FDA Expectations for Traceability in Device & Diagnostic Design
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The document summarizes FDA expectations and requirements for device and diagnostic design. It discusses regulations around traceability, design controls, and reporting requirements. It also provides examples of recent FDA enforcement actions and common inspector questions related to design documentation and traceability. Finally, it outlines practical challenges companies face in complying with requirements, and proposes an eight-step lean strategy to systematically address traceability throughout the product development lifecycle in a cost-effective manner.
FDA Expectations for Traceability in Device & Diagnostic Design
- 1. FDA Expectations for in Device & Diagnostic Design John Avellanet Cerulean Associates LLC www.CeruleanLLC.com © Cerulean Associates LLC all rights reserved
- 2. Acknowledgements Tim Ulatowski Dan O’Leary Anita Fauchier Mike Weber Nancy Singer Karen Steinberg Kerry McCarter Akos Bartha Carl Anderson Jackie Cassada John Lincoln Jim Shore Tom Colonna Terry Winchell Chris Szustkiewicz Kim Trautman Larry Nicholson Jan Welch David Elder Annamarie Kempic Doug Throckmorton Jonathan Lee 2
- 3. Agenda fda requirements practical challenges lean compliance solutions framework This is not legal advice. Information in this presentation draws upon a variety of sources, including published FDA warning letters, personal experiences, interviews and research, all or any of which may or may not have been prepared or conducted by Cerulean Associates LLC. Cerulean Associates LLC does not provide a warranty concerning the accuracy of the information contained in this presentation. The contents of this presentation are intended for general information only and should not be construed as legal advice. Cerulean Associates LLC assumes no liability for actions taken or not taken as a result of the information in this presentation. This presentation is copyrighted 2011 by Cerulean Associates LLC, all rights reserved. 3
- 4. FDA Requirements traceability regulations recent enforcement examples example inspector questions other requirements 4
- 5. 21 CFR 820.30 (a) “General. (1) Each manufacturer…shall establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met.” Translation for FDA inspectors “The purpose of the design control subsystem is to control the design process to assure that devices meet user needs, intended uses, and specified requirements: • Inputs must be documented • Outputs must be documented • Confirm that device outputs are traceable to design inputs” 5
- 6. 21 CFR 803.18 (b) (1) (i) “…including all documentation of your deliberations and decisionmaking processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable….” Translation for FDA investigators “A firm must demonstrate that it exercised “good faith” in any attempts to obtain required data…. In addition, the Center believes that the parameters of good faith must, at a minimum, comport with the level of risk/nature of the device….” 6
- 7. 21 CFR 806.20 (b) (4) “Justification for not reporting the correction or removal action to the FDA, which shall contain conclusions and any followups….” Translation for FDA investigators “Verify that non-reported device corrections or removals meet the following criteria based on design controls: • Risk is not increased • Repairs are not unexpected • Part replacement is not earlier than expected” 7
- 8. Warning Letter Excerpts “ You have failed to establish and maintain a design history file (DHF) to contain and reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of 21 CFR 820.” - warning letter to ASI Medical, 20 April 2011 8
- 9. Warning Letter Excerpts “ Failure to maintain adequate device history records…. For example, a review of (b)(4) Meniscal Insert DHRs found one DHR contained an inaccurate date.” - warning letter to Advanced Surgical Design & Manufacture, 1 December 2010 9
- 10. Warning Letter Excerpts “ When requested, design output requirements for the upgrade from Version (b)(4) to Version (b)(4) done by (b)(4)*…could not be provided.” - warning letter to 3CPM Company, 25 March 2010 *This change was done 7 years prior in 2003! 10
