Justin Metcalf, Manager, Bench Testing, MED Institute, Inc.

1. What do you do when regulatory
requirements exceed that of reasonable
engineering controls?
Examples and lessons learned from 25
years in the trenches.
Justin Metcalf MS, Brian Choules, PhD,
MED Institute, Inc.
www.medinstitute.com
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2. Overview
• Company introduction: Who is MED Institute?
• What is ISO 17025 and why is it important?
• Requirements
– Regulatory
– Company
– How they interact
• Methods for rectifying the gap between regulatory and
company requirements
• Practical examples
• Conclusion
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3. MED Institute Introduction
•
MED Institute is a Cook Group Company, located in West Lafayette, IN
•
We have been in business since 1983, and have over 30 years of experience
in the medical device industry
– Non-clinical Testing Services
– Regulatory Consulting
– Clinical Trial Management
•
ISO 17025 Accredited Laboratory (Cert # 2194-01)
•
ISO 13485 Certified (BSI)
•
Inspected to Good Laboratory Practices (GLP)
•
We contribute to 16 medical device standard committees (ISO, ASTM, AAMI)
•
250 staff members including physicians, nurses, engineers, regulatory
scientists, physiologists, biologists, veterinarians, and statisticians
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4. MED Institute Introduction
•
Experience with regulatory bodies
– FDA, CFDA, PMDA, CE notified
bodies
•
Work with companies around the globe
•
Additional areas of specialization:
– Publications and research
– Ophthalmology
– Vascular
– Obstetrics/Gynecology
– Urology
– Pediatrics
– Endoscopy
– Cardiac
– Orthopedic
– Critical Care Medicine
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5. MED Institute Introduction
•
•
•
90 test methods accredited to ISO 17025 including:
– MRI Safety Analysis and Testing
– Durability/fatigue testing
– Failure analysis (FTIR, SEM, EDS)
– Simulative use
– Corrosion
– Particulate counting and sizing
– Radiopacity
CERT #2194-01
Testing
Laboratory
Complete ISO 25539 series as well as many other standards list on
our accreditation Cert # 2194-01
Multiple areas of research and publication including fatigue to
fracture, failure analysis, and corrosion
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6. What is ISO 17025 and why is it valuable?
•
ISO/IEC 17025 is a set of general requirements for the competence of
testing and calibration laboratories and is the predominant ISO standard
used by testing laboratories
– Method validation required for non-standardized methods
– Promotes best scientific practices through:
• Uncertainty analysis
• Interlaboratory comparisons
• Test method monitoring
• Calibration traceability
•
A proper scientific foundation is important and accreditation is one
way to prove your expertise
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7. Definition of a requirement
•
A thing demanded or obligatory: Dictionary.com
•
Something that is needed or that must be done: Merriam-Webster
•
Requirement synonyms: need, wish, demand, want, necessity,
prerequisites, requisite, precondition, stipulation, specification…
•
It is crucial to assess your requirements carefully before initiating
non-clinical testing
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8. Regulatory requirements: some sources
Reference
to standards
(ISO,
ASTM…)
Equivalence
to predicate
devices
Guidance
documents
Literature
Requirements
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9. Company requirements: some sources
Physician
interactions
Requirements
for a “new
device”
Feasibility
clinical
studies
Literature
Bench and
animal
work
Company requirements are
documented in risk analyses or
design inputs.
Reference
to standards
(ISO,
ASTM…)
Guidance
documents
Equivalence
to predicate
devices
Literature
Requirements
for a device
with a
predicate
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10. Ideal Situation
We all have the same goal: a safe medical device. Occasionally, the
regulatory and company requirements are the same.
Company
Requirements
=
Regulatory
Requirements
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11. Real World
The practice of medicine may result in each global regulatory body having
requirements that differ from the company requirements. These differences
will need to be reconciled to gain approval.
Company
Requirements
Regulatory
Requirements
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12. Reasons for the differences in requirements
•
Regulatory bodies can adopt requirements without the knowledge and
clinical experience that many companies have
•
Knowledge and technology advancements occur faster than regulatory
bodies can adjust requirements
• Example: Generalized physiologic models and acceptance
criteria are rare and once they are developed, science or
medical devices have generally moved on to a new front
•
Regulatory requirements are not generally publicized and companies
must determine acceptance criteria during device development
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13. Reasons for the differences in requirements
•
Standards lag technology
– Standards might lack all the necessary requirements that help
establish the safety and effectiveness of the device.
– It should be noted that standards cannot always envision new
design concepts or can have requirements that become outdated
based on emerging knowledge. Thus, complete compliance to
standards might not always make sense.
•
We all want to help patients, but to fulfill a regulatory requirement that is
not warranted is expensive and time consuming.
•
How do we resolve a difference in a way that minimizes effort?
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14. So how do we resolve differences between regulatory
requirements and company requirements?
