1. INTRODUCTION Medical Devices ©2014 Salt Lake Community College. All rights reserved.

2. FDA REVIEW Medical Devices ©2014 Salt Lake Community College. All rights reserved.

3. MAKING SENSE OF IT ALL ©2014 Salt Lake Community College. All rights reserved. Company FDA Laws (U.S.C.) Industry-Specific CFRs Other 21 CFR 800’s Quality Management System Government Med Device Industry ISO Standards 21 CFR 820 ISO Non-gov’t Organization Other Operational Requirements 21 CFR 814 Premarket Approvals

4. FDA OVERVIEW An agency of Department of Health and Human Services Mission: 1.“responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation” ©2014 Salt Lake Community College. All rights reserved.

5. FDA OVERVIEW (cont.) Mission (cont.) : 2.“responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health” ©2014 Salt Lake Community College. All rights reserved.

6. FDA ORGANIZATION (cont.) FDA Subdivisions: SubdivisionResponsibility Office of the Commissioner Program administration Office of Regulatory Affairs Enforces FDA regulations, monitors industry for compliance, recalls Center for Biologics Evaluation & Research (CBER) Assorted biological products/biologics (these replicate natural human substances): allergenic extracts for shots, blood & blood components, gene therapy products, transplant-related human tissue and cellular products, vaccines ©2014 Salt Lake Community College. All rights reserved.

7. FDA Subdivisions (continued): SubdivisionResponsibility Center for Drug Evaluation & Research (CDER) Drugs (purely chemical substances), therapeutic biological products (e.g. monoclonal Abs, cytokines, growth factors, enzymes, thrombolytics, proteins [natural or recombinant] extracted from animals for therapeutic use, non-vaccine therapeutic immunotherapies Center for Devices & Radiological Health (CDRH) Medical devices (e.g. catheters, breast pumps, contact lenses, lab instrumentation), diagnostic test kits, GMP, compliance, postmarket tracking, radiological health screening procedures (mammography, whole body CT scanning, medical imaging) FDA ORGANIZATION (cont. 2) ©2014 Salt Lake Community College. All rights reserved.

8. FDA ORGANIZATION (cont. 3) FDA Subdivisions (continued): SubdivisionResponsibility Center for Food Safety & Applied Nutrition (CFSAN) Various food products, GMOs, cosmetics, dietary supplements, infant formula, foodborne illness, food labeling & nutrition Center for Veterinary Medicine (CVM) Food additives and drugs given to animals; animals from which human foods are derived ©2014 Salt Lake Community College. All rights reserved.

9. THE LAWS & CODE OF FEDERAL REGULATIONS ©2014 Salt Lake Community College. All rights reserved.

10. LAWS → REGULATIONS FDA United States Code (U.S.C.) – Title 21 US Federal Gov’t Code of Federal Regulations (CFRs) – Title 21, Food & Drugs Promulgated in Federal Register Laws Codified ©2014 Salt Lake Community College. All rights reserved.

11. 21 CFR OVERVIEW PartsCovers 100 seriesFood – 110 cGMPs ; Dietary supplemts – 111 cGMPs 200 & 300 seriesPharmaceuticals – 210 & 211 cGMPs 500 seriesAnimal feeds & medications 600 seriesBiological products – 606 cGMPs 700 seriesCosmetics (limited regulations) 800 seriesMedical devices – 820 cGMPs 900 seriesMammography quality requirements 1000 seriesRadiation emitting device 1200 seriesNon-FD&C Act rulings OtherGLP – 58; GCP – 50, 54, 56; Electronic Records – 11 ©2014 Salt Lake Community College. All rights reserved.

12. THE COMPANY’S OBLIGATIONS ©2014 Salt Lake Community College. All rights reserved.

13. QUALITY MANAGEMENT SYSTEM Per Part 820 of Title 21 of the Code of Federal Regulations (21 CFR 820) Covered in Quality course ©2014 Salt Lake Community College. All rights reserved.

14. FDA PREMARKET APPROVALS Per Part 814 of Title 21 of the Code of Federal Regulations (21 CFR 814) ©2014 Salt Lake Community College. All rights reserved.

15. OPERATIONAL REQUIREMENTS All legal requirements are specified in Part 800 series of Title 21 of the Code of Federal Regulations (21 CFR 800 series)21 CFR 800 series ©2014 Salt Lake Community College. All rights reserved.

16. OVERALL GOAL = COMPLIANCE ©2014 Salt Lake Community College. All rights reserved. How ?

17. INTERPRETING REGULATIONS ©2014 Salt Lake Community College. All rights reserved. 1.What message does this sign convey? 2.What (exactly) will you do to comply?

18. MAKING SENSE OF IT ALL ©2014 Salt Lake Community College. All rights reserved. Company FDA Laws (U.S.C.) Industry-Specific CFRs Other 21 CFR 800’s Quality Management System Government Med Device Industry ISO Standards 21 CFR 820 ISO Non-gov’t Organization Other Operational Requirements 21 CFR 814 Premarket Approvals

19. COMPLIANCE REQUIRES AND UNDERSTANDING OF... The FDA The relevant laws and portions of the Code of Federal Regulations Good Manufacturing Practices How to implement a quality management system Fulfilling other operational requirements ©2014 Salt Lake Community College. All rights reserved.

