Notice2022-09210
Screening Framework Guidance for Providers and Users of Synthetic Oligonucleotides
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
April 29, 2022
Issuing agencies
Health and Human Services Department
Abstract
The Assistant Secretary for Preparedness and Response is issuing this revised guidance on a screening framework guidance for providers and users of synthetic oligonucleotides. The Revised Guidance sets forth recommended baseline standards for the gene and genome synthesis industry, as well as best practices for Institutions, Principal Users, End Users, and Third-Party Vendors of oligonucleotides, regarding screening orders and maintaining records consistent with current U.S. regulations. In addition, this Revised Guidance seeks to encourage best practices to address biosecurity concerns associated with the potential misuse of synthetic oligonucleotides to bypass existing regulatory controls and commit unlawful acts.
Full Text
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<title>Federal Register, Volume 87 Issue 83 (Friday, April 29, 2022)</title>
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[Federal Register Volume 87, Number 83 (Friday, April 29, 2022)]
[Notices]
[Pages 25495-25499]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-09210]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Screening Framework Guidance for Providers and Users of Synthetic
Oligonucleotides
AGENCY: Office of the Secretary, Assistant Secretary for Preparedness
and Response (ASPR), Department of Health and Human Services (HHS).
ACTION: Notice.
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SUMMARY: The Assistant Secretary for Preparedness and Response is
issuing this revised guidance on a screening framework guidance for
providers and users of synthetic oligonucleotides. The Revised Guidance
sets forth recommended baseline standards for the gene and genome
synthesis industry, as well as best practices for Institutions,
Principal Users, End Users, and Third-Party Vendors of
oligonucleotides, regarding screening orders and maintaining records
consistent with current U.S. regulations. In addition, this Revised
Guidance seeks to encourage best practices to address biosecurity
concerns associated with the potential misuse of synthetic
oligonucleotides to bypass existing regulatory controls and commit
unlawful acts.
FOR FURTHER INFORMATION CONTACT: Dr. Mariam Lekveishvili; Division of
Policy; Office of Strategy, Policy, Planning, and Requirements; Office
of the Assistant Secretary for Preparedness and Response; U.S.
Department of Health and Human Services; phone: (202) 260-3586; email:
<a href="/cdn-cgi/l/email-protection#531e32213a323e7d1f363825363a203b253a3f3a133b3b207d343c25"><span class="__cf_email__" data-cfemail="0845697a61696526446d637e6d617b607e6164614860607b266f677e">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION: Questions regarding aspects of the Guidance
that may be appropriate to update based on changes in technologies
since the Guidance was originally issued in 2010 were published as a
Notice in the Federal Register on August 26, 2020, for a period of more
than 120 days for public comment. Fourteen individual responses were
received. The responses to that Notice are available at the following
website: <a href="https://aspr.hhs.gov/legal/syndna/Pages/comment.aspx">https://aspr.hhs.gov/legal/syndna/Pages/comment.aspx</a>.
Screening Framework Guidance for Providers and Users of Synthetic
Oligonucleotides
Introduction: Continuing advances in oligonucleotide synthesis
technology and the open availability of genetic sequence data pose
potential concerns among the scientific community, the oligonucleotide
synthesis industry, the U.S. Government, and the public that
individuals with ill intent could exploit biotechnology for harmful
purposes. The U.S. Government has acted to reduce dangers to human,
animal, and plant health due to biological pathogens and toxins. For
instance, it has issued the federal Select Agent Regulations, which
regulate a subset of microbial organisms and toxins determined to have
the potential to pose a severe threat to public health and safety,
animal health, plant health, or animal or plant products. These
regulations are administered by the Federal Select Agent Program
(FSAP), which sets forth requirements for the possession, use, and
transfer of biological select agents and toxins.\1\ A second layer of
regulation is provided by the Export Administration Regulations'
Commerce Control List (CCL) \2\ which identifies agents and genetic
sequences that require licenses before export from the United States.