- 11. Example Inspector Questions • were design characteristic acceptance criteria established and documented prior to design approval? • were design outputs verified and documented against design input requirements? • was risk analysis conducted (and documented) on the design prior to its final design approval? • do design outputs draw a distinction between those characteristics essential for functioning of the device versus those non-essential (e.g., aesthetic) characteristics? How are these verified? • review design outputs linkages wherein design outputs for one stage become design inputs for the next – how are these made clear in the documentation? • verify that changes to device design were documented and approved – are there date discrepancies between the actual change and its approval? • how were design changes tested to assess impact to risk or to adjacent design inputs or outputs? How was this documented? • is there a documented traceability analysis or matrix linking product design requirements, design specifications, risks and controls, and tests? 11
- 12. Other Requirements FDA Guidance Documents • Human Factors Points to Consider for IDE Devices (1996) • Human Factors Implications of the New GMP Rule: Overall Requirements of the New Quality System Regulations (1997) • Design Control Guidance for Medical Device Manufacturers (1997) • Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk Management (2000) • General Principles of Software Validation (2002) • Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (2005) • Radiation Safety Considerations for X-Ray Equipment Designed for Hand- Held Use (2008) • Technical Considerations for Pen, Jet, and Related Injectors Intended for Use with Drugs and Biological Products (2009) • Clinical Investigations of Devices Indicated for the Treatment of Urinary Incontinence (2011) 12
- 13. Other Requirements GHTF Guidelines • SG1 N:068 Essential Principles of Safety and Performance of Medical Devices (2010 draft) • SG1 N:11 Summary Technical Documentation for Demonstrating Conformity to the Essential Principles of Safety and Performance of Medical Devices (STED) (2008) • SG3 N:15 Implementation of Risk Management Principles and Activities Within a Quality Management System (2005) • SG5 N:2 Clinical Evaluation (2007) • SG5 N:3 Clinical Investigations (2010) • AHWG N:2 Unique Device Identification (UDI) System for Medical Devices (2010 draft) 13
- 14. Practical Constraints industry confusion costs ownership development lifecycle 14
- 15. Industry Confusion Design Requirements Issues/Defects/Anomalies Tests Risk Controls Source: Life Sciences Product Development Artifacts Survey White Paper (Seapine Software, 2011) 15
- 16. Costs tracking, verifying earlier tests, add’l tests, etc.) Cost of Change (incl. documentation, Perception Reality Requirements Early Design Protype Production Clinical Final Production Time (development cycle) Source: Adapted from Scott Ambler, Agile Modeling (2002) 16
- 17. Ownership Quality Validation / Engineering Testing Design Production 17
- 18. Development Lifecycle start traceability …? ? ? ? ? Source: Get to Market Now! Turn FDA Compliance into a Competitive Edge (2010, Logos Press) 18
- 19. Practically Speaking • address records sought by inspectors • capture logic through traceability • need a systematic approach to traceability • cost-effective • generates records • allows easy reporting • maintain clear linkages 19
- 20. Rationale (Traceability) • relationship to safety • relationship to effectiveness • relationship to risk mitigation • relationship to testing • corrective actions • design changes/fixes 20
- 21. Lean Compliance Strategy do’s v. don’ts eight-step process lifecycle placement 21
- 22. Traceability Do’s • Form a cross-functional traceability team • Clearly define accountabilities v. responsibilities in your SOPs • Start traceability efforts when you make the “go/no-go” decision on a project • Ensure that each specific feature risk/request tests production characteristics (suppliers, processes, etc.) • Plan for at least one significant change during product development • Verify progress (and identify gaps) with a mock FDA audit 22
- 23. Traceability Don’ts • Assume that you can remember dates, times and people involved in design decisions 4, 5, 7+ years ago • Rely only on internal audits by your Quality department to catch missing traceability records • Assume FDA inspector will only go back a few months in design history • Forget that traceability records help you prove safety, efficacy, and compliance • Lose sight of traceability costs – design changes include documentation changes, test changes, test re-work, etc. 23