20. WHEN COMPANIES ARE NOT COMPLIANT ©2014 Salt Lake Community College. All rights reserved.

21. 2013 TOP 10 INSPECTION VIOLATIONS – MEDICAL DEVICE ©2014 Salt Lake Community College. All rights reserved. Cite Id Ref No FrequencyShort DescriptionLong Description 3130 21 CFR 820.100(a) 378 Lack of or inadequate procedures Procedures for corrective and preventive action have not been [adequately] established. Specifically, *** 14713 21 CFR 820.198(a) 245 Lack of or inadequate complaint procedures Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been [adequately] established. Specifically,*** 3696 21 CFR 820.100(b) 133Documentation Corrective and preventive action activities and/or results have not been [adequately] documented. Specifically, *** 546 21 CFR 820.75(a) 127 Lack of or inadequate process validation A process whose results cannot be fully verified by subsequent inspection and test has not been [adequately] validated according to established procedures. Specifically, *** 630 21 CFR 803.17 124 Lack of Written MDR Procedures Written MDR procedures have not been [developed] [maintained] [implemented]. Specifically, ***

22. 2013 TOP 10 INSPECTION VIOLATIONS – MEDICAL DEVICE ©2014 Salt Lake Community College. All rights reserved. Cite Id Ref No FrequencyShort DescriptionLong Description 479 21 CFR 820.50 110 Purchasing controls, Lack of or inadequate procedures Procedures to ensure that all purchased or otherwise received product and services conform to specified requirements have not been [adequately] established. Specifically, *** 3282 21 CFR 820.90(a) 98 Nonconforming product, Lack of or inadequate procedures Procedures have not been [adequately] established to control product that does not conform to specified requirements. Specifically, *** 3103 21 CFR 820.30(i) 93 Design changes - Lack of or Inadequate Procedures Procedures for design change have not been [adequately] established. Specifically,*** 3331 21 CFR 820.181 77 DMR - not or inadequately maintained A device master record has not been [adequately] maintained. Specifically, *** 2327 21 CFR 820.22 73 Quality audits - Lack of or inadequate procedures Procedures for quality audits have not been [adequately] established. Specifically, *** (cont.)

23. 21 CFR 800 SERIES – IN-DEPTH LOOK ©2014 Salt Lake Community College. All rights reserved.

24. 21 CFR 800 SERIES Digging deeper into each parteach part ©2014 Salt Lake Community College. All rights reserved. 800 860 861 862 864 866 868 870 872 874 876

25. 21 CFR 800 General Key points? ©2014 Salt Lake Community College. All rights reserved.

26. 21 CFR 860 Medical Device Classification Procedures Key points? ©2014 Salt Lake Community College. All rights reserved.

27. 21 CFR 861 Procedures for Performance Standards Development Key points? ©2014 Salt Lake Community College. All rights reserved.

28. 21 CFR 862 Clinical Chemistry and Clinical Toxicology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

29. 21 CFR 864 Hematology and Pathology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

30. 21 CFR 866 Immunology and Microbiology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

31. 21 CFR 868 Anesthesiology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

32. 21 CFR 870 Cardiovascular Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

33. 21 CFR 872 Dental Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

34. 21 CFR 874 Ear, Nose, and Throat Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

35. 21 CFR 876 Gastroenterology-Urology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

36. 21 CFR 800 SERIES – IN-DEPTH LOOK ©2014 Salt Lake Community College. All rights reserved.

37. 21 CFR 800 SERIES Digging deeper into each parteach part ©2014 Salt Lake Community College. All rights reserved. 878 880 882 884 886 888 890 892 895 898

38. 21 CFR 878 General and Plastic Surgery Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

39. 21 CFR 880 General Hospital and Personal Use Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

40. 21 CFR 882 Neurological Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

41. 21 CFR 884 Obstetrical and Gynecological Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

42. 21 CFR 886 Ophthalmic Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

43. 21 CFR 888 Orthopedic Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

44. 21 CFR 890 Physical Medicine Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

45. 21 CFR 892 Radiology Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

46. 21 CFR 895 Banned Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

47. 21 CFR 898 Performance Standard for Electrode Lead Wires and Patient Cables Key points? ©2014 Salt Lake Community College. All rights reserved.

48. 21 CFR 800 SERIES – IN-DEPTH LOOK ©2014 Salt Lake Community College. All rights reserved.

49. 21 CFR 800 SERIES Digging deeper into each parteach part ©2014 Salt Lake Community College. All rights reserved. 801 803 806 807 808 809 810

50. 21 CFR 801 Labeling Key points? ©2014 Salt Lake Community College. All rights reserved.

51. 21 CFR 803 Medical Device Reporting Key points? ©2014 Salt Lake Community College. All rights reserved.

52. 21 CFR 806 Medical Devices; Reports of Corrections and Removals Key points? ©2014 Salt Lake Community College. All rights reserved.

