Assessment of Reliability Standards and Test Methods for Implantable Medical Devices. Bill Bader, inemi John McNulty, Exponent

Transcription

1 Assessment of Reliability Standards and Test Methods for Implantable Medical Devices Bill Bader, inemi John McNulty, Exponent

2 Outline Project background Introductions: existing members and new participants Survey results Brief overview of key findings from the survey Analysis of gaps in eight major qualification test areas: RF Biocompatibility/biostability Damp heat/corrosion MRI/X-ray Operational life Thermal Mechanical Electrical 1

3 Goal: Project Leaders: John McNulty (Exponent) and Erik Jung (Fraunhofer IZM) Issues Focus Area: Medical TIG: Medical Defining Requirements for the Development of Implantable Reliability Specifications Identify lacking standards for product testing to ensure reliable function of implantable electronic products (i.e. FDA class 3) Graphics May-15 Strategy Tactics Start: 6/2013 End: 7/2014 Focused on implantable medical devices, FDA class 3 Survey data collection - conclusions & Identification/compilation of existing reliability/quality/ recommendations safety standards specific to implantable electronic Detailed analysis of standards identified in the survey devices in addition to those identified by the working group with Information gathering: industry survey of commonly respect to: used/modified test standards; determination of devicespecific usage environments Test hierarchy (stress/screen vs. life test) Product hierarchy (component vs. assembly) Test specifications (maturity; utility) Applicable/relevant to a broad range of implantable electronic technologies Body stresses (high or low; how well understood) Standardization of qualification test methods most applicable to implantable medical devices and identification of areas most in need of standards development will offer to the industry as well as to the patient a faster level of innovation, a higher profit, and lower personal and litigation risks 2

4 Focus Area: Medical Electronics TIG: Medical Defining Requirements for the Development of Implantable Reliability Specifications Project Members May-15 3

5 Scope of the Project Goal: Standardization of qualification test methods most applicable to implantable medical devices and identification of areas most in need of standards development will offer to the industry as well as to the patient a faster level of innovation, a higher profit, and lower personal and litigation risks Our approach to achieving this goal was separated into three phases: Phase 1: Review of Reliability Standards Relevant to Implantable Medical Electronic Devices Phase 2: Gap Analysis Phase 3: Methodology Recommendations (dependent on feedback for Phase 2) may become separate working groups (WG) 4

6 Key Findings from the Survey

7 Defining Requirements for the Development of Implantable Reliability Specifications We completed the industry survey in September questions 62 respondents Survey Demographics 27% 39% 34% Medical Device Manufacturer Medical Devices Supply Chain Research Organizations, Consultants, etc 6

8 Overview of Survey Question Topics Company Description Product Sales Locations and Regulatory Governance Product Type Impacts Technology / Process Inquiry Requirements for Reliability or Safety testing Reliability Standards Referenced in: a) Operational testing b) Mechanical testing c) Environmental testing d) Electrical testing e) Radiation testing Value and Adequacy of Tests Connection to externally carried devices. Specialized Testing for External Connections External Communication Tests and Standards Software and Firmware RoHS Compatible Components RoHS Compliant Development Conclusion In your opinion, what are the most critical gaps with respect to reliability or safety testing for electronic implantable medical devices? 7

9 Defining Requirements for the Development of Implantable Reliability Specifications 5 Groups of Tests (subsequently split into 8 groups for analysis) Operational Environmental a1) Burn-in c1) Temperature cycling a2) Operating life c2) Thermal shock a3) Elevated temperature operating life c3) Biased humidity a4) In vivo testing c4) Unbiased humidity a5) Biocompatibility c5) Hermeticity - gaseous environments a6) Biostability / corrosion c6) Hermeticity - liquid (in vivo) environments Mechanical c7) Corrosive environment b1) Mechanical shock (Implanted) c8) High and low temperature storage b2) Mechanical vibration (Implanted) Electrical b3) Mechanical shock (Not Implanted) d1) ESD b4) Mechanical vibration (Not Implanted) d2) Over voltage d3) High voltage d4) Safety Radiation e1) MRI compatibility e2) X-ray exposure e3) Radiated emission 8

10 To the best of your knowledge, provide the targeted designed years of service for your products or products you support. 10~15 years 21% Unknown or Not Applicable 18% 5~10 years 36% 3~5 years 9% 15~20 years 7% < 3 years 2% > 20 years 7% 9

11 What type of implantable products do you produce or support? 10

12 Most Important Impacts of: OPERATIONAL ENVIRONMENT on the IMPLANTED DEVICE IMPLANTED DEVICE on the OPERATIONAL ENVIRONMENT Body chemistry Mechanical load (static or dynamic) Weight Electromagnetic radiation interference Temperature Operational voltage Electromagnetic radiation Other Temperature Shape finish (sharp edges) Other 11

