PDUFA VIII: FDA, industry make significant progress toward agreement

In the latest meeting minutes released by the US Food and Drug Administration (FDA), the agency noted that significant progress has been made toward an agreement with the pharmaceutical industry for the next Pharmaceutical Drug User Fee Amendments (PDUFA VIII) commitment language.

Two major issues were discussed during the latest FDA and industry steering committee meetings, as reflected in the minutes posted in early March. They include America First fee incentives and a non-orphan indication supplement fee proposal. The drug industry was represented by PhRMA, the Biotechnology Innovation Organization (BIO) and the Consumer Healthcare Products Association (CHPA) during the meetings.

Over the past year, the Trump Administration has proposed policy positions to encourage drugmakers to move their manufacturing to the US, including promoting the FDA Commissioner’s National Priority Voucher (CNPV) pilot program, which offers regulatory incentives to manufacturers that manufacture critical drugs in the US. During the 10 March steering committee meeting, FDA and industry discussed the eligibility criteria for applications with phase 1 clinical trials anchored domestically. Sponsors who qualify under the program would only pay half of the premarket application fee.

During the next meeting on 12 March, drug industry representatives proposed their preferred definition of what would constitute anchoring phase 1 clinical trials in the US. FDA raised feasibility concerns about how to verify the eligibility criteria in its response.

"Industry raised questions about how investigational new drug applications (INDs) that attempted to meet the proposed criteria but were placed on clinical hold would be handled," said the meeting minutes. "Industry also inquired about how an applicant would provide documentation to show that they meet the eligibility criteria.

"Industry agreed to revise their proposed eligibility criteria in response to the discussion, and FDA agreed to consider how sponsors might verify that they meet the criteria," the minutes added.

FDA and industry also continued to discuss FDA's proposal for a non-orphan indication supplement during the 10 March meeting, which would assess a fee for the first supplement seeking to add a non-orphan indication to an application that has already been approved for an orphan indication. Industry said the fee for such supplements should be half the non-orphan application fee, noting it would be more consistent with the fee structure used in previous PDUFA agreements. It also said that subsequent supplements for non-orphan indications should not include a fee.

FDA came back on the 12 March meeting and said it agreed with industry’s reasoning that first supplements for a non-orphan indication to an approved orphan drug application should be half the application fee.

During the 12 March meeting, FDA and industry also heard from representatives from subgroups who have been negotiating pre-market, chemistry, manufacturing, and controls (CMC), and finance issues. The representatives gave attendees a summary of the progress made in the subgroups during their 5 March meetings.

According to meeting minutes from 5 March, the pre-market subgroup provided an update and noted that the industry has proposed revisions to the draft commitment letter language for the FDA’s Rare Disease Endpoint Advancement (RDEA) program, to which the FDA said it would respond at a future meeting. Industry also agreed with FDA on several revisions to the draft language in the commitment letter.

“FDA and Industry discussed the proposed scope for the third-party assessment,” said the meeting minutes. “FDA and Industry agreed that the scope of the third-party assessment would include New Molecular Entity (NME) New Drug Applications (NDAs) and original Biologics License Applications (BLAs).

“Industry also proposed that the timing of FDA labeling comments on efficacy supplements be included in the assessment,” the minutes added. “FDA and Industry both agreed to propose draft commitment letter language regarding the scope of labeling comments in the assessment.”

In separate minutes, the CMC subgroup said that FDA and industry have agreed to simplify the language for the third-party assessment and public workshop in the PDUFA VI commitment letter, since a detailed analysis design will already be included in the contractor statement of work. They also agreed that a mutual accountability framework is critical to acknowledge that the program's success depends on both parties effectively executing their respective parts of the agreement.

During the 5 March finance subgroup meeting, FDA responded to several industry proposals. The agency said it could agree to the inflation adjustment being taken after any enterprise performance adjustment (EPA) is implemented. It also said it agrees with the industry that the funds set aside in the operating reserve tracking, reserving, and reporting (OR TRR) should be used only to hire and retain drug review staff. The agency also agreed in principle to enhanced reporting on payroll and other obligations in the annual Finance Report.

“To address Industry’s proposal regarding technical staff meetings, FDA stated the Agency could agree to offering one technical staff meeting to occur after the fee-setting Federal Register Notice each year, to occur in the August to September timeframe,” said the meeting minutes. “Topics for this meeting can include anything in the fee-setting or financial realm for PDUFA.

“FDA stated it is unable to agree to Industry’s proposal to decrease the operating reserve bounds to 9 - 11 weeks,” the agency added. “FDA had previously suggested a decreased 10-12-week range in support of standardization goals across user fee programs and could not deviate from this.”

FDA said that lowering the operating reserve funds could be dangerous for the agency and industry. As an example, it said it could lead to a perfect storm if there is under-collection and a government shutdown.

PDUFA meeting minutes