Federal Register / Vol. 87, No. 83 / Friday, April 29, 2022 / Notices 25495 

1https://www.selectagents.gov/sat/list.htm. 

2https://www.bis.doc.gov/index.php/regulations/ 

commerce-control-list-ccl. 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Crohn’s Disease: Developing Drugs for 

Treatment.’’ This guidance addresses 

FDA’s current thinking about clinical 

trials for the treatment of Crohn’s 

disease in adults, including 

recommendations for trial population, 

trial design, and efficacy and safety 

considerations. 

This draft guidance is being issued 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The draft guidance, when finalized, will 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 ‘‘Crohn’s Disease: Developing Drugs 

for Treatment.’’ 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 312 have 

been approved under OMB control 

number 0910–0014. FDA receives 

information described in FDA’s 

guidance entitled ‘‘Patient-Reported 

Outcome Measures: Use in Medical 

Product Development to Support 

Labeling Claims’’ to support the medical 

product’s effectiveness and to support 

claims in approved medical product 

labeling; the collections of information 

in 21 CFR 314.50(d)(5) and 21 CFR 

601.2 have been approved under OMB 

control numbers 0910–0001 and 0910– 

0338, respectively, and the collections 

of information in 21 CFR 201.56 and 

201.57 for medical product labeling 

have been approved under OMB control 

number 0910–0572. The collections of 

information in 21 CFR parts 50 and 56 

for protection of human subjects in 

clinical trials and institutional review 

board considerations have been 

approved under OMB control number 

0910–0130. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https:// 

www.regulations.gov. 

Dated: April 25, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–09240 Filed 4–28–22; 8:45 am] 

BILLING CODE 4164–01–P 

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. 

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 ThirdParty 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: Mariam.Lekveishvili@

hhs.gov. 

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: https://aspr.hhs.gov/ 

legal/syndna/Pages/comment.aspx. 

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. 

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 nonVerDate Sep<11>2014 17:08 Apr 28, 2022 Jkt 256001 PO 00000 Frm 00056 Fmt 4703 Sfmt 4703 E:\FR\FM\29APN1.SGM 29APN1

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3https://www.cdc.gov/labs/BMBL.html. 

4https://www.who.int/publications/i/item/ 

9789240011311. 

5Pathogenicity 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. 

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. 

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: 

https://aspr.hhs.gov/legal/syndna/ 

Pages/comment.aspx. 

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

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 


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6Providers and Third Party Vendors are 

encouraged to follow the ISA/IEC 27032:2012 & 

ISO/IEC 62443 standards for cybersecurity and 

information security. 

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 ThirdParty 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: 

• Know to whom they are distributing 

a product. 

• Know if the product that they are 

synthesizing and/or distributing 

contains, in part or in whole, SOCs. 

• Notify Customers and Principal 

Users when their order contains SOCs. 

• Implement adequate cybersecurity 

measures to protect the intellectual 

property and identity of Customers.6

• Where follow-up screening does not 

resolve concerns about an order, report 

the order to the FBI. 

• 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: 

• 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. 

• 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. 

• 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. 

• 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. 

• 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: 

• 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. 

• 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). 

• Manufacturers should provide the 

capability into their oligonucleotide 


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7Manufacturers are encouraged to follow the ISO/ 

IEC 27032:2012 & ISO ISA/IEC 62443 standards for 

cybersecurity and information security. 

8http://blast.ncbi.nlm.nih.gov/Blast.cgi. 

9https://www.trade.gov/consolidated-screeninglist. 

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. 

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. 

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 nonselect 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 ThirdParty 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 


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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. 

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: 

• Using responsible business 

practices, retain records of Customer 

orders for at least 8 years. 

• 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). 

• 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. 

• Retain screening documentation of 

all hits for at least 8 years, even if the 

order was deemed acceptable. 

• 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Allergy and 

Infectious Diseases; Notice of Closed 

Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute of 

Allergy and Infectious Diseases Special 

Emphasis Panel; NIAID Investigator Initiated 

Program Project Applications (P01 Clinical 

Trial Not Allowed). 

Date: May 31, 2022. 

Time: 10:00 a.m. to 5:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institute of Allergy and 

Infectious Diseases, National Institutes of 

Health, 5601 Fishers Lane, Room 3G41, 

Rockville, MD 20892 (Virtual Meeting). 

Contact Person: Tara Capece, Ph.D., MPH, 

Scientific Review Officer, Scientific Review 

Program, Division of Extramural Activities, 

National Institute of Allergy and Infectious 

Diseases, National Institutes of Health, 5601 

Fishers Lane, Room 3G41, Rockville, MD 

20852, 240–191–4281, capecet2@

niaid.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.855, Allergy, Immunology, 

and Transplantation Research; 93.856, 

Microbiology and Infectious Diseases 

Research, National Institutes of Health, HHS) 

Dated: April 25, 2022. 

Tyeshia M. Roberson-Curtis, 

Program Analyst, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2022–09193 Filed 4–28–22; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute on Drug Abuse; 

Notice of Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meetings. 

The meetings will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute on 

Drug Abuse Special Emphasis Panel; NIDA 

Animal Genomics Program. 

Date: May 25, 2022. 

Time: 12:00 p.m. to 2:30 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 

National Institute on Drug Abuse, 301 North 

Stonestreet Avenue, Bethesda, MD 20892 

(Virtual Meeting). 


lotter on DSK11XQN23PROD with NOTICES1