•
Educate yourself on the clinical environment
– Research
– Cadaver studies
– Physician interactions
– Clinical feedback
• Explants and clinical performance
– Endurance limit testing
•
Educate your regulatory body
– Submission specific meetings
– General information meetings
– Industry wide working groups
– Collaborative research
– Project based agreement prior to
development or after model/test
development
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15. So how do we resolve differences between regulatory
requirements and company requirements?
•
Testing (“A good test is worth 10,000 words, a bad test is worth 1,000,000”)
– Develop physiologically relevant model
• Validate with physician feedback
• Existing device performance
– Build your rationale
– Model improvement
• Clinical performance vs. bench
• Clinical feedback
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16. Practical Examples
•
Example 1: Clinically relevant bifurcation tracking model
– Company requirement
• Device must advance, deploy and withdraw in an appropriate
clinically relevant anatomy
– Regulatory requirement
• Justify your model to include tortuosity and a bifurcation radius
that is representative of a worst case anatomy
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17. Practical Examples
•
Example 1 cont.
– Option 1: Agree with the regulatory body
• Find an overall worst case
– Option 2: Justify why your current requirements are adequate
• Use literature and physician feedback
– Option 3: Work with regulators to come to an agreement on an
appropriate new solution
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18. Does a perfect model exist?
Everyone wants to find
and test out the worst case
The “one size fits all” solution
doesn’t exist
Bing images 2/5/14
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19. Practical examples
•
Example 2: Tissue replacement therapy
– Company requirement
• An experienced operator must deliver the cadaveric tissue to its
intended location without damage and results must be better
than or equal to the standard of care
– Regulatory requirement
• Model and results must match those of a recognized scientific
journal article
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20. Practical examples
•
Example 2 cont.
– Option 1: Agree with the regulatory body
• Perform the test as specified by the regulatory referenced journal article
– Option 2: Justify why your current requirements are adequate
• Physician feedback and publication
– Option 3: Work with regulators to come to an agreement on an appropriate
new solution
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21. Practical examples
•
Example 3: Breakdown Corrosion for
implantable metals
– Company requirement
• Breakdown potential to be greater than
that of a device with successful clinical
use
– ASTM agrees with the criterion
– Regulatory requirement
• Breakdown potential must be greater
than 600 mV
– This was an example of regulatory bodies
and companies reaching for a relevant
acceptance criterion without appropriate
scientific backing
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22. Practical examples
•
Example 3 cont.
– Option 1: Agree with the regulatory body
• Set 600 mV as the criterion
– Option 2: Justify why your current
requirements are adequate
• Educate the regulatory body on an
alternative appropriate criterion
• Clarify language in the standard
– Option 3: Work with regulators to come to
an agreement on an appropriate new solution
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23. Practical examples
•
Example 4: Stent durability
conditions
• Stent must maintain its
function for predetermined
number of cycles to clinically
relevant loads
– Regulatory requirement
Alternating Strain
– Engineering requirement
• 10 year fatigue life justified
but without specific loading
conditions
•
Bridging the gap between a clinically
relevant fracture rate and regulatory
is difficult in a global regulatory
environment
Mean Strain
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24. Practical examples
•
Example 4 cont.
– Option 1: Agree with the regulatory body
• Redefine loading conditions or redesign the device
– Option 2: Justify why your current requirements are adequate
• Physician feedback and publication
– Option 3: Work with regulators to come to an agreement on an
appropriate new solution
• Educate yourself on the clinical relevance of fractures
• Educate the regulatory body on clinical relevance of fracture
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25. Practical examples
•
Example 5: MR device deflection
– Engineering requirement
• Device should not have a
deflection force that is clinically
impactful
– Regulatory requirement
• “If the mean value is less than
45°, the magnetically induced
deflection force, is less than the
force on the device to due gravity
(its weight)” ASTM F2052-06
This is a statement in the standard
that has been adopted as a criterion
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26. Practical examples
•
Example 5 cont.
– Option 1: Agree with the regulatory body
• Label your device unsafe
– Option 2: Justify why your current requirements are adequate
• Physician feedback and publication
• Clarify language in the standard
– Option 3: Work with regulators to come to an agreement on an
appropriate new solution
• Educate yourself on the clinical relevance of deflection force
• Educate the regulatory body on clinical relevance of deflection
force
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27. Conclusions
•
A proper scientific foundation is of the utmost importance
•
Appropriate multi-device criteria and models are rare, most devices
require a specific model and criteria
•
Education and scientific publication is important
•
Communication with regulatory bodies early and often is necessary
•
Continuous improvement of models and methods is needed
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28. MED Institute
•
Booth 3194
•
Our Mission
– Through forward looking test development and careful bench testing,
we apply scientific and engineering principles to help safe and
effective devices efficiently reach the global market to benefit
patients
www.medinst.com
Brian Choules bchoules@medinstute.com
Justin Metcalf jmetcalf@medinstitute.com
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