Evaluation of Device Performance

for Labeled Shelf Life

Limin Sun, Ph.D., Assistant Director
Division of Joint Arthroplasty Devices
Office of Health Technology 6 (OHT6): Office of Orthopedic Devices
Office of Product Evaluation and Quality (OPEQ)
Center for Devices and Radiological Health (CDRH)
U.S. Food and Drug Administration (FDA)

Webinar for Device Stability

June 1, 2023
 Outline of Presentation
I. Shelf Life and Stability of a Medical Device
II. Product Shelf Life Testing
III. Recommendations for Product Shelf Life Testing – Examples
• Joint Arthroplasty Devices
• Resorbable Bone Void Filler Devices
• Patient-Matched Instruments to Orthopedic Implants
• Other Devices

*Disclaimers
• Language from FDA guidance documents has been excerpted or summarized to fit the purpose of this presentation.
For complete information, please review the cited FDA guidance documents.
• Our recommendations in this presentation are based on our current thinking on a particular subject, which may be
subject to change.
• Images have been obtained from online sources and are intended for illustration only.

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Shelf Life and Stability of a Medical Device
FDA guidance - Shelf Life of Medical Devices April 1991
https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/shelf-life-medical-devices

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Shelf Life of a Medical Device - Terminology
• Shelf life is the term or period during which a medical device remains stable and
suitable for the intended use.
• An expiration date is the termination of shelf life, after which a percentage of the
medical devices may no longer function as intended.
• Not all medical devices need to have a shelf life; this depends if a medical device
is susceptible to degradation that would lead to functional failure and the level of
risk that the failure would present.
• A medical device’s shelf life should not be confused with its "useful life” which is
the duration of actual use or the number and duration of repeat uses before
some change results in the device's inability to achieve its intended function.
Production Shelf life (device is stable during this period and suitable for use) Expiration
date date

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 Stability and Stability Criteria
• The United States Pharmacopoeia (USP) defines stability as "the extent to which a product retains, within
specified limits, and throughout its period of storage and use, i.e., its shelf life, the same properties and
characteristics that it possessed at the time of manufacture.“

• There is no one exhaustive set of criteria that would apply equally to all medical devices. USP section <1191>
provides five sets of criteria for acceptable levels of stability for drug products:
1. chemical
2. physical
3. microbiological
4. therapeutic
5. toxicological
6. biocompatibility (added for medical devices)
• This is the starting point for developing criteria to evaluate the stability of medical devices.

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Factors to Consider for Each Stability Criterion - Examples
Chemical Physical Microbiological
• Degradation of ingredients or • Physical characteristics, e.g., • Sterility/integrity, i.e.,
components appearance, viscosity, package integrity
• Interactions of ingredients or mechanical properties
• Environmental control
components or between device and • Manufacturing that affects the
packaging physical characteristics • Antimicrobial effectiveness
• Manufacturing that alters the • Storage (including transport) • Preservative effectiveness
chemistry of materials or components conditions, e.g., temperature,
• Radioactive decay humidity, light, vibration

Therapeutic: impact of storage or use conditions on intended therapeutic or diagnostic function

Toxicological: formation of device degradation by-products during storage or use that produce an adverse toxic
effect
Biocompatibility: potential adverse effects on biocompatibility due to storage or use

Note that the above factors are device-specific!

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 Risk Analysis
It is recommended to perform a risk analysis that

• is in accordance with the currently FDA recognized version

of ANSI/AAMI/ISO 14971 for all stability factors to
determine if and what shelf life testing is needed
• is specific to the medical device type with consideration to
• nature of the device and intended use
• materials and components used to manufacture the
device
• manufacture method and process (including
sterilization)
• packaging, storage and transportation conditions

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 Product Shelf Life Testing
FDA guidance - Shelf Life of Medical Devices April 1991
FDA guidance documents on various devices (see references at the end)

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 Shelf Life or Stability Testing
Shelf life testing is conducted to support the proposed expiration date through
• evaluation of the package integrity for maintaining device sterility (for devices provided
sterile by manufacturers) - packaging shelf life or stability testing (Mr. Steven Turtil’s
presentation)
and
• evaluation of any changes to device performance or functionality – product shelf life or
stability testing (topic for this presentation)
• The expiration date in the labeling should be in accordance with both test results if applicable,
i.e., minimum value of these two results*
test results labeled shelf life
If package shelf life > product shelf life product shelf life
If package shelf life < product shelf life package shelf life;
*unexpired sterile packaged device may be re-packaged and re-sterilized
with a reworking procedure, if a validated method has been provided.