However, these regulated pathogens and toxins do not represent the
entirety of the potential risks to public health, agriculture, plants,
animals, or the environment that could arise from the misuse of
synthetic oligonucleotides. Non-regulated pathogens and toxins as well
as other novel types of sequences or specific types of batch orders,
may also pose significant risks if they are misused.
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\1\ <a href="https://www.selectagents.gov/sat/list.htm">https://www.selectagents.gov/sat/list.htm</a>.
\2\ <a href="https://www.bis.doc.gov/index.php/regulations/commerce-control-list-ccl">https://www.bis.doc.gov/index.php/regulations/commerce-control-list-ccl</a>.
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Individuals with no legitimate, bona fide, and peaceful need should
be prevented from accessing genetic materials that could contribute to
pathogenicity or harm, even when they are not from FSAP- or CCL-listed
pathogens or toxins. Purchasing or synthesizing oligonucleotides could
enable individuals without a legitimate and peaceful purpose to possess
genetic sequences that would pose risks if misused. Such synthesis,
through directly ordering either long genomic sequences or short
genomic sequences--that can be used to create longer genomic-length
oligonucleotides, using molecular techniques that have become
increasingly available--to modify non-
[[Page 25496]]
pathogenic strains or create pathogens or toxins de novo, has obviated
the need for access to the naturally occurring agents or naturally
occurring genetic material from these agents. The potential
availability of dangerous agents has thereby been greatly expanded. The
Revised Guidance reaffirms the need to screen for genetic sequences
from regulated organisms and toxins, but also recognizes that screening
should evolve to encompass sequences that are recognized to contribute
to pathogenicity or toxicity, as information regarding these sequences
and their verified function, as well as improved methods to screen
become available (or as feasible).
This Revised Guidance is intended to guide all entities involved in
the provision and use of synthetic oligonucleotides in establishing and
operating a screening framework for oligonucleotide orders, including
mechanisms to identify sequences obfuscated to circumvent lists of
regulated organisms or toxins or sequences that are not Best Matches to
any sequences in GenBank. To minimize the risk that unauthorized
individuals or individuals with ill intent will obtain oligonucleotides
containing SOCs, the Revised Guidance now provides recommendations to
not only Providers, but also Third-Party Vendors, Institutions,
Principal Users, and End Users of synthetic oligonucleotides, to use
responsible business practices to maintain records of all orders and
transfers of SOCs. This Revised Guidance includes recommendations for
verifying the legitimacy of Customers when filling orders for synthetic
oligonucleotides that encode SOCs. The Revised Guidance further
provides recommendations for Manufacturers, as oligonucleotide
synthesis equipment may allow individuals with malintent to circumvent
regulations that restrict access to regulated pathogens and toxins or
to obtain oligonucleotides containing other SOCs without a legitimate
and peaceful purpose. As in the original Guidance, this Revised
Guidance aims to minimize any negative impacts on the conduct of
research and business operations, by leveraging ongoing best practices.
Institutional policies and procedures already in place for safe
possession, use, and transfer of these materials, as well as federal
and international guidance, such as the Department of Health and Human
Services, Centers for Disease Control and Prevention, and National
Institutes of Health Biosafety in Microbiological & Biomedical
Laboratories (BMBL) \3\ and the World Health Organization Laboratory
Biosafety Manual,\4\ should be used wherever possible to complement the
measures suggested in this Revised Guidance to maximize safe and secure
practices while seeking to minimize the burden on legitimate life
science research.
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\3\ <a href="https://www.cdc.gov/labs/BMBL.html">https://www.cdc.gov/labs/BMBL.html</a>.
\4\ <a href="https://www.who.int/publications/i/item/9789240011311">https://www.who.int/publications/i/item/9789240011311</a>.
