How Many Hours are Really in a Day?

We recently blogged on FDA’s draft guidance, Chemical Analysis for Biocompatibility Assessment of Medical Devices, which describes chemical characterization methods that may be used to demonstrate biocompatibility of a medical device as an alternative to conducting certain biological testing.  We noted that the draft guidance’s discussion on determining a device’s contact duration raised concern as it contradicted ISO 10993-1:2018, Biological evaluation of medical devices —Part 1: Evaluation and testing within a risk management process. By way of background, FDA’s general guidance for biocompatibility, Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”, references ISO 10993-1 for identification of a device’s nature and duration of contact, including cumulative effects with repeated use.  The ISO 10993-1: 2018 standard, in turn, describes contact duration as the cumulative sum of single, multiple, or repeated duration of contact, although we are aware that a draft version of the standard (ISO/DIS 10993-1:2024) may be heading in a similar direction to the draft guidance.

As we noted in the previous post, Appendix A of the draft guidance for chemical analysis states that devices with short duration but repeated use are categorized according to the total number of days and not the total amount of time.  As an example, a device used daily for 5 minutes per day over 60 days would have a total contact time of 5 hours but would need to be tested as a device with long-term (> 30 days) contact duration, similar to an implant.  Another device that is used for 20 hours during a single day would be considered to have limited (< 24 hours) contact duration with fewer tests to complete, despite having a contact time four times longer than the first device.

We have seen this come up in many device reviews over the last several years, so we are not surprised to see it make its way to the draft guidance, but the justification for this burdensome approach is not provided and having conflicting recommendations in two related documents (i.e., the new draft guidance and ISO 10993-1: 2018) leads to more uncertainty for sponsors.  Finally putting this calculation method in the draft guidance appears to be a stake in the ground for the Agency to have a document to cite when it attempts to bully sponsors into performing additional testing that was not required of its predicate device.

Another problem this raises is that this method of determining contact duration conflicts with certain product-specific guidance documents (e.g., Latex Condoms for Men – Information for 510(k) Premarket Notifications:  Use of Consensus Standards for Abbreviated Submissions, Hemodialysis Blood Tubing Sets – Premarket Notification [510(k)] Submissions, Premarket Notification (510(k)) Submissions for Electrosurgical Devices for General Surgery, and Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities) and will likely cause additional downstream issues for sponsors when attempting to determine which biocompatibility endpoints require testing.

The time needed to conduct additional biocompatibility tests or a chemical analysis with toxicological risk analysis, if FDA disagrees with a device’s contact duration, may exceed the 180-day hold cycle.  Given this and the contradictions between the draft guidance, ISO 10993-1: 2018, and product specific guidance documents, use of FDA’s pre-submission process to align on necessary biocompatibility tests is recommended for devices used for short durations over multiple days or repeated use of the device by a single patient.

*KP Medical Device Consulting LLC