On September 13, 2019 FDA issued a final guidance document The Special 510(k) Program (“Guidance”). We blogged about the prior draft guidance here. This Guidance, along with The Abbreviated 510(k) Program, supersedes the 1998 guidance document The New 510(k) Paradigm – Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications. The Abbreviated 510(k) Program reflects the Abbreviated 510(k) information from the superseded guidance. In parallel, FDA also updated Format for Traditional and Abbreviated (510(k)s) and Refuse to Accept Policy for 510(k)s (“RTA Guidance”) to reflect the updated Special 510(k) Program. The RTA Guidance includes an introductory note that FDA will not begin using this version until November 13, 2019, allowing a period for transition.
The Special 510(k) program was established to create a streamlined review of technological changes made to a manufacturer’s own cleared device, leveraging design control requirements. In its original form, changes reviewed under the Special 510(k) program were limited to those that did not affect the intended use of the device or alter the fundamental scientific technology. Over years of use, many sponsor’s experienced frustration with Special 510(k)s being converted to Traditional 510(k)s in situations where FDA wanted to review the data associated with a change, even though the change met the criteria of not affecting the indications for use or fundamental scientific technology. FDA’s focus for Special 510(k)s is now on “whether method(s) to evaluate the change(s) are well-established, and whether the results can be sufficiently reviewed in a summary or risk analysis format,” which better reflects the past practice. Guidance at 6.
There are not many differences between the previous draft and the final guidance. The overall basis for when a Special 510(k) may be appropriate is unchanged:
- “The proposed change is submitted by the manufacturer legally authorized to market the existing device;
- Performance data are unnecessary, or if performance data are necessary, well-established methods are available to evaluate the change; and
- All performance data necessary to support SE can be reviewed in a summary or risk analysis format.” at 8.
Most changes provide clarification of specific points and several new examples have been included, including five new IVD examples in Appendix B describing IVD changes that would be suitable for a Special 510(k). Also, a statement was added within the background that a “Special 510(k) would generally not be appropriate for devices that manufacture a biological product at the point of care, because there would likely be no well-established method to evaluate such changes and/or the performance data would not be reviewable in a summary or risk-analysis format.” The Guidance now also clarifies that it does not supersede device-specific policies. Thus, if another FDA document recommends submission of complete test reports, a Special 510(k) would not be appropriate even if the change met criteria with the Guidance.
With respect to discussion of “well-established methods,” there are several changes worth noting. The Guidance provides clarity that “minor deviations to a well-established method may be acceptable within the context of a Special 510(k), but significant deviations to the protocol or acceptance criteria of a well-established method can result in the 510(k) no longer being appropriate for review as a Special 510(k).” Id. at 11. It also now states that well-established methods may include qualified medical device development tools (MDDTs) and methods found in an FDA guidance document. Finally, with respect to IVD verification and validation, the Guidance clarifies that use of clinical specimens does not necessarily mean that a well-established method does not exist to evaluate the change.
In discussion of “Additional Considerations,” the draft guidance had stated that a Special 510(k) may not be appropriate when “several” scientific disciplines were necessary to evaluate the change. In the final guidance, FDA has provided a number, indicating that reviews involving “greater than three scientific disciplines (e.g., biocompatibility, sterility, electromagnetic compatibility)” would likely be too difficult to review in 30 days and would not be appropriate in a Special 510(k). Id. at 13. The list of common scenarios where FDA anticipates necessary review of complete test reports has also been amended to include submissions where use of analytical chemistry testing per ISO 10993-18 and/or toxicological risk assessment using ISO 10993-17 are used to address biocompatibility. This is noteworthy as Example C.2 for example design control activities describes material changes evaluated by biocompatibility testing in a Special 510(k) format. When deciding whether to perform biocompatibility testing or chemical characterization with toxicological risk analysis to address the biocompatibility of a device modification, the possibility of submitting a Special 510(k) should be considered.
In conjunction with release of the draft guidance, FDA began a pilot program intended to test the process to determine if it could achieve FDA’s goal of an increase to the number of 510(k)s appropriate for the Special 510(k) program. Results of the pilot have not been released, but finalization of the guidance without significant changes suggests it was deemed successful. One final clarification in the Guidance is that in cases where they do not agree that a Special 510(k) is appropriate, FDA intends to explain the basis for the conversion of the submission to a Traditional 510(k). We are hopeful that the combination of the final guidance and better information when a submission is converted will lead to a more predictable Special 510(k) review process.