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Request for Comments: A request for public comments on the issues
covered in this Notice was published in the Federal Register (85 FR
52611, August 26, 2020, Review and Revision of the Screening Framework
Guidance for Providers of Synthetic Double-Stranded DNA) for public
consideration and comment for a period of more than 120 days. This
Revised Guidance was drafted through a deliberative interagency process
to address the topics raised in public comments as well as other
concerns from the interagency.
The Office of the Assistant Secretary for Preparedness and Response
(ASPR) within the Department of Health and Human Services (HHS) is
submitting this Revised Guidance for public consideration and comment
for a period of 60 days. ASPR is the lead agency in a broad interagency
process considering possible changes to the Guidance and whether to
issue the proposed Revised Guidance as final guidance. The public is
encouraged to submit written comments on the proposed changes to the
Guidance, whether additional measures would be needed to best ensure
safety and security in life sciences research and innovation, whether
the suggested scope of screening and intended audience is feasible, and
whether impacts are expected from implementing this Revised Guidance.
Comments may be submitted at the following website: <a href="https://aspr.hhs.gov/legal/syndna/Pages/comment.aspx">https://aspr.hhs.gov/legal/syndna/Pages/comment.aspx</a>.
Definitions: The following definitions are applicable:
Customer: For the purposes of this Revised Guidance, the individual
or organization, such as an Institution, that orders or requests
synthetic oligonucleotide from a Provider, or that purchases benchtop
synthesis equipment from a Manufacturer.
End User: The laboratorian that possesses and uses synthetic
oligonucleotides that they have received from a Customer, Principal
User, or another End User.
Manufacturer: An entity that produces and sells equipment for
synthesizing oligonucleotides. Manufacturers may provide equipment to
Institutions, Principal Users, or Third-Party Vendors.
Principal User: The individual that originates the order or
synthesizes oligonucleotides themselves and oversees the use of ordered
or synthesized sequences in the laboratory. The Principal User may also
be the End User.
Provider: The entity that synthesizes and distributes
oligonucleotides. A Provider is understood to be an entity synthesizing
oligonucleotides for and distributing oligonucleotides to a Customer,
rather than a research scientist collaborating with a colleague.
Sequence of Concern (SOC): Sequences derived from or encoding
select agents and toxins or items on the CCL, except when also found in
unregulated organisms; or sequences that contribute to toxicity or
pathogenicity, whether derived from or encoding regulated or
unregulated biological agents.\5\
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\5\ Pathogenicity or toxicity that threatens public health,
agriculture, plants, animals, or the environment. SOCs include
sequences for which a direct and harmful impact on a host has been
verified based on published experimental data; and, where
experimental data do not exist, based on homology to a sequence
encoding a verified function.
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Synthetic oligonucleotides subject to screening: DNA or RNA,
single- or double-stranded, of lengths 50 base pairs (bp) or longer if
ordered in quantities of less than one micromole, or lengths 20 bp or
longer if ordered in quantities of one micromole or greater.
Third-Party Vendor: An entity that orders oligonucleotides from
Providers and sells the oligonucleotides in turn, with or without
reformulation, or resells equipment for synthesizing oligonucleotides.
Verifying Legitimacy: Information that would allow Providers,
Manufacturers, Principal Users, or End Users to authenticate the
recipient of materials or equipment as a legitimate member of the
scientific community. Information such as proposed end-use of the
order, institutional or corporate affiliation (if applicable), the name
of a biosafety officer (if available), proof of registration or
licensing with FSAP or DOC (if applicable), or other proof of a
legitimate research program (such as a publication history or business
licenses) may be helpful for such verification.
Goals and Scope of the Guidance
Goals: This Revised Guidance has two parallel goals. As in the
original Guidance, a primary goal is to minimize the risk that
unauthorized individuals
[[Page 25497]]
or individuals with malicious intent will use nucleic acid synthesis
technologies to obtain organisms for which possession, use, and
transfer is regulated by FSAP and CCL. The Revised Guidance also aims
to limit the potential for individuals with malicious intent to use
synthetic oligonucleotides to create novel high-risk pathogens using
sequences from unregulated organisms.