53. 21 CFR 807 Establishment Registration and Device Listing for Manufacturers and Initial Importers of Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

54. 21 CFR 808 Exemptions from Federal Preemption of State and Local Medical Device Requirements Key points? ©2014 Salt Lake Community College. All rights reserved.

55. 21 CFR 809 In vitro Diagnostic Products for Human Use Key points? ©2014 Salt Lake Community College. All rights reserved.

56. 21 CFR 810 Medical Device Recall Authority Key points? ©2014 Salt Lake Community College. All rights reserved.

57. 21 CFR 800 SERIES – IN-DEPTH LOOK ©2014 Salt Lake Community College. All rights reserved.

58. 21 CFR 800 SERIES Digging deeper into each parteach part ©2014 Salt Lake Community College. All rights reserved. 812 814 821 822 830

59. 21 CFR 812 Investigational Device Exemptions Key points? ©2014 Salt Lake Community College. All rights reserved.

60. 21 CFR 814 Premarket Approval of Medical Devices Key points? ©2014 Salt Lake Community College. All rights reserved.

61. 21 CFR 821 Medical Device Tracking Requirements Key points? ©2014 Salt Lake Community College. All rights reserved.

62. 21 CFR 822 Postmarket Surveillance Key points? ©2014 Salt Lake Community College. All rights reserved.

63. 21 CFR 830 Unique Device Identification Key points? ©2014 Salt Lake Community College. All rights reserved.

64. INTRODUCTION TO REGULATORY AFFAIRS ©2014 Salt Lake Community College. All rights reserved.

65. MEDICAL DEVICE APPROVALS Medical Devices Application TypePurpose Investigational Device Exemption (IDE) To request exemption of approved marketing application for shipping investigational device across state lines for clinical trials; clinical trials typically required to support premarket approvals, but occasionally needed to support premarket notifications Premarket Notification (PMN) / 510(k) Clearance To request clearance to sell and market non-exempt Class I or Class II device in US that is substantially equivalent to a legally marketed (predicate) device Premarket Approval (PMA) To request approval to sell and market non- preamendment Class III device in US ©2014 Salt Lake Community College. All rights reserved.

66. MEDICAL DEVICE APPROVALS (cont.) Medical Devices... 2 Application TypePurpose Humanitarian Device Exemption (HDE) To request exemption of certain requirements to sell and market humanitarian use device (HUD) in US that is intended to benefit patients through treatment or diagnosis of disease or condition affecting < 4,000 individuals per year; like a PMA but exempt from proof of effectiveness requirement ©2014 Salt Lake Community College. All rights reserved.

67. MEDICAL DEVICE APPROVALS (cont. 2) Medical Device Notes Device classification: o Dependent on intended use and indications for use o Over 1,700 distinct devices, grouped into 16 medical specialty panels [per 21 CFR 862-892], have been classified o 3 classes: Class I, Class II, and Class III, with regulatory control increasing from I to III – see: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance /Overview/GeneralandSpecialControls/default.htm ©2014 Salt Lake Community College. All rights reserved.

68. MEDICAL DEVICE APPROVALS (cont. 3) Medical Device Notes (cont.) Device ClassDefinition Class I Low risk Most (~74%) are exempt but non-exempt require PMN / 510(k) Exempt manufacturers must still register establishment and list generic category or classification name Exempt devices not exempt from GMP requirements; however, some are GMP exempt but not from records and complaint files Some exempt devices have limitations to exemption status Subject to general controls ©2014 Salt Lake Community College. All rights reserved.

69. MEDICAL DEVICE APPROVALS (cont. 4) Medical Device Notes (cont.) Device ClassDefinition Class II Moderate risk Most are not exempt and usually require PMN / 510(k) Some are exempt, but not from GMP requirements Subject to general controls, and special controls to assure safety and effectiveness Class III High risk - pose significant risk of illness or injury (devices usually support or sustain human life); OR not substantially equivalent to Class I or Class II predicate Not exempt and require PMA unless a preamendment (pre May 28, 1976) device Subject to general controls with PMA ©2014 Salt Lake Community College. All rights reserved.

70. MEDICAL DEVICE APPROVALS (cont. 5) Medical Device Notes Substantial equivalence: if, in comparison to predicate o Has same intended use AND technological characteristics o Has same intended use BUT different technological characteristics that are supported by data that (1) shows device is at least as safe and effective as predicate AND (2) does not raise new safety and effectiveness questions ©2014 Salt Lake Community College. All rights reserved.

71. APPROVED / CLEARED DEVICES Approved devices (PMA) Cleared devices (510(k)) Humanitarian device exemptions (HDE) ©2014 Salt Lake Community College. All rights reserved.

72. POSTMARKET REQUIREMENTS Medical Device Reporting Manufacturer and User Facility Device Experience (MAUDE) Database – searchable Medical Device Tracking Recalls / Corrections / Removals Current recalls listed Medical Device Registration and Listing Postmarket Surveillance Post-Approval Studies ©2014 Salt Lake Community College. All rights reserved.