The Food and Drug Administration (FDA) recently finalized its guidance on the Special 510(k) Program—an optional pathway to commercial medical devices that have been modified since their previous 510(k) clearance. The Special 510(k) pathway is available for certain well-defined device modifications where a manufacturer modifies its own legally marketed device, and its design control procedures produce reliable results that can form, in addition to other 510(k) content requirements, the basis for a substantial equivalence determination. Specifically, eligible device changes include certain design and labeling modifications whereby performance data are unnecessary; or if performance data are necessary, well-established methods are available to evaluate the change, and the results can be sufficiently reviewed in a summary or risk analysis format. Notably, this type of modification can even be a change to the device's indications for use, a type of change previously prohibited for this pathway. Under the new policy, instead of necessarily being converted to a Traditional 510(k) with a 90-day review clock, changes to a device's indications for use may qualify for the quicker Special 510(k) pathway's 30-day review. As described by the FDA, "a Special 510(k) provides an efficient pathway for manufacturers to provide the minimum required information necessary to establish substantial equivalence for a modified device."

To be within the scope of the Special 510(k) Program, the change must be made to the submitter's own legally marketed predicate device for two primary reasons. First, the Special 510(k) Program relies on the FDA's previous review of detailed information in the submitter's prior 510(k). Second, the Special 510(k) Program also leverages design control procedures that must be followed by medical device manufacturers as part of the overall Quality System prescribed under 21 C.F.R. Part 820. Design controls require that manufacturers conduct verification and validation to ensure that design outputs meet design inputs, and that devices conform to defined user needs and intended uses (21 C.F.R. 820.30(f) and (g)). A manufacturer that modifies its own legally marketed device is therefore able to conduct the risk analysis and necessary verification and validation activities to demonstrate to the FDA in a Special 510(k) submission that the design outputs of the modified device meet the design input requirements.

In cases where a manufacturer determines under its design control procedures that no additional verification or validation testing is necessary to evaluate a change that otherwise requires submission and clearance of a 510(k), the manufacturer may submit the change as a Special 510(k) with a clear rationale supporting its conclusion that no performance data are necessary. If, however, performance data are required, the change can still qualify for the Special 510(k) Pathway if well-established methods are available to evaluate the change and the results can be sufficiently reviewed in a summary or risk analysis format. Well-established methods are those that have been established for evaluation of the device, device type, or scientific topic area, and are validated according to scientific principles. These may include the submitter's methods, protocols, and acceptance criteria used to support the previously cleared 510(k) that can be applied to the subject 510(k); methods found in an FDA-recognized voluntary consensus standard or FDA guidance document; qualified medical device development tools (MDDTs); or widely available and accepted methods published in the public domain, scientific literature, or found acceptable by the FDA through the submitter's own 510(k)-clearance, a granted De Novo classification request, or premarket application (PMA) approval. Manufacturers should be aware 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 render the device change ineligible for review as a Special 510(k). Additionally, submissions that use methods that rely on clinical studies or animal data to support substantial equivalence are not considered appropriate for the Special 510(k) Program.

The final Special 510(k) criterion requires that the verification and validation results can be sufficiently reviewed by the FDA in a summary or risk analysis format. Put another way, when complete test reports or underlying data such as images, raw graphs, or line item data are necessary to support substantial equivalence, the device modification should not be submitted as a Special 510(k).

In the Special 510(k) guidance, the FDA also provides circumstances under which the agency believes a change would be categorically ineligible for the Special 510(k) Program. Among others, these circumstances include:

• When evaluation of the change(s) to the device generally involve more than three scientific disciplines (e.g., biocompatibility, sterility, electromagnetic compatibility);
• When a recent inspection has resulted in the issuance of a 483 Notice of Observation related to design controls that are relevant to the design changes under review in the 510(k).
• When Special 510(k)s are submitted for common scenarios that the FDA anticipates a review of complete test reports will be necessary to establish substantial equivalence, such as:
  • Changes to the indications for use that are supported by clinical, animal, or cadaver data;
  • Use of novel sterilization methods as described in the FDA guidance, "Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile;"
  • Change from single-use to reusable when reprocessing validation or human factors data should be provided; and
  • Use of analytical chemistry testing using ISO 10993-1820 and/or toxicological risk assessment using ISO 10993-17 21 to address biocompatibility.

In addition to providing examples of device changes that would qualify under each of the criteria described above, the Special 510(k) guidance also includes device changes that would fail under each criterion to help illustrate precisely where the FDA considers the threshold for Special 510(k) eligibility to be.

The Special 510(k) Program remains one of the quickest premarket review pathways for medical devices that have been modified and has become even more appealing now that it can apply to changes in indications for use. Manufacturers considering modifications to their devices are urged to evaluate whether this expeditious route to market is available for their device change, while taking into account applicable device-specific guidances, consensus standards, and other regulatory levers.

The FDA plans to host a webinar on October 31, 2019 to discuss this latest improvement to the 510(k) Program. For more information on the FDA's 510(k) Program, including the Special 510(k) Pathway, please contact David Hoffmeister, Georgia Ravitz, James Ravitz, Paul Gadiock, or any member of WSGR's FDA Regulatory, Healthcare, and Consumer Products Compliance practice groups.