[Federal Register Volume 88, Number 7 (Wednesday, January 11, 2023)]
[Notices]
[Pages 1597-1599]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-00389]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-1203]


Prescription Drug User Fee Act of 2023 VII Meetings Program for 
Model-Informed Drug Development Approaches

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The seventh iteration of the Prescription Drug User Fee Act 
(PDUFA VII), incorporated as part of the FDA User Fee Reauthorization 
Act of 2022, highlights the goal of advancing model-informed drug 
development (MIDD). The Food and Drug Administration (FDA or Agency) is 
announcing the continuation of the MIDD Paired Meeting Program that 
affords sponsors who are selected for participation the opportunity to 
meet with Agency staff to discuss MIDD approaches in medical product 
development. Meetings under the program will be conducted by FDA's 
Center for Drug Evaluation and Research (CDER) and Center for Biologics 
Evaluation and Research (CBER) during fiscal years 2023-2027. This 
program is being conducted to fulfill FDA's performance commitment 
under PDUFA VII. For this program, MIDD is defined as the application 
of exposure-based, biological, and/or statistical models derived from 
non-clinical and clinical data sources to address drug development and/
or regulatory issues (see Supplementary Information, I. Background, and 
II. Eligibility and Selection for Participation of this notice). For 
each approved proposal, the program consists of two meetings between 
sponsors or applicants and the relevant center that provide an 
opportunity for drug developers and FDA to discuss the application of 
MIDD approaches to the development and regulatory evaluation of medical 
products in development.

DATES: FDA will accept requests to participate in the program on a 
continuous basis beginning on October

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1, 2022, through June 1, 2027. See section III of this notice for 
instructions about how to request participation in the program. 
Meeting-granted and -denied decisions will be made the last 2 weeks of 
each quarter of the fiscal year based on submissions received to date. 
Requesters will receive a meeting-granted or -denied notification no 
later than the second week of the new quarter.
    The program will proceed from October 1, 2022, through September 
30, 2027. The Agency will notify sponsors of proposals not selected for 
a given quarter. Sponsors who do not participate in the program may 
seek Agency interaction through existing channels (e.g., Type C meeting 
requests, critical path innovation meetings). The listed eligibility 
criteria and procedures outlined in this Federal Register notice 
reflect the current thinking at the time of publication. Processes may 
be revised and will be communicated as this program evolves. The most 
current program eligibility criteria and procedures may be found on the 
MIDD Program website: https://www.fda.gov/drugs/development-resources/model-informed-drug-development-paired-meeting-program.

ADDRESSES: Comments about this program can be submitted until February 
10, 2023. You may submit comments about the MIDD meetings program as 
follows:

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-2018-N-1203 for ``Prescription Drug User Fee Act of 2023 VII 
Meetings Program for Model-Informed Drug Development Approaches.'' 
Received comments 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: 
    CDER: 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.''
    CBER: 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

    Under the FDA User Fee Reauthorization Act of 2022, FDA agreed, in 
accordance with the ``PDUFA Reauthorization Performance Goals and 
Procedures Fiscal Years 2023 Through 2027: I. Ensuring the 
Effectiveness of the Human Drug Review, Part L. Enhancing Regulatory 
Decision Tools to Support Drug Development and Review'' to provide 
information on how a sponsor can apply to participate in the MIDD 
Meetings Program (https://www.fda.gov/media/151712/download).
    FDA will build on the success of the MIDD Paired Meeting Pilot 
under PDUFA VI by continuing to advance and integrate the development 
and application of exposure-based, biological, and statistical models 
derived from non-clinical and clinical data sources in drug development 
and regulatory review. FDA is announcing the continuation of this 
meeting program to satisfy the above-mentioned commitment and to 
facilitate the continued use of MIDD approaches. These approaches 
exclude statistical designs involving complex adaptations, Bayesian 
methods, or other features requiring computer simulations to determine 
the operating characteristics of a confirmatory clinical trial. MIDD 
approaches use a variety of quantitative methods to help balance the 
risks and benefits of drug products in development. When successfully 
applied, MIDD approaches can improve clinical trial efficiency, 
increase the probability of regulatory success, and optimize drug 
dosing/therapeutic individualization in the absence of dedicated 
trials.

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    The goal of the early meeting discussions granted under this 
program is to provide advice on how specific, proposed MIDD approaches 
can be used in a particular drug development program. FDA has committed 
to accepting one to two appropriate meeting requests quarterly each 
fiscal year. The meetings granted will include an initial and followup 
meeting on the same drug development issues. The second meeting will 
occur within approximately 60 days of receiving the briefing package.

