[Federal Register Volume 86, Number 233 (Wednesday, December 8, 2021)]
[Notices]
[Pages 69652-69653]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-26453]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-1140]


Investigational New Drug Application Submissions for 
Individualized Antisense Oligonucleotide Drug Products for Severely 
Debilitating or Life-Threatening Diseases: Clinical Recommendations; 
Draft Guidance for Sponsor-Investigators; Availability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the availability of a draft guidance for sponsor-investigators entitled 
``IND Submissions for Individualized Antisense Oligonucleotide Drug 
Products for Severely Debilitating or Life-Threatening Diseases: 
Clinical Recommendations.'' FDA is publishing this draft guidance to 
provide sponsor-investigators (hereafter referred to as sponsors) who 
are interested in developing individualized antisense oligonucleotide 
(ASO) drug products for a rapidly progressive, severely debilitating, 
or life-threatening (SDLT) genetic disease (caused by a unique genetic 
variant or variants), with clinical recommendations for submission of 
investigational new drug applications (INDs). These recommendations 
specifically address the following clinical considerations: Ethical and 
human subject protection, diagnostic and genetic, dosing, 
administration, safety, and assessment of clinical response to 
treatment.

DATES: Submit either electronic or written comments on the draft 
guidance by February 7, 2022 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-1140 for ``IND Submissions for Individualized Antisense 
Oligonucleotide Drug Products for Severely Debilitating or Life-
Threatening Diseases: Clinical Recommendations.'' 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

[[Page 69653]]

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: Hobart Rogers, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Avenue, Bldg. 51, Rm 3114, Silver Spring, MD 20903-0002, 301-
796-2213.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for sponsor-
investigators entitled ``IND Submissions for Individualized Antisense 
Oligonucleotide Drug Products for Severely Debilitating or Life-
Threatening Diseases: Clinical Recommendations.'' FDA is publishing 
this draft guidance to provide sponsor-investigators (hereafter 
referred to as sponsors) who are interested in developing 
individualized ASO drug products for a rapidly progressive SDLT genetic 
disease (caused by a unique genetic variant or variants), with clinical 
recommendations for submission of INDs. These recommendations 
specifically address the following clinical considerations: Ethical and 
human subject protection, diagnostic and genetic, dosing, 
administration, safety, and assessment of clinical response to 
treatment.
    This draft guidance describes clinical considerations and, when 
applicable, important information to include in IND submissions for 
such ASO drug products for a small number of participants (typically 
one to two) with SDTL diseases. In general, ASO drug products referred 
to in this draft guidance belong to a well-characterized chemical class 
and for which there is considerable nonclinical and clinical experience 
that is publicly available or to which the sponsor has a right of 
reference. The draft guidance discusses considerations and information 
to submit in an IND regarding: (1) Confirmation of the participant's 
genetic diagnosis and genetic variant(s) targeted by the ASO drug 
product, (2) the requirements and procedures for informed consent of 
the participant, (3) appropriate and safe dosing and administration 
procedures that are detailed and supported by relevant nonclinical 
evidence, (4) the nature and schedule of the specific safety 
assessments (adverse events and laboratory testing) to be conducted, 
and (5) methods for continuous clinical monitoring (e.g., via clinical 
outcome assessments, pharmacodynamic biomarkers) of the participant to 
evaluate and document their clinical response(s) and to allow for an 
informed benefit-risk determination. This draft guidance is expected to 
facilitate the preparation of adequate and complete IND submissions for 
investigational ASO drug products for participants with SDLT diseases 
targeted by the specified ASO drug product.
    This draft guidance represents one guidance in a series of 
guidances that FDA intends to publish to advise and help sponsors 
planning to use individualized ASO drug products for SDLT diseases 
caused by unique genetic variant(s) and for whom there are no 
alternative therapies available 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 ``IND 
Submissions for Individualized Antisense Oligonucleotide Drug Products 
for Severely Debilitating or Life-Threatening Diseases: Clinical 
Recommendations.'' 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 new collection of information, it 
does refer to previously approved FDA collections 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 for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. 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 parts 50 and 
56 for obtaining informed consent for prospective patients have been 
approved under OMB control number 0910-0130.

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, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: December 1, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-26453 Filed 12-7-21; 8:45 am]
BILLING CODE 4164-01-P


