[Federal Register Volume 89, Number 86 (Thursday, May 2, 2024)]
[Notices]
[Pages 35834-35836]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-09279]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-2648]


Heritable Intentional Genomic Alterations in Animals: The 
Approval Process; Draft Guidance for Industry; Availability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, Agency, or we) is 
announcing the availability of a draft guidance for industry (GFI) 
#187B entitled ``Heritable Intentional Genomic Alterations in Animals: 
The Approval Process.'' This draft guidance is intended to clarify 
FDA's requirements and recommendations for developers of intentional 
genomic alterations (IGA) in animals. The draft guidance is being 
issued as one of two companion documents. ``Heritable Intentional 
Genomic Alterations in Animals: The Approval Process'' describes how 
the FDA approval process applies to heritable IGAs in animals. FDA is 
issuing GFI #187B as a draft guidance to solicit comments that will 
enable the Agency to update, and make as efficient as possible, the 
approval process for IGAs in animals. In addition, FDA requests 
comments on questions that it intends to address in the final version 
of this guidance document. The companion final guidance, GFI #187A 
entitled ``Heritable Intentional Genomic Alterations in Animals: Risk-
Based Approach,'' describes FDA's risk-based regulatory approach to the 
oversight of heritable IGAs in animals. This means that, for people or 
companies developing certain types of IGAs in animals, FDA may not 
expect them to submit an application or get approval before marketing 
their product.

DATES: Submit either electronic or written comments on the draft 
guidance by July 31, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:

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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-2019-D-2648 for ``Heritable Intentional Genomic Alterations in 
Animals: The Approval Process.'' 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 guidance to the 
Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine, 
Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855. 
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: Adam Moyer, Center for Veterinary 
Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, 
MD 20855, 301-796-2319, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of January 19, 2017 (82 FR 6561), FDA 
published the notice of availability for a draft GFI #187 entitled 
``Regulation of Intentionally Altered Genomic DNA in Animals'' giving 
interested persons until April 19, 2017, to comment on the draft 
guidance. On April 13, 2017, we published a notice announcing the 
extension of the comment period to June 19, 2017 (82 FR 17844). FDA 
received numerous comments on the draft guidance GFI #187 and those 
comments were considered as the guidance was revised. As noted, this 
draft guidance, GFI #187B, is intended to explain how FDA's approval 
process applies in the context of products related to heritable IGAs in 
animals.
    The draft guidance is being issued as one of two companion 
documents. Draft GFI #187B, ``Heritable Intentional Genomic Alterations 
in Animals: The Approval Process,'' describes how the FDA approval 
process applies to heritable IGAs in animals. Final GFI #187A, 
``Heritable Intentional Genomic Alterations in Animals: Risk-Based 
Approach,'' whose notice of availability is published elsewhere in this 
edition of the Federal Register, describes FDA's risk-based approach to 
the oversight of IGAs in animals.
    FDA received and reviewed comments on the draft guidance that came 
from industry (companies that produce IGAs and trade associations), 
individual consumers, academics, non-governmental organizations 
(consumer, environmental), other Federal and State government agencies, 
and individual developers of IGAs in animals. Among the changes made to 
the draft guidance, we have:
     Indicated our willingness to consider multiple heritable 
IGAs or a single IGA in multiple lines or breeds of animals of the same 
species under a single application;
     Clarified that FDA's review of applications is subject to 
specific timeframes;
     Acknowledged that it may not be feasible to gather data on 
multiple generations and encourage developers of heritable IGAs in 
animals to contact FDA to discuss alternative approaches of 
demonstrating durability;
     Indicated that alternative disposition methods for 
investigational animals may be acceptable if the sponsor contacts FDA's 
Center for Veterinary Medicine;
     Further described post-market records and reports 
requirements and clarified who they apply to; and
     Provided additional information on establishment 
registration requirements, including explaining that, as a general 
matter, pet stores, farms, or other animal production facilities do not 
have to register or list with FDA and can engage in ordinary activities 
(e.g., breeding, growing, etc.) without contacting FDA.
    FDA is issuing this draft guidance to solicit public comment that 
will further

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improve it. To help inform our thinking as we begin the process of 
further updating the guidance, we invite comment on the following 
questions:
    1. What are some alternative strategies for providing data that 
would support approval of heritable IGAs in animals?
    a. How can a developer demonstrate the durability of a heritable 
IGA over time in situations where collection of data on multiple 
generations of animals is difficult or not possible?
    b. What are possible strategies a developer could utilize to 
address the approval requirements for multiple heritable IGAs (e.g., 
multiple iterations of the same alteration resulting in the same 
intended phenotype or multiple alterations resulting in more than one 
intended phenotype) under a single approval?
    2. What areas of current good manufacturing practices and good 
laboratory practices specific to the production of heritable IGAs in 
animals do you believe need clarification through the publication of 
additional guidance?
    3. Are there process improvements (e.g., combining steps of the 
approval process) (see page 16, section IV.C. Recommended Process for 
Completing Pre-approval Assessments for IGAs in Animals, of the 
guidance) that you believe would make the approval process easier to 
navigate?
    This level 1 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 
``Heritable Intentional Genomic Alterations in Animals: The Approval 
Process.'' 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 25 have been approved under OMB control number 0910-
0322; the collections of information in 21 CFR part 58 have been 
approved under OMB control number 0910-0119; the collections of 
information in 21 CFR part 207 have been approved under OMB control 
number 0910-0045; the collections of information in 21 CFR part 211 
have been approved under OMB control number 0910-0139; the collections 
of information in 21 CFR part 511 have been approved under OMB control 
number 0910-0117; the collections of information in 21 CFR part 514 
have been approved under OMB control number 0910-0284; and the 
collections of information in 21 CFR 558.6(a)(4) have been approved 
under OMB control number 0910-0363.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: April 25, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-09279 Filed 5-1-24; 8:45 am]
BILLING CODE 4164-01-P