[Federal Register Volume 89, Number 86 (Thursday, May 2, 2024)]
[Notices]
[Pages 35832-35834]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-09278]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0394]


Heritable Intentional Genomic Alterations in Animals: Risk-Based 
Approach; 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 final guidance for industry (GFI) 
#187A entitled ``Heritable Intentional Genomic Alterations in Animals: 
Risk-Based Approach.'' This guidance is intended to clarify FDA's 
requirements and recommendations with respect to heritable intentional 
genomic alterations (IGAs) in animals. The guidance is being issued as 
one of two companion documents. This guidance, 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. 
For other types of IGAs in animals that do go through the approval 
process, the companion draft guidance document, GFI #187B entitled 
``Heritable Intentional Genomic Alterations in Animals: The Approval 
Process'' describes how the approval process applies to heritable IGAs 
in animals.

DATES: The announcement of the guidance is published in the Federal 
Register on May 2, 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:

[[Page 35833]]

     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-2008-D-0394 for ``Heritable Intentional Genomic Alterations in 
Animals: Risk-Based Approach.'' 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Adam Moyer, Center for Veterinary 
Medicine (HFV-108), 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 and those comments 
were considered as the guidance was finalized. As noted, this guidance 
is intended to clarify our risk-based regulatory approach for 
developers of heritable IGAs in animals.
    The guidance is being issued as one of two companion documents. GFI 
#187A, ``Heritable Intentional Genomic Alterations in Animals: Risk-
Based Approach,'' describes FDA's risk-based approach to the oversight 
of 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 FDA approval before marketing their product. These 
are IGAs in animals and animal products for which FDA finds that we 
understand the product's risks for the specified intended use, any 
identified risks are appropriately mitigated, and we have no further 
questions for which we would need to see additional data to address. 
The guidance explains that FDA's approach is risk-based and ranges 
from:
     Category 1 products for which we do not expect developers 
to consult with us prior to marketing an animal containing an IGA where 
the risk is best understood and mitigated; to
     Category 2 products for which we may not expect developers 
to submit an application for approval of the IGA if, after looking at 
data submitted about that product's risk, we find that we understand 
the product's risks for the specified intended use, any identified 
risks are appropriately mitigated, and we have no further questions for 
which we would need to see additional data to address; to
     Category 3 products for which FDA will review and, where 
the data supports it, approve a product using data requirements that 
are proportionate to the risk associated with the particular product.
    Draft GFI #187B, ``Heritable Intentional Genomic Alterations in 
Animals: The Approval Process,'' whose notice of availability is 
published elsewhere in this edition of the Federal Register, describes 
how the FDA approval process applies to heritable IGAs in animals.
    FDA received 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. In the Federal Register 
notice announcing availability of the draft guidance, FDA posed 
questions regarding whether there

[[Page 35834]]

are categories of IGAs in animals that pose less risk and, if so, what 
data or information supports that contention. No commenters provided 
data to address the Agency's questions other than scientific literature 
references that were not directly applicable or conclusive.
    In the notice announcing availability of the draft guidance, FDA 
also asked for comment on the appropriate terminology for animals with 
intentional genomic alterations. Commenters expressed different 
preferences, but there was no general consensus on an appropriate term. 
FDA has adopted ``intentional genomic alteration'' or ``IGA'' in 
animals as the term it will use to refer to intentional genomic 
alterations in animals regardless of whether they are developed with 
genetic engineering, including genome editing, or some other modern 
molecular technology. This term is simple and sufficiently broad to 
encompass intentional genomic alterations achieved through means that 
currently exist and those yet to be developed. Moreover, section 
740(d)(4)(B) of the Federal Food, Drug, and Cosmetic Act uses this term 
(21 U.S.C. 379j-12(d)(4)(B)). However, the scope of the guidance does 
not include induction of polyploidy by heat, pressure, or chemical 
treatment, or selective breeding or other assisted reproductive 
technologies. Non-heritable intentional genomic alterations in animals 
are also outside the scope of this guidance document.
    Changes FDA has made in response to comments include:
     Reorganization and use of plain language to make FDA's 
regulatory approach clearer to stakeholders;
     Expansion of IGAs for which FDA may decide it does not 
expect submission of an application for approval following a review of 
data and a determination that the IGA meets the Category 2 description 
in the guidance. The new types of IGAs include:
    [ssquf] IGAs that are equivalent to genomic sequences that are 
found in animals of the same species with a history of safe use in 
animal agriculture food production and
    [ssquf] IGAs that are equivalent to what could be theoretically 
achieved through conventional breeding under certain conditions,
including that the IGAs are not expected to result in changes to food 
composition and their intended use does not include any effect on 
disease or other health outcome;
     Clarification that if you are:
    [ssquf] ;a farmer, grower, or other entity that just has animals 
with IGAs that FDA has approved or determined are Category 2 on your 
farm or other premises, including the offspring of those animals,
    [ssquf] and you are not the developer of the IGA in the animal or 
marketing the animals with any new claims,
then, as a general matter, you do not have to register or list with FDA 
and you can engage in your ordinary activities (e.g., breeding, 
growing, etc.) without contacting FDA; and
     Clarification that those who breed an animal containing an 
IGA that FDA has approved or has determined is Category 2:
    [ssquf] with another animal containing an IGA that FDA has approved 
or also determined is Category 2 or
    [ssquf] with an animal that does not contain an IGA
and make no new claims do not need to contact FDA and nothing further 
is required.
    The guidance announced in this notice finalizes the draft guidance 
dated January 2017.
    This level 1 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 ``Heritable Intentional Genomic 
Alterations in Animals: Risk-Based Approach.'' 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 
regarding environmental analysis in 21 CFR part 25 have been approved 
under OMB control number 0910-0322; the collections of information 
regarding applications in 21 CFR part 514 have been approved under OMB 
control number 0910-0284; and the collections of information regarding 
investigational exemptions in 21 CFR part 511 have been approved under 
OMB control number 0910-0117.

III. Electronic Access

    Persons with access to the internet may obtain the 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. 2024-09278 Filed 5-1-24; 8:45 am]
BILLING CODE 4164-01-P