The FDA has posted a draft guidance in response to legislation directed to the opioid epidemic, which will supplant a similar guidance finalized in 2011. Despite the presence of the legacy guidance, the October 2019 draft enacts a new statutory feature that allows the agency to require postmarket studies for drugs and biologics to answer questions about any apparent reduction in efficacy.
Section 3041 of the SUPPORT Act, which was crafted as a response to the opioid epidemic, amended the statute so that the definition of an adverse drug experience includes scenarios in which the therapeutic agent’s efficacy is reduced over time. Any such data regarding diminished effectiveness would have to be included in product labels per the data generated by post-approval studies.
The text of the legislation as it appears at Congress.gov offers little insight as to how the FDA is to interpret the phrase “reduced effectiveness.” This would seem to leave this question to the agency’s discretion, although the draft guidance also omits any suggestion as to how the agency will interpret the term.
Another point of consideration in connection with the SUPPORT Act and the FDA draft guidance is whether Congress had intended to apply this reduced effectiveness framework to all prescription pharmaceuticals and biologics. The text of the statute as amended by the SUPPORT Act does not seem restricted to opioids, but there is little doubt as to the intention of Congress in passing the legislation. Absent another change to the statute, it will be entirely at the FDA’s discretion as to how broadly it will enforce this edict, assuming the final guidance provides no clarity.
Few Quick Answers for Metal Implants
The FDA’s device center has also been busy of late, particularly on the advisory committee front. Among the recent FDA advisory hearings was a two-day hearing on the use of metals in device implants, including dental amalgams, and as is often the case with these hearings, there were at least as many questions as answers by the end of the proceedings.
Two messages came through loud and clear, however, one of which was that the time has passed for the use of mercury in dental amalgams. The other message was that labels for devices such as hip implants should disclose all the materials used in the device, not just the materials used to coat patient-contacting surfaces.
The FDA posted a summary of the Nov. 13-14 meeting which included an expression of interest in tests that would disclose whether a patient is likely to experience an immunological reaction to the metals commonly used in device implants. However, the science has not yet established the biomarkers that would disclose such propensities, leaving this goal more aspirational than operational at present. Part of the underlying difficulty is that collection of the requisite data will be costly and time consuming, suggesting that several more years are likely to pass before the science is up to the task.
The FDA’s meeting summary fails to disclose the intensity of the opposition to the use of mercury in dental amalgams, although a Nov. 18 statement gives some idea of the seemingly growing hostility toward mercury. It might be noted, however, that the oft-cited cessation of mercury in amalgams for pediatric use in the European Union was undertaken at least as much for environmental concerns as for patient safety considerations. The FDA’s position as of the date of the meeting was that there are few compelling data to suggest that the small amount of mercury used in amalgams presents any real threat to patient well-being.
An industry representative on the advisory committee backed the disclosure of all materials used in implanted devices, something the FDA could presumably mandate with its current statutory authorities. Nonetheless, a fundamental scientific question still hovers over the immune response hypothesis outside the context of a localized immunological reaction. As the summary notes, there was a discussion of “the biological plausibility of systemic immune responses arising from the presence of a metal implant and though some panelists agreed that it was possible, others expressed uncertainty.”