Device changes and how they may impact biocompatibility

Medical devices will go through many changes throughout their product lifecycle, such as change of suppliers for raw materials, change of production site, or development in subsequent product generations where technical improvements are central.

Impact on the biological safety

Throughout these processes, it is crucial to not forget the biocompatibility aspect. Whenever a device is subject to a change, big or small, it should undergo a review to determine the impact of the change on the biological safety of the device. While many changes may be justified based on a minimal impact on previous risk assessments, other changes could pose a serious biological safety impact and require a revalidation of processes or generation of new test data to allow assessment of the novel risk and a conclusion on continued biological safety of the device. 

It is also possible that a change that is perceived as minor, such as change in patient group, actually might lead to that the whole biological evaluation needs to be redone as basic assumptions for the evaluation have been changed, affecting everything from design of individual tests to selection of parameters for toxicological assessments. 

Plan and fill GAPs

Planning for a change to an existing device should immediately trigger a reopening of the biological evaluation plan, to allow the change to be assessed from all aspects that might affect the biocompatibility of the final device. By reviewing the existing plan and incorporating the planned change, it is possible to see how the change fits in with the already performed biological risk assessment performed for the device, and to see whether more information would be needed to conclude the risk assessment and sum up the conclusions in the biological evaluation report. 

An example of such information could be to repeat chemical or biological tests using the novel device version, to get input to how the change impacts that specific endpoint. It is also possible to design smart testing strategies already from the start, anticipating and planning for future changes so that repetition of costly, time-consuming, and/or ethically problematic tests is minimized. Here, chemical tests evaluating the extractables/leachable profile of a device version can be an especially useful tool. 

Records

It is crucial to keep good records of performed changes, and also of the identity and composition of any device that is subjected to chemical or biological testing. It is always the responsibility of the manufacturer to show that old test results are still relevant for a new device version, and to do so of course the basic requirement is to know what was tested in the first place, sometimes a long time ago. Any failure to properly document test materials in a way fulfilling e.g., GLP requirements will inevitably lead to that new tests will have to be performed. 

A continuous process

In short, the biological evaluation is a continuous process, starting with a plan, filling in any information gaps, concluding on biological risks in the report, and then a review of the plan (as documented in a recent version) following any change to the device that was originally evaluated. The review of the plan would result in another completed circle of filling in information gaps and redoing the risk assessment. 

Changes triggering a review can be not only in the device design, selection and source of raw materials, or in production processes such as selection of subcontractors for specific procedures, change in sterilization method, formulation, use of additives, etc., but also in the intended use of the device, the type and/or duration of body contact, or the patient group. 

It might also be that emerging post market information regarding the biological safety of the device triggers the need for a reassessment of the original assumptions in the performed risk assessment. Another reason to re-open the plan could be new regulatory requirements or the publication of new standards. 

We can assist

At GBA Key2Compliance we can help you determine the impact of your changes and how to assess the possible impact on biocompatibility. We can also help you to implement efficient change management procedures, where all possible risks related to each change will be addressed in a streamlined process, and unnecessary novel testing is avoided.