[Federal Register Volume 87, Number 37 (Thursday, February 24, 2022)]
[Notices]
[Pages 10373-10375]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-03915]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-1311]


Nonclinical Considerations for Mitigating Nonhuman Primate Supply 
Constraints Arising From the COVID-19 Pandemic; 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 entitled 
``Nonclinical Considerations for Mitigating Nonhuman Primate Supply 
Constraints Arising from the COVID-19 Pandemic.'' The COVID-19 pandemic 
has resulted in a significant reduction in the supply of nonhuman 
primates (NHPs) available for conducting toxicology studies for new 
pharmaceuticals. This has the potential to significantly delay the 
development of new medications for the treatment of diseases currently 
without effective treatment options. This guidance provides FDA's 
recommendations to industry to help mitigate the NHP supply issue by 
reducing the demand for NHPs during the COVID-19 pandemic. Given the 
public health emergency presented by COVID-19, this guidance document 
is being implemented without prior public comment because FDA has 
determined that prior public participation is not feasible or 
appropriate, but it remains subject to comment in accordance with the 
Agency's good guidance practices.

DATES: The announcement of the guidance is published in the Federal 
Register on February 24, 2022.

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:
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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-1311 for ``Nonclinical Considerations for Mitigating 
Nonhuman Primate Supply Constraints Arising from the COVID-19 
Pandemic.'' 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.
    <bullet> 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 
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; or the Office of 
Communication, Outreach, and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, 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 guidance document.

[[Page 10374]]


FOR FURTHER INFORMATION CONTACT: Ronald Wange, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 3342, Silver Spring, MD 20993-0002, 301-
796-1304; or Stephen Ripley, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Nonclinical Considerations for Mitigating Nonhuman Primate 
Supply Constraints Arising from the COVID-19 Pandemic.''
    The COVID-19 pandemic has caused a marked reduction in the supply 
of NHPs available for conducting nonclinical toxicity assessments. 
Before the pandemic, China was the largest supplier of NHPs used in 
pharmaceutical development, accounting for 60 percent of NHPs imported 
to the United States.\1\ Early in the pandemic, China implemented a ban 
on the trade of wild animals--including NHPs--in an effort to 
potentially curb the spread of SARS-CoV-2. This ban remains in effect. 
In conjunction with this reduction in supply, there has been a 
substantial increase in the demand for NHPs for the testing of 
experimental COVID-19 treatments and vaccines.\2\
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    \1\ See ``Rapid Response by Laboratory Animal Research 
Institutions During the COVID-19 Pandemic: Lessons Learned: 
Proceedings of a Workshop--in Brief''; available at https://www.nap.edu/catalog/26189/rapid-response-by-laboratory-animal-research-institutions-during-the-covid-19-pandemic-lessons-learned.
    \2\ FDA supports the principles of the 3Rs, to reduce, refine, 
and replace animal use in testing when feasible. We encourage 
sponsors to consult with us if they wish to use a nonanimal testing 
method they believe is suitable, adequate, validated, and feasible. 
We will consider if such an alternative method is adequate to meet 
the regulatory need.
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    This reduction in supply and prioritization for COVID-19-related 
studies have severely restricted the availability of NHPs for other 
pharmaceutical development programs, resulting in a disruption in 
supply that has the potential to significantly delay the development of 
new medications for the treatment of diseases currently without 
effective treatment options. While the disruption affects the NHP 
supply generally, there is a particularly acute shortage of sexually 
mature NHPs that are often the only pharmacologically relevant species 
with which to assess developmental and reproductive toxicity endpoints 
for biotherapeutic proteins (biological products).
    This guidance provides recommendations regarding the use of NHPs in 
development programs for small molecule drugs as well as for biological 
products, covering both general toxicity studies and developmental and 
reproductive toxicity (DART) studies. The guidance provides FDA's 
recommendations for sponsors to use alternative nonrodent species, 
whenever possible, in general toxicology studies and, in general, to 
not use NHPs for DART assessment of small molecule drugs. For DART 
studies of biological products, the guidance provides FDA's 
recommendation that sponsors fully utilize non-NHP approaches to assess 
DART. These approaches include, when scientifically appropriate, the 
use of a weight-of-evidence approach to risk assessment, the use of 
species-specific surrogate proteins in rodents, and the use of rodents 
genetically modified to (1) respond to the clinical candidate or (2) 
evaluate the effects of altered activity of the target of the 
biological product. In instances with no scientifically appropriate 
alternatives to the NHP, the sponsor may be able to reduce the number 
of NHPs used per study by reducing the number of treatment groups in 
the study. The guidance also addresses the potential for delaying the 
conduct of DART studies to the postmarketing setting. Taken together, 
these recommendations are expected to help mitigate the constrained 
supply of NHPs until such time as the NHP supply recovers sufficiently 
from the effect of the COVID-19 pandemic.
    In light of the public health emergency related to COVID-19 
declared by the Secretary of Health and Human Services (HHS), pursuant 
to section 319(a)(2) of the Public Health Service Act (42 U.S.C. 
247d(a)(2)), FDA has determined that prior public participation for 
this guidance is not feasible or appropriate and is issuing this 
guidance without prior public comment (see section 701(h)(1)(C)(i) of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 371(h)(1)(C)(i) and 
21 CFR 10.115(g)(2)). This guidance document is being implemented 
immediately, but it remains subject to comment in accordance with the 
Agency's good guidance practice statute and regulation.
    This guidance is intended to remain in effect for the duration of 
the public health emergency related to COVID-19 declared by the 
Secretary of HHS, including any renewals.\3\ However, the 
recommendations and processes described in the guidance are expected to 
help mitigate the COVID-19 pandemic-related NHP supply constraints 
affecting pharmaceutical development that are expected to persist 
beyond the termination of the COVID-19 public health emergency (e.g., 
time required to rebuild breeding stocks and for NHPs to reach sexual 
maturity) and reflect the Agency's current thinking on this issue. 
Therefore, within 60 days following the termination of the public 
health emergency, FDA intends to revise and replace this guidance with 
any appropriate changes based on comments received on this guidance and 
the Agency's experience with implementation.
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    \3\ See https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx.
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    This 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 ``Nonclinical Considerations for Mitigating 
Nonhuman Primate Supply Constraints Arising from the COVID-19 
Pandemic.'' 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. 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 314 have been approved under OMB control 
number 0910-0001; the collections of information in 21 CFR part 312 
have been approved under OMB control number 0910-0014; and the 
collections of information in 21 CFR part 601 have been approved under 
OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, 
https://

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www.fda.gov/regulatory-information/search-fda-guidance-documents, 
https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-related-guidance-documents-industry-fda-staff-and-other-stakeholders, or https://www.regulations.gov.

    Dated: February 16, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-03915 Filed 2-23-22; 8:45 am]
BILLING CODE 4164-01-P