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 Considerations for Establishing Product Shelf Life
• Define a set of specifications or criteria for the final device’s critical characteristics and
performance with tolerance based on the intended use.
• Identify raw materials, components, packaging, and process factors; determine if
materials and components have their individual shelf life characteristics in addition to
their effect on final device shelf life.
• Develop an appropriate final device sampling plan (e.g., purpose, number, frequency,
criteria and lots) and a sample storage plan (storage and environmental conditions).
• Develop a simulation of shipping and handling stresses plan (e.g., vibration) to
determine the effect of unusual circumstances.
• Establish appropriate accelerated aging parameters when appropriate.
• For absorbable devices, their sensitivity to moisture and temperature should be
addressed by packaging description (e.g., use of foil) and testing.

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General Recommendations for Product Shelf Life Testing
• Product shelf life testing should evaluate all critical characteristics and performance of aged device
samples to ensure they are within the established specifications or criteria. Test report should include test
methods, results, and conclusions drawn from the results.
• Accelerated studies are acceptable for some products to support tentative dates and storage conditions, as
long as they are followed and supported by real time studies. For accelerated aging, we recommend:
• using the currently FDA-recognized version of ASTM F1980 and specifying the environmental
parameters established to attain the expiration date.
• specifying the way in which the devices were aged and provide a rationale to explain how the results
of shelf life testing are representative of the results if the device were aged in real time.
• Accelerated studies may not be appropriate for some products because of their complexity, degradative
properties, lack of adequate methodology, or insufficient historical data. In this case, the shelf life should be
based on the real-time aged sample test only, e.g., with a short initial shelf life, which will be extended after
additional test results.

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 General Regulatory Requirements for Shelf Life
510(k) – Premarket Notification
• The shelf life of the device should correspond to the duration of aging completed; a summary of test reports should
be submitted prior to 510(k) clearance.
• Changes in device expiration date do not require a new 510(k). However, where methods or protocols not described
in the original 510(k) are used to support new package integrity or shelf life claims, a new 510(k) may be necessary.
• For certain devices or components, testing should be conducted on real-time aged samples to confirm the results of
the accelerated aging study. This testing should be conducted in parallel with 510(k) review and clearance, with
results documented to file in the design history file.
PMA – Premarket Approval
• The approval order shall include the shelf life of the device; test reports should be submitted prior to FDA approval.
• If FDA has previously reviewed and accepted a protocol for changes to the expiration date and testing was
performed in accordance with that protocol, the change to the expiration date can be made and reported in an
annual report. If not, a PMA supplement should be submitted for FDA approval (https://www.fda.gov/medical-
devices/premarket-approval-pma/pma-frequently-asked-questions#9).

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Product Shelf Life Testing – Examples
FDA guidance documents on various devices

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 Example 1. Joint Arthroplasty Devices
components materials product shelf life
testing
acetabular cup metals (e.g., titanium Not needed
alloy)
femoral stem Surface coating (e.g., Yes for coatings in
titanium, calcium blue
phosphate)
femoral head metals (e.g., cobalt Yes for materials in
chrome alloy) or blue
ceramics (e.g., alumina,
https://www.orthopaedicandsportsclinic.com/about/education.s
zirconia)
tryker_brochures.english.total_hip.5.php
acetabular polyethene or ceramics Yes for materials in
liner (e.g., alumina, zirconia) blue

