FDA Regulatory Requirements to Market Medical Devices in the United States (U.S.)

1. FDA Regulatory Requirements to Market Medical Devices in the United States (U.S.) Carole C. Carey Director CDRH International Staff U.S. FDA Center for Devices and Radiological Health

2. Outline • Who are we? What we do? (structure and background • Device classification, level of regulatory controls, pathways to market, postmarket requirements • Others: importation, medical device provisions of FDAAA 2007, in recent news…

3. U.S. Food and Drug Administration (US FDA) Department of Health and Human Services Scientific, Regulatory, Public Health Agency that oversees items accounting for 25 cents of every dollar spent by consumers. Mission: • Protect and Promote Public Health • Cooperate/Harmonize with other countries • Collaborate with scientific experts, clinical researchers, academia, industry and consumers http://www.fda.gov/

4. 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 Office of Regulatory Affairs Lead for field activities National Center for Toxicological Research 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 US FDA Organization

5. FDA Definition of a “Device” Section 201(h) of the FD&C Act • An instrument, apparatus, implement, machine, contrivance, implant, in-vitro reagent, or other similar or related article… • which is intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease, or • Intended to affect the structure or any function of the body of man and other animals

6. FDA Definition of a Medical Device Section 201(h) of the FD&C Act (cont’d) • Andwhich does not achieve its primary intended purposes through chemical reaction within or on the body. • Is notmetabolized to achieve its primary intended purposes.

7. “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.

8. CDRH MissionBalancing 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.

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

10. 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

11. 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

12. Tiered Risk-based DeviceClassification Scheme 1700 generic type of devices

13. 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

14. Regulatory Class Determines the Premarket submission • Class I – exempt from premarket review unless 510(k) or premarket notification is required by regulation • Class II – 510(k) required unless exempt from 510(k) requirements by regulation • Class III – Premarket Approval (PMA) – demonstrate safety and effectiveness without relying on a grandfathered predicate device

15. Go to Similarities/Differences Global Regulatory Approaches

16. ISO 13485 • International standard’s main goal of ISO 13485 is to provide a harmonized model • that specifies quality management system requirements for medical device manufacturers in the international market. • ISO 13485 2003 has replaced ISO 13485 1996. Return to Chart

17. CE Marking • Conformite Europene • A mark (visible declaration) by the manufacturer that the equipment complies with the requirements of the applicable directives. • Products circulate freely within the EU member countries. Return to Chart

18. NCAR • National Competent Authority Reporting • Also known as Adverse Event Reporting Exchange • Final Document at GHTF website http://www.ghtf.org/documents/sg2/SG2-N79-R8-2006-NCAR-Report-Form-FINAL.pdf “Medical Devices: Post Market Surveillance: National Competent Authority Report Exchange Criteria and Report Form” Return to Chart

19. Three Main Pathways to Enter the U.S. Market • Premarket Notification or 510(k) • Premarket Approval (PMA) • Humanitarian Device Exemption (HDE) Note: The route to market for preamendment Class III devices in which PMA’s have not been called for is a 510(k). Examples: Automated external defibrillator, Ventricular bypass (assist) device, electroconvulsive therapy device.

20. What is a 510(k) [Premarket Notification]? • Most common path to market medical devices. • FDA review to determine “substantial equivalence” (SE) to a predicate device. • Preamendment devices (Legally marketed prior to May 28, 1976) and for which PMA’s have not been required. • Postamendment devices (marketed after May 28, 1976) • SE means same intended use, same technological characteristics (if different, does not raise different S&E questions), as safe and effective as the predicate device.

21. 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 (now electronic) 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)

22. 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)

23. 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

24. 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. Humanitarian Device Exemption • An incentive for development of devices intended for treatment or diagnosis, in small populations where otherwise a device manufacturer’s R&D costs could exceed market returns • Fewer than 4,000 patients annually • Do not pose unreasonable risk of illness or injury (i.e., safety) and probable benefit outweighs the risk. Example: (14-Feb-1997) Harrison Fetal Bladder Stent Set (Lowery Modification) Cook OB/GYN®, Spencer, IN 47460For fetal urinary tract decompression following the diagnosis of fetal post-vesicular obstructive uropathy in fetuses of 18 to 32 weeks gestational age

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

27. 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

28. 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 • eMDR • FDA CDRH eSubmitter (CeSub) provides the 3500A form in an electronic format • Health Level 7 (HL7) format for Individual Case Safety Report

29. 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

30. Enforcement • 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:

31. Subject to examination by FDA even if the product is authorized for marketing in another country. Devices must be safe and effective. Must contain informative and truthful labeling in English. Imported products are required to meet the same standards as domestic goods. Appropriate Marketing Applications unless exempt 510(k) PMA Establishment Registration & Medical Device Listing Compliant Labeling GMP/Quality Systems Adverse Event Reporting, Records/Complaint Files Legal Importation of Medical Devices Section 801(a)-(d) of the FD&C Act

32. Foreign Medical Device Establishments (8/21/09) not included are the Unclassified data I II III R L R L R L

33. 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

34. 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

35. Summary: 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 medical device classification determines the level of regulatory control and the type of premarket submission. • There are 3 pathways to market. Once in the market, there are postmarket regulatory requirements.

36. Thank you! Contact Information Carole C. Carey Director, CDRH International Staff Medical Devices Coordinator for Global HBD (Harmonization By Doing) Programs 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