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[Federal Register Volume 89, Number 221 (Friday, November 15, 2024)]
[Notices]
[Pages 90296-90298]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-26682]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-4624]

Nonclinical Safety Assessment of Oligonucleotide-Based 
Therapeutics; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled 
``Nonclinical Safety Assessment of Oligonucleotide-Based 
Therapeutics.'' FDA is publishing this draft guidance which, when 
finalized, will provide recommendations on approaches for the 
nonclinical safety evaluation of oligonucleotide-based therapeutics 
(ONTs) to support clinical development and marketing of these products. 
ONTs present unique challenges and opportunities in the nonclinical 
evaluation of safety that differ in many regards from those appropriate 
for small molecule drugs or therapeutic proteins.

DATES: Submit either electronic or written comments on the draft 
guidance by January 14, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-4624 for ``Nonclinical Safety Assessment of Oligonucleotide-
Based 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.

[[Page 90297]]

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access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Ronald Wange, Center for Drug 
Evaluation and Research (HFD-510), Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 22, Rm. 3342, Silver Spring, MD 20903, 301-
796-1304.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Nonclinical Safety Assessment of Oligonucleotide-Based 
Therapeutics.'' ONTs represent a rapidly evolving therapeutic modality, 
which is seeing application to a broad range of indications, including 
rare diseases, and have the potential to act on therapeutic targets 
that are not amenable to the action of small molecule drugs or 
therapeutic proteins. To further support the development of ONTs, FDA 
is publishing this draft guidance which, when finalized, will assist 
sponsors in optimizing the design of their nonclinical development 
package for ONTs.
    The scope of the draft guidance includes single-stranded or double-
stranded ONTs created synthetically or derived naturally, with native 
or modified backbone or nucleoside structures that increase or decrease 
expression and/or function of proteins. Examples of included 
oligonucleotides are antisense, small interfering RNA, microRNA, 
transfer RNAs, decoys, and aptamers. Immune stimulatory 
oligonucleotides (e.g., CpG motifs acting via Toll-like receptors) are 
excluded, as are Center for Biologics Evaluation and Research-regulated 
ONTs (e.g., DNA/RNA vaccines, messenger RNA, virally delivered ONTs, 
and RNA used for gene editing).
    ONTs present unique opportunities and challenges in the nonclinical 
evaluation of safety that differ in many regards from that appropriate 
for small molecule drugs or therapeutic proteins. This draft guidance 
provides specific recommendations on approaches for the nonclinical 
safety evaluation of ONTs to support clinical development and marketing 
of these products. The draft guidance, when finalized, will provide 
recommendations on the nonclinical evaluation of oligonucleotides in 
multiple areas, including genotoxicity, safety pharmacology, general 
toxicity, carcinogenicity, and reproductive and developmental toxicity. 
These recommendations have been developed based on industry best 
practices and Agency experience to date with this category of drug 
products.
    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 ``Nonclinical 
Safety Assessment of Oligonucleotide-Based 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 parts 50 and 56 pertaining to protection of human subjects 
have been approved under OMB control number 0910-0130. The collections 
of information in 21 CFR part 58 pertaining to good laboratory practice 
for nonclinical laboratory studies have been approved under OMB control 
number 0910-0119. The collections of information in 21 CFR 201.56 and 
201.57 pertaining to content and format of labeling for human 
prescription drug and biological products have been approved under OMB 
control numbers 0910-0572. The collections of information in 21 CFR 
parts 210 and 211 pertaining to current good manufacturing practice 
have been approved under OMB control number 0910-0139. The collections 
of information in 21 CFR part 312 relating to the content and format of 
investigational new drug applications have been approved under OMB 
control number 0910-0014. The collections of information in 21 CFR part 
314 relating to the content and format of new drug applications have 
been approved under OMB control number 0910-0001. The collections of 
information in 21 CFR part 601 relating to the content and format of 
biologics license applications are approved under OMB control number 
0910-0338. The collections of information for MEDWATCH Adverse Event 
and Product Experience Reporting system have been approved under OMB 
control number 0910-0291.

III. Electronic Access

    Persons with access to the internet may obtain the draft 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.

[[Page 90298]]

    Dated: November 6, 2024.
Kimberlee Trzeciak,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2024-26682 Filed 11-14-24; 8:45 am]
BILLING CODE 4164-01-P
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