[Federal Register Volume 88, Number 169 (Friday, September 1, 2023)]
[Notices]
[Pages 60513-60516]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-18906]


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OFFICE OF SCIENCE AND TECHNOLOGY POLICY


Request for Information; Potential Changes to the Policies for 
Oversight of Dual Use Research of Concern (DURC) and the Potential 
Pandemic Pathogen Care and Oversight (P3CO) Policy Framework

AGENCY: Office of Science and Technology Policy (OSTP).

ACTION: Notice of request for information.

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SUMMARY: Life sciences research is vital for improving health outcomes 
and protecting the Nation from infectious disease threats, but a small 
subset of this research could potentially pose risk of accidents or 
misuse that could harm human health. It is important to regularly 
evaluate and update biosafety and biosecurity oversight policies to 
keep pace with new technological developments and the evolving risk 
landscape. The Office of Science and Technology Policy (OSTP) invites 
comments on potential changes to the Policies for Federal and 
Institutional Oversight of Life Sciences Dual Use Research of Concern 
(DURC) and Recommended Policy Guidance for Departmental Development of 
Review Mechanisms for Potential Pandemic Pathogen Care and Oversight 
(P3CO). These policies establish frameworks for review and oversight 
requirements for certain categories of life sciences research, namely 
research with certain pathogens and toxins, including at institutions 
that accept Federal funding for such research. These requirements are 
intended to complement activities under existing Federal regulations or 
guidelines such as the Federal Select Agent Program. OSTP requests 
comments on how potential changes to these research oversight policies 
could mitigate risks associated with DURC and research with enhanced 
potential pandemic pathogens (ePPP) while minimizing undue burden on 
institutions. The public input provided through this Request for 
Information (RFI) will inform policy evaluations and issuance of a 
revised policy (Revised Policy).

DATES: Responses are due by 11:59 p.m. Eastern Time on October 16, 
2023. Submissions received after the deadline may not be taken into 
consideration.

ADDRESSES: Comments must be submitted via the Federal eRulemaking 
Portal at regulations.gov. However, if you require an accommodation or 
cannot otherwise submit your comments via regulations.gov, please use 
the email or phone number listed under FOR FURTHER INFORMATION CONTACT. 
OSTP will not accept comments by fax or by email. To ensure that OSTP 
does not receive duplicate copies, please submit your comments only 
once. Additionally, please include the Docket ID (EOP-2023-0001) at the 
top of your comments.
    Federal eRulemaking Portal: Go to www.regulations.gov to submit 
your comments electronically. Information on how to use 
Regulations.gov, including instructions for accessing agency documents, 
submitting comments, and viewing the docket, is available on the site 
under ``FAQ'' (https://www.regulations.gov/faq).
    Privacy Note: OSTP's policy is to make all comments received from 
members of the public available for public viewing in their entirety on 
the Federal eRulemaking Portal at www.regulations.gov. Therefore, 
commenters should be careful to include in their comments only 
information that they wish to make publicly available. OSTP requests 
that

[[Page 60514]]

no proprietary information, copyrighted information, or personally 
identifiable information be submitted in response to this RFI.
    Instructions: Response to this RFI is voluntary. Each individual or 
organization is requested to submit only one response. Commenters can 
respond to one or multiple questions. Submissions are suggested to not 
exceed the equivalent of ten (10) pages in 12 point or larger font. 
Submissions should clearly indicate which questions are being 
addressed. Responses should include the name(s) of the person(s) or 
organization(s) filing the response. Responses containing references, 
studies, research, and other empirical data that are not widely 
published should include copies of or electronic links to the 
referenced materials. Responses containing profanity, vulgarity, 
threats, or other inappropriate language or content will not be 
considered.
    Please note that the U.S. Government will not pay for response 
preparation, or for the use of any information contained in the 
response. A response to this RFI will not be viewed as a binding 
commitment to develop or pursue the project or ideas discussed.

FOR FURTHER INFORMATION CONTACT: Direct questions to Asad Ramzanali, 
[email protected], or 202-456-4444.

