in Sec 201(h) of the FD&C Act 895 Banned devices

15. Class I / II ExemptionsFD&C Act 513(d)(2A) • Over 800 generic types of Class I devices and 60 Class II devices are exempted from the premarket notification requirement http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm • Devices exempt from 510(k) are: • “preamendment devices” not significantly changed or modified; or • Class I/II devices specifically exempted by regulation. • 510(k) Exempt Devices - approximately 47% Class I - 93% (stethoscope, spectacle lens/frame) Class II - 9% (radiologic table, dental noble metal alloy) Not all Exempt devices are exempt from GMP

16. Basic authorities that provide FDA with the means to regulate medical devices. Applies to all medical devices regardless of classification; all subject to premarket and postmarket regulatory controls. Premarket notification or 510(k), if not exempt Register and List Labeling requirements Prohibit Misbranding Prohibit Adulteration Quality Systems /GMP Records and Reports / (MDR) Report device failures Corrective action plans What are General Controls?(Class I, II, III devices)

17. Postmarket Surveillance Study Patient Registries Guidelines (e.g., Glove Manual) Mandatory Performance Standard Recommendations or Other Actions Special Labeling (e.g., 882.5970, Cranial Orthosis) General controls alone are insufficient to assure safety and effectiveness of Class II devices Existing methods are available to provide such assurances. Special controls may include special labeling requirements, mandatory performance standards, tracking and postmarket surveillance. A few Class II devices are exempt from the premarket notification. What are Special Controls?(Class II devices)

18. Class III Premarket Approval • A demonstration of safety and effectiveness supported by component level tests, bench tests, clinical data (may include animal study) • IDE (investigational device exemption) allows study of unapproved devices • New, high-risk devices, may have new indications, predicate device does not apply • Labeling, Instructions for Use, Training requirements

19. Risk-based ClassificationLevel of Regulatory Control 1700 generic type of devices

20. 2. Balancing Risks and Benefits … while keeping unsafe and ineffective devices out of the market. Getting safe and effective devices to market as quickly as possible… Benefits Risks Helping the public get science-based accurate information about medical devices and radiological products needed to improve health.

21. 1990 SMDA (Safe Medical Devices Act) Required user facilities (hospitals) to report adverse events Mandated postmarket surveillance for certain devices FDA may order a recall Established humanitarian device exemption process 1997 FDAMA ( FDA Modernization Act) Allows exemption of Class I devices “Third party” review Risk-based approach to postmarket surveillance MedSun Program (a network of reporting facilities) Quality System Regulation effective CDRH Health Milestones“practicing risk-based”

22. Reclassification, another example of risk-based approach • As experience and knowledge about a device increase, FDA may calibrate theoriginal classificationand readjustbased on FDA’s receipt of new information. • May be an “up” classification or a “down” classification • If reclassified to a lower class, must convince the FDA that less stringent class requirements will be sufficient to provide reasonable assurance of safety and effectiveness.

23. Example of “Down” Classification • Arrhythmia detectors and alarms were originally classified as Class III devices • Down classified to Class II with special controls sufficient to mitigate risks to patients. • “Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Arrhythmia Detector and Alarm” (October 28, 2003) It is important to describe what is to be reclassified.

24. 3. Use valid scientific evidence Effectiveness is to be determined by: • Well-controlled investigationsOne or more clinical investigations where appropriate • Well documented case histories by qualified experts • Other valid scientific evidence, if acceptable (e.g., reports of significant human experience, non-clinical data, etc.). • Does NOT include • Isolated case reports • Random experience • Reports lacking sufficient details • Unsubstantiated opinions [§513(a)(3)] 21 CFR 860.7

25. 4. Consider Least Burdensome Means • “Least Burdensome” concept, FDAMA 1997 • help to expedite the availability of new device technologies without compromising scientific integrity in the decision-making process or FDA’s ability to protect the public health. • Guidance The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085994.htm

26. 5. Provide “reasonable assurance” “No regulatory mechanism can guarantee that a product will never cause injury, or will always produce effective results. Rather, the objective of the legislation is . . . reasonable assurance that medical devices are safe and effective.” -- Report by the House Committee on Interstate and Foreign Commerce, to accompany the Medical Device Amendments of 1976

27. “Total Product Life Cycle” Vision applied across Center activities

28. Postmarketing Requirements • Quality System/GMP • Adverse Event Reporting • Postmarket surveillance

29. Quality System (QS) Regulation (21 CFR Part 820) Quality Assurance System covering the design and manufacture of medical devices sold in the U.S. • Similar to ISO 13485 • Standard for audit of device establishment

