[Federal Register Volume 90, Number 11 (Friday, January 17, 2025)]
[Notices]
[Pages 5892-5893]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-01182]
[[Page 5892]]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2024-N-5975]
Use of a Type V Drug Master File for Model Master File
Submissions To Support Abbreviated New Drug Applications; Establishment
of a Public Docket; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; establishment of a public docket; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency), Center for
Drug Evaluation and Research (CDER), Office of Generic Drugs is
establishing a public docket entitled ``Use of a Type V Drug Master
File (DMF) for Model Master File (MMF) Submissions to Support
Abbreviated New Drug Applications (ANDAs).'' The purpose of this docket
to solicit input from interested parties on this topic.
DATES: Submit either electronic or written comments on the notice by
April 17, 2025 to ensure that the Agency considers your comment. The
docket number is FDA-2024-N-5975.
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 April 17, 2025. 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-5975 for ``Use of a Type V Drug Master File for Model Master
File Submissions to Support Abbreviated New Drug Applications;
Establishment of a Public Docket; Request for Comments.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 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: Lanyan (Lucy) Fang, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave. Bldg. 75, Rm. 4686, Silver Spring, MD 20993-0002, 301-
796-5005, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Computational (in silico) modeling and simulation (M&S) is a
regulatory science priority at FDA given the rapid growth in drug
developers' use of data science and model-based technologies. An
example is the increasing use of quantitative methods and modeling
(QMM) and simulation approaches by the generic drug industry and
regulatory agencies, including FDA, to support generic product
development and ANDA regulatory assessments.\1\ These QMM approaches
generally involve mechanistic modeling such as physiologically based
pharmacokinetic (PBPK) modeling and computational fluid dynamics (CFD)
modeling, quantitative clinical pharmacology tool sets such as
population pharmacokinetics (PPK) approaches, and advanced data
analytics methodologies. Generic drug developers are utilizing QMM and
simulation approaches to generate MIE to, for example, support
alternative BE approaches and to minimize the burden
[[Page 5893]]
of, or even eliminate the need for, in vivo studies to establish BE.
---------------------------------------------------------------------------
\1\ See, e.g., guidance for industry ``Physiologically Based
Pharmacokinetic Analyses--Format and Content'' (August 2018); see
also, draft guidance for industry ``The Use of Physiologically Based
Pharmacokinetic Analyses--Biopharmaceutics Applications for Oral
Drug Product Development, Manufacturing Changes, and Controls''
(October 2020). When final, this guidance will represent the FDA's
current thinking on this topic. FDA updates guidances periodically;
the most recent version of a guidance can be found at FDA's Drugs
guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
---------------------------------------------------------------------------
While QMM approaches that generate MIE provide significant value to
the development, review, and approval of high-quality generic drugs,
these frameworks are evolving amidst challenges and complications
facing industry that are incidental to the growing use of new and
complex modeling technologies. For example, the data and information
needed to verify and validate a model may not be available to the
general public (e.g., proprietary), or if publicly available,
insufficient, and generating original data for model verification and
validation (V&V) can be a time-consuming and costly investment. At the
same time, certain M&S approaches may provide an opportunity for
certain models, once they are supported by sufficient V&V, to be viewed
as shareable across different products and formulations and utilized by
multiple ANDA applicants for the same context of use. For purposes of
this notice, an ``MMF'' or ``MMF submission'' refers to a set of
information and data on an in silico quantitative model or modeling
platform supported by sufficient V&V. MMFs can be established to
support MIE in a broad range of quantitative models, including, but not
limited to, PBPK, CFD, PPK, and mechanistic in vitro in vivo
correlation models. There are different types of MMFs, including, but
not limited to, drug product-specific models, a verified and validated
in silico framework for products following the same route of
administration, and a recognized modeling methodology or framework for
a particular context of use (Ref. 1).
FDA recognizes the evolving role MIE plays in generic drug
development and other regulatory applications, as well as industry's
corollary desire for an improved framework for in silico model-sharing,
model acceptance, and related communication with and submission to FDA.
Use of the Type V DMF to efficiently leverage MMFs within the scope of
successful MIE approaches may help advance generic drug development and
facilitate the ANDA review and approval processes.
A DMF is a voluntary submission that may be used to provide
confidential detailed information to the Agency (Ref. 2). A DMF is
submitted solely at the discretion of the DMF holder. There are several
types of DMFs; a Type V is used for ``FDA-accepted reference
information.'' (Sec. 314.420(a)(5) (21 CFR 314.420(a)(5))). The use of
a DMF is not a requirement for the submission of MMFs to the Agency;
however, the holder of a Type V DMF can authorize one or more ANDA
applicants to incorporate by reference information and data contained
in the DMF without having to disclose that information and data to the
applicant(s). When authorized by the DMF holder, ANDA applicants can
use information and data contained in the DMF to support, but not
substitute for, their ANDA submissions. A DMF is neither approved nor
disapproved. Its technical content (in this case, the MMF) is typically
reviewed by FDA only in connection with the review of a premarket
application (Ref. 2 at 6). A Type V DMF, including a Type V DMF for MMF
submissions to support an ANDA, may be submitted on an ongoing basis.
Prospective DMF holders who are interested in using a Type V DMF,
including a Type V DMF for MMF submissions to support ANDAs, must first
email a letter of intent to the DMF staff (see Ref. 2 at 16 (citing
Sec. 314.420(a)(5))). The draft guidance for industry ``Drug Master
Files'' provides detailed information about preparing and submitting
DMFs and FDA's DMF review process, including that an emailed letter of
intent should be sent to ([email protected]) and include a
clearly stated subject field and other necessary information (Ref. 2 at
16). For example, applicants that have submitted a Type V DMF for MMF
submissions to support ANDAs have submitted the letter of intent with a
subject field, such as ``Letter of Intent to Submit Type V DMF for MMF
Submission to Support ANDAs''. For more information on submitting Type
V DMFs, see FDA's DMF web page and the FDA Guidance for Industry
``Providing Regulatory Submissions in Electronic Format--Certain Human
Pharmaceutical Product Applications and Related Submissions using the
eCTD Specifications'' (Ref. 3).\2\
---------------------------------------------------------------------------
\2\ See also, FDA's DMF web page, available at https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs.
---------------------------------------------------------------------------
II. Request for Comments
FDA is opening a docket to solicit feedback from the public on the
use of a Type V DMF for MMF submissions to support ANDAs. FDA welcomes
any relevant information that interested parties and other members of
the public wish to share. At the close of the comment period, the
Agency will collect this feedback for consideration.
III. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
Although FDA has verified the website addresses, as of the date this
document publishes in the Federal Register, but websites are subject to
change over time.
1. Fang, L., Y. Gong, A.C. Hooker, et al., 2024, ``The Role of
Model Master Files for Sharing, Acceptance, and Communication with
FDA,'' The AAPS Journal, 26(2):28-35 available at 10.1208/s12248-
024-00897-8.
* 2. FDA Draft Guidance for Industry ``Drug Master Files,''
October 2019: https://www.fda.gov/media/131861/download.
* 3. FDA Guidance for Industry ``Providing Regulatory
Submissions in Electronic Format--Certain Human Pharmaceutical
Product Applications and Related Submissions using the eCTD
Specifications,'' September 2024, Rev. 8: https://www.fda.gov/media/135373/download.
Dated: January 14, 2025.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2025-01182 Filed 1-16-25; 8:45 am]
BILLING CODE 4164-01-P