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[Federal Register Volume 85, Number 232 (Wednesday, December 2, 2020)]
[Notices]
[Pages 77425-77426]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-26560]

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Notices
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains documents other than rules 
or proposed rules that are applicable to the public. Notices of hearings 
and investigations, committee meetings, agency decisions and rulings, 
delegations of authority, filing of petitions and applications and agency 
statements of organization and functions are examples of documents 
appearing in this section.

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Federal Register / Vol. 85, No. 232 / Wednesday, December 2, 2020 / 
Notices

[[Page 77425]]

DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

[Docket No. APHIS-2020-0054]

Petition To Manufacture Foot-and-Mouth Disease Vaccine in the 
United States

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Notice of petition and request for information; reopening of 
comment period.

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SUMMARY: We are reopening the comment period for our notice of receipt 
of a petition from Zoetis, Inc. requesting approval for the manufacture 
within the continental United States of a vaccine derived from a 
leaderless strain of the foot-and-mouth disease (FMD) virus. Although 
introduction of live FMD virus into the United States is prohibited by 
law, the petition states that this leaderless strain should not be 
considered live FMD virus as it is non-infectious, non-transmissible, 
and incapable of causing FMD. We are taking this action in order to 
provide commenters with additional scientific information supporting 
our determination that the leaderless virus strain from which Zoetis, 
Inc. intends to produce FMD vaccine in the United States poses no risk 
of causing FMD infection in animals. This action gives interested 
persons the opportunity to review the additional information and submit 
comments.

DATES: The comment period for the notice published on July 14, 2020 (85 
FR 42346-42347) is reopened. We will consider all comments that we 
receive on or before January 4, 2021.

ADDRESSES: You may submit comments by either of the following methods:
     Federal eRulemaking Portal: Go to http://www.regulations.gov/#!docketDetail;D=APHIS-2020-0054.
     Postal Mail/Commercial Delivery: Send your comment to 
Docket No. APHIS-2020-0054, Regulatory Analysis and Development, PPD, 
APHIS, Station 3A-03.8, 4700 River Road, Unit 118, Riverdale, MD 20737-
1238.
    Supporting documents and any comments we receive on this docket may 
be viewed at http://www.regulations.gov/#!docketDetail;D=APHIS-2020-
0054 or in our reading room, which is located in Room 1620 of the USDA 
South Building, 14th Street and Independence Avenue SW, Washington, DC. 
Normal reading Room hours are 8 a.m. to 4:30 p.m., Monday through 
Friday, except holidays. To be sure someone is there to help you, 
please call (202) 799-7039 before coming.

FOR FURTHER INFORMATION CONTACT: Dr. Byron Rippke, Director, Center for 
Veterinary Biologics, APHIS, Veterinary Services, Diagnostics and 
Biologics, 1920 Dayton Ave., Ames, IA 50010; (515) 337-6101; 
[email protected].

SUPPLEMENTARY INFORMATION: On July 14, 2020, we published in the 
Federal Register (85 FR 42346-42347, Docket No. APHIS-2020-0054) a 
notice and request for information \1\ on a petition submitted by 
Zoetis, Inc. (Zoetis), a U.S. vaccine manufacturer, seeking approval 
from the Animal and Plant Health Inspection Service (APHIS) to 
manufacture within the continental United States a vaccine produced 
using a leaderless strain \2\ of the foot-and-mouth disease (FMD) 
virus. A leaderless virus lacks part of the genetic code (the leader) 
critical for determining virulence in a host. Responses to this request 
for information will help us determine whether to authorize Zoetis to 
manufacture the vaccine in the United States for commercial 
distribution.
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    \1\ To view the notice, the supporting document, and the 
comments we have received, go to http://www.regulations.gov/#!docketDetail;D=APHIS-2020-0054.
    \2\ Referred to in the Zoetis petition as FMD-LL3B3D A24 
Cruzeiro vaccine platform virus.
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    In the notice, we invited commenters to respond to questions about 
the risks of manufacturing an FMD vaccine in the United States and what 
safeguards might be necessary to address risk. We also asked commenters 
whether the leaderless strain of the virus intended for manufacture of 
a vaccine should be considered as a live FMD virus based on the Zoetis 
petition and information we supplied in the notice. This question is 
important in determining whether the prohibition in 21 U.S.C. 113a on 
introducing live FMD virus into the United States is applicable to a 
leaderless virus strain shown to be incapable of causing FMD infection 
in animals.
    We solicited comments concerning our proposal for 60 days ending 
September 14, 2020. We received a total of 140 comments. While many 
commenters agreed that the Zoetis leaderless virus poses no FMD risk to 
U.S. livestock, several others raised safety concerns about using it to 
manufacture FMD vaccine in the United States. They stated that the 
notice and petition did not provide enough data to support a 
determination that the leaderless virus is not a live virus and that it 
poses no risk of causing FMD infection in animals. To address these 
concerns, we are providing additional data in this notice supporting 
the safety of the leaderless FMD virus and its use in manufacturing FMD 
vaccine and are reopening the comment period for 30 days.

Risk Assessment Summary

    In 2017, Zoetis requested from the U.S. Department of Agriculture 
(USDA) a select agent exclusion for a leaderless strain of FMD virus 
intended to be used as a platform for producing FMD vaccine. In 
accordance with the regulations in 9 CFR part 122, USDA issued a permit 
allowing Zoetis to bring attenuated live FMD virus into the mainland 
United States for possible vaccine development. Before issuing the 
permit, USDA reviewed multiple documents and studies related to the 
request. The review encompassed synthetic virus production, virulence 
and safety, seroconversion, and concerns related to diagnostic 
differentiation of vaccinated and naturally infected animals. We 
concluded from these reviews that the Zoetis leaderless virus is 
incapable of infecting animals with FMD, and that vaccines produced 
using the leaderless virus as a platform are safe and efficacious in 
cattle and swine. Further details of our review findings are included 
in a risk assessment summary available via the link in footnote 1.

