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Federal Register / Vol. 86, No. 161 / Tuesday, August 24, 2021 / Notices
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from the meeting, including a transcript and webcast recording, can be found at https www.fda.gov/drugs/news-eventshuman-drugs/public-meetingreauthorization-prescription-drug-userfee-act-pdufa-07232020-07232020.
Following the July 2020 public meeting, FDA conducted negotiations with the regulated industry and held monthly consultations with stakeholders from September 2020
through February 2021. As directed by Congress, FDA posted minutes of these meetings on its web page PDUFA VII:
Fiscal Years 20232027, available at https www.fda.gov/industry/
prescription-drug-user-fee-amendments/
pdufa-vii-fiscal-years-2023-2027.
The proposed enhancements for PDUFA VII address many of the top priorities identified by public stakeholders, the regulated industry, and FDA. While some of the proposed enhancements are new, many either build on successful enhancements or refine elements from the existing program. The enhancements are proposed in the following areas: Center for Biologics Evaluation and Research CBER product review support, premarket review, regulatory decision tools, postmarketing evaluation, digital health and informatics, chemistry, manufacturing, and controls CMC, and financial management. The full text of the proposed PDUFA VII commitment letter can be found on the Agencys web page PDUFA VII: Fiscal Years 2023
2027, available at https www.fda.gov/
industry/prescription-drug-user-feeamendments/pdufa-vii-fiscal-years2023-2027. Each significant new or modified enhancement is described briefly below:
A. NME Milestones and Postmarketing Requirements PMRs To ensure the timely availability of information on the safety and efficacy of therapies, FDA proposes to establish new timelines, performance goals, and a new process for pre-approval review of PMRs. Sponsors would also have the opportunity to request a review of existing PMRs for release. Any adopted changes and adjustments will be updated in relevant manuals of policies and procedures, standard operating procedures, and guidances. This enhancement is described in section I.C
of the proposed PDUFA VII
commitment letter.
B. Split Real Time Application Review Pilot Program To allow earlier patient access to therapies that address an unmet medical need, FDA proposes establishing a pilot program for efficacy supplements that
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meet specific criteria. Applications that are accepted into the pilot program will be submitted in a split fashion, specifically in two parts with each component submitted approximately 2
months apart. The goal is to shorten the time from the date of complete submission of the application to the action date. This enhancement is described in section I.D of the proposed PDUFA VII commitment letter.
C. Meeting Management Goals To improve overall meeting management, FDA proposes creating two new meeting types to better define the purpose of certain meeting requests:
Type D and INTERACT. The Type D
meeting allows for quicker discussion on a narrow set of issues no more than two focused topics between FDA and a sponsor, such as a followup question that raises a new issue after a formal meeting. The INTERACT meeting facilitates Investigational New Drug Application IND enabling efforts where a sponsor is facing a novel, challenging issue that might otherwise delay progress of the product towards entry into the clinic in the absence of this early FDA input. There would also be a new followup opportunity to pose clarifying questions after meetings or a written-response-only communication.
These enhancements are described in section I.J of the proposed PDUFA VII
commitment letter.
D. Enhancing Regulatory Science and Expediting Drug Development The extension and continuation of FDAs efforts to enhance regulatory science and expedite drug development will encompass further evaluation and enhancement of FDA-sponsor communications, ensuring the sustained success of the breakthrough therapy program, continuing early consultations between FDA and sponsors on the use of new surrogate endpoints as the primary basis for product 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. These enhancements are described in section I.K of the proposed PDUFA VII commitment letter.
Highlights from those sections are included below.
1. Advancing Development of Drugs for Rare Diseases The lack of regulatory precedent, small trial populations, and/or limited understanding of natural history associated with rare diseases creates unique challenges when determining
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the appropriate efficacy endpoints for clinical trials intended to evaluate the effectiveness of rare disease therapies.
Though difficult to establish, welldeveloped efficacy endpoints, especially those that could apply to other rare diseases with similar manifestations, drive the general advancement of rare disease drug development. In addition to challenges associated with developing endpoints that appropriately capture key signs and symptoms of a rare disease and directly measure how patients feel, function, or survive, surrogate endpoint development is also challenging in diseases with slow progression, small patient populations, or other challenges commonly associated with drug development in rare diseases.
To support the advancement of rare disease treatments, FDA proposes a pilot program for supporting efficacy endpoint development for drugs that treat rare diseases by offering additional engagement opportunities with the Agency to sponsors of development programs that meet specific criteria.
2. Advancing Development of DrugDevice and Biologic DeviceCombination Products Regulated by CBER and the Center for Drug Evaluation and Research CDER
Sponsors employ Use-Related Risk Analyses URRA studies to identify the need for risk mitigation strategies and to design a human factors HF validation study. Based on a URRA, a sponsor may propose that an HF validation study submission is not required to support the safe and effective use of a drugdevice or biologic-device combination product. FDA proposes establishing new procedures for the review of URRAs along with performance goals.
HF validation studies are conducted to evaluate the user interface of a drugdevice or biologic-device combination product to eliminate or mitigate userelated hazards that may affect the safe and effective use of the combination product. Over the past decade, more combination products have been developed to deliver therapeutics via different routes of administration e.g., parenteral, inhalation with complex engineering designs. HF validation protocols are reviewed during the IND
stage with the goal towards developing a final finished combination product that supports the marketing application.
To achieve this objective, FDA proposes updating the procedures for HF
validation study protocols along with a new performance goal.

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