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Regulatory Focus™ > News Articles > 2021 > 4 > PDUFA VII postmarketing talks focus on REMS, Sentinel

PDUFA VII postmarketing talks focus on REMS, Sentinel

Posted 07 April 2021 | By Kari Oakes 

PDUFA VII postmarketing talks focus on REMS, Sentinel

As the US Food and Drug Administration (FDA) and industry worked through FDA commitments for the upcoming reauthorization of the Prescription Drug User Fee Act (PDUFA VII), a series of meetings in early 2021 defined where postmarketing priorities would lie. Risk evaluation and mitigation, best uses of the Sentinel safety system, and a pregnancy demonstration project were top of mind for both industry and FDA.
Recently released minutes from three additional meetings of the FDA-Industry postmarket subgroup are more detailed than those that chronicle most other user fee reauthorization meetings, giving additional insight into sticking points and areas of agreement as representatives from FDA met three times in January 2021.
In the 13 January meeting, a pregnancy safety demonstration proposal was fine-tuned and brought to the point where commitment language could be finalized. Industry asked for, and FDA agreed to, an attempt to include electronic health records and claims data in all of the projects detailed in the proposal. Attendees also discussed the possibility of linking to CBER’s BEST project, and FDA agreed it could begin to nail down timing for the project.
Addressing the Sentinel System, industry asked for three analytics projects within the Sentinel work. The first is to perform analyses using negative controls; the second would look at inverse probability of censoring weighted (IPCW), and the third would examine qualitative bias analysis (QBA). Industry, according to the minutes, expects that useful tool will be developed from the projects, though representatives are also concerned about the cost of these projects.
The negative controls project cost could be reduced if a tool were not developed from this portion of the Sentinel work, FDA said in a later meeting. “Even without a tool, the demonstration project findings may be applicable to data sets outside of the Sentinel System,” according to the minutes. However, parallel projects would have to be run in FDA’s Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER), since target populations and products vary so much.
“The CDER project would focus on safety while the CBER project would focus on effectiveness. The CDER project will focus on automation of negative control selection while the CBER project will focus on biases related to health seeking behavior,” noted the minutes.
To reduce the cost of the IPCW project, the parties discussed focusing on just a few data sources rather than gathering data from all Sentinel data partners. “FDA agreed to think through the IPCW proposal more and provide industry with update resource requirements,” according to the minutes.
FDA observed that multiple factors play into the uncertain, but perhaps high, cost of such a project. “One cost determinant with Sentinel projects is Sentinel’s use of a distributed database with multiple partners in multiple platforms,” noted the minutes. “Projects involving EHR data are more complex when working in a distributive environment. Additionally, FDA/Sentinel is just learning how to operate in the EHR environment—it is part of the FDA five-year goal for Sentinel.
Industry and FDA came to agreement on the commitment language for Sentinel by the end of January, “including language to report annually on how Industry’s contributions associated with PDUFA VI Sentinel commitments are being used,” according to the minutes.
Attendees agreed that one part of the PDUFA VII Sentinel efforts should be finding a way to communicate the mission and value of the Sentinel program to the general public.
Industry and FDA were close to agreement with the proposal for Risk Evaluation and Mitigation Strategy (REMS) assessments, with industry expressing “general satisfaction” with the proposal. Still, industry would like to see a more systematic way to review REMS and sunset them when indicated.
In a meeting held later in January, FDA walked through its proposed hiring cadence and laid out its proposed commitment language that addressed industry’s desire for REMS elimination protocols. “Industry asked that FDA consider accelerating the timelines for the proposed MaPP (manual of policies and procedures) and including additional commitment language describing the timeline for finalizing draft guidance,” according to those minutes.
Another aspect of REMS adjustments for PDUFA VII, said industry, would be for FDA to update guidances to reflect how the agency will “incorporate REMS assessment planning into the design of the REMS.” Participants hammered out a proposed timeline for draft and final versions of the updated REMS-related guidances.


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