SUPPLEMENTARY INFORMATION: Life sciences research is essential to the 
scientific advances that underpin improvements in the health and safety 
of the public, agricultural crops, and other plants, animals, and the 
environment. While life sciences research provides enormous benefits to 
society, there can be risks associated with certain subsets of work, 
typically related to biosafety and biosecurity, that can and should be 
mitigated. The United States has existing, complementary statutes, 
regulations, policies, and guidelines that address these potential 
biosafety and biosecurity risks, particularly those associated with 
research oversight and management.\1\ Together these existing 
regulatory authorities and guidelines provide a foundation to ensure 
that scientific research and innovation is safe and secure.
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    \1\ Examples include: Select Agents and Toxins Regulations (42 
CFR part 73, 9 CFR part 121, and 7 CFR part 331); National 
Institutes of Health Guidelines on Research Involving Recombinant 
and Synthetic Nucleic Acids; (https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf); Biosafety in Microbiological & 
Biomedical Laboratories (BMBL) 6th Edition (https://www.cdc.gov/labs/BMBL.html); Additional U.S. Laws, Regulations and Guidelines 
(https://www.phe.gov/s3/law/Pages/default.aspx).
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    Scientists, institutions, and the USG have gained valuable insight 
over the past decade from implementing research oversight policies such 
as the policies for oversight of DURC \2\ and the P3CO Policy 
Framework.\3\ During this time, advances in science and technology have 
occurred that present realized and potential future benefits. However, 
these advances also present potential risks of misuse. The National 
Science Advisory Board for Biosecurity (NSABB), a Federal advisory 
committee that addresses issues related to biosecurity and dual use 
research, provided recommendations in a March 2023 report \4\ to inform 
United States Government (USG) policy evaluations and the development 
of a more comprehensive and integrated framework for the oversight of 
research with pathogens and toxins that may pose significant biosafety 
or biosecurity risks. Since the release of this report, OSTP has been 
working with Federal departments and agencies to review, harmonize, and 
revise these policies in accordance with USG goals of promoting safe 
and secure biological practices and strengthening responsible conduct 
for biological research as outlined in the 2022 National Biodefense 
Strategy and Implementation Plan.\5\
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    \2\ United States Government Policy for Oversight of Life 
Sciences Dual Use Research of Concern (https://www.phe.gov/s3/dualuse/Documents/us-policy-durc-032812.pdf); United States 
Government Policy for Institutional Oversight of Life Sciences Dual 
Use Research of Concern (https://www.phe.gov/s3/dualuse/Documents/durc-policy.pdf).
    \3\ Recommended Policy Guidance for Departmental Development of 
Review Mechanisms for Potential Pandemic Pathogen Care and Oversight 
(P3CO) (https://www.phe.gov/s3/dualuse/Documents/P3CO-FinalGuidanceStatement.pdf).
    \4\ Proposed Biosecurity Oversight Framework for the Future of 
Science (nih.gov); https://osp.od.nih.gov/wp-content/uploads/2023/03/NSABB-Final-Report-Proposed-Biosecurity-Oversight-Framework-for-the-Future-of-Science.pdf.
    \5\ National Biodefense Strategy and Implementation Plan: 
https://www.whitehouse.gov/wp-content/uploads/2022/10/National-Biodefense-Strategy-and-Implementation-Plan-Final.pdf.
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    The policy review and revision process has three broad goals:
    1. Assess whether and how to merge the existing Federal DURC, 
Institutional DURC, and P3CO policies into a harmonized policy that 
addresses oversight for research with pathogens and toxins.
    2. Consider revising the scope of the Federal DURC, Institutional 
DURC, and P3CO policies to include a broader set of pathogens and 
toxins, including--but not limited to--biological select agents and 
toxins (BSAT) that impact humans or have the potential to impact 
humans.
    3. Examine ways to strengthen effective implementation of oversight 
for life sciences research on pathogens and toxins throughout the 
research lifecycle.
    The USG acknowledges that effective oversight helps maintain public 
trust in the life sciences research enterprise by demonstrating that 
the scientific community recognizes the implications of research 
conducted and is acting responsibly to protect public welfare and 
preserve national security.
    Scope: OSTP invites comment from any interested stakeholders. In 
particular, OSTP is interested in input from research institutions, 
including both domestic and international entities, currently subject 
to the PC3O Policy or the DURC policies or that may be subject to the 
revised scope of a potential policy update, researchers within those 
institutions, scientific and professional organizations, and 
organizations representing diverse interests across the U.S. research 
ecosystem.
    Information Requested: Respondents may provide information for one 
or more of the topics included below. Respondents are asked to note the 
corresponding number/s to which responses pertain.
    1. The NSABB recommended that USG develop an integrated approach to 
oversight of research that raises significant biosafety and biosecurity 
concerns, including ePPP research and DURC (Recommendation 1). By 
merging the existing Federal DURC, Institutional DURC, and P3CO 
policies into a harmonized policy, a merged policy could potentially 
adopt the institutional applicability outlined in the Institutional 
DURC policy framework, making the following entities subject to a 
Revised Policy:
     U.S. Government departments and agencies that fund, 
sponsor, or conduct life sciences research.
     Institutions within the United States or its territories 
that both:
    [ssquf] Receive U.S. Government funds to conduct or sponsor life 
sciences research; and,
    [ssquf] Conduct or sponsor research that is within the revised 
scope, regardless of the source of the funding for the specific 
project.
     Institutions outside of the United States that receive 
U.S. Government funds to conduct or sponsor research that falls under 
the scope.
    (a) What are the anticipated benefits and challenges of applying a 
Revised Policy, inclusive of both DURC and