II. Eligibility and Selection for Participation in the MIDD Program

    The sponsor should be a drug/biologics development company 
(interested consortia or software/device developer should come in 
partnership with a drug development company) and have an 
investigational new drug application (IND) or pre-IND (PIND) number for 
the relevant program. FDA welcomes submissions related to any relevant 
MIDD topics, such as:
     Dose selection or estimation (e.g., for dose/dosing 
regimen selection or refinement)
     Clinical trial simulation (e.g., based on drug-trial-
disease models to inform the duration of a trial, select appropriate 
response measures, predict outcomes, etc.)
     Predictive or mechanistic safety evaluation (e.g., use of 
systems pharmacology/mechanistic models for predicting safety or 
identifying critical biomarkers of interest)

III. Procedures and Submission Information

A. General Information

    The MIDD program will be jointly administered by CDER's Office of 
Clinical Pharmacology, in the Office of Translational Sciences, which 
is the point of contact for all communications for CDER products, and 
CBER's Office of Biostatistics and Pharmacovigilance, which is the 
point of contact for all communications for CBER products.

B. How To Submit a Meeting Request and Meeting Package

    Meeting requests should be submitted electronically to the relevant 
application (i.e., PIND, IND) with ``MIDD Program Meeting Request for 
CDER'' (CDER applications) or ``MIDD Program Meeting Request for CBER'' 
(CBER applications) in the subject line. Information about providing 
regulatory submissions in electronic format is available at: https://www.fda.gov/drugs/development-approval-process-drugs/forms-submission-requirements.

C. Content and Format of the Meeting Request

    Include the following information in the meeting request (no more 
than three to four pages):
    1. Product name.
    2. Application number.
    3. Chemical name and structure.
    4. Proposed indication(s) or context of product development.
    5. A brief statement of the purpose and objectives of the meeting. 
The statement should include a brief background of the MIDD issues 
underlying the agenda.
    6. MIDD approach(es) considered for the product under development 
and how MIDD can assess uncertainties about issues (e.g., dosing, 
duration, patient selection) in a way that can inform regulatory 
decision-making.
    7. A list of issues for discussion with the Agency about the 
specific MIDD proposed approach for the applicable drug development 
program.

D. Content and Format of the Meeting Information Package

    Sponsors whose meeting requests are granted as part of the program 
should submit a meeting information package electronically with ``MIDD 
Program Meeting Package for CDER'' (CDER applications) or ``MIDD 
Program Meeting Package for CBER'' (CBER applications) in the subject 
line no later than 47 days before the initial meeting and 60 days 
before the follow-up meeting. This meeting package should include the 
following information:
    1. Product name.
    2. Application number.
    3. Chemical name and structure.
    4. Proposed indications or context of product development.
    5. Background section that includes a brief history of the 
development program and the events leading up to the meeting as well as 
the status of product development.
    6. Proposed agenda, including estimated times needed for discussion 
of each agenda item.
    7. List of questions for discussion along with a brief summary 
explaining the question of interest and the context of use for each 
question. State whether the model will be used to inform future trials, 
to provide mechanistic insight, or in lieu of a clinical trial.
    8. The drug development issue (e.g., dosing, clinical trial design, 
safety prediction, etc.), the proposed MIDD approach to the solution, 
information to support discussion (e.g., a description of the data 
utilized for developing the models, model development, simulation plan, 
results), assessment of model risk, and how the Agency can help guide 
any next steps relative to the regulatory decision-making process 
should be summarized and clearly articulated with any supporting data 
imperative to the discussion.

E. Meeting Summaries

    A meeting summary will be sent to the requester within 30 days of 
each meeting.

IV. Paperwork Reduction Act of 1995

    While this notice contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this notice. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information pertaining to Prescription Drug User Fee Program have 
been approved under OMB control number 0910-0297. The collections of 
information for requesting meetings with FDA about drug development 
programs have been approved under OMB control number 0910-0001. The 
collections of information in 21 CFR part 312 for INDs and clinical 
trials have been approved under OMB control number 0910-0014. The 
collections of information in 21 CFR part 601 for biologics license 
applications have been approved under OMB control number 0910-0338.

    Dated: January 5, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-00389 Filed 1-10-23; 8:45 am]
BILLING CODE 4164-01-P