82 FR 6561 - Regulation of Intentionally Altered Genomic DNA in Animals; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 12 (January 19, 2017)

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry (GFI) #187 entitled ``Regulation of Intentionally Altered Genomic DNA in Animals.'' This draft guidance revises GFI #187 entitled ``Regulation of Genetically Engineered Animals Containing Heritable Recombinant DNA Constructs'' (current GFI #187). Current GFI #187 clarifies FDA's requirements and recommendations for producers and developers of genetically engineered (GE) animals and their products. It describes how the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) apply with respect to GE animals. This draft revision of current GFI #187 expands the scope of the guidance to include animals intentionally altered through use of genome editing techniques. The draft revised GFI #187 now applies to ``those animals whose genomes have been intentionally altered using modern molecular technologies.'' The Agency is seeking comment on the draft revised GFI #187, including the nomenclature that best describes these animals and on any existing empirical evidence indicating that certain types of genome editing may pose minimal risk.

[Federal Register Volume 82, Number 12 (Thursday, January 19, 2017)]
[Notices]
[Pages 6561-6564]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-00839]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Regulation of Intentionally Altered Genomic DNA in Animals; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry (GFI) #187 entitled 
``Regulation of Intentionally Altered Genomic DNA in Animals.'' This 
draft guidance revises GFI #187 entitled ``Regulation of Genetically 
Engineered Animals Containing Heritable Recombinant DNA Constructs'' 
(current GFI #187). Current GFI #187 clarifies FDA's requirements

[[Page 6562]]

and recommendations for producers and developers of genetically 
engineered (GE) animals and their products. It describes how the new 
animal drug provisions of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) apply with respect to GE animals. This draft revision of 
current GFI #187 expands the scope of the guidance to include animals 
intentionally altered through use of genome editing techniques. The 
draft revised GFI #187 now applies to ``those animals whose genomes 
have been intentionally altered using modern molecular technologies.'' 
The Agency is seeking comment on the draft revised GFI #187, including 
the nomenclature that best describes these animals and on any existing 
empirical evidence indicating that certain types of genome editing may 
pose minimal risk.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by April 19, 2017.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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 ``Regulation of Intentionally Altered Genomic DNA 
in Animals.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at http://www.regulations.gov or at the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.
     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    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, 7519 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: Laura R. Epstein, Center for 
Veterinary Medicine (HFV-1), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, 301-796-8558, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability, for public comment, of draft 
revised GFI #187 entitled ``Regulation of Intentionally Altered Genomic 
DNA in Animals.'' This draft guidance revises current GFI #187 entitled 
``Regulation of Genetically Engineered Animals Containing Heritable 
recombinant DNA Constructs'' to expand the scope of the guidance to 
address animals intentionally altered through use of genome editing 
techniques. FDA is also requesting comment on nomenclature and on 
whether certain types of genome editing may pose minimal risk. Before 
finalizing the draft revised guidance, the agency intends to modify its 
regulatory approach if it receives evidence demonstrating low risk.
    In the National Strategy for Modernizing the Regulatory System for 
Biotechnology Products (the Strategy; released by the White House 
Office of Science and Technology Policy on September 16, 2016),\1\ FDA 
noted its intent to clarify its policy on the regulation of products 
derived from genome editing techniques, including, as appropriate, 
identifying and/or updating relevant existing guidance documents. FDA 
also stated, as an example, its intent to update GFI #187, ``Regulation 
of Genetically Engineered Animals Containing Heritable Recombinant DNA 
Constructs,'' to clarify how developers of animals produced using 
emerging technologies (e.g., genome editing) may meet applicable 
statutory and regulatory requirements. FDA is issuing this draft 
revised guidance for public comment consistent with this commitment in 
the Strategy document. Under the Coordinated Framework for the

[[Page 6563]]

Regulation of Biotechnology, we intend to work cooperatively with other 
relevant agencies that may also be considering their policies or 
approaches related to genome editing applications within their 
jurisdictions. As we finalize the draft revised guidance, we will be 
consistent with the principles for the regulation of biotechnology 
products articulated in the 2017 Update to the Coordinated Framework 
(https://www.whitehouse.gov/sites/default/files/microsites/ostp/2017_coordinated_framework_update.pdf) and the goals and objectives of 
the July 2015 EOP memorandum (https://www.whitehouse.gov/sites/default/files/microsites/ostp/modernizing_the_reg_system_for_biotech_products_memo_final.pdf).
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    \1\ https://www.whitehouse.gov/sites/default/files/microsites/ostp/biotech_national_strategy_final.pdf.
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A. Key Draft Revisions

