CDRH Finalizes Benefit-Risk Factors in Making Compliance and Enforcement Decisions Guidance

In June 2016 CDRH released the draft guidance “Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, Enforcement Decisions” (see our earlier post here). In the waning days of 2016, CDRH finalized the guidance.

The final guidance is largely unchanged from the draft with CDRH making mostly minor clarifying changes. A few of these changes are noteworthy, including:

• Clarifying that manufacturers wishing to provide relevant risk-benefit information, including data and calculations, should contact FDA or provide it to the FDA contact person for the matter.
• Noting that the guidance is adopting the definitions for serious injury and malfunction from 21 C.F.R. Part 803.
• Adding further information regarding how the Agency will assess uncertainty, one of the factors considered as part of the overall benefit-risk assessment. The added language focuses on the real-world data being assessed, including its type, the degree to which it is representative of the intended use population, and statistical inferences and limitations.

Finally, CDRH also added one new example of a benefit-risk assessment in the hypotheticals section of the guidance. This additional hypothetical is a situation in which a marketed OTC pregnancy test is found to have a higher rate of false positive results than expected based on data submitted in the 510(k).  CDRH reviewed the benefits, risks, patient tolerance for risk, mitigation, and patient impact, and concluded that, given the number of other similar products on the market, and the possibility that a false positive could delay certain medically necessary treatments, the risks of continuing to make the affected lots available outweighed any potential benefits.  In the hypothetical, the manufacturer notified retailers and distributors to remove the affected lots, and FDA classified that removal as a Class II recall.

Both the draft and final guidances state, almost in passing, that FDA intends to use pilots “to help determine how to apply the benefit-risk framework described” in the guidance. There is no further discussion of what these pilots will include, when they will be conducted, whether the public will have any input, or whether FDA will provide the results of the pilots to the public. It would be very useful to industry for FDA to publish the results of these initial pilot cases to further allow the public to see how CDRH plans to implement the guidance. The information could be published in an anonymized fashion as to protect the companies with whom CDRH is working.  Even if it does not give industry any further information, it is clear that any company facing an enforcement action or a potentially significant product shortage situation due to a recall should contact CDRH and make as strong a case as it can for enforcement discretion based on the factors laid out in the final guidance.