[Federal Register Volume 91, Number 120 (Wednesday, June 24, 2026)]
[Notices]
[Pages 37996-38000]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-12621]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-N-4699]
Expedited Investigational New Drug Pilot Program; Request for
Information
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for information; establishment of a public
docket.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
opening a public docket to solicit input and comments on a proposal to
establish a pilot program, the Expedited Investigational New Drug (IND)
pilot program, to shorten the time it takes from drug identification to
first-in-human (FIH) study, while protecting clinical trial
participants. FDA is
[[Page 37997]]
requesting information on the potential pilot program which would
establish a network of qualified research institutions, such as
academic medical centers (AMCs), healthcare networks (HNs), contract
research organizations (CROs), regulatory advisors, and/or other
research or third-party review organizations (collectively called
Qualified Research Institutions, or ``QRIs''), who would partner with
sponsors to develop and review protocols for FIH clinical trials
intended for a IND submission to FDA. Information provided through this
public docket will help the Agency refine our approach and consider
other opportunities to accelerate time to FIH clinical trials.
DATES: Either electronic or written comments, data, or information must
be received by July 22, 2026.
ADDRESSES: You may submit comments, data, and information as follows.
Please note that late, untimely filed comments will not be considered.
The https://www.regulations.gov electronic filing system will accept
comments until 11:59 p.m. Eastern Time at the end of July 22, 2026.
Comments received by mail/hand delivery/courier (for written/paper
submissions) will be considered timely if they are received on or
before that date.
Electronic Submissions
Submit electronic comments in the following way:
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:
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.
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 Docket No. FDA-
2026-N-4699 for ``Expedited Investigational New Drug Pilot Program;
Request for Information.'' 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 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
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.
FOR FURTHER INFORMATION CONTACT: Benjamin Cook, Office of the
Commissioner, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 2, Rm. 2114, Silver Spring, MD 20993-0002, 240-338-4685,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is committed to accelerating development of therapies and cures
for the American people. In 2025, 70 percent of novel drugs were
approved in the U.S. before any other country, meaning American
patients and health care providers had access first.\1\ However, other
countries are focusing on increasing early-stage biomedical research
and rapidly advancing in technical ability. For example, in 2021 China
surpassed the U.S. in global share of phase 1 clinical trials, and from
2020 to 2025, 11 of the largest pharmaceutical companies spent over
$150 billion to access early drug assets developed in China.\2\ Given
the public health importance of access to novel therapies, FDA is
committed to streamlining requirements and innovating processes to
advance our global regulatory leadership and facilitate early-stage
research to continue in the U.S.
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\1\ https://www.fda.gov/media/190705/download?attachment.
\2\ https://www.nature.com/articles/d43747-025-00065-7.
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Biopharmaceutical companies able to accelerate FIH milestones have
a material advantage in creating a successful novel therapy that
reaches patients, which may be because the FIH milestone assists in
securing partnerships, investment, and ultimately approved therapies.
Early human clinical data represents the first value inflection point,
and unlocks the additional investment required for late-stage
development critical to the marketing of safe and effective drugs. It
is imperative for the U.S. to foster early clinical development that
ultimately provides patients with access to novel therapies, and
partnering with the innovation ecosystems and streamlining regulatory
requirements may help achieve that goal.
FDA reviewers manage substantial portfolios of INDs, New Drug
Applications (NDAs)/Biologics License Application (BLAs), and
postmarket
[[Page 37998]]
responsibilities. FDA aims to provide a regulatory environment for
sponsors to accelerate early clinical development while maintaining
rigorous oversight and safety protections for clinical trial
participants. This requires reimagining the IND process to address
regulatory considerations that account for pressures facing U.S.
innovators who seek to develop safe and effective drugs and
longstanding resource constraints facing FDA reviewers. The proposed
pilot program is being designed to test the feasibility of helping to
address overall time to the first in human trials. Specifically, the
pilot aims to test whether it is possible to improve the quality of IND
submissions such that there are fewer instances where it is necessary
to impose phase 1 clinical holds; reduce FDA review time through a
rolling submission process; and test whether clinical trial initiation
activities, such as Institutional Review Board (IRB) review and site
contracting, can be conducted in parallel with IND development and
review, thereby accelerating the time from when FDA permits a clinical
investigation to begin to FIH study initiation.
The role of third parties during the initial pilot program will be
restricted to providing advice and preliminary review, not engaging in
regulatory decision-making. FDA will remain solely responsible for
making decisions about whether a clinical investigation can begin or
whether a clinical hold may be imposed. Participation in the pilot is
voluntary. Sponsors may continue to submit INDs to FDA without
participating in the pilot.
