[Federal Register Volume 86, Number 161 (Tuesday, August 24, 2021)]
[Notices]
[Pages 47316-47322]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-18094]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0891]


Reauthorization of the Prescription Drug User Fee Act; Public 
Meeting; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
hosting a virtual public meeting entitled ``Reauthorization of the 
Prescription Drug User Fee Act.'' The purpose of the public meeting is 
to discuss proposed recommendations for the reauthorization of the 
Prescription Drug User Fee Act (PDUFA) for fiscal years (FYs) 2023 
through 2027. PDUFA authorizes FDA to collect user fees to support the 
process for the review of human drug applications. The current 
legislative authority for PDUFA expires in September 2022. At that 
time, new legislation will be required for FDA to continue collecting 
prescription drug user fees in future fiscal years. Following 
discussions with the regulated industry and periodic consultations with 
public stakeholders, the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) directs FDA to publish the recommendations for the reauthorized 
program in the Federal Register, hold a meeting at which the public may 
present its views on such recommendations, and provide for a period of 
30 days for the public to provide written comments on such 
recommendations. FDA will then consider such public views and comments 
and revise such recommendations, as necessary.

DATES: The public meeting will be held on September 28, 2021, from 9 
a.m. to 2 p.m. Eastern Time, and will be held by webcast only. Submit 
either electronic or written comments on this public meeting by October 
28, 2021.

ADDRESSES: Registration to attend the virtual meeting and other 
information can be found at https://pdufavii-reauthorization.eventbrite.com. See the SUPPLEMENTARY INFORMATION 
section for registration date and information.
    You may submit comments as follows. Please note that late, untimely 
filed comments will not be considered. Electronic comments must be 
submitted on or before October 28, 2021. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of October 28, 2021. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
    <bullet> Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
    <bullet> Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    <bullet> For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked, and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2021-N-0891 for ``Reauthorization of the Prescription Drug User Fee 
Act; Public Meeting; Request for Comments.'' Received comments, those 
filed in a timely manner (see ADDRESSES), will be placed in the docket 
and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff between 9

[[Page 47317]]

a.m. and 4 p.m., Monday through Friday, 240-402-7500.
    <bullet> Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500. Transcripts of the meeting 
will be available on FDA's website at https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027 
approximately 30 days after the meeting.

FOR FURTHER INFORMATION CONTACT: Patrick Zhou, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 1148, Silver Spring, MD 20993-0002, 301-
348-1817, <a href="/cdn-cgi/l/email-protection#4818293c3a212b23661220273d082e2c296620203b662f273e"><span class="__cf_email__" data-cfemail="24744550564d474f0a7e4c4b51644240450a4c4c570a434b52">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Introduction

    FDA is announcing a virtual public meeting to discuss proposed 
recommendations for the reauthorization of PDUFA, the legislation that 
authorizes FDA to collect user fees to support the process for the 
review of human drug applications. The current authorization of the 
program (PDUFA VI) expires in September 2022. Without new legislation, 
FDA will no longer be able to collect user fees for future fiscal years 
to fund the process for the review of human drug applications. Section 
736B(f)(4) of the FD&C Act (21 U.S.C. 379h-2(f)(4)) requires that after 
FDA holds negotiations with regulated industry and periodic 
consultations with stakeholders, we do the following: (1) Present 
recommendations to the relevant Congressional committees, (2) publish 
recommendations in the Federal Register, (3) provide a period of 30 
days for the public to provide written comments on the recommendations, 
(4) hold a meeting at which the public may present its views, and (5) 
after consideration of public views and comments, revise the 
recommendations as necessary.
    This notice, the 30-day comment period, and the public meeting will 
satisfy some of these requirements. After the public meeting, we will 
revise the recommendations as necessary and present our proposed 
recommendations to the Congressional committees. The purpose of the 
meeting is to hear the public's views on the proposed recommendations 
for the reauthorized program (PDUFA VII). The following information is 
provided to help potential meeting participants better understand the 
history and evolution of the PDUFA program and the status of the 
proposed PDUFA VII recommendations.

