April 13, 2023
Use of Off-Label Clinical Data in Premarket Submissions
The supporting clinical data for a U.S. 510(k) notification (or other U.S. premarket submission) must generally meet FDA’s standard for “valid scientific evidence”. Specifically, that means (21 CFR 860.7) evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. The evidence required may vary according to the characteristics of the device, its conditions of use, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use. However, isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence to show safety or effectiveness.
These provisions would need to be carefully considered when assessing the utility of off-label clinical data/experience for the purposes of supporting eventual market authorization.
In terms of soliciting additional off-label experience/data, that gets to be a tricky scenario. Specifically, FDA has strongly established that it can, and has, considered off-label use to actually become intended use once the manufacturer’s corresponding awareness reaches a certain level. So this can get us in hot water quick once there is a known intended use for which no premarket authorization has yet been obtained.