A. Proposed Expedited IND Pilot Program Structure
FDA proposes leveraging America's world-class research institutions
as collaborative partners in early clinical development for drugs
intended for commercial distribution. The proposed expedited IND pilot
program will serve to identify a network of qualified research
institutions, such as AMCs, HNs, CROs, regulatory advisors, and/or
other research organizations (collectively called QRIs), who will
partner with sponsors to develop and review protocols for FIH clinical
trials in the U.S. intended for IND submission to FDA. These QRIs would
specifically assess and make recommendations for the pharmacology and
toxicology, clinical, and chemistry, manufacturing and controls (CMC)
components of the Phase 1 FIH IND submission. QRIs are intended to
serve as expert partners to sponsors in developing higher-quality
submissions that will expedite the timeframe to FIH trials and QRI
recommendations are, by nature, advisory. Sponsors will maintain
ownership over the IND submission. Throughout the proposed pilot, FDA
will maintain full oversight of IND submissions, retaining full
authority to make regulatory determinations, including the ability to
issue a clinical hold, disqualify investigators, and conduct
inspections.
As part of the proposed pilot, FDA is exploring the use of a
rolling submission platform that would allow FDA to review QRI
recommendations regarding completed components of the IND submission on
a rolling basis. Similar to the rolling review of an NDA or BLA under
FDA's expedited review programs, this approach would facilitate FDA
review of completed individual IND components prior to formal IND
submission. Once the last component of the Phase 1 IND is submitted,
the IND would be considered submitted such that the 30-day IND review
clock starts. Since all the IND submission components would have been
reviewed by FDA on a rolling basis, the sponsor may receive a safe to
proceed notification before the 30-day IND review period ends. The
rolling review could minimize the need for FDA to impose a clinical
hold because it would provide an earlier opportunity for FDA to
identify deficiencies, prior to the 30-day review period starting.
Similarly, the rolling review could minimize the need for FDA to issue
a clinical hold or information request. The pilot aims to test whether
these processes may accelerate Phase 1 FIH study initiation.
Additionally, FDA intends to work with sponsors and QRIs to review
and refine QRI performance objectives and key deliverables as part of
the pilot, with the goal of gathering information that could inform a
potential process for establishing a process for QRI certification by
FDA. FDA will monitor and evaluate QRI performance through clearly
defined metrics. FDA will implement a new technology platform to
perform a rolling IND submission by submitting individual IND
components and receiving FDA feedback in real time. Using this
platform, FDA will maintain oversight of recommendations regarding the
program's clinical protocol, pharmacology and toxicology package, or
CMC package, and ultimately provide FDA with the necessary information
to expedite IND submission review. FDA would retain full regulatory
authority including:
Authority to disqualify an investigator from conducting
clinical research;
Authority to disqualify or impose other administrative
restrictions on an IRB or its parent institution;
Current Good Clinical Practice clinical trial inspection
program;
Requirements for safety reporting;
Ability to issue a clinical hold.
The goal of this new pilot program is to accelerate the time from
nonclinical research to FIH studies while maintaining full FDA
oversight and regulatory authority. FDA seeks stakeholder input on the
processes, operational requirements, structural factors, and other
considerations that may impact pilot implementation. At the conclusion
of the pilot, FDA intends to use learnings from the pilot to further
provide regulatory oversight that facilitates early-stage, first in
human research in the U.S., and potentially refine its IND review
process broadly going forward. Following the pilot, FDA expects that
sponsors will pay fees directly to QRIs. FDA will not be involved in
the setting or collection of any fees.
B. QRI Responsibilities
FDA is considering the following responsibilities for QRIs
participating in the proposed pilot. FDA is seeking input on the
appropriate scope and structure of these responsibilities through
questions outlined in Section II. For the purpose of the pilot, QRI
responsibilities would include:
Conducting conflict of interest screening and establishing
a formal engagement agreement with the sponsor;
Conducting regular meetings with the sponsor and
appropriate subject matter experts to discuss IND development progress,
and maintaining comprehensive documentation of discussions and
recommendations;
Providing expert consultation and written recommendations
to sponsors on nonclinical, clinical, and CMC components of the IND
submission on a rolling basis;
Maintaining documentation of recommendations and sponsor
interactions and sharing with FDA through the rolling submission
platform;
Supporting parallel activities such as IRB review and
clinical trial site activation to facilitate timely trial initiation
upon FDA IND review; and
Participating in pilot evaluation activities, including
providing metrics and lessons learned to FDA.
C. QRI Qualification Criteria
The following reflects FDA's current thinking on eligibility
criteria for consideration for participating in the proposed pilot
program as a QRI. For
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the purposes of the proposed pilot, QRIs would be expected to
demonstrate:
Comprehensive expertise across nonclinical (pharmacology/
toxicology), clinical, and CMC disciplines relevant to first-in-human
IND submissions;
Clinical trial infrastructure supporting Phase 1 studies,
including IRB and clinical trial site capabilities, either through
direct ownership and operation or through established partnerships;
Leadership and personnel with suitable drug development
and first-in-human IND execution expertise across relevant disciplines,
including pharmacology-toxicology, clinical, CMC, and regulatory
affairs; and
A track record of success in regulatory affairs, including
supporting IND submissions across relevant therapeutic areas and
product modalities.