II. What is PDUFA and what does it do?

    The following information is provided to help potential meeting 
participants better understand the history and evolution of PDUFA and 
its status. PDUFA is a law that authorizes FDA to collect fees from 
drug companies that submit marketing applications for certain human 
drug and biological products. PDUFA was originally enacted in 1992 as 
the Prescription Drug User Fee Act (Pub. L. 102-571) for a period of 5 
years. In 1997, Congress passed the Food and Drug Administration 
Modernization Act of 1997 (FDAMA, Pub. L. 105-115), which renewed the 
program (PDUFA II) for an additional 5 years. Congress then extended 
PDUFA again for another 5 years (PDUFA III), through FY 2007, in the 
Public Health Security and Bioterrorism Preparedness and Response Act 
of 2002 (Pub. L. 107-188). In 2007, Title I of the Food and Drug 
Administration Amendments Act of 2007 (FDAAA, Pub. L. 110-85) 
reauthorized PDUFA through FY 2012 (PDUFA IV, Pub. L. 112-144) and in 
2012 the Food and Drug Administration Safety and Innovation Act 
(FDASIA) reauthorized the law through FY 2017 (PDUFA V). PDUFA was most 
recently renewed in 2017 under Title I of the FDA Reauthorization Act 
of 2017 (FDARA) which lasts through FY 2022 (PDUFA VI).
    PDUFA's intent is to provide additional revenues so that FDA can 
hire more staff, improve systems, and establish a better managed human 
drug review process to make important therapies available to patients 
sooner without compromising review quality or FDA's high standards for 
safety, efficacy, and quality. As part of FDA's negotiated agreement 
with industry during each reauthorization, the Agency agrees to certain 
performance and procedural goals and other commitments that apply to 
aspects of the human drug review program. These goals apply, for 
example, to the process for the review of original new human drug and 
biological product applications, postmarket safety activities, and new 
data standards and technology enhancements.
    During the first few years of PDUFA I, the additional funding 
enabled FDA to eliminate backlogs of original applications and 
supplements. Phased in over the 5 years of PDUFA I, the goals were to 
review and act on 90 percent of priority new drug applications (NDAs), 
biologics license applications (BLAs), and efficacy supplements within 
6 months of submission of a complete application; to review and act on 
90 percent of standard original NDAs, BLAs, and efficacy supplements 
within 12 months, and to review and act on resubmissions and 
manufacturing supplements within 6 months. Over the course of PDUFA I, 
FDA exceeded all these performance goals and significantly reduced 
median review times of both priority and standard NDAs and BLAs.
    Under PDUFA II, the review performance goals were shortened, and 
new procedural goals were added to improve FDA's interactions with 
industry sponsors and to help facilitate the drug development process. 
The procedural goals, for example, articulated time frames for 
scheduling sponsor-requested meetings intended to address issues or 
questions regarding specific drug development programs, as well as time 
frames for the timely response to industry-submitted questions on 
special study protocols. FDA met or exceeded all the review and

[[Page 47318]]