Scope: The Revised Guidance pertains to the sale or transfer of
synthetic oligonucleotides, i.e., DNA and RNA, whether single- or
double-stranded. The Revised Guidance recommends that a database of
known SOCs for pathogens, toxins, or otherwise illicit or dangerous
substances is developed and used to determine if the purchase or
transfer includes SOCs. It also recommends methods to ensure the
legitimacy of Customers, Principal Users, and End Users of synthetic
oligonucleotides. The Revised Guidance also aims to ensure that
entities maintain records of transfers for oligonucleotides containing
SOCs.
The Revised Guidance was developed to align with Providers' and
Customers' existing protocols and business practices; to be implemented
without unnecessary cost; and to minimize any negative impacts on the
conduct of research and business operations. Where practical to do so,
entities can use existing business practices to verify the legitimacy
of Principal Users and End-Users and to track the transfer of materials
containing SOCs. Many Providers have already instituted measures to
address these concerns. The ongoing development of best practices in
this area is commendable and encouraged, particularly in light of the
continued advances in oligonucleotide sequencing and synthesis
technologies.
Recommendations for Providers, Users, and Manufacturers: The
Revised Guidance aims to ensure that Customers, Principal Users, and
End Users ordering SOCs are legitimate. It also recommends that
Manufacturers install certain safeguards in oligonucleotide synthesis
equipment that ensure only legitimate customers can synthesize SOCs. It
also recommends that transfers of SOCs, from Principal Users to End
Users, and from Third-Party Vendors to Principal Users and End Users,
are reported to the original Customer, such as the Institution that
originated the order. This Revised Guidance encourages entities
transferring synthetic oligonucleotides containing SOCs (i.e., the
Third-Party Vendor, Principal User, or Institution) to know to whom
they are transferring and to conduct screening to verify that the
recipients have a legitimate, bona fide, and peaceful purpose to use
the oligonucleotides. The Revised Guidance recommends that the
Customers who place these orders use responsible business practices to
maintain records of transfers.
Principal Users and End Users are best positioned to understand the
nature of the oligonucleotides and oversee and shepherd their
responsible use. Users may also transfer oligonucleotides to other End
Users, such as colleagues, and certain recommendations are made for
this case in the Revised Guidance. To this end, Customers are
encouraged to streamline the screening of their synthetic
oligonucleotide orders by providing verification of their legitimacy to
Providers and Third-Party Vendors, if they know that their order
contains SOCs. Information such as proposed end-use of the order,
institutional or corporate affiliation (if applicable), the name of a
biosafety officer (if available), proof of registration or licensing
with FSAP or DOC (if applicable), or other proof of a legitimate
research program (such as a publication history or business licenses)
will be helpful to the Provider or Third-Party Vendor of the synthetic
oligonucleotides in verifying legitimacy. Preemptively providing this
information is likely to limit the time and expense for Providers in
fulfilling these orders in a manner that ensures safety and security.
Providers and Third-Party Vendors of synthetic oligonucleotides are
encouraged to do the following in this context:
<bullet> Know to whom they are distributing a product.
<bullet> Know if the product that they are synthesizing and/or
distributing contains, in part or in whole, SOCs.
<bullet> Notify Customers and Principal Users when their order
contains SOCs.
<bullet> Implement adequate cybersecurity measures to protect the
intellectual property and identity of Customers.\6\
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\6\ Providers and Third Party Vendors are encouraged to follow
the ISA/IEC 27032:2012 & ISO/IEC 62443 standards for cybersecurity
and information security.
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<bullet> Where follow-up screening does not resolve concerns about
an order, report the order to the FBI.
<bullet> This Revised Guidance recommends archiving for at least 8
years the following information for orders containing SOCs: Customer
information (point-of-contact name, organization, address, email, and
phone number), order sequence information (nucleotide sequences
ordered, vector used), and order information (date placed and shipped,
shipping address, receiver name).
