By Allyson B. Mullen –
On June 16, FDA issued the final guidance “Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.’” This final guidance replaces the draft guidance issued on April 23, 2013.
Biocompatibility testing is an area where many device struggle to meet FDA’s requirements. For example, some companies think simply because its patient contacting material is widely used in the industry it should not need to be tested. FDA, on the other hand, generally expects that nearly all patient contacting devices will be subjected to biocompatibility testing, unless the manufacturer provides a suitable scientific rationale justifying why testing is not required (e.g., materials and manufacturing/processing are identical to the predicate). This final guidance should provide manufacturers with guidance as they work to identify what biocompatibility testing is needed for their devices.
The final guidance is mainly unchanged from the draft, with a few notable exceptions:
- Based on comments from industry requesting additional clarification, FDA removed devices in contact with gas pathways and color additives from this guidance. Biocompatibility of these materials/devices will be covered in separately in other guidances.
- New Attachment B outlines the information that FDA would expect (although presumably not require, because this is a guidance document) to have in a device master file for biocompatibility assessments.
- The final guidance includes a helpful glossary of key biocompatibility terms.
In our view, the most important change in the final guidance is that it takes a risk-based view of biocompatibility assessments. The guidance now begins with a section entitled “Risk Management for Biocompatibility Evaluations.” Rather than simply assessing the contact type and duration to determine, based on FDA’s modified matrix, which biocompatibility tests are required, the guidance suggests beginning by performing a risk analysis of the device materials. Once the risks are identified, a gap analysis can be performed to see what information, if any, is available to mitigate the identified risks. Any regulating gaps would be excepted to be filled in with biocompatibility testing.
The guidance provides advice on how to perform such a risk analysis. It also outlines several types of information that may mitigate biocompatibility risks, including manufacturer’s prior experience, published literature, clinical information, animal studies, and other previously cleared devices. Now, in the biocompatibility section of premarket submissions for devices, FDA suggests that applicants begin with their risk assessment rather than the contact type and duration as specified in ISO 10993-1, although we expect FDA will still want to manufacturers to identify the later.
The guidance appears to suggest that biocompatibility testing may not always be needed so long as other information as to the biocompatibility of the material exists. However, FDA is quick to note that it does not clear individual materials. The biocompatibility of the material is affected by device-specific features, including the manufacturing processes, tissue contact type and duration of contact. Although not stated in a guidance, FDA has historically said that biocompatibility can be shown through alternative information (not just ISO 10993 testing). In our experience, however, FDA is rarely accepting of such alternative information because, for example, the manufacturing processes are different between the material that is the subject of the alternative information and the proposed device, or the alternative information did not specifically consider biocompatibility (e.g., in a clinical or animal study). We find it encouraging that FDA has put this policy in the final guidance. We will be interested to see if FDA becomes more accepting in practice of alternative information to support biocompatibility.
Consistent with its practice for other recent final guidances, FDA plans to hold a webinar to discuss the final guidance on July 21, 2016. Registration information for the webinar can be found on FDA’s website.