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Example 1a. Polyethylene Implants - Guidance
Characterization of Ultrahigh Molecular Weight Polyethylene (UHMWPE) Used in Orthopedic
Devices Guidance, issued on April 26, 2019 (https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/characterization-ultrahigh-molecular-weight-
polyethylene-uhmwpe-used-orthopedic-devices )
• The mechanical properties of UHMWPE that contains unstable free radicals may degrade if
the product is exposed to air during shelf storage. In addition, the shelf life of UHMWPE that https://www.zimmerbiomet.com/en/products-and-
has been irradiated and packaged in an inert environment may be limited by the integrity of solutions/specialties/hip/longevity-high-cross-
linked-polyethylene.html
the packaging material. Therefore, FDA recommends that the stability of UHMWPE materials
used in implantable devices be assessed for the duration of their specified shelf life.
• With respect to evaluating the effects of aging on device performance or functionality, shelf
life studies should evaluate the critical device properties… (Note: materials and mechanical
testing) and repeat all tests that evaluate design components or characteristics that are
potentially affected by aging.
• We recommend devices undergo real-time aging to determine definitively the effects of aging
on the maintenance of sterility and device performance. If you use devices subjected to
https://www.zimmerbiomet.com/en/products-and-
accelerated aging, we recommend that you specify the way in which the device was aged and solutions/specialties/hip/vivacit-e-vitamin-e-highly-
develop a rationale to explain how the results of shelf life testing based on accelerated aging crosslinked-polyethylene.html
are representative of the results if the device were aged in real time…

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 Example 1a. Polyethylene Implants – a recall case
Nonconformance in the integrity of packaging significantly affects the device performance
• The FDA recently issued a safety communication on Risks with Exactech Joint Replacement Devices
with Defective Packaging to remind patients and health care providers about the joint replacement
devices manufactured by Exactech and their recalls in 2021 and 2022.
(https://www.fda.gov/medical-devices/safety-communications/risks-exactech-joint-replacement-
devices-defective-packaging-fda-safety-communication).
• All Exactech joint replacement devices contain a plastic (polyethylene) component which should be
in packaging that contains multiple oxygen barrier layers as indicated in the package specification.
• The recalled devices (including knees, ankles, and hips) were packaged in defective bags that
were missing one of the oxygen barrier layers that protect devices from oxidation, a chemical
reaction with oxygen that can degrade plastics over time. Oxidation can lead to accelerated
device wear/failure, and component cracking or fracture, all leading to corrective revision surgery
and even bone loss.

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 Example 1b. Surface Coatings
Recommendations based on current review practices
• With respect to evaluating the effects of aging on performance or functionality of a
calcium phosphate coated device, shelf life studies should evaluate the critical physical,
chemical and mechanical properties of the calcium phosphate coating to ensure the
coated device will perform adequately and consistently during the entire proposed shelf www.depuysynthes.com

life. We recommend that you repeat all tests that evaluate critical coating characteristics
that are potentially affected by aging using aged devices.
• We recommend that you provide the protocol(s) used for your shelf life testing, results,
and the conclusions drawn from your results. For some resorbable calcium phosphate www.stryker.com

coatings, you should conduct testing on real-time aged samples to confirm the results
of the accelerated aging study. This testing should be conducted in parallel with
submission review, with results documented to file in the design history file.

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 Example 2. Resorbable Bone Void Filler Devices
Recommendations based on current review practices
• Shelf life studies should evaluate the critical chemical, physical and mechanical properties of
the device that are required to ensure it will perform adequately and consistently.
• Data supporting the expiration date for the final, finished, sterilized, resorbable bone void filler
device should be submitted based on real- time stability testing. The following parameters
should be evaluated upon real time storage over the shelf-life of the product and collected
from at least three production lots:
a. Final device chemical characterization (e.g., XRD, FTIR)
https://www.techsciresearch.com/blog/top-
b. Endotoxin level industry-players-in-the-bone-void-fillers-
c. pH market/1308.html
d. Water/moisture content
e. Handling (e.g., ability to absorb hydration fluids, mixing time, setting time, and hardening times, intact, viscosity
f. Molecular weight distribution for resorbable bone void filler devices with a polymer component
g. SDS-PAGE and/or differential scanning calorimetry (DSC) to assess the stability (e.g., degradation, physical size
assessment, molecular weight, etc.) of resorbable bone void filler devices that contain biologically-derived polymers
h. Any other parameters identified as part of the device release specification (e.g., appearance, color, dimensions, etc.)

