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

2. QUALITY SYSTEM Required by the FDA per 21 CFR 820.5 quality system Quality system – Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured, and that meets the requirements of this part. ©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. WHY A QUALITY SYSTEM ? To provide a framework within which a company can operate in a consistent manner toward regulation-compliant goals and outcomes ©2014 Salt Lake Community College. All rights reserved.

5. REMEMBER INTERPRETING REGULATIONS ? ©2014 Salt Lake Community College. All rights reserved. 1. Goal(s) will depend on the company’s interpretation 2. Outcome(s) will depend on how well company operations are executed

6. QUALITY SYSTEM BENEFITS By establishing a quality system (based on appropriate interpretation of regulations), a company is setting the ground rules to guide the work of its employees By following the quality system, employees ensure work is done in a compliant manner Thus, a quality system helps achieve regulatory compliance ©2014 Salt Lake Community College. All rights reserved.

7. WHAT IF... A poor quality system was established ? The quality system was not followed by all employees? ©2014 Salt Lake Community College. All rights reserved.

8. THEN... ©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, ***

9. ©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, *** THEN... (cont.)

10. CONSEQUENCES OF NON-COMPLIANCE Need to fix the issues – e.g. corrective/ preventive actions, quality system improvements, employee training Or else:  Warning letter  Seizure  Injunction  Fines  Criminal prosecution ©2014 Salt Lake Community College. All rights reserved.

11. WHAT DOES A QUALITY SYSTEM COVER? ©2014 Salt Lake Community College. All rights reserved.

12. THE FDA SAYS... In 21 CFR 820 – Quality System RegulationQuality System Regulation *** The QSR is considered to be the GMP for Medical Devices ©2014 Salt Lake Community College. All rights reserved.

13. 21 CFR 820 SUBPARTS A.General Provisions B.Quality System Requirements C.Design Controls D.Document Controls E.Purchasing Controls F.Identification and Traceability G.Production and Process Controls H.Acceptance Activities ©2014 Salt Lake Community College. All rights reserved.

14. 21 CFR 820 SUBPARTS (cont.) I.Nonconforming Product J.Corrective and Preventive Action K.Labeling and Packaging Control L.Handling, Storage, Distribution, and Installation M.Records N.Servicing O.Statistical Techniques ©2014 Salt Lake Community College. All rights reserved.

15. SUBPART A – GENERAL PROVISIONS § 820.1ScopeScope... govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use.... intended to ensure that finished devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (the act).... applicable to manufacturers of finished medical devices. ©2014 Salt Lake Community College. All rights reserved.

16. SUBPART A – GENERAL PROVISIONS § 820.1ScopeScope Authority. Part 820 is established and issued under authority of sections 501, 502, 510, 513, 514, 515, 518, 519, 520, 522, 701, 704, 801, 803 of the act (21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 360l, 371, 374, 381, 383). The failure to comply with any applicable provision in this part renders a device adulterated under section 501(h) of the act. Such a device, as well as any person responsible for the failure to comply, is subject to regulatory action. ©2014 Salt Lake Community College. All rights reserved. (cont.)

17. SUBPART A – GENERAL PROVISIONS § 820.3Definitions - important vocabulary:Definitions Complaint Control number Design: history file (DHF), input, output, review Device: history record (DHR), master record (DMR) Finished device Lot or batch Quality Quality system ©2014 Salt Lake Community College. All rights reserved. (cont. 2)

18. SUBPART A – GENERAL PROVISIONS § 820.3Definitions - important vocabulary:Definitions Specification Validation Verification Unique device identifier § 820.5Quality system ©2014 Salt Lake Community College. All rights reserved. (cont. 3)

19. SUBPART B – Q SYSTEM REQUIREMENTS § 820.20Management responsibilityManagement responsibility a. Quality policy b. Organization c. Management review d. Quality planning e. Quality system procedures § 820.22Quality auditQuality audit § 820.25PersonnelPersonnel a. General b. Training ©2014 Salt Lake Community College. All rights reserved.

20. SUBPART C – DESIGN CONTROLS § 820.30Design controls a. General b. Design and development planning c. Design input d. Design output e. Design review f. Design verification g. Design validation h. Design transfer i. Design changes j. Design history file ©2014 Salt Lake Community College. All rights reserved.

21. SUBPART D – DOCUMENT CONTROLS § 820.40Document controls a. Document approval and distribution b. Document changes ©2014 Salt Lake Community College. All rights reserved.

22. SUBPART E – PURCHASING CONTROLS § 820.50Purchasing controls a. Evaluation of suppliers, contractors, and consultants b. Purchasing data ©2014 Salt Lake Community College. All rights reserved.

23. SUBPART F – IDENTIFICATION & TRACEABILITY § 820.60Identification § 820.65Traceability ©2014 Salt Lake Community College. All rights reserved.

24. SUBPART G – PRODUCTION & PROCESS CONTROLS § 820.70Production and process controls a.General b.Production and process changes c.Environmental control d.Personnel e.Contamination control f.Buildings g.Equipment h.Manufacturing material i.Automated processes ©2014 Salt Lake Community College. All rights reserved.