procedural goals under PDUFA II. However, concerns grew that overworked 
review teams often had to return applications as ``approvable'' because 
they did not have the resources and sufficient staff time to work with 
the sponsors to resolve issues so that applications could be approved 
in the first review cycle.
    A sound financial footing and support for limited postmarket risk 
management were key themes of PDUFA III. Base user fee resources were 
significantly increased and a mechanism to account for changes in human 
drug review workload was adopted. PDUFA III also expanded the scope of 
user fee activities to include postmarket surveillance of new therapies 
for up to 3 years after marketing approval. FDA committed to the 
development of guidance for industry on risk assessment, risk 
management, and pharmacovigilance, as well as guidance to review staff 
and industry on review management principles. The draft guidance for 
industry entitled ``Good Review Management Principles and Practices for 
New Drug Applications and Biologics License Applications'' (GRMPs) was 
originally published in April 2005 and was subsequently revised and 
republished in September 2018 (available at https://www.fda.gov/media/72259/download (83 FR 48435, September 25, 2018)).\1\ Initiatives to 
improve application submission and Agency-sponsor interactions during 
the drug development and application review processes were also 
adopted.
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    \1\ When final, this guidance will represent the FDA's current 
thinking on this topic. For the most recent version of a guidance, 
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
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    With PDUFA's reauthorization under FDAAA Title I (PDUFA IV), FDA 
obtained a significant increase in base fee funding and committed to 
full implementation of GRMPs, which included providing a planned review 
timeline for premarket review, development of new guidance for industry 
on innovative clinical trials, modernization of postmarket safety, and 
elimination of the 3-year limitation on fee support for postmarket 
surveillance. Additional provisions in FDAAA (Titles IV, V, and IX) 
gave FDA additional statutory authority that increased the pre- and 
postmarket review process requirements, added new deadlines, and 
effectively increased review workload. Specifically, the new provisions 
expanded FDA's drug safety authorities, such as the authority to 
require risk evaluation mitigation strategies (REMS), order safety 
labeling changes, and require postmarket studies.
    Under Title I of FDASIA, the fourth renewal of PDUFA, FDA 
implemented a new review program (the Program) to promote greater 
transparency and increase communication between FDA's review team and 
the applicant on the most innovative products reviewed by the Agency. 
The Program applied to all new molecular entity (NME) NDAs and original 
BLAs received by the Agency from October 1, 2012, through September 30, 
2017. The Program added new opportunities for communication between the 
FDA review team and the applicant during review of a marketing 
application, including mid-cycle communications and late-cycle 
meetings, while adding 60 days to the review clock to provide for this 
increased interaction and to address review issues for these complex 
applications. PDUFA V also required an assessment of the impact of the 
Program. The independent assessment of the Program entitled 
``Assessment of the Program for Enhanced Review Transparency and 
Communication for NME NDAs and Original BLAs in PDUFA V,'' is available 
at https://www.fda.gov/media/101907/download.
    In August 2017, FDARA was enacted, which renewed the prescription 
drug user fee program for a fifth time. This iteration of the program 
continued and built upon the successes of PDUFA V. In PDUFA VI, FDA and 
industry members agreed to continue the Program model developed in 
PDUFA V to continue to promote the efficiency and effectiveness of the 
first cycle review process. PDUFA VI includes commitments to enhance 
regulatory science and expedite drug development by focusing on 
enhancing communication between FDA and sponsors during drug 
development, early consultation on the use of new surrogate endpoints, 
and exploring the use of real-world evidence for use in regulatory 
decision making, among other enhancements. This reauthorization also 
included commitments to enhance the use of regulatory tools to support 
drug development and review through incorporation of the patient's 
voice in drug development, expanded use of a benefit-risk framework in 
drug reviews, and advancing the use of complex innovative trial designs 
and model informed drug development. More information on these 
commitments can be found in the PDUFA VI commitment letter at https://www.fda.gov/media/99140/download.
    As part of the current authorization, FDA also modernized the user 
fee structure to improve program funding predictability, stability, and 
administrative efficiency. The new structure eliminated the supplement 
fees, replaced the establishment and product fees with a program fee, 
and shifted a greater proportion of the target revenue to the new more 
predictable and stable annual program fee. The agreement also included 
commitments to enhance management of user fee resources through the 
development of a resource capacity planning capability and third-party 
evaluation of program resource management, along with the publication 
and annual update of a 5-year financial plan.
    Recognizing the challenges with hiring in PDUFA V, the current 
authorization also includes several commitments to improve the hiring 
and retention of critical review staff through modernization of FDA's 
hiring system, augmentation of hiring staff capacity and capabilities, 
creation of a dedicated function focused on staffing the program, 
reporting on hiring metrics, and a comprehensive and continuous 
assessment of hiring and retention. Annual performance reports for the 
PDUFA program can be found through FDA's web page ``PDUFA Performance 
Reports,'' available at https://www.fda.gov/about-fda/user-fee-performance-reports/pdufa-performance-reports. Additionally, a list of 
some public-facing deliverables developed to meet PDUFA VI commitments 
is available on FDA's web page ``Completed PDUFA VI Deliverables,'' 
available at https://www.fda.gov/industry/prescription-drug-user-fee-amendments/completed-pdufa-vi-deliverables.

III. Proposed PDUFA VII Recommendations

    In preparing the proposed recommendations to Congress for PDUFA 
reauthorization, FDA conducted discussions with the regulated industry 
and consulted with stakeholders, as required by the law. We began the 
PDUFA reauthorization process by publishing a notice in the Federal 
Register requesting public input on the reauthorization and announcing 
a public meeting that was held on July 23, 2020.\2\ The meeting 
included presentations by FDA and a series of panels with 
representatives of different stakeholder groups, including patient 
advocates, consumer groups, regulated industry, health professionals, 
and academic researchers. The materials

