On August 8, 2016, the U.S. Food and Drug Administration (FDA) issued draft guidance on the important topic of deciding when to submit a new 510(k) premarket notification application (510(k)) for a change to an existing medical device.1 Manufacturers commonly make changes to their medical devices, including: labeling changes (e.g., adding a contraindication), changing one or more device materials (e.g., from stainless steel to titanium), and changing the device's specification(s) (e.g., to improve the device's performance).
Deciding when to submit a new 510(k) is important to the medical device industry because:
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assembling, submitting, and gaining clearance for a 510(k) application can be time consuming, expensive, and logistically challenging;2
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the FDA can stop the sale of a changed medical device lacking a new 510(k) premarket clearance; and
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the U.S. Department of Justice (DOJ) (after referral from the FDA) can criminally prosecute device companies and executives for failure to obtain required additional clearances (e.g., a misbranding charge).3,4,5
The 2016 Guidance
The FDA's 2016 guidance,6 which runs 73 pages, is roughly divided into the following sections: guiding principles; decision aiding flow charts and accompanying clarifications; examples; and documenting a decision to not file a new 510(k). While a complete analysis of the 2016 guidance is beyond the scope of this alert, we've highlighted several important guidance aspects below.
Guiding Principles
The 2016 guidance lays out a set of higher-level guiding principles which manufacturers should consider when determining whether a new 510(k) submission is needed. The FDA first notes that modifications made with the intent to significantly affect safety or effectiveness of the device will likely require submission of a new 510(k) application.7 Also, even if a risk assessment concludes that safety and effectiveness will not be significantly affected, a situation can arise where the modification(s) significantly affect routine device evaluation, or where routine verification and validation activities produce unexpected issues. In these circumstances, the FDA notes that "any prior decision that a new 510(k) is not required should be reconsidered."8 The FDA also suggests employing risk management as an evaluating tool, and that changes should be assessed individually and in the aggregate.9 When submitting a new 510(k), the FDA recommends describing all changes that trigger the requirement for a new 510(k), as well as those additional changes that were made but do not trigger a new submission requirement.10 Finally, the 2016 guidance also suggests that if multiple changes are made, but only one change triggers the requirement for a new 510(k), then the changes "that do not require a new 510(k) may be immediately implemented, as long as those changes can be implemented independently of changes that do require a new 510(k)."11
Flow Charts and Accompanying Clarifications
Like the 1997 guidance, the 2016 guidance includes flow charts that aid in the 510(k) new filing decision-making process. Individual flow charts are included for: labeling changes; technology, engineering, and performance changes (separate charts for non-in vitro diagnostic devices, and in vitro diagnostic devices (IVDs)); and considerations for risk assessments of modified devices. Flow chart endpoints are binary, ending either in "New 510(k)" or "Documentation," and the flow charts are accompanied by text that expands on flow chart decision points.
Examples
Over thirty examples are provided in the 2016 guidance. Some examples appear to be based on recent court cases. For example, in the recent Vascular Solutions case,12,13 the government charged Vascular Solutions, Inc., and its CEO Howard Root, with conspiracy and several counts of introducing misbranded and adulterated devices into interstate commerce. The case outcome turned on whether the company's promotion of its Vari-Lase product line for the treatment of perforator veins (deeper veins) was outside of the general indication that was cleared by the FDA—which the government maintained covered only superficial veins. The jury ultimately acquitted the company and its CEO of all counts, finding that the general indication encompassed deeper veins.
Example 6 of the 2016 guidance, for instance, appears to be related to the Vascular Solutions case. Example 6 recites that a catheter guidewire was originally cleared for accessing specific tissues. The guidewire's manufacturer expanded the labeling to include tissues not found original labeling. The FDA asserts this expansion could significantly affect safety and effectiveness, and recommends submitting a new 510(k).
Documenting a Decision to Not File a New 510(k)
Appendix B of the 2016 guidance reminds readers that if the manufacturer "determines that the device modification(s) does not require a new 510(k), it should document the decision-making process and the basis for that conclusion."14 Appendix B includes a bulleted list of material that should be included in the documentation, including reference to the 2016 guidelines.
Conclusion
The comment period for the FDA's newly published draft 2016 guidance is currently open. Interested stakeholders should submit their comments for the agency's consideration, as these may result in favorable draft guidance changes.