25. SUBPART G – PRODUCTION & PROCESS CONTROLS § 820.72Inspection, measuring, and test equipment a.Control of inspection, measuring, and test equipment b.Calibration § 820.75Process validation a. b. c. ©2014 Salt Lake Community College. All rights reserved. (cont.)

26. SUBPART H – ACCEPTANCE ACTIVITIES § 820.80Receiving, in-process, and finished device acceptance a.General b.Receiving acceptance activities c.In-process acceptance activities d.Final acceptance activities e.Acceptance records § 820.86Acceptance status ©2014 Salt Lake Community College. All rights reserved.

27. SUBPART I – NONCONFORMING PRODUCT § 820.90Nonconforming product a.Control of nonconforming product b.Nonconformity review and disposition ©2014 Salt Lake Community College. All rights reserved.

28. SUBPART J – CORRECTIVE & PREVENTIVE ACTION § 820.100Corrective and preventive action a. b. ©2014 Salt Lake Community College. All rights reserved.

29. SUBPART K – LABELING & PACKAGING CONTROL § 820.120Device labeling a.Label integrity b.Labeling inspection c.Labeling storage d.Labeling operations e.Control number § 820.130Device packaging ©2014 Salt Lake Community College. All rights reserved.

30. SUBPART L – HANDLING, STOR- AGE, DISTRIB’N, & INSTALL’N § 820.140Handling § 820.150Storage § 820.160Distribution § 820.170Installation ©2014 Salt Lake Community College. All rights reserved.

31. SUBPART M – RECORDS § 820.180General requirements a.Confidentiality b.Record retention period c.Exceptions § 820.181Device master record § 820.184Device history record § 820.186Quality system record ©2014 Salt Lake Community College. All rights reserved.

32. SUBPART M – RECORDS § 820.198Complaint files a. b. c. d. e. f. g. ©2014 Salt Lake Community College. All rights reserved. (cont.)

33. SUBPART N – SERVICING § 820.200Servicing a. b. c. d. ©2014 Salt Lake Community College. All rights reserved.

34. SUBPART O – SERVICING § 820.250Statistical techniques a. b. ©2014 Salt Lake Community College. All rights reserved.

35. CASE STUDIES – FDA INSPECTION REPORTS ©2014 Salt Lake Community College. All rights reserved.

36. INTUITIVE SURGICAL, INC. Form 483Form 483 for inspection 4/1/2013 through 5/30/2013 ©2014 Salt Lake Community College. All rights reserved.

37. STRYKER Form 483Form 483 for inspection 5/4/2009 through 5/14/2009 ©2014 Salt Lake Community College. All rights reserved.

38. UTAH MEDICAL PRODUCTS, INC. Form 483Form 483 for inspection 2/2/2004 through 3/3/2004 *** FDA filed a lawsuit against Utah Medical; case went to US District Court in SLC; Utah Medical prevailed and lawsuit was dismissedlawsuit was dismissed ©2014 Salt Lake Community College. All rights reserved.

39. WHAT ABOUT ISO ? ©2014 Salt Lake Community College. All rights reserved.

40. 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

41. QUALITY-RELATED ISO STANDARDS ISO 13485 – Medical devices – Quality management systems – Requirements for regulatory purposes [based on ISO 9001 – Quality management systems – Requirements, but with additional parts] ISO 17025 – General requirements for the competence of testing and calibration laboratories ©2014 Salt Lake Community College. All rights reserved.

42. ISO 13485:2003 0.Introduction 1.Scope 1.1General 1.2Application 2.Normative references 3.Terms and definitions 4.Quality management system 4.1General requirements 4.2Documentation requirements ©2014 Salt Lake Community College. All rights reserved.

43. ISO 13485:2003 5.Management responsibility 5.1Management commitment 5.2Customer focus 5.3Quality policy 5.4Planning 5.5Responsibility, authority and communication 5.6Management review ©2014 Salt Lake Community College. All rights reserved. (cont.)

44. ISO 13485:2003 6.Resource management 6.1Provision of resources 6.2Human resources 6.3Infrastructure 6.4Work environment ©2014 Salt Lake Community College. All rights reserved. (cont.)

45. ISO 13485:2003 7.Product realization 7.1Planning of product realization 7.2Customer-related processes 7.3Design and development 7.4Purchasing 7.5Production and service provision 7.6Control of monitoring and measuring devices ©2014 Salt Lake Community College. All rights reserved. (cont.)

46. ISO 13485:2003 8.Product realization 8.1General 8.2Monitoring and measurement 8.3Control of nonconforming product 8.4Analysis of data 8.5Improvement ©2014 Salt Lake Community College. All rights reserved. (cont.)

47. 21 CFR 820 vs. ISO 13485 See comparison chart: http://www.compliance-alliance.com/wp- content/uploads/2010/05/Kimmelman-Chart.pdf ©2014 Salt Lake Community College. All rights reserved.

48. 21 CFR 820 vs. ISO 13485 See comparison chart: http://www.compliance-alliance.com/wp- content/uploads/2010/05/Kimmelman-Chart.pdf ©2014 Salt Lake Community College. All rights reserved.

49. 21 CFR 820, QMS, & YOU Given what you now know, what considerations must employees of medical device companies keep in mind while working? What are do’s vs don’ts ? ©2014 Salt Lake Community College. All rights reserved.