5892 Federal Register / Vol. 90, No. 11 / Friday, January 17, 2025 / Notices 

1See, 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Content’’ (August 2018); see also, draft guidance for 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. 

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, mmf@fda.hhs.gov. 

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 


KHAMMOND on DSK9W7S144PROD with NOTICES
Federal Register / Vol. 90, No. 11 / Friday, January 17, 2025 / Notices 5893 

2See also, FDA’s DMF web page, available at 

https://www.fda.gov/drugs/forms-submissionrequirements/drug-master-files-dmfs. 

of, or even eliminate the need for, in 

vivo studies to establish BE. 

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.’’ (§ 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 

§ 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 (dmfquestion@fda.hhs.gov) 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

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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–D–5663] 

Prevention and Treatment of 

Chemotherapy-Induced Peripheral 

Neuropathy: Developing Drug and 

Biological Products in Oncology; Draft 

Guidance for Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a draft 

guidance for industry entitled 

‘‘Prevention and Treatment of 

Chemotherapy-Induced Peripheral 

Neuropathy: Developing Drug and 

Biological Products in Oncology.’’ 

Chemotherapy-induced peripheral 

neuropathy (CIPN), a painful, disabling, 

and potentially irreversible condition 

commonly affecting patients receiving 

neurotoxic chemotherapies, could 

diminish survival by potentially 

increasing chemotherapy treatment 

interruptions, dose reductions, and 

discontinuations. This guidance 


KHAMMOND on DSK9W7S144PROD with NOTICES