    Draft revised GFI #187 is intended to clarify that, unless 
otherwise excluded,\2\ the altered genomic DNA in an animal (referred 
to in this document as ``animals with intentionally altered genomic 
DNA'') that is intended to affect the structure or function of the body 
of the animal or, in some cases, to diagnose, cure, mitigate, treat, or 
prevent disease in the animal, meets the drug definition in section 
201(g) of the FD&C Act. For the purposes of draft revised GFI #187, 
``altered genomic DNA'' refers to the portion of an animal's genome 
that has been intentionally altered. Such intentional alterations may 
be made, for example, through the use of ``nucleases'' or ``genome 
editing technologies,'' including engineered nuclease/nucleotide 
complexes such as zinc finger nucleases (ZFN), transcription activator-
like effector nucleases (TALENs), and the clustered regulatory 
interspersed short palindromic repeats (CRISPR) associated systems.
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    \2\ In Draft Guidance for Industry #236, ``Regulation of 
Mosquito-Related Products,'' FDA has proposed to clarify that the 
phrase ``articles (other than food) intended to affect the structure 
or any function of the body of man or other animals'' does not 
include articles intended to prevent, destroy, repel, or mitigate 
mosquitoes for population control purposes. Instead, such products 
are pesticides regulated by the Environmental Protection Agency 
(EPA) (http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM533600.pdf).
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    Similar to current GFI #187, draft revised GFI #187 is intended to 
clarify FDA's requirements and recommendations for producers and 
developers of animals with intentionally altered genomic DNA. Current 
GFI #187 and draft revised GFI #187 describe how the new animal drug 
provisions of the FD&C Act apply with respect to the intentionally 
altered genomic DNA of such animals.
    Animals may have intentional genomic alterations that are heritable 
or non-heritable (e.g., those alterations intended to be used as gene 
therapy). Although much of draft revised GFI #187 is relevant to non-
heritable intentional genomic alterations, and FDA intends to regulate 
non-heritable intentional genomic alterations in much the same way as 
described in this draft revised guidance, this draft revised guidance 
primarily addresses animals whose genomes have been intentionally 
altered for heritable purposes.

B. Additional Issues for Consideration and Comment

    FDA requests comment on draft revised GFI #187. In particular, we 
request comments on two major categories of questions.
    1. In the first, we seek the public's input on how to refer to 
these animals. In the past, FDA has used the term ``genetically 
engineered'' to refer to animals containing recombinant DNA constructs 
intended to alter the structure or function of the body of the animal. 
For this draft revised guidance, we have used the phrase ``animals 
whose genomes have been altered intentionally.'' Other terms that could 
be used include ``genome edited animals,'' ``intentionally altered 
animals,'' or expanding the term ``genetically engineered'' to include 
the deliberate modification of the characteristics of an organism by 
manipulating its genetic material. The public is encouraged to suggest 
other phrases that are accurate and inclusive.
    2. The second set of questions for which we seek public input is on 
whether there is any existing empirical evidence demonstrating that 
certain types of genome editing may pose minimal risk, with particular 
emphasis on the following:
    a. Are there categories of animals whose genomes have been 
intentionally altered for which specific empirical evidence indicates 
that there are no significant target animal, user safety, food safety, 
or environmental risks? If so, what is that evidence?
    b. Are there categories of animals whose genomes have been 
intentionally altered for which empirical evidence exists to 
demonstrate that genome editing is durable on a genotypic and 
phenotypic level and would continue to be durable over the lifetime of 
a particular product? If so, what is that evidence?
    c. Is there empirical evidence to demonstrate that there are 
degrees of introduced changes (e.g., insertions or deletions of any 
size or single nucleotide substitutions) that are likely to pose less 
risk than other changes? If so, what is that evidence?
    d. Is there empirical evidence that indicates that the degree of 
taxonomic relationship between the introduced gene and the recipient 
animal influences the health of that recipient animal or the extent to 
which the trait is expressed? If so, what is that evidence?
    We noted in current GFI #187 that we might issue a separate 
guidance on the regulation of GE animals bearing non-heritable 
alterations. Draft revised GFI #187 removes references to this and 
other guidance documents that we intend to develop in the future. This 
was not done to indicate that we no longer intend to issue such 
guidance documents. In light of changing priorities over time, we may 
issue other guidance documents before developing those identified in 
current GFI #187, and therefore decided we should not indicate in the 
text of the revised guidance any additional guidance documents that we 
may develop in the future.
    Current GFI #187 states, ``FDA is discussing with other agencies 
the best approach for oversight of GE insects. Future guidance may be 
developed to address them.'' Draft revised GFI #187 eliminates this 
language. As indicated in the Strategy, FDA, EPA, and USDA intend to 
``continue to examine their regulatory structures with the goal of 
clarifying how the U.S. Federal Government will regulate genetically 
engineered insects in an integrated and coordinated fashion to cover 
the full range of potential products.'' FDA is continuing to work with 
EPA and USDA, and will address this issue through action(s) separate 
from this draft revision to current GFI #187. Elsewhere in this issue 
of the Federal Register, we have published a notice announcing the 
availability of a draft guidance for industry on regulation of 
mosquito-related products.

II. Significance of Guidance

    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 
Regulation of Intentionally Altered Genomic DNA in Animals. 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.

[[Page 6564]]

III. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information have been approved under OMB Control Nos. 
0910-0032, 0910-0045, 0910-0117, and 0910-0284.

IV. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
at either http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm or http://www.regulations.gov.

    Dated: January 11, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-00839 Filed 1-18-17; 8:45 am]
 BILLING CODE 4164-01-P