[[Page 60515]]

ePPP research, to the scope of entities outlined above?
    (b) What are the anticipated benefits and challenges of 
investigators and institutions having primary responsibility for 
identification of both DURC and ePPP research?
    (c) What types of resources or tools would be useful for 
researchers and institutions to determine if their research falls into 
a revised policy scope that is risk-based rather than list-based, and 
adequately conduct risk assessments to identify DURC and ePPP research?
    2. Currently, the scope of the DURC policies is research that uses 
one or more of 15 listed agents or toxins and that produces, or is 
anticipated to produce, any of seven listed experimental effects. The 
NSABB recommended that the scope of research requiring review for 
potential DURC should include research that directly involves any 
human, animal, or plant pathogen, toxin, or agent that is reasonably 
anticipated to result in one or more of the seven experimental effects 
outlined in the DURC policy \6\ (Recommendation 10.1).
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    \6\ United States Government Policy for Oversight of Life 
Sciences Dual Use Research of Concern (https://www.phe.gov/s3/dualuse/Documents/us-policy-durc-032812.pdf); United States 
Government Policy for Institutional Oversight of Life Sciences Dual 
Use Research of Concern (https://www.phe.gov/s3/dualuse/Documents/durc-policy.pdf).
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    a. Considering the diversity of federally-funded research settings 
and portfolios, how would adoption of NSABB's Recommendation 10.1 
affect policy implementation and research programs at the institutional 
level?
    b. Rather than including any pathogen within the scope of DURC 
review, one possible modification of Recommendation 10.1 would be to 
include DURC experiments that utilize:
    i. HHS and Overlap Biological Select Agent and Toxins (BSAT) List 
\7\ and/or
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    \7\ Select Agents and Toxins Regulations (42 CFR part 73, 9 CFR 
part 121, and 7 CFR part 331).
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    ii. Pathogen risk group (RG) classification of 3 or 4 \8\ and/or
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    \8\ Risk groups as defined in ``NIH Guidelines for Research 
Involving Recombinant or Synthetic Nucleic Acid Molecules'' (https://osp.od.nih.gov/wp-content/uploads/2019_NIH_Guidelines.htm).
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    iii. Any pathogen where the conduct of work (e.g., one of the DURC 
experimental categories) would require biosafety level 3 or 4 
containment.
    Would a modification of Recommendation 10.1, in line with the 
outlined scope of pathogens above, be useful for policy implementation? 
What specific benefits, challenges, and/or gaps are anticipated by this 
revised scope?
    c. Are there other risk-based approaches that would expand the 
scope beyond the current list of 15 agents and toxins provided in the 
DURC policy that would facilitate the identification of research that 
poses significant risks by investigators and institutions while not 
resulting in undue burdens?
    d. Given the possible revised scope of research requiring review 
for potential DURC, what modifications, if any, to the current DURC 
policy list of 7 experimental effects should be considered for a 
Revised Policy that captures appropriate research without hampering 
research progress?
    e. What resources or tools would be valuable to assist with 
implementation of a DURC policy with a scope that is revised to include 
more than the current list of 15 agents and toxins?
    3. A PPP is currently defined in the P3CO policy framework \9\ as: 
``a pathogen that satisfies both of the following: 1. It is likely 
highly transmissible and likely capable of wide and uncontrollable 
spread in human populations; and 2. It is likely highly virulent and 
likely to cause significant morbidity and/or mortality in humans.''
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    \9\ Recommended Policy Guidance for Departmental Development of 
Review Mechanisms for Potential Pandemic Pathogen Care and Oversight 
(P3CO) (https://www.phe.gov/s3/dualuse/Documents/P3CO-FinalGuidanceStatement.pdf).
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    The NSABB recommended that the definition of PPP be modified to: 
(1) Likely moderately or highly transmissible and likely capable of 
wide and uncontrollable spread in human populations; and/or (2) Likely 
moderately or highly virulent and likely to cause significant morbidity 
and/or mortality in humans; and, in addition (3) Likely to pose a 
severe threat to public health, the capacity of public health systems 
to function, or national security'' (Recommendation 2).
    (a) How would the change in the definition of PPP affect the 
overall scope of a Revised Policy and its subsequent implementation?
    (b) One possible modification to the NSABB PPP definition is to 
specify a respiratory route of transmission within clause (1). Would 
that definition of PPP be an appropriate scope to mitigate risks and 
enhance effective implementation?
    (c) Do you have additional suggestions to modify the PPP definition 
to mitigate the most significant risks not currently addressed and 
enhance effective implementation, while limiting negative or unintended 
consequences and burden on researchers, institutions, and the Federal 
government?
    (d) Are there characteristics related to human pathology, pathogen 
characteristics, or other features that would be helpful to clarify the 
intent of ``moderately virulent''? Are there characteristics related to 
human pathology that would be helpful to clarify the intent of 
``moderately transmissible''?
    4. A Government Accountability Office (GAO) report from January 
2023 \10\ recommended that the Department of Health and Human Services 
funding agencies should develop and document a standard to define 
``reasonably anticipated'' to ensure consistency in identifying 
research that falls within scope of a Revised Policy. One possible 
definition of ``reasonably anticipated'' is:
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    \10\ Public Health Preparedness: HHS Could Improve Oversight of 
Research Involving Enhanced Potential Pandemic Pathogens. (GAO-23-
105455).
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    `` `Reasonably anticipated' describes an assessment of an outcome 
that an individual with scientific expertise relevant to the research 
in question would expect this outcome to occur with a non-trivial 
likelihood. It does not require high confidence that the outcome will 
definitely occur and excludes experiments in which an expert would 
anticipate the outcome to be technically possible, but highly 
unlikely.''
    (a) Does this definition of ``reasonably anticipated'' provide 
additional clarity to ensure greater consistency in identifying 
research that falls within scope of the Revised Policy? What 
modifications to this definition (if any) would be most helpful?
    5. NSABB recommends the removal of blanket exclusions for research 
activities associated with surveillance and vaccine development or 
production for research with ePPPs (Recommendation 3).
    (a) Should exemptions for certain activities be included in a 
Revised Policy?
    (b) What are the benefits and drawbacks of including exemptions for 
domestic and international pandemic preparedness, biosafety, 
biosecurity, and global health security?
    (c) If exemptions are included, how could they be bounded to 
maximize safety and security and minimize negative impact on domestic 
and global public health including outbreak and pandemic preparedness 
and response? For example, would vaccine research and development 
activities be unjustifiably impeded if the current P3CO policy 
framework exemption for ``Activities associated with developing and 
producing vaccines, such as generation of high growth strains'' was 
either removed completely or modified

