PDUFA III “Good Review Management Principles” To Stress Early Action

FDA's "Good Review Management Principles" guidance will recognize the need for the completion of second- and third-round reviews of NDAs and BLAs before the action goal date under the Prescription Drug User Fee Act III.

The guidance will urge completion of primary reviews early enough to "[allow] time for secondary and tertiary reviews prior to the action goal date," the ¹ PDUFA III performance goals state.

Under the FDA/industry agreement submitted to Congress on March 13, the Center for Drug Evaluation & Research and the Center for Biologics Evaluation & Research will publish the joint guidance by the end of FY 2003.

The guidance will represent the first of several initiatives "targeted to improve the drug review process" that FDA will undertake using "at least $7 mil. of PDUFA III funds over five years," the agreement states.

The GRMP guidance will also emphasize "early communication of easily correctable deficiencies" identified in the initial filing review, the agreement adds.

Under the agreement, FDA will have deadlines for providing notification of "substantive deficiencies" in an application identified in the initial filing review.

FDA will inform sponsors "within 14 calendar days after the 60 day filing date" for 50% of applications in FY 2003, 70% in FY 2004, and 90% for FY 2005-2007.

The notification may take the form of "letter, telephone conference, facsimile, secure e-mail, or other expedient means," the agreement states.

"If no deficiencies were noted, FDA will so notify the sponsor," the agreement adds.

In addition to discussing the filing and primary reviews, the GRMP guidance will focus on agency efforts at "ongoing communication" with sponsors during the review process.

FDA will initiate two pilot programs to increase correspondence with new drug and biologics licensing application sponsors with fast track designation under PDUFA III (see ² ).

The guidance will also discuss agency efforts to provide feedback on labeling before the review clock deadline.

"Labeling feedback - planning to provide labeling comments and scheduling time for teleconferences with the sponsor in advance of the action goal date" will be addressed in the guidance, the goals letter states.

The agreement seeks to correct deficiencies and inconsistencies seen by industry as contributing to a "slowdown" of drug approvals at FDA (³ (Also see "Pfizer, PhRMA See Signs Of Drug Approval "Slowdown" At FDA" - Pink Sheet, 29 Jan, 2001.), p. 12).

The agency has acknowledged the lengthening of review times under PDUFA II, but indicated that industry's slower response time has contributed to the problem (⁴ (Also see "Industry Response Time Is Contributing To Slower Drug Approvals, FDA Says" - Pink Sheet, 12 Nov, 2001.), p. 15).

The inclusion of a new metric for Class 1 and 2 efficacy supplement resubmissions under the PDUFA III agreement represents one acknowledgement by industry that the review process is sometimes slowed by resubmissions.

FDA's performance goal for efficacy supplements is to review and act on 90% of Class 1 and Class 2 filings within six months in 2003 and 30% of Class 1 filings within two months of receipt.

A second initiative FDA will undertake with PDUFA III money, under the coaxing of the Biotechnology Industry Organization, is an analysis of the differences in review practices between CDER and CBER.

"FDA will contract with an outside consultant to conduct a...thorough analysis of information utilization, review management, and activity cost," the goals letter states.

"The outcome of this review will be a thorough documentation of the process, a re-map of the process indicating where efficiencies can be gained, activity-based project accounting, optimal use of review tools, and a suggested path for implementing the recommendations."

BIO recently voiced concerns that CBER's review process is less effective than its drug counterpart's (⁵ , p. 5).

"FDA would anticipate delivery of a report of the consultant's findings and recommendations in FY 2004-2005. The agency would consider these recommendations in planning any redesign or process reengineering to enhance performance," the agreement states.

Future initiatives launched with the remainder of the $7 mil. "performance fund" would likely include studies of the results of PDUFA III implementation and the adoption of any process changes based on recommendations from the first two studies.

The PDUFA III agreement also includes a BIO proposal concerning the use of outside experts by FDA in trial design meetings.

The agreement states that selected product sponsors will have the option to request that FDA hire an independent expert of its choice, paid for by the sponsor, to give advice on the protocol of pivotal trials.

The option will be reserved for biotech products that represent "a significant advance in the treatment, diagnosis or prevention of a disease or condition, or have the potential to address an unmet medical need."

Sponsors must submit a written request to the agency, designated a "Request for Appointment of Expert Consultant," in conjunction with a formal meeting request. The request should include the sponsor's arguments for why a consultant is necessary.

"The performance goals for scheduling the formal meeting...may be extended for an additional sixty days" to allow for choosing the expert, the agreement notes.

The agreement allows sponsors to submit a list of recommended consultants for consideration by the agency.

FDA will agree to the request "except in the most unusual circumstances," and will in those cases, provide "written rationale" to the requester within 14 days.

A markup of PDUFA III legislation in the House may be scheduled in the Energy & Commerce Committee over the next month, following its review of the FDA/industry agreement.