ISO 10993-1 provides the governing foundation for the biological evaluation of medical devices, explaining the fundamental requirements and general principles. The eagerly awaited update to ISO 10993-1, relevant to all kinds of medical device, is due to be published in November this year. Below, our Senior Operations Consultant and Biocompatibility Specialist Dr. Silvio Peng highlights five important updates from the draft standard.

Closer alignment with ISO 14971

The updated, reorganised standard shares an even closer alignment with the risk management framework as per ISO 14971.

This affects the terminology in the standard, including a consistent use of “biological hazard” (i.e., the potential source of a biological harm), the replacement of the term “biological endpoint” with “biological effect”, and the definition of “biological equivalence”.

The useful addition of the definition of biological equivalence explains in more detail which kind of attributes require consideration to declare biological equivalence, which can help to limit or even avoid testing by utilising existing data. Effectively evaluating biological equivalence requires discussing chemical and physical equivalence as part of material equivalence as well as contact equivalence of the medical devices in scope.

Within the updated standard, the application of risk management includes performing biological risk estimation and biological risk control. Undertaking these tasks facilitates the estimation of the severity and occurrence probability of harm of the biological risks, for example, by applying the guidance included in Annex C of the standard. Consequently, for biological risks which show considerable residual risks, additional risk control is required to further mitigate to the greatest extent possible, for example, via design changes, protective measures, and/or provision of information to users.

Inclusion of “reasonably foreseeable misuse”

Whilst the scope of ISO 10993-1 remains the same, i.e., covering medical devices with direct or indirect body contact, it now includes not only the intended use of the device, but also the reasonably foreseeable misuse.

This means additional considerations for evaluators, who will need to discuss the potential misuse and consequently the associated risks by applying the same steps as for the intended use, such as the above-described risk estimation and control.

Reorganisation of biological endpoints (effects)

ISO 10993-1’s reorganisation includes the removal of the categorisation matrix highlighting the relevant biological endpoints (now called biological effects as noted above), and instead several tables have been added, which cover only a specific contact type.

In addition, the biological endpoint “Physical and chemical information” has been removed from the tables and omitted as a biological effect. Nonetheless, the respective information, which includes an assessment of the device’s materials, will still be required, but is now covered in other sections of the standard (for example, biological risk analysis). The importance of this step is given additional awareness in Annex A, to support material selection and characterisation.

Furthermore, the updated standard provides specific guidance for certain types of medical devices and their individual biological effects, which are outlined including a description of relevance for certain categories of devices.

Expanded explanation for exposure duration

The updated standard introduces the term “Contact Day”, which refers to any day a device has contact with the user, irrespective of the duration.

In addition, the calculation of exposure duration for devices with daily contact and intermittent contact (i.e., used in a certain frequence but with minimum resting period of one day) is explained.

Both changes can affect the device’s exposure duration and trigger a re-categorisation. As such, depending also on the type of body contact, consideration of additional biological effects might be required.

Additional emphasis on life cycle & animal welfare

The medical device’s life cycle and animal welfare receive additional emphasis in the updated standard. Medical devices require evaluation over the entire life cycle, i.e., potential changes in characteristics such as the device’s material require consideration during transport, storage, and use. For reusable devices, this also requires consideration of processing cycles. Whilst this is not a new requirement, the expectations are specified in more detail in the updated standard.

Regarding animal welfare, the 3R principle (replace, reduce, refine) is further substantiated to limit in vivo testing to evaluations where it is strictly necessary.

In summary…

The update to ISO 10993-1 is not a complete overhaul but rather a refinement of the biological evaluation as performed to date.

Emphasis on strengthening the already established risk-based approach of the biological evaluation is evident, tying ISO 10993-1 more closely to the general requirements of ISO 14971.

Consequently, the updated standard does not mandate re-testing of medical devices which are already on the market. Nonetheless, careful assessment and documentation of historical information is required to determine if any differences impact the conclusions of the biological safety evaluation.

On a final note, bear in mind that this article is based on a draft of the standard. Medical device manufacturers should carefully review the final published version and adapt any biological assessments to the updated requirements.

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