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to ``Research on PPPs directly associated with testing and/or producing 
vaccines, such as generation of high growth strains''?
    6. NSABB recommends that continued assessment of the risks and 
benefits associated with advances and applications of bioinformatics, 
modeling, and other in silico experimental approaches and research 
involving genes from or encoding pathogens, toxins, or other agents 
must inform future evaluations of the scope of research oversight 
policies to help ensure that associated risks are appropriately 
identified and managed. (Recommendation 10.2). This type of research is 
not currently included in the DURC and ePPP oversight policies.
    (a) Is there a subset of such in silico research that should 
require risk assessment and review in a Revised Policy, and if so, how 
should this research be defined so that the Policy captures the 
appropriate research without hampering activities with limited 
biosecurity risks?
    (b) One possible way to define this category of in silico research 
within a Revised Policy would be to include experiments that are 
reasonably anticipated to:
    ``(i) Develop in silico models that directly enable the predictive 
design of an enhanced potential pandemic pathogen or novel pathogen or 
toxin covered under a Revised Policy that could be constructed via 
genomic editing or de novo synthesis; and/or
    (ii) Develop a dataset(s) connecting nucleic acid or amino acid 
sequences with experimentally-determined pathogenic functions in a 
manner sufficient to enable the development of in silico models 
described in (i).''
    If a new category of research, similar to the examples provided 
above, were to require risk assessment and review in a Revised Policy, 
what would be the benefits and challenges with implementation?

    Dated: August 28, 2023.
Stacy Murphy,
Deputy Chief Operations Officer/Security Officer.
[FR Doc. 2023-18906 Filed 8-31-23; 8:45 am]
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