assessment of reliability standards and test methods...
TRANSCRIPT
Assessment of Reliability Standards and Test Methods for Implantable Medical
Devices
Bill Bader, iNEMI
John McNulty, Exponent
1
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
Project Leaders:
Strategy Tactics Start: End:
Issues Graphics
Focus Area:
May-15TIG:
Goal:
2
Identify lacking standards for product testing to ensure reliable function of implantable electronic products (i.e. FDA class 3)
Medical
Medical
Defining Requirements for the Development of Implantable Reliability Specifications
• Survey data collection - conclusions & recommendations
• Detailed analysis of standards identified in the survey in addition to those identified by the working group with respect to:
– Product hierarchy (component vs. assembly)
– Test hierarchy (stress/screen vs. life test)
– Test specifications (maturity; utility)
– Body stresses (high or low; how well understood)
• Focused on implantable medical devices, FDA class 3
• Identification/compilation of existing reliability/quality/ safety standards specific to implantable electronic devices
• Information gathering: industry survey of commonly used/modified test standards; determination of device-specific usage environments
• Applicable/relevant to a broad range of implantable electronic technologies
• 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
6/2013 7/2014
John McNulty (Exponent) and Erik Jung (Fraunhofer IZM)
Focus Area:
May-15TIG:
Project Members
3
Medical Electronics
Medical
Defining Requirements for the Development of Implantable Reliability Specifications
4
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)
Key Findings from the Survey
6
Defining Requirements for the Development of
Implantable Reliability Specifications
Survey Demographics
27%
39%
34%
Medical Device Manufacturer
Medical Devices Supply Chain
Research Organizations, Consultants, etc
•We completed the industry
survey in September 2012
– 37 questions
– 62 respondents
7
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?
8
Defining Requirements for the Development of
Implantable Reliability Specifications
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
5 Groups of Tests (subsequently split into 8 groups for analysis)
9
To the best of your knowledge, provide the targeted
designed years of service for your products or products
you support.
5~10 years36%
10~15 years21%
Unknown or Not Applicable
18%
3~5 years9%
15~20 years7%
> 20 years7%
< 3 years2%
10
What type of implantable products do you
produce or support?
11
Most Important Impacts of:
OPERATIONAL ENVIRONMENT on the
IMPLANTED DEVICE
Electro-magnetic radiation
Body chemistry
Mechanical load (static or dynamic)
Temperature
Other Shape finish (sharp edges)
Temperature
Weight
Electro-magnetic radiation
interference
Operational voltage
Other
IMPLANTED DEVICE on the
OPERATIONAL ENVIRONMENT
Survey Analysis
13
Discrepancy Index
Test Method ID
MO
ST
LE
AS
T
Inad
eq
uate
Dis
cre
pan
cy
Identified Specifications
(medical specific standards in bold)
Op
era
tio
na
l
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
Me
ch
an
ica
l 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
En
vir
on
me
nta
l
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
Ele
ctr
ica
l 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
Rad
iati
on 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, IEC60601
Analysis of Particular Test
Groups
15
Method of Standards Analysis
• How often does the test provide useful results?
• How mature/developed are the specs?
• Are the life/usage stresses understood?
• Are they high enough to ever be a concern?
• Is test applied as stress/screen test to industry standards or as a life test for IMED usage conditions?
• Is test most commonly applied to COTS components or product assemblies?
Product Hierarchy
Test Hierarchy
Tests &Specs
are:
Body Stressesare:
YES NO
Understood?
HIGH
LOW
Rele
van
t?
ASSEMBLIES
Components
Ap
pli
ed
to
?
YES NO
Useful?
HIGHM
atu
re?
LOW
LIFE
Stress/scre
en
RF Test Standards
Lead: Jason CoderNIST
17
Summary of Existing RF Test Standards
• 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 14117
– ISO 14117: EMC test protocols for implantable cardiac pacemakers and cardio-verter
defibrillators as well as cardiac resynchronization devices
– EN 45502-1/-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
Standards Body
Standard & Description Test Typically Used
As:
Screen Life Test
IEC
61000-4-2: Focuses on testing and measurement of electrostatic characteristics
X -
61000-4-3: Focuses on testing and measurement of radiated emissions and susceptibility
X -
61000-4-8: Focuses on the testing and measurement of magnetic fields
X -
60601-1: Specifies limits for the tests described in IEC 61000-X-X and covers general safety requirements for medical electrical
systems.
X -
18
Analysis of RF Test Standards
• Discussion:
– 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
19
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
Biocompatibility/ Biostability Test
Standards
Lead:Maaike Op de Beeck
imec
21
Summary of Existing Biocompatibility Test StandardsStandards
Body Standard & Description
Test Typically Used As:
Screen Life Test
EN
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.
X -
ISO
10993, Part 1: Evaluation and testing within a risk management process.
X -
10993, Part 2: Animal welfare requirements.
X -
10993, Part 3: Tests for genotoxicity, carcinogenicity, and reproductive toxicity.
X -
10993, Part 4: Selection of tests for interactions with blood.
X -
10993, Part 5: Tests for in vitro cytotoxicity.
X -
10993, Part 6: Tests for local effects after implantation.
X -
10993, Part 10: Tests for irritation and skin sensitization.
X -
10993, Part 11: Tests for systemic toxicity.
X -
10993, Part 12: Sample preparation and reference materials.
X -
10993, Part 16: Toxico-kinetic study design for degradation products and
leachables.
X -
10993, Part 17: Establishment for allowable limits for leachable substances.
X -
10993, Part 18: Chemical characterization of materials.
X -
10993, Part 19: Physico-chemical, morphological, and topographical (PMT) characterization of materials (Technical Specification).
X -
10993 Part 20: Principles and methods for immuno-toxicology testing of medical devices (Technical Specification).
X -
22
Summary of Existing Biostability Test Standards
Standards
Body Standard & Description
Test Typically Used As:
Screen Life Test
EN
45502, Section 14.2: Leaching test in saline solution, 8-18 h at 37°C X -
45502, 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
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.
X -
ISO
10993, Part 9: Framework for identification and quantification of potential degradation products.
X -
10993, Part 10: Identification and quantification of degradation products from polymeric medical devices.
X -
10993, Part 14: Identification and quantification of degradation products from ceramics.
X -
10993, Part 15: Identification and quantification of degradation products from metals and alloys.
X -
23
Analysis of Biocompatibility/Biostability Test Standards
• Discussion:
– ISO-10993 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
24
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
Damp Heat/Corrosion Test
Standards
Lead: Kevin Knadlei3 Electronics
26
Summary of Existing Damp Heat & Corrosion Test
Standards
Damp Heat Tests
Corrosion Tests
27
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.
28
Recommendations for Damp Heat Test Standards
• Maintain component level tests for
screening/qualification to evaluate constituent
materials, particularly for encapsulated non-
hermetic 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.
29
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.
Conclusion & Next Steps
31
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
Dedicated to
Jim Arnold
www.inemi.orgEmail contacts:
Bill Bader
Bob Pfahl
Dave Godlewski