[[Page 47319]]

from the meeting, including a transcript and webcast recording, can be 
found at https://www.fda.gov/drugs/news-events-human-drugs/public-meeting-reauthorization-prescription-drug-user-fee-act-pdufa-07232020-07232020.
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    \2\ See ``Reauthorization of the Prescription Drug User Fee Act; 
Public Meeting; Request for Comments,'' 85 FR 35096, June 8, 2020.
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    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 2023-2027,'' 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 Agency's web page ``PDUFA 
VII: Fiscal Years 2023-2027,'' available at https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027. 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 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 FDA's 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 the appropriate efficacy 
endpoint(s) for clinical trials intended to evaluate the effectiveness 
of rare disease therapies. Though difficult to establish, well-
developed 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 Drug-Device and Biologic Device-Combination 
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 drug-device 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 drug-device or biologic-device combination product to eliminate or 
mitigate use-related 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.

[[Page 47320]]

3. Advancing Real-World Evidence for Use in Regulatory Decision Making
    In accordance with Section 3022 of the 21st Century Cures Act, and 
by providing earlier and increased Agency advice, FDA proposes a new 
pilot program around real-world evidence (RWE) to improve the quality 
and acceptability of RWE-based approaches in support of new intended 
labeling claims, including approval of new indications of approved 
medical products or to satisfy post-approval study requirements.

E. Enhancing Regulatory Decision Tools To Support Drug Development and 
Review

    Building on the success of PDUFA VI, the enhancements under this 
section focus on enhancing regulatory decision tools to support drug 
development and review in the areas of patient focused drug 
development, benefit-risk assessment in regulatory decision making, 
drug development tools for qualification pathway for biomarkers, model-
informed drug development, and complex innovative clinical trial 
designs. The details of these enhancements can be found in section I.L 
of the proposed PDUFA VII commitment letter.

F. Enhancement and Modernization of the FDA Drug Safety System

    FDA will continue to utilize user fees to enhance the drug safety 
system, including adopting new scientific approaches, improving the 
utility of existing tools for the detection, evaluation, prevention, 
and mitigation of adverse events, modernizing REMS assessments, and 
coordinating regulatory activity in the premarket and postmarket 
settings. Enhancements to the drug safety system will improve public 
health by increasing patient protection while continuing to enable 
access to needed medical products.
    Specifically, PDUFA VII user fees will provide support for 
modernization and improvement of REMS assessments and optimization of 
the Sentinel Initiative (https://www.fda.gov/safety/fdas-sentinel-initiative) through: (1) Maintenance of Sentinel Initiative 
capabilities and continued integration into FDA drug safety activities 
and (2) enhancement of the analytic capabilities of the Sentinel 
Initiative to address questions of product safety and advance the 
understanding of how RWE can be used for studying effectiveness. These 
enhancements are described in section I.M of the proposed PDUFA VII 
commitment letter.

G. Enhancements Related to Product Quality Reviews, Chemistry, 
Manufacturing, and Controls Approaches, and Advancing the Utilization 
of Innovative Manufacturing Technologies

    To ensure new and innovative products are developed and available 
to patients in a timely manner, FDA proposes several enhancements 
related to communication between FDA and sponsors during product 
quality reviews, CMC approaches, and advancing use of innovative 
manufacturing technologies.
    For product quality reviews, these enhancements would include 
promoting the use of structured information requests, a third-party 
assessment on current practices related to information requests, and a 
goal to notify sponsors of certain pre-approval inspections. Given the 
accelerated development of certain human drug products, FDA also 
proposes a new pilot program to facilitate the expedited CMC 
development of products under an IND based upon the anticipated 
clinical benefit of earlier patient access to products. Additionally, 
FDA proposes holding a public workshop to help advance utilization and 
implementation of innovative manufacturing by facilitating and 
discussing best practices, barriers, and overall strategies. These 
enhancements are described in section I.N of the proposed PDUFA VII 
commitment letter.

H. Enhancing CBER's Capacity To Support Development, Review, and 
Approval of Cell and Gene Therapy Products

    To ensure that new and innovative cell and gene therapy products 
are developed and available to patients in a timely manner, FDA 
proposes to build on the success of the Cell and Gene Therapy Program 
(CGTP) in CBER to further support and advance a balanced approach to 
product development and regulation. To this end, FDA will strengthen 
staff capacity and capability to meet the increasing challenges and 
demands in this growing field. Increasing staff capacity will overcome 
existing resource limitations, allowing staff to spend additional time 
on meetings and submission reviews including those with breakthrough or 
regenerative medicine advanced therapy designations, expand stakeholder 
outreach, invest in new policy and guidance, and facilitate development 
and use of regulatory tools and scientific technologies. These 
enhancements are described in section I.O of the proposed PDUFA VII 
commitment letter.