Customers, Principal Users, and End Users of synthetic
oligonucleotides are encouraged to develop best practices in four main
areas in this context:
<bullet> Customers, Principal Users, and End Users who know that
their synthetic oligonucleotide order contains SOCs are encouraged to
preemptively provide information that will assist the Provider or
Third-Party Vendor in verifying their legitimacy.
<bullet> Customers, Principal Users, End Users, and Third-Party
Vendors are encouraged to only transfer synthetic oligonucleotides
containing SOCs to suitable and trustworthy individuals with a
scientifically sound reason to use these oligonucleotides.
<bullet> Customers, Principal Users, End Users, and Third-Party
Vendors are also encouraged to maintain records of these transfers and
to communicate them to their biosafety officer, or equivalent, using
the responsible business practices in place in their organizations.
<bullet> The Revised Guidance recommends recording transfers of
oligonucleotides containing SOCs from Principal Users and End Users to
any other individuals not listed in the original order, such as through
a Material Transfer Agreement (MTA) or another sample tracking process.
The Revised Guidance also recommends that records of SOCs and their
transfers are retained for at least 8 years. Business practices already
in place at Institutions may be used to fulfill this recommendation.
<bullet> Institutions with in-house oligonucleotide synthesis
capabilities are also encouraged to apply these recommendations for use
or transfers of oligonucleotides synthesized in-house.
Manufacturers of benchtop synthesis equipment are encouraged to
consider three areas for developing best practices in this context:
<bullet> Manufacturers should screen Customers seeking
oligonucleotide synthesizers to ensure customer legitimacy, and that
the equipment is appropriate for their needs. If the Customer indicates
plans to produce SOCs, Manufacturers should develop prescreening
mechanisms to determine legitimate use.
<bullet> Manufacturers and their Customers should implement
mechanisms to track continuously the legitimacy of users of their
equipment, including when it is potentially transferred to new
Principal and End Users during the lifecycle of these equipment (see
CUSTOMER SCREENING for criteria to verify legitimacy of User).
<bullet> Manufacturers should provide the capability into their
oligonucleotide
[[Page 25498]]
synthesizers to enable secure internet connectivity to screen sequences
for SOCs and to authenticate legitimate users.\7\ Manufacturers are
also encouraged to include a data logging function to maintain a record
of the oligos synthesized on the equipment. Furthermore, Manufacturers
should develop a mechanism to authenticate the user of these equipment
before synthesizing oligonucleotides containing SOCs.
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\7\ Manufacturers are encouraged to follow the ISO/IEC
27032:2012 & ISO ISA/IEC 62443 standards for cybersecurity and
information security.
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Sequence Screening Methodology: Providers should screen orders to
determine whether they contain SOCs. Appropriate sequence screening
software must be selected by providers of synthetic oligonucleotides.
This Revised Guidance recommends that providers use a local sequence
alignment technique, such as the BLAST family of tools. BLAST is
available for download for free at the National Center for
Biotechnology Information (NCBI) website.\8\ Similar tools are also
freely or commercially available or could be designed by the provider
to meet their sequence screening needs. Specific criteria for the
statistical significance of the hit (BLAST's e-values) or percent
identity values are not included in this Revised Guidance because these
details depend on the specific screening protocol. Providers are
encouraged to determine whether synthetic oligonucleotide orders
contain sequences that are Best Matches over 50 bp windows to any SOC.
By using the Best Match approach, the sequence with the greatest
percent identity over each 16 amino acid or 50 bp fragment, in all six
reading frames, should be considered the Best Match, regardless of the
statistical significance or percent identity. The Best Match approach
is intended to minimize the number of sequence hits due to sequences
that are shared among both SOCs and non-SOCs.
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\8\ <a href="http://blast.ncbi.nlm.nih.gov/Blast.cgi">http://blast.ncbi.nlm.nih.gov/Blast.cgi</a>.
