[Federal Register Volume 89, Number 117 (Monday, June 17, 2024)]
[Notices]
[Pages 51354-51355]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-13271]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0235]


Clinical Pharmacology Considerations for the Development of 
Oligonucleotide Therapeutics; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``Clinical 
Pharmacology Considerations for the Development of Oligonucleotide 
Therapeutics,'' which provides recommendations for the development of 
oligonucleotide therapeutics. Specifically, this guidance addresses 
FDA's current thinking regarding clinical pharmacology considerations 
and recommendations for oligonucleotide therapeutic development 
programs, including characterizing the potential for QT interval 
prolongation, performing immunogenicity risk assessment, characterizing 
the impact of hepatic and renal impairment, and assessing the potential 
for drug-drug interactions. This guidance finalizes the draft guidance 
of the same name issued on June 27, 2022.

DATES: The announcement of the guidance is published in the Federal 
Register on June 17, 2024.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances 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-2022-D-0235 for ``Clinical Pharmacology Considerations for the 
Development of Oligonucleotide Therapeutics.'' 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

[[Page 51355]]

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 this 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. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Anuradha Ramamoorthy, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20903, 240-402-6426, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Clinical Pharmacology Considerations for the Development of 
Oligonucleotide Therapeutics.'' Oligonucleotide therapeutics are an 
emerging therapeutic modality with increasing numbers of drugs in 
development. While antisense and siRNA oligonucleotide therapeutics 
have been approved in recent years to treat rare diseases, many 
oligonucleotide therapeutics are in development to treat common chronic 
diseases. This guidance provides recommendations to assist industry in 
the development of oligonucleotide therapeutics. Specifically, this 
guidance represents FDA's recommendations for certain pharmacokinetic 
and pharmacodynamic investigations including characterizing QT interval 
prolongation potential, performing immunogenicity risk assessment, 
characterizing the impact of hepatic and renal impairment, and 
assessing the potential for drug-drug interactions during 
oligonucleotide therapeutic development. This guidance provides 
recommendations on when these assessments may be appropriate and what 
types of assessments can help address these issues.
    This guidance finalizes the draft guidance of the same name issued 
on June 27, 2022 (87 FR 38161). FDA considered comments received on the 
draft guidance as the guidance was finalized. Changes from the draft to 
the final guidance include: (1) updates to terms used in the guidance 
to provide clarity, (2) additional references to FDA guidance that have 
been published since publication of the draft guidance, and (3) 
editorial changes to improve clarity.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Clinical Pharmacology Considerations for 
the Development of Oligonucleotide Therapeutics.'' 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 
in 21 CFR part 312 for investigational new drug applications have been 
approved under OMB control number 0910-0014. The collections of 
information in 21 CFR part 314 for new drug applications have been 
approved under OMB control number 0910-0001. The collections of 
information in 21 CFR part 601 for biologics license applications have 
been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: June 12, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-13271 Filed 6-14-24; 8:45 am]
BILLING CODE 4164-01-P