I. Supporting Review of New Allergenic Extract Products

    FDA proposes to incorporate and include new allergenic extract 
products into the PDUFA program. Allergenic extract products licensed 
after October 1, 2022, would generally be included in user fees. 
Allergenic extract products licensed before October 1, 2022, and 
standardized allergenic extract products submitted pursuant to a 
notification to the applicant from the Secretary of Health and Human 
Services regarding the existence of a potency test that measures the 
allergenic activity of an allergenic extract product licensed by the 
applicant before October 1, 2022, would remain excluded from PDUFA. All 
performance goals, procedures, and commitments in this letter apply to 
the allergenic products included in the PDUFA program under PDUFA VII. 
These enhancements are described in section I.P of the proposed PDUFA 
VII commitment letter.

J. Continued Enhancement of User Fee Resource Management

    FDA is committed to ensuring the sustainability of PDUFA program 
resources and to enhancing the operational agility of the PDUFA 
program. FDA will build on the financial enhancements included in PDUFA 
VI and continue activities in PDUFA VII to ensure optimal use of user 
fee resources and the alignment of staff to workload through the 
continued maturation and assessment of the Agency's resource capacity 
planning capability. This would also include an independent assessment 
of the resource capacity planning capability. FDA will also continue 
activities to promote transparency of the use of financial resources in 
support of the PDUFA program through annual public meetings, publishing 
a 5-year financial plan (along with annual updates), and additional 
reporting in the annual PDUFA Financial Report. These enhancements are 
described in section II of the proposed PDUFA VII commitment letter.

K. Enhancing Transparency and Leveraging Modern Technology

    FDA is committed to enhancing the transparency of its information 
technology (IT) activities and modernization plans and will continue 
maintaining catalogs, standards, and plan updates that are published 
regularly to FDA's website in addition to the publication of a Data and 
Technology Modernization Strategy document and sharing regular updates 
on CBER IT modernization progress.

[[Page 47321]]

FDA will continue regular meetings between FDA and industry IT 
leadership to discuss challenges, emerging needs, and progress on IT 
initiatives relevant to PDUFA VII. Additionally, FDA will advance the 
use of cloud-based technology in the PDUFA program to modernize the 
Electronic Submission Gateway and promote innovation in drug 
development and the regulatory review process. These enhancements are 
described in section IV.A of the proposed PDUFA VII commitment letter.

L. Expanding and Enhancing Bioinformatics Support

    Bioinformatics and computational biology are increasingly being 
used to assess product quality, safety, and efficacy, and facilitate 
the development, characterization, and manufacture of human drugs and 
biologics. Recognizing the substantial increase in the volume and 
diversity of bioinformatics and computational biology information and 
data in regulatory submissions, such as Next Generation Sequencing, FDA 
proposes numerous activities to meet this growing need. These 
activities will include developing additional expertise and staff 
capacity in both CDER and CBER to efficiently review and provide 
technical and timely feedback, assessing and strengthening the 
computational infrastructure to support and advance our informatics 
platforms, and continuing to develop data standards and to issue/revise 
guidances on these topics. These enhancements are described in section 
IV.B of the proposed PDUFA VII commitment letter.

M. Enhancing Use of Digital Health Technologies (DHTs) To Support Drug 
Development and Review

    While the biomedical field has experienced rapid development and 
implementation of DHTs, FDA has limited experience evaluating novel 
DHT-based measurements in human drug development. FDA recognizes the 
potential for DHTs to provide scientific and practical advantages in 
supporting the assessment of patients by generating information outside 
of the traditional clinic visit. FDA also recognizes the need to build 
capacity and expertise to advise the biopharmaceutical industry in 
their development and implementation and to evaluate DHT outputs 
including the impact of regulatory initiatives (or regulatory science). 
To support new drug registration, label expansion, and safety 
monitoring, DHT-based data need to be fit for the intended purpose. 
Toward these ends, FDA proposes to undertake numerous activities, 
including the publication of a framework document to guide the use of 
DHT-derived data in regulatory decision making, the formation of a 
committee to provide support to DHT-related efforts, and a series of 
public meetings, demonstration projects, and new or updated guidances. 
These enhancements are described in section IV.C of the proposed PDUFA 
VII commitment letter.

