106504 Federal Register / Vol. 89, No. 249 / Monday, December 30, 2024 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–D–5580] 

M15 General Principles for ModelInformed Drug Development; 

International Council for 

Harmonisation; Draft Guidance for 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 ‘‘M15 

General Principles for Model-Informed 

Drug Development.’’ The draft guidance 

was prepared under the auspices of the 

International Council for Harmonisation 

of Technical Requirements for 

Pharmaceuticals for Human Use (ICH). 

The draft guidance discusses the 

multidisciplinary principles of modelinformed drug development (MIDD). 

This includes recommendations on 

MIDD planning, model evaluation, and 

evidence documentation. The draft 

guidance also includes a harmonized 

framework for assessing evidence 

derived from MIDD. The draft guidance 

is intended to facilitate 

multidisciplinary understanding, 

appropriate use, and harmonized 

assessment of MIDD and its associated 

evidence. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by February 28, 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draft guidance before it begins work on 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–5580 for ‘‘M15 General 

Principles for Model-Informed Drug 

Development.’’ 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 the Office of Communication, 

Outreach and Development, Center for 

Biologics Evaluation and Research 

(CBER), 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. The draft guidance may 

also be obtained by mail by calling 

CBER at 1–800–835–4709 or 240–402– 

8010. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Regarding the guidance: Hao Zhu, 

Center for Drug Evaluation and 

Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 3134, Silver Spring, 

MD 20993–0002, Hao.Zhu@fda.hhs.gov; 

or James Myers, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 7301, 

Silver Spring, MD 20993–0002, 240– 

402–7911. 

Regarding the ICH: Jill Adleberg, 

Center for Drug Evaluation and 

Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 6364, Silver Spring, 

MD 20993–0002, 301–796–5259, 

Jill.Adleberg@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘M15 General Principles for ModelInformed Drug Development.’’ The draft 


ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 89, No. 249 / Monday, December 30, 2024 / Notices 106505 

guidance was prepared under the 

auspices of ICH. ICH seeks to achieve 

greater regulatory harmonization 

worldwide to ensure that safe, effective, 

high-quality medicines are developed, 

registered, and maintained in the most 

resource-efficient manner. 

By harmonizing the regulatory 

requirements in regions around the 

world, ICH guidelines enhance global 

drug development, improve 

manufacturing standards, and increase 

the availability of medications. For 

example, ICH guidelines have 

substantially reduced duplicative 

clinical studies, prevented unnecessary 

animal studies, standardized the 

reporting of important safety 

information, and standardized 

marketing application submissions. 

The six Founding Members of the ICH 

are FDA; the Pharmaceutical Research 

and Manufacturers of America; the 

European Commission; the European 

Federation of Pharmaceutical Industries 

Associations; the Japanese Ministry of 

Health, Labour, and Welfare; and the 

Japanese Pharmaceutical Manufacturers 

Association. The Standing Members of 

the ICH Association include Health 

Canada and Swissmedic. ICH 

membership continues to expand to 

include other regulatory authorities and 

industry associations from around the 

world (refer to https://www.ich.org/). 

ICH works by engaging global 

regulatory and industry experts in a 

detailed, science-based, and consensusdriven process that results in the 

development of ICH guidelines. The 

regulators around the world are 

committed to consistently adopting 

these consensus-based guidelines, 

realizing the benefits for patients and for 

industry. 

As a Founding Regulatory Member of 

ICH, FDA plays a major role in the 

development of each of the ICH 

guidelines, which FDA then adopts and 

issues as guidance for industry. FDA’s 

guidance documents do not establish 

legally enforceable responsibilities. 

Instead, they describe the Agency’s 

current thinking on a topic and should 

be viewed only as recommendations, 

unless specific regulatory or statutory 

requirements are cited. 

In November 2024, the ICH Assembly 

endorsed the draft guideline entitled 

‘‘M15 General Principles for ModelInformed Drug Development’’ and 

agreed that the guideline should be 

made available for public comment. The 

draft guideline is the product of the 

Multidisciplinary Expert Working 

Group of the ICH. Comments about this 

draft will be considered by FDA and the 

Multidisciplinary Expert Working 

Group. 

The draft guidance promotes 

multidisciplinary understanding and 

harmonized assessment of MIDD by 

discussing principles, assessment 

frameworks, evaluation, and reporting 

of MIDD and its generated evidence. 

Appropriate use of MIDD can enable 

greater efficiency in drug development, 

while harmonized approaches to 

assessment can promote consistent and 

transparent evaluation of MIDD 

evidence to inform regulatory decision 

making. 

This draft guidance has been left in 

the original ICH format. The final 

guidance will be reformatted and edited 

to conform with FDA’s good guidance 

practices regulation (21 CFR 10.115) and 

style before publication. The draft 

guidance, when finalized, will represent 

the current thinking of FDA on ‘‘M15 

General Principles for Model-Informed 

Drug Development.’’ 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 

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 for submission of regulatory 

information, including nonclinical and 

clinical data, prior information of drug 

and disease characteristics derived from 

model-informed drug development, 

have been approved under OMB control 

numbers 0910–0014, 0910–0001, and 

0910–0338. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.regulations.gov, https://

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

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

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

www.fda.gov/regulatory-information/ 

search-fda-guidance-documents. 

Dated: December 16, 2024. 

P. Ritu Nalubola, 

Associate Commissioner for Policy. 

[FR Doc. 2024–31027 Filed 12–27–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. FDA–2024–E–0440 and FDA– 

2024–E–0441] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; ROCTAVIAN 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) has 

determined the regulatory review period 

for ROCTAVIAN and is publishing this 

notice of that determination as required 

by law. FDA has made the 

determination because of the 

submission of applications to the 

Director of the U.S. Patent and 

Trademark Office (USPTO), Department 

of Commerce, for the extension of a 

patent which claims that human 

biological product. 

DATES: Anyone with knowledge that any 

of the dates as published (see 

SUPPLEMENTARY INFORMATION) are 

incorrect must submit either electronic 

or written comments and ask for a 

redetermination by February 28, 2025. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

June 30, 2025. See ‘‘Petitions’’ in the 

SUPPLEMENTARY INFORMATION section for 

more information. 

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 

February 28, 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 


ddrumheller on DSK120RN23PROD with NOTICES1