Mission of the FDA

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2. Mission of the FDA To promote and protect the health of the public by ensuring the safety (or safety and effectiveness) of: food (except meat and poultry) prescription and non-prescription drugs medical devices radiation-emitting products animal feed, veterinary drugs and devices vaccines, transplant tissues, blood products cosmetics (except soap and shampoo)

4. Examples of electronic radiation emitting products that are also medical devices MRI CAT Scanners Surgical Lasers Diagnostic Ultrasound Microwave Diathermy Mammography Equipment Radiation Therapy Lithotriptors

5. The World of Devices 11,000,000 Americans have at least one medical device implant In the U.S. annually: >290,000 hip replacement surgeries >300,000 knee reconstructive implants >151,000 pacemaker implants >2,000,000 lens implant surgeries

6. History:Before the FDA

7. Harvey W. Wiley (1844-1930)

8. Mr. Wiley Goes to Washington

9. What is �misbranding�? �...the addition of any ingredients that would substitute for the food, conceal damage, pose a health hazard, or constitute a filthy or decomposed substance�

10. Wiley�s �Poison Squad� Experiments to test for effects of chemicals, food preservatives on human body Sets of 12 volunteers given 3 free meals a day Meals included: borax, salicylic acid, formaldehyde, sulfuric acid Weekly exams by medical doctors to check for symptoms

11. Wiley�s �Poison Squad� "O, they may get over it but they'll never look the same, That kind of bill of fare would drive most men insane. Next week he'll give them mothballs, a la Newburgh or else plain; O, they may get over it but they'll never look the same." Chorus from "Song of the Poison Squad," Lew Dockstader's Minstrels, October 1903

12. 1879 - 1906 Over 100 food and drug bills are put before Congress None of them are passed

13. Public Outrage

14. 1906 � Pure Food and Drugs Act Prohibited the interstate transport of unlawful (adulterated or misbranded) food and drugs Product labeling (not pre-market approval) Labels on packaging could not be false or misleading If a manufacturer opted to list weight or amount of food, it had to be accurate 11 �dangerous ingredients� could be used, but had to be listed on label (e.g., alcohol, heroin, cocaine)

15. 1912 1927 1930 Harvey Wiley resigns Takes over labs at Good Housekeeping Magazine Creates �Good Housekeeping Seal of Approval�

16. Bureau of Chemistry becomes the �Food, Drug, and Insecticide Administration�

17. Harvey Wiley dies Franklin Roosevelt elected president �Food, Drug, and Insecticide Administration� becomes the Food and Drug Administration Consumer protection groups & journalists pushing for a new and improved law 1912 1927 1930

18. �The American Chamber of Horrors� FDA assembles a traveling road-show of horrible products that were technically �legal� under the old, 1906 law

19. 1937 Tennessee company markets an �Elixir Sulfanilamide,� a wonder drug for children Drug contains chemical analog of antifreeze, kills >100 children Public outcry!!!

20. 1938: Food, Drug & Cosmetic Act Drug labels must include directions for safe use Required pre-market approval for new drugs to ensure safety Prohibited false therapeutic claims for drugs Authorized factory inspections FDA also given regulatory authority over medical devices (and cosmetics) for the first time Devices treated very similarly to drugs, except no pre-market approval for devices

21. 1976 Medical Device Amendments Prompted by Dalkon Shield IUD contraceptive device � caused injury, miscarriage, infertility Established three classes of medical devices Required safety and efficacy of all medical devices including diagnostic products Required manufacturers to register with FDA and follow quality control procedures Divided all devices into preamendment and postamendment Required pre-market approval for new (postamendment) devices

22. What does FDA do? Evaluate new devices for marketing Monitor devices already on the market Act against firms that violate the law Perform research on devices, develop standard testing methods Educate professionals and consumers on safe use of devices

23. What the FDA does not do test new medical devices; manufacturers do clear promotional materials for marketing see all medical devices; a large number of simple device types are exempt from review regulate medical procedures or how doctors choose to use devices

24. Evaluating New Devices for Marketing

25. What is a device?

26. What is a device? �an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory� [which is]: intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or 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 metabolized for the achievement of its primary intended purposes.�

27. 3 Classes of Device

28. Device Classification System Class I Devices whose safety & effectiveness are well-established Subject only to �General Controls� (registration, device listing, GMPs) About 40% of all devices are Class I Examples: elastic bandages, scalpels

29. Device Classification System Class II For devices which need �Special Controls� (guidances, postmarket surveillance, labeling, preclinical testing) About half of all devices are Class II Examples: daily-wear contact lenses, powered wheelchairs, bone cement

