FDA’s Sentinel Initiative appears to be gaining support through the Prescription Drug User Fee Act, although industry is not interested in blindly pumping user fee revenue into the project.

Given the expected shortage of appropriations to help pay for Sentinel’s growth and implementation, the agency has made it a target for outside funding. Commissioner Margaret Hamburg included Sentinel among several regulatory science improvements she wanted negotiated as part of the PDUFA reauthorization, which is required next year.

Only specific Sentinel projects would be funded by user fees and an open process would be required to make the determinations, according to industry suggestions.

FDA does not appear to be offering much of a return on the industry investment. It told industry negotiators that post-marketing commitment standards will not change as a result of Sentinel’s implementation.

Sentinel was mandated as part of PDUFA IV and is an attempt to improve post-marketing surveillance activity. The agency intends to create public-private partnerships to use several existing databases to look for potential safety problems with drugs and medical devices, and many in industry are watching warily (Also see "Sentinel Research, Communication Transparency Needed, GSK’s Troy Urges" - Pink Sheet, 31 January, 2011.).

Pilot projects now are getting off the ground, including Mini-Sentinel, a project focusing on diabetes drugs and cardiovascular risk (Also see "Onglyza Data From Sentinel Pilot Can Be Validated By Phase IV Trial, FDA Says" - Pink Sheet, 17 January, 2011.).

In previous PDUFA V reauthorization talks, the agency indicated it wants to expand Sentinel to evaluate safety signals in population-based databases (Also see "User Fee Discussions Include Funding Parts Of FDA Regulatory Science Plan" - Pink Sheet, 25 October, 2010.).

Industry questioned whether user fee funds should go toward Sentinel projects, according to the minutes of a Jan. 7 REMS-Sentinel Sub-Group meeting.

FDA and industry also talked about possibilities of establishing a process for determining which Sentinel projects were eligible for user fees, according to minutes of a Jan. 10 meeting.

The proposal would limit user-fee funded Sentinel projects to those that would “emphasize safety issues that affect classes of drugs or multiple products,” according to the minutes.

Also required would be an assessment of Sentinel’s value to regulatory decision-making on safety issues and adjustments to resource needs accordingly, with the evaluations targeted for fiscal years 2015 and 2017.

The minutes indicated both sides have agreed to the proposal and will present it to the full committee for consideration.

Post-Marketing Requirements Will Not Change Under Sentinel, Agency Says

During the Jan. 7 meeting, industry asked whether Sentinel could reduce the agency’s reliance on sponsors’ post-marketing studies.

FDA said the existing version of the proposal would not change requirements for post-market commitments or post-market requirements, but could help streamline methods for conducting them, according to the minutes.

Sentinel, even when fully implemented, is envisioned to augment, not replace, FDA’s existing post-marketing system by allowing the agency to conduct its own safety inquiries using electronic data.

Observational studies are expected to be an important part of the project, though the value of those studies is often debated (Also see "Sentinel Initiative's Potential Shortcomings Illuminated At Avandia Panel" - Pink Sheet, 9 August, 2010.).

The agency said in the minutes information derived through Sentinel would be used along with all other risk and benefit information known about the drug and safety problem.

It still was an interesting question from industry, since recently FDA has made a point to emphasize the importance of post-marketing studies.

The Oncology Drugs Advisory Committee decided Feb. 8 it would hold regular meetings to review cancer drugs granted accelerated approval as a means to keep pressure on sponsors to meet post-marketing commitments (Also see "FDA Will Make Advisory Committee Review Of Accelerated Approvals An Annual Event" - Pink Sheet, 14 February, 2011.).

The agency also has made its post-marketing study authority an important part of its approval of new drug applications, including in situations where certain risks cannot be studied in a pre-marketing setting or when a Risk Evaluation and Mitigation Strategy is not needed ([A#006110101019]).

Biomarker Team Already Overloaded

Other regulatory science proposals, including biomarker research and patient-reported outcome tools and non-inferiority trial design development, also remain on the table for user fee support.

The agency is looking for more resources to grow its biomarker and pharmacogenomics teams. It said the workforce capacity in those departments already is being exceeded and submissions are expected to increase during PDUFA V, according to minutes of a Jan. 6 Premarket Sub-Group meeting.

PDUFA resources would be divided between the clinical, biostatistics and clinical pharmacology disciplines, according to the minutes.

Industry said during a Jan. 10 meeting it supported user fee as well as appropriations funding for the proposals. However, representatives indicated user fee support for the entire regulatory science package likely would depend how revisions to the application review system shake out (see related story, Also see "FDA May Require NDA Pre-Filing Meeting Under PDUFA V Review Model; Pilot Launching Soon" - Pink Sheet, 28 February, 2011.).

FDA also agreed to better describe how regulatory science upgrades would be relevant to the review model and PDUFA, according to the minutes.

Adding regulatory science funding would be another philosophical expansion of the user fee program, which began in 1992 as a way to speed product review, and added limited funding for post-marketing safety efforts in the 2002 renewal.

By Derrick Gingery

PDUFA V: Sentinel, Regulatory Science Upgrades Could Gain User Fee Funding

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