30. Medical Device Reporting (MDR)“Adverse Event Reporting”(21 CFR Part 803) • Mechanism for FDA to identify and monitor significant adverse events involving medical devices Events: Death, Serious Injury and Malfunction Reported by: Manufacturer, User Facility, and Importers of medical devices

31. Postmarket Surveillance • Postapproval Studies for various permanent implants after approval to monitor unexpected problems • Device Tracking - system for locating permanent implants/life-sustaining devices after they leave the hospital

32. Enforcement and the Office of Compliance • Ensuring compliance with applicable laws and regulations • Enforcement, when needed • Mitigating risks to the public health Protect the public health by ensuring that device and radiological health products are safe and effective by:

33. A CT scan is a special X-ray procedure, where a computer collects the information from the X-rays and produces images or pictures of cross-sections through the head or the body. Regulatory Requirements for Radiation-Emitting Devices

34. Sunlamps Ultrasound therapy Laser therapy and surgical devices Radiation therapy Microwave or ultrasound diathermy devices Microwave blood warmers or sterilizers Ultraviolet dental curing devices Televisions receivers and monitors (cathode ray tubes only) X-ray security systems Microwave ovens Laser products ( CD players, light shows, welding lasers) Metal halide lighting Cordless and cellular telephones Industrial RF sealers of plastics and laminates Medical and Non-Medical Products

35. CT System as a medical device Class II device (General & Special Controls) • Submit Premarket notification or 510k • Meet device safety & effectiveness requirements “substantially equivalent” in characteristics, performance and safety • Manufacturer establishment registration & Device listing • Good manufacturing practices/(QS) regulations • Labeling • Continue to be cleared for marketing for general imaging purposes • A new indication such as CT scanning for whole-body screening for individuals without symptoms will require a PMA

36. Comply with minimum radiation safety requirements of the performance standard (including labeling) for diagnostic x-ray systems CT equipment Manufacturers must provide certification meeting the standards. Certification is not an FDA approval! 21 CFR PART 1020 Performance Standards for ionizing radiation § 1020.10 - Television receivers. § 1020.20 - Cold-cathode gas discharge tubes. § 1020.30 - Diagnostic x-ray systems and their major components. § 1020.31 - Radiographic equipment. § 1020.32 - Fluoroscopic equipment. § 1020.33 - Computed tomography (CT) equipment. § 1020.40 - Cabinet x-ray systems. CT system as a radiation-emitting device

37. Regulations under the laws control the requirements The responsibility for the safety regulation of radiation-emitting electronic products is shared. • FDA regulates the level of controls and requirements on the manufacture of the CT systems. • The use of CT systems for medical purposes is controlled, in the U.S. largely at the state & local government level. • Practice of medicine • License of the medical practitioners • License or register facilities operating x-ray system

38. Reporting RequirementsApplies to products listed in Table 1 of 21CFR, 1002.1 • 21 CFR 1002.10, 11, 12 Product Reports (Initial, Supplemental, Abbreviated) • Documents information on manner of conformity to standards, labeling, test instrumentation, test procedures, quality control, • Must be submitted at least one month before actual shipment to commerce. • 21 CFR 1002.13 Annual Reports • Documents annual production, results of testing, and user safety concerns In our case example, a CT system will require an Initial, Supplemental and Annual Reports

39. 2007 FDA Amendments ActMedical Device Provisions • 2007 Amendments, Medical Device User Fee • Electronic Registration and Listing System • Requires Establishment of Unique Device Identification (UDI) system • Streamlines Inspection by Accredited Persons • Promotes Development of Pediatric Devices • FDAAA sunsets on October 01, 2012

40. To summarize, in the U.S. all medical devices are regulated by FDA A risk-basedregulatory paradigm is used to establish reasonable assurance of safety and effectiveness. The law gives us the flexibility to balance out our regulatory way of thinking to the level of potential risk posed by new products, new technology, inspections, postmarket surveillance, etc.

41. In Recent News…. FDA Proposes Mandatory Electronic Safety ReportingNew Rules will Help Strengthen Postmarket Safety Data Collection, August 20, 2009 FDA to Review Medical Devices Marketed Prior to 1976 Action Addresses GAO Recommendation, April 9, 2009

42. Thank you! Contact Information Carole C. Carey Director, CDRH International Staff FDA Federal Research Center at White Oak, WO 66, R-4618 Direct: 1- 301-796-5708 10903 New Hampshire Ave. Fax : 1- 301-847-8149 Silver Spring, MD 20993-0002 carole.carey@fda.hhs.gov U.S.A