30. Device Classification System Class III Less than 10% of all devices are Class III Devices where general and special controls are insufficient to assure safety and effectiveness Devices that are life-sustaining, life-supporting, or present unreasonable risk of illness or injury Examples: heart valves, breast implants, refractive lasers

31. Getting A Device to Market:PMA or 510(k) For a new device: Pre-market Approval or PMA: Manufacturer must show safety and effectiveness of new device For a �Me Too� device: 510(k) Notification: Manufacturer must show substantial equivalence to marketed device

32. What is a 510(k)? Premarket Notification Section 510(k) of FD&C Act Is not the name of a specific form Allows FDA to determine substantial equivalence (SE)

33. Substantial Equivalence (SE) A device is found substantially equivalent (SE) if, in comparison to a legally marketed device, it: Has the same intended use, and Has the same technological characteristics as the pre-existing (predicate) device; or Does not raise new questions of safety and effectiveness, or demonstrates equal safety and effectiveness

34. Information Requested in 510(k) Proposed labels, labeling Indications for Use statement Truthful and Accurate statement Photographs, engineering drawings Statement of similarities and/or differences with predicate device

35. Information Requested in 510(k) Performance data (bench, animal, clinical) Sterilization, software, hardware information Clinical data only requested in 10-15% of all 510(k)�s Only needed if there is an important difference with the predicate device Must be collected under an IDE Investigation, similar to PMA�s

36. Devices Exempt from 510(k) Class I Exempt and Class II Exempt devices Unfinished Device Finished device not sold in U.S. Preamendment Device (before 1976) Veterinary Device

37. Class I Exemptions 74% of Class I devices are exempt Non-exempt Class I devices are: Those �intended for a use which is of substantial importance in preventing impairment of human health� Those that �present a potential unreasonable risk of illness or injury�

38. Class I Exemptions Examples of Exempt Class I devices: Stethoscopes Bone cement mixers Air conduction hearing aids Gauze Examples of Non-Exempt Class I devices Surgical gloves Hot or cold disposable pack Dental mercury Mechanical wheelchairs

39. Examples of Exempt Class II Devices Mercury thermometer Adjustable hospital beds Below-the-knee external artificial legs Powered heating pads Examples of Non-Exempt Class II Devices Bone conduction hearing aids Infusion pumps PMMA bone cements Blood pressure cuffs Class II Exemptions

40. For a New Device (in Class III): Premarket Approval (PMA) Valid Scientific Evidence showing safety and effectiveness Laboratory and Animal Research Clinical Research Getting A Device to Market:PMA

41. What is �valid scientific evidence�? Well-controlled investigations Partially controlled studies or studies without matched controls Well-documented case histories by qualified experts Reports of significant human experience with a marketed device

42. Clinical Trials - IDEs Studies on �significant risk� devices require an Investigational Device Exemption (IDE) Sponsors must usually complete bench, animal testing before proceeding to human IDE trials An IDE helps assure good study design Data from IDE studies are used to support PMAs and sometimes 510(k)s

43. Review Times FDA has 90 days to review a 510(k) FDA has 180 days to review a PMA--applicant must be notified within 45 days whether or not PMA can be reviewed FDA has 30 days to review an IDE

44. Monitoring Devices Already On the Market Important because pre-market testing may not always reveal: Long-term device durability Latent toxic effects Rare adverse effects User-related problems

45. When the Monitoring System Indicates a Problem FDA may: Use in-house laboratories to diagnose the problem and develop testing standards Alert health professionals and consumers about a use-related problem Require that additional warnings or information appear in the labeling Take regulatory action against the manufacturer

46. Acting Against Firms that Violate the Law FDA field investigators: Regularly inspect manufacturers to assure: Compliance with the law (Good Manufacturing Practice regulations) The device approved is what is actually being made Clinical studies guard against fraud and incompetence, and ensure that patients are protected (bioresearch monitoring)

47. Enforcement Actions Can Include Recalling the device Seizing the device Enjoining the firm Levying civil penalties Pursuing criminal prosecution Withdrawing the IDE Disqualifying the investigators

48. Current �Hot Topic� Devices Drug Eluting Stents Intervertebral Disc Replacements

49. Stents (& Drug Eluting Stents)

50. In-Stent Restenosis = Hyperplasia

51. Drug Eluting Stents

52. Challenges Stents weren�t originally designed to carry drugs Drugs weren�t originally designed to be delivered on stents Combination Product � drugs and device

53. Drug Eluting Stents

54. Spinal Implants

55. Total Disc Replacements

56. Total Disc Replacements Metal-on-Metal Metal-on-Polymer Multiaxial loads, motions Wear testing required! Standard test methods needed!