[Federal Register Volume 89, Number 170 (Tuesday, September 3, 2024)]
[Notices]
[Pages 71374-71376]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-19712]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-N-3904]


Identifying Priority Focus Areas for Future Guidance Development 
and Engagement With Interested Parties in Model-Informed Drug 
Development; Request for Information

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for Information.

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SUMMARY: The Center for Drug Evaluation and Research (CDER) and Center 
for Biologics Evaluation and Research (CBER) within the Food and Drug 
Administration (FDA or Agency) are announcing a request for information 
(RFI) for advancing model-informed drug development (MIDD). The purpose 
of this request is to obtain feedback on how to increase application of 
established MIDD approaches in regulatory decision making, to identify 
how emerging MIDD approaches are being incorporated within drug product 
development, and to identify opportunities to enhance interactions with 
FDA when discussing MIDD approaches. We intend to use the information 
submitted in response to this request to identify and prioritize 
potential focus areas for future policy or guidance development and 
enhance engagement with interested parties, including interactions as 
part of the

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MIDD Paired Meeting Program and other formal meetings with drug 
developers.

DATES: Either electronic or written comments on the notice must be 
submitted by November 4, 2024.

ADDRESSES: You may submit comments 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 November 4, 2024. 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 the Docket No. 
FDA-2024-N-3904 for ``Identifying Priority Focus Areas for Future 
Guidance Development and Engagement with Interested Parties in Model-
Informed Drug Development; 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: Yvonne Knight, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 2142, Silver Spring, MD 20993, 301-796-
2133, [email protected], with the subject line ``MIDD Meetings 
Program for CDER''; or Christopher Egelebo, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 5340, Silver Spring, MD 20993, 240-402-
8625, [email protected], with the subject line ``MIDD 
Meetings Program for CBER.''

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing a request for information entitled ``Identifying 
Priority Focus Areas for Future Guidance Development and Engagement 
with Interested Parties in Model-Informed Drug Development.'' 
Information submitted in response to this notice will be used by CDER, 
including by its Quantitative Medicine Center of Excellence, and CBER 
to assist in identifying and prioritizing potential focus areas for 
future policy or guidance development and engagement with interested 
parties.
    MIDD approaches integrate exposure-based biological and statistical 
models derived from nonclinical and clinical data sources in drug 
development and decision making. MIDD applications span the life cycle 
of new drug product development. MIDD approaches use a variety of 
quantitative methods (e.g., population pharmacokinetic (popPK) 
modeling, exposure-response (E-R) modeling, physiologically based 
pharmacokinetic (PBPK) modeling, systems pharmacology/mechanistic 
modeling, disease progression modeling, drug-trial-disease modeling and 
simulation, artificial intelligence/machine learning (AI/ML) 
approaches) to help assess the risks and benefits of drug products, 
contribute to the evidentiary framework for efficacy and/or safety, and 
optimize dosing regimens for patients, among other applications. When 
successfully applied, MIDD approaches might reduce animal testing, 
improve clinical trial design and efficiency, inform identification of 
dosing regimens with improved benefit-risk profiles, increase the 
probability of regulatory success through synergetic engagement with 
interested parties, and optimize drug dosing/therapeutic 
individualization in the absence of dedicated trials.
    Beginning with Prescription Drug User Fee Act (PDUFA) VI, FDA began 
granting focused meetings as part of the MIDD Paired Meeting Pilot to: 
(1) provide a forum for regulatory interaction between drug developers 
and FDA on the application of MIDD approaches in specific drug 
development programs; and (2) provide

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an opportunity for FDA to provide advice regarding how particular MIDD 
approaches can be used in a specific drug development program. Other 
deliverables as part of PDUFA VI included increasing regulatory science 
and review capacity in MIDD approaches and convening multiple workshops 
to identify best practices for MIDD (topics including E-R, PBPK, 
disease progression modeling, and immunogenicity assessments). In 
addition, FDA published or revised multiple guidances on MIDD. As part 
of PDUFA VII, the MIDD Paired Meeting Program has been continued and 
this RFI is to elicit public input on future focus areas for advancing 
MIDD. More information on the MIDD Paired Meeting program can be found 
at https://www.fda.gov/drugs/development-resources/model-informed-drug-development-paired-meeting-program.

II. Request for Information

    FDA is interested in detailed comments on the topics listed in this 
section below to identify and inform future priorities for MIDD-related 
policy, including guidance development and engagement with interested 
parties. The topics identified in this section are not meant to be 
exhaustive. FDA is also interested in any other pertinent information 
that interested parties would like to share related to guidance and 
enhancing MIDD-related interactions with FDA. FDA encourages interested 
parties to provide the specific rationale and basis for their comments, 
including any available supporting data and information.

A. Methods and Best Practices

    Several quantitative approaches, such as popPK, E-R, and PBPK, are 
routinely employed in drug development and regulatory assessment. The 
Agency aims to identify areas within these approaches that would 
benefit from the development of additional policies or guidance on 
methodology and best practices. In addition, with this RFI, the Agency 
is seeking input to explore potential guidance needs and appropriately 
identify and prioritize potential topics for guidance development in 
all emerging MIDD approaches for drug and biological products, 
including but not limited to, AI/ML used in both drug design and 
evaluation and digital-twin technology.

B. Context-Specific Considerations

    MIDD approaches that leverage comprehensive information--including 
disease and patient population characteristics (e.g., intrinsic and 
extrinsic factors), drug properties, placebo effects, nonclinical and 
clinical E-R relationships--are potent tools and can be utilized across 
all stages of the drug development life cycle to support decision 
making. This is particularly important for rare diseases and emerging 
therapeutic and prophylactic/preventative modalities where there may be 
practical and ethical challenges in conducting traditional drug 
development programs or where there is limited drug development 
experience. We seek input on the need to develop guidances that discuss 
considerations to facilitate MIDD methods development, application, 
uptake, and acceptance in specific therapeutic areas. Related topics 
include identification of opportunities for incorporation of real-world 
data, specific therapeutic modality considerations, and preclinical to 
clinical translations and to appropriately identify and prioritize 
potential topics in this area.

C. Regulatory Engagement

    Building on the success of the MIDD Paired Meeting Program, FDA is 
interested in better understanding ways to facilitate discussion around 
MIDD approaches outside the MIDD Paired Meeting Program as part of 
regulatory meetings and regulatory submissions. This includes 
identifying what is currently working well and what are the barriers 
(e.g., technical, regulatory) encountered while trying to interact with 
FDA on MIDD-related activities.

D. Communication of Policies and Interested Parties' Engagement

    FDA continues to engage on MIDD approaches as part of external 
workshops with interested parties, including workshops described and 
completed under PDUFA VI. FDA seeks to identify and prioritize 
potential topics and better ways for communication and engagement with 
interested parties.

    Dated: August 28, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-19712 Filed 8-30-24; 8:45 am]
BILLING CODE 4164-01-P