- 24. Eight-Step Process design control SOPs 1 product concept sheet 8 2 product specs 7 3 risk controls traceability matrix 6 4 QC “yea/nay” 5 management review audit 24
- 25. 1 8 2 Design Control SOPs 7 3 6 4 5 25
- 26. 1 8 2 Product Concept Sheet 7 3 6 4 5 • focus on: • intended use • desired features • distinguishing characteristics • development considerations Source: Get to Market Now! Turn FDA Compliance into a Competitive Edge (2010, Logos Press) 26
- 27. 1 8 2 Product Specs 7 3 6 4 5 Product Component Requirement seal integrity seal integrity specifications 1. does not allow loss of product or moisture over shelf life 2. retain sterility over shelf life 3. does not allow alteration to finished product over shelf life stopper stopper specifications 1. biocompatible 2. not contain silicon 3. 20mm serum stopper 27
- 28. 1 8 2 Risk Controls 7 3 6 4 5 Product Specifications Control for seal integrity specifications seal integrity controls 1. does not allow loss of product or USP <1207> moisture over shelf life 2. retain sterility over shelf life stability study (ICH Q6A) 3. does not allow alteration to USP <381> finished product over shelf life USP <87> stopper stopper controls 1. biocompatible USP <88> or USP <381> 2. not contain silicon purchasing control 3. 20mm serum stopper see drawing 28
- 29. 1 8 2 Traceability Matrix 7 3 6 4 5 • manual (logs, spreadsheets) • automated (database) • clear linkages • systemic reviews • red flag assessments 29
- 30. 1 8 2 Traceability Matrix (cont’d) 7 3 6 4 5 30
- 31. 1 8 2 QC “Yea/Nay” 7 3 6 4 5 • are the test results…? • within specification ranges • have a “Plan B” • if results indicate failure, what will you do? • decide potential actions ahead of time based on design and risk 31
- 32. 1 8 2 Management Review 7 3 6 4 5 • during design transfer • relate traceability data to… • risk assessments • design specifications for materials / suppliers • do not forget: relate to cost • senior management must factor in ROI 32
- 33. 1 8 2 Audit 7 3 6 4 5 • audit traceability records prior to • IDE submission (if any) • market application submission (510(k)) • any licensing agreements (due diligence) • patent applications / changes • long-term archival • every 2 years otherwise • consider a mock FDA audit and gap analysis 33
- 34. Development Lifecycle & 8 Steps (until longer of two Formal traceability years after end of device/life of design OR statute of limitations) 2 3 6 7 1 4 5 8 8 Adapted from: Get to Market Now! Turn FDA Compliance into a Competitive Edge (2010, Logos Press) 34
- 35. Key Takeaway Review core regulatory requirements four practical constraints eight-step lean compliance strategy 35
- 36. Want More? Traceability Resources http://www.seapine.com/traceability.html Six Exercises To Strengthen Traceability http://downloads.seapine.com/pub/papers/SixExercisesStrengthenTraceability.pdf How To Have A Painless FDA Audit http://downloads.seapine.com/pub/papers/PainlessFDAAudit.pdf The Seapine View Blog http://blogs.seapine.com/ Seapine Life Science Solutions http://www.seapine.com/lifesciences.html 36
- 37. About Your Presenter John Avellanet solves compliance problems for clients with practical solutions. Winner of the 2009 Best of Business award by the Small Business Commerce Association, Mr. Avellanet has earned international acclaim for his business-savvy, pragmatic compliance advice. His latest book, Get to Market Now! Turn FDA Compliance into a Competitive Edge in the Era of Personalized Medicine, has earned multiple five-star reviews from industry publications, blogs, Amazon.com readers, and former FDA officials. He has a breadth of experience designing, implementing, and being accountable for quality systems and compliance programs for FDA, the ICH, GHTF, and ISO. For more than 15 years, John served as an executive accountable for compliance, records www.Ceruleanllc.com management, and information technology, most recently as a C- level executive for a Fortune 50 combination medical device and www.Get2MarketNow.com biotech subsidiary. In 2006, Mr. Avellanet founded his private FDA compliance consulting and training firm, Cerulean Associates LLC. 37
- 38. Picture Credits Photos, images and clip art that appear on these slides have been used to enhance this presentation and may NOT be used for commercial or promotional purposes without permission from copyright holders. Do not remove or copy from this presentation. Contact: iStockphoto.com Microsoft Corporation Seapine Software Cerulean Associates LLC 38