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These sequence screening recommendations do not preclude the use of
a curated database of sequences that may contribute to pathogenicity or
toxicity to identify SOCs. This Revised Guidance recognizes that a
database of known sequences that contribute to pathogenicity and
toxicity in humans, animals, and plants, and that have a direct and
harmful impact on a host, may not yet exist, and encourages the
development of such a database for screening SOCs, provided that
measures are taken to prevent such a database from being misused. These
measures should include establishing a security office, protocols, and
personnel reliability program, based on an assessment of risk, to guide
selection, implementation, and monitoring of cybersecurity and
information security capabilities and protection. Measures should
ensure database confidentiality and integrity (including user access
controls and sequence encryption in transit and at rest) and compliance
with applicable laws such that sequences of concern data are protected
against unauthorized access, exfiltration, or other use. Providers may
also choose to use other screening approaches that they assess to be
equivalent or superior to the Best Match approach or supplement it,
including a customized database or approaches that evaluate the
biological risk associated with non-select agents and toxins sequences
or, for international orders, sequences not associated with items on
the CCL. This Revised Guidance encourages the continued development of
best practices to address risks associated with oligonucleotide
synthesis technologies.
Although no curated database of sequences from regulated and
unregulated pathogens that pose no biosecurity concerns (i.e., white
list of genes that pose no pathogenic risk) is presently available,
Providers may wish to consider developing solutions for determining
which sequences from pathogens, regulated or unregulated, should not
cause concern (such as housekeeping genes).
Providers, Third-Party Vendors, and professional consortia are
encouraged to develop secure mechanisms designed to respect privacy,
security, commercial, Intellectual Property, and other concerns to
detect SOCs that may be broken up among multiple Providers or Vendors,
or among multiple orders at a single Provider or Vendor over a period
of time, to evade screening.
Batch Orders: Some synthetic oligonucleotide orders may be
appropriate for screening even if all components of the order are
oligonucleotides shorter than 50 bp in length. In some cases, orders of
oligonucleotides in quantities of one micromole or more may indicate
that the Customer, Principal User, or End User may intend to use
molecular biological techniques to ligate oligonucleotides into larger
oligonucleotide complexes. Such an approach could be used to construct
50 bp or longer oligonucleotides that themselves may constitute SOCs.
To minimize the risk in this scenario, this Revised Guidance encourages
screening all constituents of batch orders of oligonucleotides 20 bp or
longer if ordered in quantities of one micromole or greater, using a
short oligonucleotide alignment software package. If the resulting
ungapped alignment of any constituents of the batch order is a Best
Match to any 50 bp window of any SOC, Providers should consider that
order as containing SOCs and perform standard follow-up Customer
screening.
Customer Screening: In addition to verifying the Customer identity
for all orders, verifying legitimacy of Customers and Users is
recommended when orders contain SOCs and for orders of benchtop
synthesis equipment. Customers and Users are encouraged to streamline
the Customer screening process by providing verification of their
legitimacy when submitting an order containing SOCs. Information about
the proposed end-use of the order, institutional or corporate
affiliation (if applicable), the name of a biosafety officer (if
available), proof of registration or licensing with FSAP or DOC (if
applicable), or other proof of a legitimate research program (such as a
publication history or business licenses) will be helpful to the
Provider or Third-Party Vendor.
This Revised Guidance encourages Customers and Principal Users to
also verify the legitimacy of End Users receiving SOCs. Records of such
verification and transfer can be created and maintained by using
business practices that document such transfers (e.g., MTAs). The
Principal User is best positioned to determine the legitimacy of any
End User to whom SOCs are transferred. Keeping a record of such
transfers should not cause undue burden on the essential research
carried out across the biotechnology enterprise, and may therefore
entail only a minor adaptation of responsible business practices
already in place.
