PDUFA Discussions Continue, New Review Models Proposed

The US Food and Drug Administration posted on its website the minutes of the latest meetings between the agency and industry, and among stakeholders, regarding the reauthorization of the Prescription Drug User Fee Act V. The meetings were held Nov. 17–18.

Participating in the industry meeting with the FDA Centers for Drug Evaluation and Research, and Biologics Evaluation and Research, were Pfizer’s Hilary Malone, BIO’s Sara Radcliffe, and PhRMA’s Theresa Mullin. The primary goal was to discuss proposals related to human drug review timelines.

According to the minutes, both industry and the agency expressed the need for more time during the review cycle of new drug applications (NDAs) and biologic license applications (BLAs). Industry specifically would like more “substantive feedback during the application review cycle to better plan for AC [advisory committee] meetings, inform planning related to manufacturing scale-up, product launch, follow-on clinical development activities, and to potentially address issues identified in the applications.” For its part, FDA would like “more time to plan and conduct foreign inspections, address new authorities from the FDA Amendments Act (FDAAA) of 2007 such as risk evaluation and mitigation strategies (REMS) of greater complexity, plan for more frequent [AC] meetings, and address issues that can be resolved in the first cycle to reduce the need for multi-cycle reviews.”

To address these needs, the agency proposed a review model for NDAs and BLAs that would include a late-phase meeting after primary and secondary reviews are complete. The late-phase meeting would provide a chance for the sponsor company and regulators to discuss any concerns identified during the agency review, including potential risk-management plans as well as any analyses or new data from the sponsor that may help resolve any noted deficiencies.

The agency also suggested submitting the AC background package to sponsors 21 business days prior to the AC meeting. This change would allow sponsor companies to prepare for the discussions in advance. To allow time for the late-phase communications being proposed, FDA suggested starting the review period after the two-month period in which FDA conducts filing and application validation activities. Agency representatives reiterated, however, that NDAs and BLAs must be fully completed upon submission for review. Otherwise, the review model proposed will not work.

FDA also noted the following during the meeting: unsolicited amendments would not be reviewed by the agency; any solicited major amendments could result in a three-month clock extension (a REMS submission could be considered a major amendment). 

The full minutes of the FDA-industry meeting can be found here.

A separate stakeholder meeting focused on AC meetings, comparative effectiveness research (CER), off-label prescribing, REMS, and PDUFA enhancement. Representatives from FDA and various healthcare and nonprofit organizations were present. Participants discussed current practice and challenges in the above noted areas and offered a few suggestions.

For example, with regard to CER, FDA noted that comparative studies “often require enrollment of very large numbers of patients, making them very difficult and expensive to conduct, particularly in the case of demonstrating a comparative advantage for a symptomatic benefit.” FDA participants noted that a randomized withdrawal trial design can demonstrate whether a new therapy is effective in patients who have failed existing treatments and pointed out that the information being collected in the agency’s Sentinel database [see back story] could be helpful with CER determinations down the road.

On the subject of REMS, FDA participants “acknowledged that concerns have been raised about REMS that involve only a Medication Guide and noted that the agency is currently working on a guidance to address those concerns,” according to the minutes. The agency is working to standardize REMS materials and facilitate the use of existing pharmacy systems to implement them. For stakeholders, the agency suggested that their involvement in preapproval discussions would be best served through AC meetings because otherwise, REMS are considered confidential.

The National Health Council, one of the participating stakeholders in the meeting, discussed conflicts of interest and noted that these should be more transparent. At the same time, the Council suggested that conflicts be managed to ensure that the right expertise is available within ACs. The Union of Concerned Scientists also made suggestions regarding conflicts of interest such as making it easier for the public to track FDA progress on the matter.

Other stakeholders, the Consumer’s Union, National Women’s Health Network, and the Union of Concerned Scientists/Scientific Integrity Program raised questions about the agency’s Sentinel Initiative and the level of resources being spent on the project. FDA responded, according to the minutes, that a PDUFA proposal may add resources to the Sentinel project. The full stakeholder meeting minutes can be read here.

The fourth version of PDUFA expires in September 2012. FDA has been and will continue to hold meetings with industry and other patient and consumer groups until its final recommendations are due to Congress on Jan. 15, 2012.

See related story
“FDA Posts Minutes to PDUFA V Discussion Meeting” (ePT)