13 Survey Analysis

14 Radiation Electrical Environmental Mechanical Operational ID MOST LEAST Inadequate Discrepancy Discrepancy Index Test Method Identified Specifications (medical specific standards in bold) a1) Burn-in a1) 77% 6% 17% 32% MIL-STD-883, JESD22-A108 a2) Operating life a2) 75% 13% 13% 38% MIL-STD-883, MIL-STD-202, JESD22-A108 a3) Elevated temperature operating life a3) 52% 29% 19% 67% MIL-STD-883, MIL-STD-202, JESD22-A108 a4) In vivo testing a4) 79% 21% 0% 21% ISO10993, ISO14155, EN540 a5) Biocompatibility a5) 67% 25% 8% 42% ISO10993 a6) Biostability / corrosion a6) 85% 15% 0% 15% ASTM F2129, EN45502, ISO10993 b1) Mechanical shock (Implanted) b1) 55% 30% 15% 60% JESD22-B104, MIL-STD-202, IEC60068, EN45502 b2) Mechanical vibration (Implanted) b2) 61% 28% 11% 50% JESD22-B103, MIL-STD-202, IEC60068, EN45502 b3) Mechanical shock (Not Implanted) b3) 55% 23% 23% 68% MIL-STD-883, MIL-STD-202, JESD22-B104, IEC60068, EN45502 b4) Mechanical vibration (Not Implanted) b4) 53% 23% 23% 71% MIL-STD-883, JESD22-B103, IEC60068, EN45502 c1) Temperature cycling c1) 84% 4% 12% 20% JESD22-A104, MIL-STD-883, MIL-STD-202 c2) Thermal shock c2) 37% 37% 26% 89% JESD22-A106A, MIL-STD-883, MIL-STD-202 c3) Biased humidity c3) 43% 30% 26% 83% JESD22-A101C, MIL-STD-883 c4) Unbiased humidity c4) 24% 29% 47% 76% JESD22-A101, MIL-STD-202 c5) Hermeticity - gaseous environments c5) 64% 18% 18% 55% EN13185, MIL-STD-202 c6) Hermeticity - liquid (in vivo) environments c6) 69% 15% 15% 46% ISO10993, ISO1478, EN1593 c7) Corrosive environment c7) 64% 14% 21% 50% MIL-STD-883 c8) High and low temperature storage c8) 67% 17% 17% 50% JESD22-A103, EN45502 d1) ESD d1) 93% 0% 7% 7% JS-001, JESD22-C101E, IEC6100, MIL-STD-883, AEC Q200, EN45502 d2) Over voltage d2) 75% 17% 8% 33% JESD78D d3) High voltage d3) 75% 12% 12% 38% EN45502, IEC61000 d4) Safety d4) ISO14708, IEC60601, IPC9252 e1) MRI compatibility e1) 82% 0% 18% 18% ASTM F2052, ASTM F2182, ASTM F2213 e2) X-ray exposure e2) 67% 17% 17% 50% EN45502 e3) Radiated emission e3) 42% 33% 25% 83% IEC61000, IEC

15 Analysis of Particular Test Groups

16 Relevant? Mature? Applied to? Method of Standards Analysis Is test most commonly applied to COTS components or product assemblies? Product Hierarchy Components Stress/scre en Test Hierarchy Is test applied as stress/screen test to industry standards or as a life test for IMED usage conditions? ASSEMBLIES LIFE YES NO YES NO Understood? Useful? Are the life/usage stresses understood? Are they high enough to ever be a concern? Body Stresses are: HIGH LOW LOW HIGH Tests & Specs are: How often does the test provide useful results? How mature/developed are the specs? 15

17 RF Test Standards Lead: Jason Coder NIST

18 Summary of Existing RF Test Standards Standards Body IEC Standard & Description : Focuses on testing and measurement of electrostatic characteristics : Focuses on testing and measurement of radiated emissions and susceptibility : Focuses on the testing and measurement of magnetic fields : Specifies limits for the tests described in IEC X-X and covers general safety requirements for medical electrical systems. Test Typically Used As: Screen Life Test X - X - X - X - Additional standards relevant to implantable medical devices include: CISPR 11: specifies limits and measurement methods for EM disturbance characteristics ANSI/AAMI PC 69: superseded by ISO ISO 14117: EMC test protocols for implantable cardiac pacemakers and cardio-verter defibrillators as well as cardiac resynchronization devices EN /-2/-3: -1 is generally applicable to all implantable devices, whereas -2 applies to pacemakers and -3 applied to cochlear and auditory implants What about devices that have a wireless link? ANSI C63.27 new standard under development 17

19 Discussion: Analysis of RF Test Standards This is the most significant single gap with respect to standards for implantable devices, due to substantial evolution in technology within the last 10 years. Product hierarchy: invariably applied at the assembly level Test hierarchy: tests attempt to characterize typical worst-case life environments Test specs: poorly developed, but highly useful Difficult to develop test procedures and metrics for a poorly understood environment Body stresses: the RF environment is currently complex, and anticipated to only increase in severity/complexity 18

