[Federal Register Volume 86, Number 135 (Monday, July 19, 2021)]
[Notices]
[Pages 37988-37989]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-15236]


-----------------------------------------------------------------------

DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

[Docket No. APHIS-2020-0072]


Movement of Organisms Modified or Produced Through Genetic 
Engineering; Notice of Exemptions

AGENCY: Animal and Plant Health Inspection Service, Agriculture (USDA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: We are advising the public that we are proposing to exempt 
plants with additional modifications that could otherwise be achieved 
through conventional breeding from the regulations that govern the 
introduction (importation, interstate movement, or release into the 
environment) of certain organisms modified or produced through genetic 
engineering. The exempt plants would have distinct modifications on the 
paternal and maternal alleles of a single gene resulting from repair of 
a targeted DNA break; deletions generated using an externally provided 
repair template; or deletions resulting from repair of two targeted 
double strand breaks on a chromosome. This action would reduce the 
regulatory burden for developers of certain plants modified or produced 
through genetic engineering that are unlikely to pose plant pest risks 
while enabling the Animal and Plant Health Inspection Service to focus 
its regulatory resources on risk analyses of unfamiliar products and 
those more likely to pose a plant pest risk.

DATES: We will consider all comments that we receive on or before 
August 18, 2021.

ADDRESSES: You may submit comments by either of the following methods:
     Federal eRulemaking Portal: Go to www.regulations.gov. 
Enter APHIS-2020-0072 in the Search field. Select the Documents tab, 
then select the Comment button in the list of documents.
     Postal Mail/Commercial Delivery: Send your comment to 
Docket No. APHIS-2020-0072, 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 www.regulations.gov 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. Neil Hoffman, Science Advisor, 
Biotechnology Regulatory Services, APHIS, 4700 River Road Unit 98, 
Riverdale, MD 20737-1238; (301) 851-3947.

SUPPLEMENTARY INFORMATION: The regulations in 7 CFR part 340 govern the 
introduction (importation, interstate movement, or release into the 
environment) of certain organisms modified or produced through genetic 
engineering. The Animal and Plant Health Inspection Service (APHIS) 
first issued these regulations in 1987 under the authority of the 
Federal Plant Pest Act of 1957 and the Plant Quarantine Act of 1912, 
two acts that were subsumed into the Plant Protection Act (PPA, 7 
U.S.C. 7701 et seq.) in 2000, along with other provisions. Since 1987, 
APHIS has amended the regulations seven times, in 1988, 1990, 1993, 
1994, 1997, 2005, and 2020.
    On May 18, 2020, we published in the Federal Register (85 FR 29790-
29838, Docket No. APHIS-2018-0034) a final rule \1\ that marked the 
first comprehensive revision of the regulations since they were 
established in 1987. The final rule provided a clear, predictable, and 
efficient regulatory pathway for innovators, facilitating the 
development of organisms developed using genetic engineering that are 
unlikely to pose plant pest risks.
---------------------------------------------------------------------------

    \1\ To view the final rule and supporting documents, go to 
https://www.regulations.gov, and enter APHIS-2018-0034 in the Search 
field.
---------------------------------------------------------------------------

    The May 2020 final rule included regulatory exemptions for certain 
categories of plants that have been modified. Specifically, Sec.  
340.1(b) exempted plants that contain a single modification of one of 
the following types, specified in Sec.  340.1(b)(1) through (3):
     The genetic modification is a change resulting from 
cellular repair of a targeted DNA break in the absence of an externally 
provided repair template; or
     The genetic modification is a targeted single base pair 
substitution; or
     The genetic modification introduces a gene known to occur 
in the plant's gene pool or makes changes in a targeted sequence to 
correspond to a known allele of such a gene or to a known structural 
variation present in the gene pool.
    In addition to the modifications listed above, Sec.  340.1(b)(4) 
provides that the Administrator may propose to exempt plants with 
additional modifications, based on what could be achieved through 
conventional breeding. Such proposals may either be APHIS-initiated or 
may be initiated via a request that is accompanied by adequate 
supporting information and submitted by another party. In either case, 
APHIS will publish a notice in the Federal Register of the proposal, 
along with the supporting documentation, and will request public 
comments. After reviewing the comments, APHIS will publish a subsequent 
notice in the Federal Register announcing its final determination. A 
list specifying modifications a plant can contain and be exempt 
pursuant to paragraph (b)(4) is available on the APHIS website at 
https://www.aphis.usda.gov/aphis/ourfocus/biotechnology.
    In this document, we are proposing to add three modifications that 
plants can contain and be exempt from regulation pursuant to Sec.  
340.1. These modifications are similar and functionally equivalent to 
modifications that commonly occur within conventional breeding and to 
the

