Can the safe history of clinical use (no complaints registered in PMS) be used as justification not to assess degradation as well as risk for leachables/extractables/ particle release in the biocompatibility evaluation of a medical device? That depends largely on what material or manufacturing change for your subject device is under examination. The short answer is it may be possible, but there are a lot of caveats. The fuller answer is much more complex. You should start by referring to ISO 10993-1:2018 for the “history of safe clinical use” concept. In the standard, Clause 6.1 states:
“If the combination of all materials, chemicals and processes has an established history of safe use in the intended application, and the physical properties have not changed, then it is possible that further characterization and additional data sets (e.g., chemical analysis of extracts or biological testing) will not be necessary. In this case the rationale shall be documented.”
ISO 10993-18:2020, Annex C, describes the principles for establishing biological equivalence. If the predicate device is biocompatible according to Part 1 requirements, the only testing necessary will be that to verify equivalence to the biocompatible device. On that basis (i.e., thinking in the context of 10993-1 and the risk assessment process, in general), the question needs to be considered in two parts–one for each of the biological endpoints under consideration (degradation and leachables).
Regarding degradation, 10993-1, Clause 220.127.116.11 states degradation need only be considered for some devices; specifically, those “that have the potential for degradation within the human body.” The standard also gives a couple of example cases for which degradation would need to be considered: devices designed to be absorbable, and devices for which “an informed consideration of the finished medical device composition indicates that toxic degradation products might be released during body contact.”
For cases in which the degradation endpoint *does* need to be addressed, the previously cited clause of 10993-1 states:
“In vivo degradation tests might not be necessary if an in vitro / in vivo comparison for the absorbable medical device has been previously demonstrated and in vitro degradation studies show that only the probable products of degradation are present in the predicted quantities, and produced at a rate similar to those that have a history of safe clinical use.”
Thus, it is reasonably clear it may be possible for history of safe clinical use to be part of a rationale for no in vivo degradation test to assess this endpoint. Clearly such an approach would also need to include a robust demonstration of equivalence, including bench testing results. If your device has the potential to release degradation products through a mechanical process (e.g., a metal on metal hip implant), physical and material equivalence to the clinically established device is verified (e.g., wear testing, corrosion studies, particulate analysis, SEM, light microscopy, X-ray analysis, etc.). If your device is absorbable or has the potential to biodegrade, an in vitro degradation study is generally unnecessary if you can demonstrate equivalence (i.e., you have sufficient material formulation information and degradation data relevant to degradation products in the intended use).
For leachables, the endpoint needs to be considered for all device types (e.g., see 10993-1:2018, Table A.1). It may be possible to use history of safe clinical use with a robust demonstration of equivalence to support no need for additional testing. Just one sticking point (of many) could be whether there is already robust chemical information for the predicate device with a history of safe clinical use.
Other factors that go into the leachables assessment process include the device contact type and duration (i.e., nature and level of exposure), the indications for use (i.e., underlying patient risk), and the manufacturing processes.
Be aware that “history of safe clinical use” is a somewhat contentious concept. Part 1 gives only scant information, but implies that clinical data may need to be part of the history. This is because complaint processes are known to generally under-report adverse events. Even if you have clinical data, this approach may well not succeed because the endpoints measured in the study may have very poor sensitivity for some biological endpoints (e.g., genotoxicity).
A technically competent risk assessor will review all available information to determine if there are potential patient safety concerns not addressed through characterization, testing, or clinical use. We have helped a great number of clients successfully navigate biocompatibility issues with regulators. Please contact us today to learn more about how we can partner with you. 855.463.1633 | email@example.com | Request a Quote | medinstitute.com
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