Providers should be aware of regulatory and statutory prohibitions
for U.S. persons from dealing with certain foreign persons, entities,
and companies. Providers are encouraged to check the Customer against
the International Trade Administration consolidated list of individuals
and entities for which the United States Government maintains
restrictions on certain exports, reexports, or transfers of items.\9\
In the event that a company, entity, or person on the list appears to
match that of a Customer or User, additional due diligence should be
conducted before proceeding. There may be a strict export prohibition,
requirement for seeking a license application, evaluation of Customers
[[Page 25499]]
and Users to ensure it does not result in an activity prohibited by any
U.S. export regulations, or other restriction. Before taking further
action, to ensure full compliance with all the terms and conditions of
the restrictions placed on the parties on this list, the Provider must
check the official publication of restricted parties in the Federal
Register. They should also check the official lists of restricted
parties maintained on the websites of the Departments of Commerce,
State, and the Treasury.
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\9\ <a href="https://www.trade.gov/consolidated-screening-list">https://www.trade.gov/consolidated-screening-list</a>.
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Following up with the U.S. Government in Cases Where Malintent is
Suspected by Providers or Third-Party Vendors: If sequence or Customer
screening raises concerns that are not alleviated through follow-up
screening, Providers and Third-Party Vendors are encouraged to contact
the nearest FBI Field Office Weapons of Mass Destruction (WMD)
Coordinator. Institutions are encouraged to work with their Principal
Users and End Users to help them understand that only individuals with
legitimate, bona fide, and peaceful need should obtain oligonucleotides
containing SOCs.
Records Retention: The Revised Guidance recommends that Providers,
Third-Party Vendors, and Manufacturers:
<bullet> Using responsible business practices, retain records of
Customer orders for at least 8 years.
<bullet> Archive the following information: Customer information
(point-of contact name, organization, address, email, and phone
number), order sequence information (nucleotide sequences ordered,
vector used), and order information (date placed and shipped, shipping
address, receiver name).
<bullet> Develop and document protocols for sequence screening and
for determining whether a sequence hit qualifies as a SOC and maintain
records of these protocols--even if no longer current--for at least 8
years.
<bullet> Retain screening documentation of all hits for at least 8
years, even if the order was deemed acceptable.
<bullet> Retain records of any follow-up screening, even if the
order was ultimately filled, for at least 8 years.
Periodic Review, Evaluation, and Improvement of This Guidance: This
Revised Guidance is addressing biosecurity risks that have emerged in a
dynamic and rapidly developing technological landscape. It is likely
that new risks will emerge and that new technological approaches will
also appear to address biosecurity risks. As such, this Revised
Guidance encourages the further development of mechanisms to detect
SOCs and screening strategies for sequences that contribute to
pathogenicity and toxicity. For instance, strategies may be used by
malicious Customers to obfuscate SOCs, including engineering pathogenic
or toxic proteins with completely novel sequences. In such cases,
synthetic oligonucleotide orders may contain 50 bp windows that are not
a match to any known sequence. Although there are likely several
legitimate explanations for orders of sequences with no matches in
nature (e.g., oligonucleotides to populate microarrays or to store
digital information), in such cases, it may be possible to use
predictive bioinformatic algorithms to screen sequences that are not a
match to any known sequences to determine if they could produce
proteins that are structurally and functionally identical to SOCs. This
Revised Guidance encourages Providers to continue to develop these
methods to best ensure the safety of the synthetic oligonucleotide
research enterprise. Likewise, while there is not a comprehensive and
curated database available presently for sequences that may contribute
to pathogenicity or toxicity by enabling the circumvention of medical
countermeasures (MCM), such as therapeutics or vaccines, such
information may become increasingly available in coming years. This
Revised Guidance encourages the identification of such MCM-evasive
sequences and may revisit the definition of SOCs in the future, given
advances in this field.
Dawn O'Connell,
Assistant Secretary for Preparedness and Response.
[FR Doc. 2022-09210 Filed 4-28-22; 8:45 am]
BILLING CODE 4150-37-P
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