[[Page 77426]]

    In addition to the risk assessment summary, we wish to provide the 
following information regarding our evaluation.

Development and Safety of the FMD-LL3B3D Leaderless FMD Virus

    The FMD-LL3B3D leaderless vaccine platform virus was created by 
deleting the leader (L) and one of three 3B genetic sequences of the 
FMD virus (L is a part of the virus that determines virulence), 
resulting in an attenuated virus that is innocuous for cattle and pigs 
but capable of growing in cell culture.\3\ As a result, if the FMD-
LL3B3D leaderless virus were to escape a manufacturing facility, it 
would be incapable of causing FMD in any animals exposed to it, nor 
could such animals spread the virus to other animals. In contrast, the 
risk of escape from facilities using traditionally virulent FMD viruses 
to manufacture vaccine is why many countries restrict FMD vaccine 
production to only local endemic strains. The deletion of L and the 
relevant 3B genetic sequence was therefore a key consideration in our 
evaluation.
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    \3\ See the following studies for leaderless FMD virus safety 
data: Uddowla S., et al. A Safe Foot-and-Mouth Disease Vaccine 
Platform with Two Negative Markers for Differentiating Infected from 
Vaccinated Animals. Journal of Virology Oct 2012, 86(21) 11675-
11685: DOI: 10.1128/JVI.01254-12; Eschbaumer M., et al. Foot-and-
mouth disease virus lacking the leader 2 protein and containing two 
negative DIVA markers 3 (FMDV LL3B3D A24) is fully attenuated in 
pigs. Pathogens. (2020) 17:1-8: DOI: 10.3390/pathogens9020129; 
Hardham, John M., et al., Novel Foot-and-Mouth Disease Vaccine 
Platform: Formulations for Safe and DIVA-Compatible FMD Vaccines 
with Improved Potency. Frontiers in Veterinary Science, 25 September 
2020; https://doi.org/10.3389/fvets.2020.554305.
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    Of similar importance was our review of available data regarding 
virulence of FMD-LL3B3D vaccines. Several FMD-LL3B3D vaccine viruses 
have been derived in vitro and characterized for their virulence in 
cattle and pigs. The cumulative data have shown that these FMD-LL3B3D 
marker viruses are highly attenuated in their natural hosts. Safety 
studies involving direct inoculation of live FMD-LL3B3D virus in cattle 
and pigs (see table 1) showed a high restriction of the novel vaccine 
virus to replicate and resulted in no clinical disease or 
transmission.\4\
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    \4\ In a 2018 meeting report drafted by the Global Foot-and-Moth 
Disease Research Alliance that reviewed FMD vaccine platforms, the 
FMDLL3B3D platform received the highest score. Global Foot-and-Mouth 
Disease Research Alliance, Gap Analysis Report. December 2018: 
https://go.usa.gov/xdrKh.

      Table 1--Live Innocuity Studies Using a Variety of FMDLL3B3D Vaccine Strains in Cattle and Swine \1\
----------------------------------------------------------------------------------------------------------------
                                                                         Number of
                Construct                      Inoculation route          animals               Results
----------------------------------------------------------------------------------------------------------------
Cattle:
    FMD-LL3B3D-A24 Cruzeiro.............  Intralingual (7x10\6\)....               2   No clinical
                                                                                       disease.
    FMD-LL3B3D-A24 Cruzeiro.............  Aerosol (1x10\6\ to                      3   No viral
                                           3x10\6\).                                   shedding.
    FMD-LL3B3D-A24 Cruzeiro.............  Aerosol and Contact/                     9   No fever spikes.
                                           (1x10\6\).
                                                                                       No contact
                                                                                       transmission.
                                                                                       Very limited if
                                                                                       any immune response.
Swine:
    FMD-LL3B3D-A24 Cruzeiro.............  Heelbulb and Contact                     4   No clinical
                                           (1x10\5\).                                  disease.
    FMD-LL3B3D-Asia1 Shamir.............  Heelbulb and Contact                     5   No viral
                                           (1x10\6\).                                  shedding.
    FMD-LL3B3D-A Turkey 06..............  Heelbulb and Contact                     5   No fever spikes.
                                           (1x10\6\).
    FMD-LL3B3D-O1 Campos................  Heelbulb and Contact                     4   No contact
                                           (1x10\6\).                                  transmission.
    FMD-LL3B3D-A Argentina..............  Heelbulb and Contact                     4   Very limited if
                                           (2x10\6\).                                  any immune response.
    FMD-LL3B3D-C3 Indaial...............  Heelbulb and Contact                     4  ..........................
                                           (2.8x10\6\).
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\1\ Data prepared by Foreign Animal Disease Research Unit, USDA/ARS, Plum Island Animal Disease Center.

    We are therefore reopening the comment period on Docket No. APHIS-
2020-0054 for an additional 30 days. This action will allow interested 
persons to prepare and submit comments on the additional information we 
provided. We will also consider all comments received between September 
14, 2020, and the date of this notice.

    Authority: 7 U.S.C. 1633, 7701-7772, 7781-7786, and 8301-8317; 
21 U.S.C. 136 and 136a; 31 U.S.C. 9701; 7 CFR 2.22, 2.80, and 371.4.

    Done in Washington, DC, this 25th day of November 2020.
Mark Davidson,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 2020-26560 Filed 12-1-20; 8:45 am]
BILLING CODE 3410-34-P
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