FDA will encourage pilot applicants to describe their capabilities
based on the qualifications outlined above. Additional capabilities may
be described if they advance applicants' ability to support IND
development.
II. Considerations for Pilot Development
FDA seeks input on these topics from sponsors, contract research
organizations, academic institutions, health networks/systems,
institutional review boards, patient advocacy organizations, investors,
and other interested parties. To help FDA review comments efficiently,
please identify the question to which you are responding by its
associated category and number. If you are responding to more than one
question, please identify each question to which you are responding,
and categorize each response by question. After reviewing input
provided on these topics, FDA intends to provide additional information
about how QRIs can request to participate in the pilot.
A. Pilot Program Design and Implementation
1. QRI Qualification and Capabilities
i. What specific changes, if any, would you recommend regarding
FDA's thinking on the capabilities, infrastructure, and/or leadership
expertise research institutions must demonstrate to qualify for the
pilot program?
ii. Are there additional required capabilities FDA should assess
across clinical and translational science expertise, CMC capabilities,
or therapy/domain area knowledge?
iii. Are any of the listed QRI qualification considerations
unfeasible or unattainable by potential QRIs?
iv. Should different specializations exist based on QRI therapeutic
area focus or therapeutic modality expertise?
v. To ensure faster FIH initiation, should QRIs be required to have
a self-owned and operated IRB and/or clinical trial site? If not, would
a partnership with an IRB and/or trial site network be sufficient?
vi. If the QRI serves in a dual capacity as both an IRB and
regulatory advisor, are there additional considerations or reporting
that would be helpful to prevent potential conflicts of interest and
ensure QRIs are objective and reliable?
2. Pre-IND and IND Review Process
i. What changes, if any, would you recommend regarding QRI
responsibilities and expected tasks during the pilot? Are any tasks
unfeasible or should be undertaken by the sponsor rather than the QRI?
ii. What should be the output of QRI advice and review? What
information from this review should be submitted to FDA?
iii. How can the pilot ensure QRIs provide independent, objective
review while partnering with sponsors?
iv. How should expedited INDs during the pilot differ in
requirement from standard IND submission, if at all?
3. Drug Eligibility and Participation
i. Should all drug products be considered in the pilot or are there
specific types of drug products and/or specific disease or conditions
that are better suited for the pilot (e.g., small molecules, large
molecules, cellular & gene therapies, nucleic acid-based therapies,
combination products, etc.)?
ii. How should drug products be prioritized for participation in
the pilot and why?
4. Pilot Scope and Scale
i. How many QRIs and therapeutic areas/modalities be included in
the pilot to represent industry research and different public health
needs?
ii. What duration or volume of participation is appropriate for the
pilot phase before evaluation?
5. Implementation and Feasibility
i. What resources would QRIs need to develop and maintain IND
review and recommendation capabilities (staff, quality systems,
technology infrastructure, estimated costs)?
ii. Are there existing models, research networks, pilot programs,
or international examples that could inform implementation? Please
describe relevant examples and lessons learned.
B. Risks, Oversight, and Evaluation
1. Risks and Safeguards
i. Are there any risks worth noting associated with the proposed
pilot program?
ii. Could the pilot inadvertently compromise clinical trial
participants' safety, scientific rigor, or ethical standards, and if
so, what suggestions does the commenter have for mitigating such an
outcome?
iii. Could this pilot create inequitable access favoring well-
resourced sponsors over smaller companies?
iv. Please include how identified risks can be mitigated.
2. Oversight and Accountability
i. In the case of disagreement between FDA and QRIs/sponsors on
recommendations, what processes, timeline, discussion forums, or
mitigation should be used to quickly reach a resolution?
ii. What oversight and compliance mechanisms should apply if QRIs
fail to meet performance standards? What performance thresholds or
other events should trigger FDA intervention or removal of QRIs?
iii. How can the pilot ensure transparency while safeguarding the
sponsor's confidential commercial, trade secrets, and other sensitive
information?
3. Success Metrics and Evaluation
i. What data should be collected throughout the pilot to enable
evaluation? Who should collect this data (FDA, QRIs, sponsors, third
party evaluators)?
ii. What metrics should define pilot success? Please address time,
quality, safety, and specify any others.
iii. At what point is the pilot deemed successful (i.e., after the
first successful IND submission, after the entire pilot cohort is
finished with IND submission, etc.)?
iv. If successful, how should the pilot expand? How can innovation
from the pilot be scaled to maximize impact for the FIH clinical trial
ecosystem?
C. Additional Considerations
1. What additional/alternative approaches could achieve similar
goals of accelerating Phase 1 FIH IND study initiation in the U.S.?
2. What are the advantages and disadvantages of the proposed pilot
compared to these alternatives?
3. How should FDA take into account the information submitted, and
should
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that be different depending on the risk of the product under
investigation?
4. Are there important considerations or concerns not addressed in
the questions above?
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-12621 Filed 6-22-26; 11:15 am]
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