[[Page 37989]]

modification described in Sec.  340.1(b)(1), but enable a developer to 
more efficiently obtain a complete loss of function of a targeted gene. 
We are also making available for public review scientific literature 
that we consulted prior to initiating the proposal. The literature 
supports exempting plants with these additional modifications.
    Under the first additional genetic modification proposed, plants 
would not be subject to the regulations when cellular repair of a 
targeted DNA break in the same location on two homologous chromosomes, 
in the absence of a repair template, results in homozygous or 
heterozygous biallelic mutations, each of which is a loss of function 
mutation. A double strand break followed by cellular repair often 
occurs in both paternal and maternal alleles (biallelic) during genome 
editing. As a range of DNA indels frequently occur after a double 
strand break, the mutation in the paternal allele often differs from 
the mutation in the maternal allele. Biallelic knockout mutations are 
easily obtained in conventional breeding through self-fertilizing or 
backcrossing and selection. In this case, the biallelic mutation is 
usually homozygous. However, in cases where the deletions are not 
identical but both deletions lead to a loss of function of the allele, 
the phenotype will be the same as the homozygous biallelic mutation 
obtained through conventional breeding. If both alleles are modified by 
indels such that neither allele is functional, the size, position, and 
sequence of the indels within the gene need not be identical to qualify 
for the exemption.
    The second additional genetic modification proposed is a contiguous 
deletion of any size resulting from cellular repair of a targeted DNA 
break in the presence of an externally supplied repair template. The 
deletion can occur on one or two homologous chromosomes. This 
modification is similar to the one described in Sec.  340.1(b)(1), 
except that it allows an externally supplied repair template to be 
used. When genome editing is used to create a single DNA break, a range 
of indels result from the cellular repair mechanism. To limit the range 
of mutations recovered and, therefore, to more efficiently obtain a 
complete loss of function of the targeted gene(s), some developers also 
add a template to guide the repair process. To limit this proposed 
additional modification to what is achievable through conventional 
breeding, it would only apply to deletions created by the double strand 
break and externally supplied repair template.
    The third additional genetic modification proposed is for a change 
resulting from cellular repair of two targeted DNA breaks on a single 
chromosome or at the same location on two homologous chromosomes, when 
the repair results in a contiguous deletion of any size in the presence 
or absence of a repair template, or in a contiguous deletion of any 
size combined with an insertion of DNA in the absence of a repair 
template. The insertion cannot result from the insertion of exogenous 
construct DNA. The modifications on two homologous chromosomes can be 
heterozygous as long as each results in a loss of function of the 
targeted gene(s). To qualify for the exemption, the plant must have 
mutations that are restricted to a pair of homologous chromosomes in 
diploids and allopolyploids or any two homologous chromosomes in 
autopolyploids. Radiation mutagenesis, which is commonly used in 
conventional breeding, can create any size deletion. As mutations are 
typically detrimental to the organism, what is achievable in practice 
is limited by the viability and fertility of the organism. Large 
mutations can be maintained in a heterozygous state but do not tend to 
undergo homozygous inheritance (Naito, 2005).\2\ For example, in 
Arabidopsis, which has a genome size of 135 Mb (Arabidopsis Genome 
Initiative, 2000), a radiation-induced deletion of 3.1 Mb was obtained 
that disrupted 852 genes and was maintainable only as a heterozygote, 
presumably because genes essential for survival are present in the 
deleted region (Kazama, et al., 2017).\3\ Polyploid plants and those 
with large genomes are better able to accommodate even larger deletions 
(Men et al., 2002).\4\ For example, in hexaploid wheat, X-ray 
mutagenesis was used to create a mutant, ph1, widely used in breeding 
programs, that has a 70 Mb deletion (Sears, 1977).\5\ To put the size 
of this wheat deletion in perspective, it is larger than half of the 
entire genome of Arabidopsis. Based on the use of plants with large 
deletion mutations in conventional breeding programs, any size 
contiguous deletion created by two double strand breaks should be 
exempted because it falls well within what could be achieved through 
conventional breeding.
---------------------------------------------------------------------------

    \2\ Naito, K., M. Kusaba, N. Shikazono, T. Takano, A. Tanaka, T. 
Tanisaka, and M. Nishimura (2005). Transmissible and 
nontransmissible mutations induced by irradiating Arabidopsis 
thaliana pollen with gamma-rays and carbon ions. Genetics, 169, 881-
889.
    \3\ Kazama, Y., K. Ishii, T. Hirano, T. Wakana, M. Yamada, S. 
Ohbu, and T. Abe (2017). Different mutational function of low- and 
high-linear energy transfer heavy-ion irradiation demonstrated by 
whole-genome resequencing of Arabidopsis mutants. Plant J. 92, 1020-
1030.
    \4\ Men, A.E., T.S. Laniya, I.R. Searle, I. Iturbe-Ormaetxe, I. 
Gresshoff, Q. Jiang, B.J. Carroll, and P.M. Gresshoff (2002). Fast 
Neutron Mutagenesis of Soybean (Glycine soja L.) Produces a 
Supernodulating Mutant Containing a Large Deletion in Linkage Group 
H. Genome Letters 3: 147-155.
    \5\ Sears, E.A. (1977). An induced mutant with homoeologous 
pairing in common wheat. Canadian J of Genetics and Cytology 19: 
585-593.
---------------------------------------------------------------------------

    After reviewing any comments we receive, we will announce our 
decision regarding the three new modifications that plants could 
contain and qualify for exemption in a subsequent notice.
    Authority: 7 U.S.C. 7701-7772 and 7781-7786; 31 U.S.C. 9701; 7 CFR 
2.22, 2.80, and 371.3.

    Done in Washington, DC, this 14th day of July, 2021.
Michael Watson,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 2021-15236 Filed 7-16-21; 8:45 am]
BILLING CODE 3410-34-P