N. Enhancements to Fee Mechanisms for Increased Predictability, 
Stability, and Efficiency

    The PDUFA VII agreement continues to build on the resource capacity 
planning capability established in PDUFA VI and continues financial 
transparency initiatives. In addition, PDUFA VII enhances mechanism to 
manage financial risks by establishing a minimum amount of available 
operating reserves to be maintained each year. This minimum amount will 
start at an amount equivalent to 8 weeks of operations and increase to 
10 weeks of operations by FY 2025. PDUFA VII also adds a strategic 
hiring and retention adjustment to ensure FDA has the funding necessary 
to provide for the costs of retaining and hiring highly qualified 
scientific and technical staff for the process for the review of human 
drug applications under PDUFA. This strategic hiring and retention 
adjustment will add $9 million to the base revenue amount in FY 2023 
and $4 million in each subsequent year.

O. Impact of PDUFA VII Enhancements on User Fee Revenue

    To implement the proposed enhancements for PDUFA VII, funding for a 
cumulative total of 352 full-time equivalent staff is proposed to be 
phased in over the course of PDUFA VII. The new funding will be phased 
in as follows:

<bullet> $65,773,693 for FY 2023
<bullet> $25,097,671 for FY 2024
<bullet> $14,154,169 for FY 2025
<bullet> $4,864,860 for FY 2026
<bullet> $1,314,620 for FY 2027

    In addition, to support the other additional direct costs 
associated with PDUFA VII enhancements, the following amounts will be 
added:

<bullet> $44,386,150 for FY 2023
<bullet> $60,967,993 for FY 2024
<bullet> $35,799,314 for FY 2025
<bullet> $35,799,314 for FY 2026
<bullet> $35,799,314 for FY 2027

IV. Public Meeting Information

A. Purpose and Scope of the Meeting

    The meeting will include a presentation by FDA and a series of 
panels with FDA and Industry representatives to present and discuss the 
agreed-upon proposed enhancements. For members of the public who would 
like to make verbal comments on the proposed enhancements (see 
instructions below), there will be a public comment period at the end 
of the meeting. We will also provide an opportunity for individuals to 
submit written comments to the docket before and after the meeting.

B. Participating in the Public Meeting

    Registration: Registration is optional and not required to attend 
this virtual public meeting. However, registering will allow FDA to 
provide you with email updates if any meeting details change. If you 
wish to register, you can do so at https://pdufavii-reauthorization.eventbrite.com.
    Opportunity for Verbal Public Comment: Those who register online 
will receive a confirmation email that includes a link to a request 
form to make a verbal public comment at the meeting. If you wish to 
speak during the public comment session, follow the instructions in 
that email and identify which topic(s) you wish to address. We will do 
our best to accommodate requests to make public comments. Individuals 
and organizations with common interests are urged to consolidate or 
coordinate their comments and request time jointly. All requests to 
make a public comment during the meeting must be received by September 
14, 2021, 11:59 p.m. Eastern Time. Depending on the number of requests, 
we will determine the amount of time allotted to each commenter, the 
approximate time each comment is to begin, and will select and notify 
participants by September 21, 2021. No commercial or promotional 
material will be permitted to be presented at the public meeting.
    Streaming Webcast of the Public Meeting: The Zoom Webinar ID for 
this public meeting is 161 932 6064. The webcast link for this public 
meeting can be found here: https://fda.zoomgov.com/j/1619326064?pwd=WWZhZXhYRDNoYmg0WFRvSVgvdE5BUT09.
    The link above should allow you to enter the webinar directly. If 
Zoom asks for a passcode, please use the case-sensitive passcode below.
    Case-Sensitive Passcode for Zoom Webinar: PDUFa7!
    Transcripts: Please be advised that as soon as a transcript of the 
public meeting is available, it will be accessible at https://www.regulations.gov. It may be viewed at the Dockets Management Staff 
(see ADDRESSES). A link to the

[[Page 47322]]

transcript will also be available on the internet at https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027.

    Dated: August 18, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-18094 Filed 8-23-21; 8:45 am]
BILLING CODE 4164-01-P


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