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
5894 Federal Register / Vol. 90, No. 11 / Friday, January 17, 2025 / Notices 

provides recommendations to sponsors 

for the clinical development of drug and 

biological products intended for the 

prevention and treatment of CIPN in 

oncology patient populations. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by March 18, 2025 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance at any time 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– 

2024–D–5663 for ‘‘Prevention and 

Treatment of Chemotherapy-Induced 

Peripheral Neuropathy: Developing 

Drug and Biological Products in 

Oncology.’’ 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. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of the draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002 or to the Office of Communication, 

Outreach and Development, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

3128, Silver Spring, MD 20993–0002. 

Send one self-addressed adhesive label 

to assist the office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Mirat Shah, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, Rm. 2135, Silver Spring, 

MD 20993, 301–796–8547; or James 

Myers, Center for Biologics Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 71, Rm. 7301, Silver Spring, 

MD 20993, 240–402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA 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.’’ CIPN 

is a painful, disabling, and potentially 

irreversible condition commonly 

affecting patients receiving neurotoxic 

chemotherapies. CIPN could lead to 

chemotherapy treatment interruptions, 

dose reductions, and discontinuations. 

In addition, there is a concern that 

CIPN-mitigating drugs may decrease the 

efficacy of cancer treatment or possibly 

promote tumor growth. Thus, CIPN can 

negatively affect overall cancer 

treatment outcome and survival. This 

guidance provides recommendations to 

sponsors for the clinical development of 

drug and biological products intended 

for the prevention and treatment of 

CIPN in oncology patient populations. 

The recommendations include trial 

population, design, and selection of 

appropriate oncology-specific 

endpoints. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Prevention and Treatment of 

Chemotherapy-Induced Peripheral 

Neuropathy: Developing Drug and 

Biological Products in Oncology.’’ It 

does not establish any rights for any 

person and is not binding on FDA or the 

public. You can use an alternative 

approach if it satisfies the requirements 

of the applicable statutes and 

regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 


KHAMMOND on DSK9W7S144PROD with NOTICES
Federal Register / Vol. 90, No. 11 / Friday, January 17, 2025 / Notices 5895 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (PRA) (44 U.S.C. 

3501–3521). The collections of 

information related to the protection of 

human subjects under 21 CFR part 50 

have been approved under OMB control 

number 0910–0130. The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001. The collections of 

information in 21 CFR part 601 have 

been approved under OMB control 

number 0910–0338. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, https://

www.fda.gov/regulatory-information/ 

search-fda-guidance-documents, or 

https://www.regulations.gov. 

Dated: January 10, 2025. 

P. Ritu Nalubola, 

Associate Commissioner for Policy. 

[FR Doc. 2025–01197 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–N–3112] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Postmarketing 

Adverse Experience Reporting 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Submit written comments 

(including recommendations) on the 

collection of information by February 

18, 2025. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0230. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

JonnaLynn Capezzuto, Office of 

Operations, Food and Drug 

Administration, Three White Flint 

North, 10A–12M, 11601 Landsdown St., 

North Bethesda, MD 20852, 301–796– 

3794, PRAStaff@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

Postmarketing Adverse Experience 

Reporting 

OMB Control Number 0910–0230— 

Revision 

This information collection helps 

support provisions found in sections 

201, 502, 505, 701, and 760 of the 

Federal Food, Drug, and Cosmetic Act 

(FD&C Act) (21 U.S.C. 321, 352, 355, 

371, and 379aa) governing adverse 

experience reporting (AER) and 

associated recordkeeping for FDAregulated drug products. FDA has 

issued applicable regulations in part 4 

and §§ 310.305, 314.80, 314.81, 314.98, 

and 329.100 (21 CFR part 4 and 21 CFR 

310.305, 314.80, 314.81, 314.98, and 

329.100) that implement the statutory 

requirements, identify specific content 

and format elements, and establish 

reporting and retention schedules for 

the required information. Postmarketing 

safety data collection and adverse event 

reporting are critical elements of FDA’s 

monitoring of drugs. For more 

information, please visit https://

www.fda.gov/drugs/surveillance/ 

postmarketing-adverse-event-reportingcompliance-program. 

Respondents to the information 

collection are manufacturers, packers, 

distributors, and applicants of FDAregulated drug and biologic products 

marketed with or without an FDAapproved application, including overthe-counter (OTC) drug products 

marketed without an approved 

application; OTC drug products 

marketed under the OTC Drug 

Monograph Review process (whether 

subject to a final monograph or not); and 

drug products marketed outside the 

monograph system. All reports and 

followup reports must be submitted to 

FDA in electronic format, although 

waivers of the electronic requirements 

are available for good cause. 

Adverse experience reporting for 

products associated with drug 

marketing applications are governed by 

regulations in §§ 314.80, 314.81, and 

314.98. The regulations identify 

required reporting content and format 

elements, as well as establish followup 

reporting requirements and mandatory 

reporting schedules. The regulations 

also establish associated recordkeeping 

and require that written procedures be 

developed for the surveillance, receipt, 

evaluation, and reporting of 

postmarketing adverse experiences to 

FDA. The regulations require reporting 

in an electronic format that FDA can 

process, although temporary waivers 

may be granted on a limited basis for 

good cause. A final guidance for 

industry entitled ‘‘Providing 

Submissions in Electronic Format— 

Postmarketing Safety Reports’’ (April 

2022) is available for general 

information pertaining to electronic 

submission of postmarketing safety 

reports for certain human drugs, 

biological products, and combination 

products. The guidance is available at 

https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments/providing-submissionselectronic-format-postmarketing-safetyreports. 

We have established and maintain the 

FDA Adverse Event Reporting System 

(FAERS) at https://www.fda.gov/drugs/ 

questions-and-answers-fdas-adverseevent-reporting-system-faers/fdaadverse-event-reporting-system-faerselectronic-submissions. Information 

may be submitted via FDA’s Electronic 

Submissions Gateway or utilizing the 

‘‘Safety Reporting Portal,’’ developed by 

FDA and the National Institutes of 

Health to streamline reporting and 

review of adverse events. 

The primary purpose of FDA’s 

adverse drug experience reporting 

system is to enable identification of 

signals for potentially serious safety 

problems with marketed drugs. 

Although premarket testing discloses a 

general safety profile of a new drug’s 

comparatively common adverse effects, 

the larger and more diverse patient 

populations exposed to the marketed 

product provide the opportunity to 

collect information on rare, latent, and 

long-term effects. Signals are obtained 

from a variety of sources, including 

reports from patients, treating 

physicians, foreign regulatory agencies, 

clinical investigators, and literature. 

Information derived from the adverse 

drug experience reporting system 

contributes directly to increased public 


KHAMMOND on DSK9W7S144PROD with NOTICES