FDA Focus: What’s in Store for PDUFA Reauthorization?

The US Food and Drug Administration (FDA) will hold a public meeting on August 15, 2016, to discuss proposed recommendations for the reauthorization of the Prescription Drug User Fee Act (PDUFA) for fiscal years (FYs) 2018 through 2022. PDUFA authorizes FDA to collect fees and use them for the review of human drug applications. The current legislative authority for PDUFA expires in September 2017. So what is the FDA proposing?

The FDA issued a 46-page document to outline the performance goals and procedures for PDUFA reauthorization for FYs 2018-2022. These goals include new review times for new drug applications (NDAs) and biologics license applications (BLAs) as well as for original manufacturing supplements. The FDA further outlines how it plans to incorporate greater patient input into the regulatory process and other issues of topical importance, such as incorporating real-world evidence into regulatory decisions.

PDUFA reauthorization at a glance
The review goals of the FDA under its proposed PDUFA reauthorization for FY 2018 through 2022 are outlined in Table I below:

Table I: The US Food and Drug Administration's Review Goals under the Prescription Drug User Fee Act Reauthorization for Fiscal Years 2018 to 2022.
Submission Cohort Standard review Priority review
NMEs, NDAs and Original BLAs 90% in 10 months of the 60-day filing date 90% in 6 months of the 60-day filing date
Non-NME NDAs 90% in 10 months of the receipt date 90% in 6 months of the receipt date
Class I Resubmissions 90% in 2 months of the receipt date 90% in 2 months of the receipt date
Class II Resubmissions 90% in 6 months of the receipt date 90% in 6 months of the receipt date
Original Efficacy Supplements 90% in 10 months of the receipt date 90% in 6 months of the receipt date
Class I Resubmitted Efficacy Supplements 90% in 2 months of the receipt date 90% in 2 months of the receipt date
Class 2 Resubmitted Efficacy Supplements 90% in 6 months of the receipt date 90% in 6 months of the receipt date
Submission Cohort Prior approval All other
Manufacturing Supplements 90% in 4 months of the receipt date 90% in 6 months of the receipt date

NME is new molecular entity; NDA is new drug application; BLA is biologics license application
Source: US Food and Drug Administration.

To promote transparency and communication between the FDA review team and the applicant, the FDA is seeking to promote the efficiency and effectiveness of the first-cycle review process and minimize the number of review cycles necessary for approval. Key elements of such an approach include a pre-submission meeting for a NDA for a new molecular entity and original BLA, to be held generally not less than 2 months prior to the planned submission of the application. Original applications for NDAs and BLAs should include a comprehensive and readily located list of all clinical sites and manufacturing sites included or referenced in the application. Following the submission of the NDA or BLA, the FDA will provide the applicant, within 74 days of the receipt by the FDA of its submission, a planned review timeline, which will also include preliminary plans to hold a mid-cycle review and late-cycle review. For NDAs and original BLAs, the FDA will be required to act on 90% of the standard NME NDA and original BLA applications within 10 months of the 60-day filing date, and within six months for priority review. In addition, the FDA's goal is to complete all GCP (good clinical practice), GLP (good laboratory practice) and GMP (good manufacturing practice) inspections within six months of the date of original receipt for priority application and within 10 months of the date of original receipt for standard applications. The timeline will allow two months at the end of the review cycle to attempt to address any deficiencies identified by the inspections.

In the first PDUFA, the FDA issued guidance in 2005 to ensure an efficient and effective first-cycle review process. The FDA said that it plans to update this guidance in PDUFA VI (the reauthorization for PDUFA for FY 2018 through 2022) to include: review activities that have since been added; principles regarding notification to applicants regarding issues identified during the FDA's initial review of applications; principles regarding the FDA's notification to applicants regarding planned review timelines; and internal review timelines that govern human drug review that are not part of PDUFA. FDA will publish a revised draft guidance for public comment no later than the end of FY 2018. In addition, the FDA plans to publish revised draft guidance on formal meetings between the FDA and sponsors no later than September 30, 2018.

The FDA also is seeking to build on its success of its regulatory science program that included among several items, advancing the science of meta-analysis technologies, advancing the use of biomarkers and p haromacogenomics, enhancing communication between the FDA and sponsors during drug development, and advancing the development of rare diseases. The FDA plans to extend and continue this work by encompassing further evaluation and enhancement of FDA-sponsor communications, ensuring the continued success of the breakthrough therapy program, establishing early consultations between the FDA and sponsor of new surrogate endpoints for the primary basis for drug approval, advancing rare-disease drug development, advancing the development of combination products, and exploring the use of real-world evidence for use in regulatory decision-making. Some key highlights in some of these areas are noted below.

Enhanced communication. To enhance communication during drug development, the FDA plans to contract with an independent third party to assess its current practices of FDA and sponsors in communicating during development. The third party will identify best practices and areas for improvement for both FDA staff and sponsor. The FDA plans to publish the final report on this assessment no later than the end of FY 2020. The FDA will then convene a public workshop by the end of March 2021 to discuss the findings of the independent assessment.

Combination products. The FDA also plans to streamline the process for combination-product review and better assess the needed resources and review times for such products. By December 31, 2017, the FDA will complete a lean process mapping for combination-product review and will be tracking workload and times for cross-center consultations. No later than September 30, 2018, the FDA will outlined the agency's process for resolving internally scientific or regulatory issues. It will establish Manuals of Policy and Procedures (MAPPs and Standard Operating Policy and Procedures (SOPPs). Among topics to be addressed and expected completion dates for the related documents are: human factor assessments (March 31, 2019); quality assessment of combination products, including coordination of facility inspections (September 30, 2019); patient-oriented labeling (September 30, 2019), key points of contact with the FDA (December 31, 2018), submission procedures for human factors protocols (September 30, 2018), staff training for development, review and approval of drug-device and biologic-device combination products (December 31, 2018), and related updated draft guidance (end of FY 2019) and final guidance (end of FY 2022).

Real-world evidence in regulatory decision-making. Some key milestones in this area include: the FDA holding a public workshop by the end of FY 2018 related to real-world evidence with stakeholders; initiation by the FDA for a pilot study (end of FY 2019), and draft guidance (end of FY 2021).

Enhancing the patient voice in drug development and regulatory decision-making. FDA plans to strengthen the staff capacity to facilitate development and use of patient-focused methods to inform drug development and regulatory decisions. The FDA will develop a series of guidance documents to focus on approaches and methods to bridge from initial patient-focused drug development meeting, like those piloted under PDUFA V, to fit-for-purpose tools to collect meaningful patient and caregiver input for ultimate use in regulatory decision-making. Prior to the issuance of each guidance, as part of the development, the FDA will conduct a public workshop to gather input from the wider community of patients, patient advocates, academic researchers, expert practitioners, industry, and other stakeholders.

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