20 Recommendations for RF Test Standards The following areas should be addressed by inemi or industry working groups: Protocol security Broadband signal response Response to modulated signals Wireless charging Unintentional coupling Wireless coexistence Focus of ANSI C63.27 Body area networks 19

21 Biocompatibility/ Biostability Test Standards Lead: Maaike Op de Beeck imec

22 Summary of Existing Biocompatibility Test Standards Standards Body EN ISO Standard & Description 45502, Section 14.3: Biocompatibility of the device shall be demonstrated: a) by analogy with published data; or b) by the selection of materials already shown to be biocompatible by proven clinical use in a similar application; or c) by experience with similar devices already on the market together with evidence of traceability to the materials used in those devices; or d) by compliance with published procedures for biological evaluation of medical devices , Part 1: Evaluation and testing within a risk management process , Part 2: Animal welfare requirements. Test Typically Used As: Screen Life Test X - X - X , Part 3: Tests for genotoxicity, carcinogenicity, and reproductive toxicity. X , Part 4: Selection of tests for interactions with blood , Part 5: Tests for in vitro cytotoxicity , Part 6: Tests for local effects after implantation , Part 10: Tests for irritation and skin sensitization , Part 11: Tests for systemic toxicity , Part 12: Sample preparation and reference materials. X - X - X - X - X - X , Part 16: Toxico-kinetic study design for degradation products and leachables. X , Part 17: Establishment for allowable limits for leachable substances. X , Part 18: Chemical characterization of materials. X , Part 19: Physico-chemical, morphological, and topographical (PMT) characterization of materials (Technical Specification). X Part 20: Principles and methods for immuno-toxicology testing of medical devices (Technical Specification). X - 21

23 Summary of Existing Biostability Test Standards Standards Body EN ISO Test Typically Used Standard & Description As: Screen Life Test 45502, Section 14.2: Leaching test in saline solution, 8-18 h at 37 C X , Section 19.1: Demonstration that any gradual, long term change that might occur within the lifetime of an implantable medical device is not an unacceptable hazard: a) by analogy with published data, or b) by the selection of materials already shown to be stable by proven clinical use in a similar application; or X - c) by experience with similar devices already on the market together with evidence of traceability to the materials used in those devices; or d) by compliance with published procedures for elution of materials for implantation , Part 9: Framework for identification and quantification of potential degradation products. X , Part 10: Identification and quantification of degradation products from polymeric medical devices. X , Part 14: Identification and quantification of degradation products from ceramics. X , Part 15: Identification and quantification of degradation products from metals and alloys. X - 22

24 Analysis of Biocompatibility/Biostability Test Standards Discussion: ISO is the most comprehensive standard, but it is a guideline instead of a standard with clear pass/fail criteria; hence, variability exists in how the tests are implemented by outside labs as well as in the cell cultures used for in vitro testing Product hierarchy: typically applied at the assembly level, except for non-hermetic devices Test hierarchy: tests attempt to capture typical body life environments Test specs: well-developed, but inconsistently implemented Body stresses: highly relevant, but only moderately understood for new classes of devices 23

25 Recommendations for Biocompatibility/Biostability Test Standards There is a clear lack of accelerated tests for long term issues Additional guidance should be provided regarding in vitro testing Mechanical loading considerations like environmental stress cracking (ESC) should be explicitly discussed in the main text of the standard, rather than the annex 24

26 Damp Heat/Corrosion Test Standards Lead: Kevin Knadle i3 Electronics

27 Summary of Existing Damp Heat & Corrosion Test Standards Damp Heat Tests Corrosion Tests 26

28 Analysis of Damp Heat & Corrosion Standards Discussion: Biased damp heat testing will likely remain important for screening/qualification tests because of its perceived value as a reliability test and the associated need for high reliability in IMEDs. Unbiased damp heat is widely considered as a low value test in general. Regarding use as a life test, the primary question is whether the device is hermetic or not; it may certainly be applicable as a life test for emerging non-hermetic technologies. Current corrosion standards are likely acceptable for hermetic devices, though the exact test conditions and their correlations to lifetime may be proprietary. 27

29 Recommendations for Damp Heat Test Standards Maintain component level tests for screening/qualification to evaluate constituent materials, particularly for encapsulated nonhermetic devices. Unify around biased damp heat for encapsulated systems, though with appropriate temperature limits. For hermetic systems, the focus should be on tests ensuring the long-term integrity of the seal. For emerging non-hermetic implanted technologies, work is needed to quantify acceleration models for corrosion and temperature/humidity bias as a function of various bodily fluids. 28

30 Recommendations for Corrosion Test Standards Consider a follow-on working group with an experimental emphasis to evaluate corrosion conditions for various non-hermetic IMEDs throughout the body. 29

31 Conclusion & Next Steps

32 Summary We identified three key areas of qualification standards for implantable medical devices that require substantial development of new standards or modification of existing standards Separate inemi working groups will address each area Our review of all major areas of qualification standards will be contained in a white paper shared with inemi members 31

33 Dedicated to Jim Arnold

34 contacts: Bill Bader Bob Pfahl Dave Godlewski