Notice2021-18094
Reauthorization of the Prescription Drug User Fee Act; Public Meeting; Request for Comments
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Published
August 24, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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.
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[Federal Register Volume 86, Number 161 (Tuesday, August 24, 2021)]
[Notices]
[Pages 47316-47322]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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 <a href="https://pdufavii-reauthorization.eventbrite.com">https://pdufavii-reauthorization.eventbrite.com</a>. 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027">https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027</a>
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 <a href="https://www.fda.gov/media/72259/download">https://www.fda.gov/media/72259/download</a> (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 <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>.
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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 <a href="https://www.fda.gov/media/101907/download">https://www.fda.gov/media/101907/download</a>.
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 <a href="https://www.fda.gov/media/99140/download">https://www.fda.gov/media/99140/download</a>.
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 <a href="https://www.fda.gov/about-fda/user-fee-performance-reports/pdufa-performance-reports">https://www.fda.gov/about-fda/user-fee-performance-reports/pdufa-performance-reports</a>. 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 <a href="https://www.fda.gov/industry/prescription-drug-user-fee-amendments/completed-pdufa-vi-deliverables">https://www.fda.gov/industry/prescription-drug-user-fee-amendments/completed-pdufa-vi-deliverables</a>.
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 <a href="https://www.fda.gov/drugs/news-events-human-drugs/public-meeting-reauthorization-prescription-drug-user-fee-act-pdufa-07232020-07232020">https://www.fda.gov/drugs/news-events-human-drugs/public-meeting-reauthorization-prescription-drug-user-fee-act-pdufa-07232020-07232020</a>.
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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 <a href="https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027">https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027</a>.
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 <a href="https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027">https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027</a>. 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 (<a href="https://www.fda.gov/safety/fdas-sentinel-initiative">https://www.fda.gov/safety/fdas-sentinel-initiative</a>) 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 <a href="https://pdufavii-reauthorization.eventbrite.com">https://pdufavii-reauthorization.eventbrite.com</a>.
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: <a href="https://fda.zoomgov.com/j/1619326064?pwd=WWZhZXhYRDNoYmg0WFRvSVgvdE5BUT09">https://fda.zoomgov.com/j/1619326064?pwd=WWZhZXhYRDNoYmg0WFRvSVgvdE5BUT09</a>.
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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 <a href="https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027">https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vii-fiscal-years-2023-2027</a>.
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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