FDA released two new draft guidances on Monday, August 8 in an attempt to help device manufacturers determine when a modification triggers the obligation to file a new 510(k) under 21 C.F.R. § 807.81(a)(3). The first draft guidance, entitled Deciding When to Submit a 510(k) for a Change to an Existing Device (“2016 Device Change Guidance”), is a revision to FDA’s 1997 final guidance of the same name (“1997 Final Guidance.") The other is a spinoff guidance, entitled Deciding When to Submit a 510(k) for a Software Change to an Existing Device (“2016 Software Device Change Guidance”), which is specific to software modifications. It is important to note that the 1997 Final Guidance represents FDA’s official current policy on regulatory responsibilities stemming from device modifications, but in our experience, elements of the policy in the draft guidances may be used by the FDA immediately even before finalization.

History in the Making

Back in 2011, FDA attempted to revise the 1997 device modification guidance by removing the iconic flowcharts (which, incidentally, have become a major component of manufacturers’ Quality Management System policies relevant to device modifications) and including some additional guiding questions and examples based on new technology. The medical device industry roundly castigated the 2011 draft guidance as being grossly over-inclusive such that every possible change, especially to software, “could significantly affect” a device’s safety and effectiveness.  Congress heard the industry’s criticism, particularly U.S. Senators Richard Burr and Al Franken, who championed a provision in FDASIA to require FDA to remove the burdensome guidance “that could triple the number of required submissions for existing devices.” FDASIA was enacted with a provision adding Section 510(n)(2)(B) to the Food, Drug, and Cosmetic Act (21 U.S.C. § 360(n)(2)(B)), which forced FDA to withdraw the 2011 Draft Guidance.

Less Change, More Guidance

In contrast to the withdrawn 2011 guidance, the new draft guidances focus more on helping manufacturers through the decision-making process and to make reasonable decisions about when a modification significantly alters a device’s risk profile or its indications for use. To that end, FDA has retained the flowchart or logic tree model and has honed the questions to be more descriptive and applicable to real-world device changes. The 2016 Device Change Guidance emphasizes FDA’s intent to distinguish between significant, new changes and changes that have only superficial impact on the device using three approaches:

1. Questions acknowledging that risk-profile changes stemming from a device modification may already be mitigated. For example:

   1. “Does a risk assessment identify new or significantly modified risks?” (Questions A5.2, B5.2)

   2. “Is the same method or protocol, described in previous 510(k), used to support change?” (Question B4.1)

   3. “Has the manufacturer used the same material in a similar legally marketed device?” (Question C4.1)

2. General risk-based analysis categories with relevant guidelines. For example:

   1. “Does a risk assessment identify any new or significantly modified risks?” (Question A5.2, B5.2)

   2. “Does a risk assessment identify any new or increased biocompatibility concerns?” (Question C4)

   3. “Any unexpected issues from V&V activities?” (Question B5.4)

   4. “Do the design verification and validation activities produce any unexpected issues of safety or effectiveness?” (Question D4)

3. A separate Appendix A with a range of examples relevant to each flowchart question.

Separate Software Modification Guidance?! Welcome to the 21st Century, FDA!

One of the main ambiguities in the 1997 Final Guidance is the process of determining whether modifications to medical device software necessitate a new 510(k). FDA received much criticism for attempting to handle software device modifications with the same process as non-software devices in the withdrawn 2011 Draft Guidance.  On August 8, FDA released separate draft guidance specific to 510(k) decisions involving software changes.  Although certain sections of the 2016 Software Device Change Guidance closely mirror the 2016 Device Change Guidance, such as the guiding principles and general focus on possible new risks or hazards related to changes, the software guidance flowchart and examples focus on version control, coding issues, and other software-specific design considerations.  This approach allowed FDA to treat modifications involving coding and software-hardware interaction issues separate from hardware-specific issues, instead of forcing software and hardware considerations together into one, confused process.

The 2016 Software Device Change Guidance flowchart calls out the most significant changes that would clearly trigger the new 510(k) requirement in 21 C.F.R. § 807.81(a)(3) (e.g., changes to cybersecurity, software specifications, risks, and clinical functionality), but also includes an overall, risk-based strategy for catching more general or cumulative changes that could affect the device’s risk profile or indication. Appendix A of the draft guidance also includes multiple examples specific to each flowchart question.  The inclusion of relevant examples with answers and rationales directly connected to guiding questions specific to software helps provide a clearer path to a reasonable reporting decision, and is an element that was sorely lacking in the 2011 withdrawn guidance.

Another helpful element included in the 2016 Software Device Change Guidance is the “Common Software Change Types” section which describes different types of modifications, such as to software “infrastructure” and the “core algorithm,” and provides general advice about whether such types of modifications typically will or will not require new 510(k)s (for example, “cosmetic changes” which only alter the appearance of the device likely would not require a new 510(k)). Oddly, FDA includes brief descriptions of different, general types of software modifications (i.e., “adaptive,” “corrective,” “perfective”) in the Scope section, but then never incorporates those descriptors into the flowchart considerations or the general, risk-based guidelines.

Comments

Guidance concerning manufacturer responsibilities with respect to medical device software modifications has been one of the critical missing links in FDA guidance. FDA has attempted to take a balanced approach in the two draft guidances, but all manufacturers that produce medical devices with a software component should consider both guidances and determine whether the flowcharts guide reporting decisions to a reasonable conclusion based on the proposed modification.

FDA is currently accepting comments on the draft guidances in separate dockets on Regulations.gov:

• Docket FDA-2016-D-2021 for Deciding When to Submit a 510(k) for a Change to an Existing Device

• Docket FDA-2011-D-0453 for Deciding When to Submit a 510(k) for a Software Change to an Existing Device

FDA recommends sending comments by November 7, 2016 so that the Agency can consider the comment before it begins working to finalize the guidances.