[Federal Register Volume 86, Number 79 (Tuesday, April 27, 2021)]
[Notices]
[Pages 22213-22214]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-08675]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-0320]


Nonclinical Testing of Individualized Antisense Oligonucleotide 
Drug Products for Severely Debilitating or Life-Threatening Diseases; 
Draft Guidance for Sponsor-Investigators; Availability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the availability of a draft guidance for industry entitled 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 Testing of Individualized Antisense Oligonucleotide Drug 
Products for Severely Debilitating or Life-Threatening Diseases.'' FDA 
is publishing this draft guidance to help sponsor-investigators 
(hereafter referred to as sponsors) with developing the nonclinical 
information that FDA recommends to support an investigational new drug 
application (IND) for certain individualized antisense oligonucleotide 
(ASO) drug products. ASO drug products that are the focus of this draft 
guidance are those being developed to treat rapidly progressing, 
severely debilitating or life-threatening (SDLT) disease attributable 
to a unique genetic variant or variants that may be amenable to RNA-
directed treatment.

DATES: Submit either electronic or written comments on the draft 
guidance by June 28, 2021 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2021-D-0320 for ``Nonclinical Testing of Individualized Antisense 
Oligonucleotide Drug Products for Severely Debilitating or Life-
Threatening Diseases.'' 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. 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 Testing of Individualized Antisense 
Oligonucleotide Drug Products for Severely Debilitating or Life-
Threatening Diseases.'' FDA is publishing this draft guidance, that, 
when finalized, will help sponsors with developing the nonclinical 
information that FDA recommends to support an IND for certain 
individualized ASO drug products. ASO drug products that are the focus 
of this draft guidance are those being developed to treat a rapidly 
progressing, SDLT disease attributable

[[Page 22214]]

to a unique genetic variant or variants that may be amenable to RNA-
directed treatment.
    The draft guidance addresses the nonclinical information that FDA 
recommends to support an IND for the development of an antisense 
oligonucleotide from a well-characterized chemical class, for which 
there is substantial nonclinical information and clinical experience 
that is publicly available or to which the sponsor has a right of 
reference. The draft guidance discusses the importance of sponsors 
providing convincing in vitro and/or in vivo proof of concept data as 
part of any such IND submission. The draft guidance describes 
recommended nonclinical safety studies that should be submitted with 
such IND submissions, the duration and timing of general toxicity 
studies, first-in-human dose selection, and dose escalation, each 
within the context stipulated above. Finally, the draft guidance 
describes certain factors, present in the context of an IND for an 
individualized investigational antisense oligonucleotide developed to 
treat a rapidly progressing SDLT disease, that support differences in 
the nonclinical safety package recommended in this context from that 
generally recommended for non-SDLT diseases, for modalities other than 
antisense oligonucleotides, and for use in larger patient populations.
    The draft guidance is intended to help sponsors of such development 
programs, who may be relatively unfamiliar with FDA regulations, 
processes, and practices, seek feedback from FDA on their development 
programs and make regulatory submissions related to these development 
programs. The draft guidance is expected to facilitate the preparation 
of adequate pre-IND and IND submissions for review by the Agency that 
will enable prompt initiation of the clinical trial.
    This draft guidance represents the second in a series of guidances 
FDA intends to publish to advise and help sponsors developing 
individualized ASO drug products for individuals who have SDLT diseases 
or conditions and no approved products available to them to treat their 
disease.
    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 
Testing of Individualized Antisense Oligonucleotide Drug Products for 
Severely Debilitating or Life-Threatening Diseases.'' 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

    FDA tentatively concludes that this draft guidance contains no 
collection of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3521) is not required.
    However, this draft guidance refers to previously approved FDA 
collections of information. These collections of information are 
subject to review by OMB under the PRA.
     The following collections of information in 21 CFR part 
312 (IND regulations) have been approved under OMB control number 0910-
0014: (1) Submissions of IND applications, amendments, safety reports, 
and investigator brochures and (2) requests for pre-IND meetings.
     The collections of information in 21 CFR parts 50 and 56 
for obtaining informed consent for prospective patients have been 
approved under OMB control number 0910-0130.
     The collections of information for paper submissions of 
Form FDA 3500A (Mandatory Reporting) have been approved under OMB 
control number 0910-0291.
     The collections of information in the final guidance 
entitled ``Formal Meetings Between the FDA and Sponsors or Applicants'' 
have been approved under OMB control number 0910-0429.
     The collections of information relating to electronic 
submissions of Form FDA 3500 used for voluntary reporting (not mandated 
by law or regulation) by healthcare professionals, including safety 
reporting submissions relating to bioavailability and bioequivalence 
studies under 21 CFR 320.31(d)(3), have been approved under OMB control 
number 0910-0645.

III. Electronic Access

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

    Dated: April 20, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-08675 Filed 4-26-21; 8:45 am]
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