• Because accelerated stability conditions can detrimentally alter the characteristics of

resorbable bone void filler devices containing biologically-derived components (e.g., collagen,
alginate, gelatin), it is necessary to validate any accelerated stability test with real -time https://www.zimvie.com/en/spine/biolog
stability testing for the same stability parameters. Once validated, the accelerated stability ic-solutions/copios-bone-void.html

tests may be used for future stability assessments.

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Example 3: Patient-Matched Guides and Implants
Recommendations based on current review practices
• For patient-matched guides and implants, shelf life should reflect an
appropriate duration between the acquisition of patient imaging and the
planned surgical intervention to ensure that the anatomical situation has not
changed such that guide performance can be affected.
• Consideration should be taken for the age and growth rate of the patients.
• The shelf life should be based upon the indicated patient pathology and
sensitivity of the patient-matched regions to continued disease progression.
• As patient-matched guides rely upon a specific geometrical configuration to
establish a unique alignment onto the patient’s anatomy, we also recommend
that guide deformation as a result of shipping be considered. Additional
dimensional testing should demonstrate that guides do not deform following
https://fit2patient.com/clinical-cases/patient-
simulated distribution testing. specific-surgical-guides-for-femoral-osteotomy

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 Other Devices
• Product shelf life testing is device-specific; please check with
the OHT office that regulates the specific device for relevant
guidance documents or standards:
• e.g., ISO 11979-6:2014(E) Ophthalmic implants —
Intraocular lenses — Part 6: Shelf-life and transport
stability testing
• For more specific questions, please submit a Pre-Submission
to request feedback per the FDA Guidance entitled “Requests
for Feedback and Meetings for Medical Device Submissions: https://en.wikipedia.org/wiki
/Intraocular_lens
The Q-Submission Program” (https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/requests-
feedback-and-meetings-medical-device-submissions-q-
submission-program)

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 References
• Shelf Life of Medical Devices https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-life-
medical-devices
• Bone Anchors - Premarket Notification (510(k)) Submissions https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/bone-anchors-premarket-notification-510k-submissions
• Characterization of Ultrahigh Molecular Weight Polyethylene (UHMWPE) Used in Orthopedic Devices
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/characterization-ultrahigh-molecular-
weight-polyethylene-uhmwpe-used-orthopedic-devices
• Deciding When to Submit a 510(k) for a Change to an Existing Device https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/deciding-when-submit-510k-change-existing-device
• Recognized consensus standards database https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm
• FDA Guidance Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-
device-submissions-q-submission-program
• PMA Frequently Asked Questions | FDA: https://www.fda.gov/medical-devices/premarket-approval-pma/pma-frequently-
asked-questions#9
• ANSI/AAMI/ISO 14971: 2019 Medical devices—Application of risk management to medical devices
• ASTM F1980-21 Standard Guide for Accelerated Aging of Sterile Barrier Systems and Medical Devices
• ISO 11979-6:2014(E) Ophthalmic implants — Intraocular lenses — Part 6: Shelf-life and transport stability testing
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 Acknowledgments
OHT6 - Office of Orthopedic Device, OPEQ, CDRH FDA International Offices
• Mr. Steven Turtil (DHT6B) • Vesa Vuniqi, US FDA International
Relations Specialist
• Dr. Melissa Ramcharan (DHT6C)
• Patty Pineda, International Regulatory
• Mr. Christopher Ferreira (Team Lead, DHT6A)
Analyst, Latin America Office
• Dr. Jesse Muir (Acting Assistant Director, DHT6A)
• Katherine Serrano, US FDA Regional
• Dr. Constance Soves (Associate Director for Policy) Director, Latin America Office
• Dr. Jiping Chen (Division Director, DHT6A)
• CAPT Raquel Peat (Office Director)

• Dr. Jinrong (Jinny) Liu (Team Lead, OHT1)

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 Thank You!

QUESTIONS?

Email: [email protected]

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