[Federal Register Volume 88, Number 42 (Friday, March 3, 2023)]
[Rules and Regulations]
[Pages 13322-13328]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-04323]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 73

[Docket No. CDC-2021-0119]
RIN 0920-AA79


Possession, Use, and Transfer of Select Agents and Toxins--
Addition of SARS-CoV/SARS-CoV-2 Chimeric Viruses Resulting From Any 
Deliberate Manipulation of SARS-CoV-2 To Incorporate Nucleic Acids 
Coding for SARS-CoV Virulence Factors to the HHS List of Select Agents 
and Toxins

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Final rule.

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SUMMARY: The Centers for Disease Control and Prevention (CDC) located 
within the Department of Health and Human Services (HHS) has amended 
the select agents and toxins regulations to add SARS-CoV/SARS-CoV-2 
chimeric viruses resulting from any deliberate manipulation of SARS-
CoV-2 to incorporate nucleic acids coding for SARS-CoV virulence 
factors to the list of HHS select agents and toxins. With this final 
rule, regulated entities are required to obtain prior approval from CDC 
to conduct deliberate manipulation of SARS-CoV-2 to incorporate nucleic 
acids coding for SARS-CoV virulence factors because these chimeric 
viruses have the potential to pose a severe threat to public health and 
safety.

DATES: Effective March 3, 2023.

FOR FURTHER INFORMATION CONTACT: Samuel S. Edwin Ph.D., Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE, Mailstop H21-4, Atlanta, Georgia 
30329. Telephone: (404) 718-2000. Email: [email protected].

SUPPLEMENTARY INFORMATION: The final rule is organized as follows:

I. Background and Legal Authority
II. Summary of Public Comments and Response to Comments
III. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. The Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. E.O. 12988: Civil Justice Reform
    E. E.O. 13132: Federalism
    F. Plain Language Act of 2010

I. Background and Legal Authority

    On November 17, 2021, HHS/CDC published an interim final rule (IFR) 
(86 FR 64075) that amended the select agents and toxins regulations to 
add SARS-CoV/SARS-CoV-2 chimeric viruses resulting from any deliberate 
manipulation of SARS-CoV-2 to incorporate nucleic acids coding for 
SARS-CoV virulence factors \1\ to the list of HHS select agents and 
toxins. The IFR also required the regulated entity obtain prior 
approval from CDC to conduct deliberate manipulation of SARS-CoV-2 to 
incorporate nucleic acids coding for SARS-CoV virulence factors and 
vice versa, because these chimeric viruses have the potential to pose a 
severe threat to public health and safety.
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    \1\ Virulence factors are genes or gene modifications that are 
associated with virulence. Virulence factors determine a pathogen's 
ability to replicate, modify host defenses, spread within the host 
and to other individuals, and produce products that are toxic to the 
host. These factors may impact infectivity, transmissibility, 
immunity, vaccine sensitivity, pathogenicity, and disease severity. 
Viral virulence factors (e.g., structures, molecules, and regulatory 
systems) can impact features of viral pathogenicity including 
infectivity, replication, host tropism, the ability to evade the 
host response, and/or resistance to medical countermeasures, among 
other viral characteristics.
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    Legal Authority:

[[Page 13323]]

    HHS/CDC is promulgating this rule under the authority of sections 
201-204 and 221 of Title II of Public Law 107-188(42 U.S.C. 262a).
    Title II, Subtitle A, of the Public Health Security and 
Bioterrorism Preparedness and Response Act of 2002, (42 U.S.C. 262a), 
requires HHS to regulate the possession, use, and transfer of 
biological agents or toxins that have the potential to pose a severe 
threat to public health and safety (select agents and toxins). 
Accordingly, HHS has promulgated regulations requiring individuals or 
entities that possess, use, or transfer select agents and toxins to 
register with CDC. See 42 CFR part 73.

II. Summary of Public Comments and Response to Comments

    The IFR solicited public comments, based on the following criteria, 
regarding whether SARS-CoV/SARS-CoV-2 chimeric viruses resulting from 
any deliberate manipulation of SARS-CoV-2 to incorporate nucleic acids 
coding for SARS-CoV virulence factors should be regulated as a select 
agent:
    (1) The effect on human health of exposure to the agent;
    (2) The degree of contagiousness of the agent and the methods by 
which the agent is transferred to humans;
    (3) The availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent any illness resulting from infection 
by the agent; and
    (4) Any other criteria, including the needs of children and other 
vulnerable populations that the commenter considers appropriate.
    In addition, HHS/CDC invited comments specifically on any virulence 
factors found in SARS-CoV that would increase virulence in SARS-CoV-2.
    HHS/CDC received three comments regarding the IFR.
    Comment: One commenter, from academia, asked whether there is a 
need to create a new rule specific to SARS-CoV/SARS-CoV-2 chimeras 
because the regulation of the chimeras is covered in the ``Guidance on 
the Regulation of Select Agents and Toxin Nucleic Acids'' document. The 
commenter also stated that they did not support the addition of SARS-
CoV/SARS-CoV-2 chimeric viruses to the HHS select agents list because 
the action would be an incremental step that could result in decreased 
scientific advances and thus reduced preparedness at the detriment of 
public health broadly. Finally, the commenter stated that the IFR does 
not adhere to federal standards set forth for rulemaking, and the goals 
of the IFR can be accomplished using existing regulatory 
infrastructure.
    Response: HHS/CDC made no changes based on the comment. The 
``Guidance on the Regulation of Select Agents and Toxin Nucleic Acids'' 
document includes information provided by HHS/CDC to assist registered 
entities with achieving regulatory compliance with the select agent and 
toxin regulations. SARS-CoV-2 is not a select agent and, previously, 
the select agent and toxins regulations only applied to nucleic acids 
capable of producing infectious select virus, which would be the 
majority of the genome and not a gene in isolation. The select agent 
and toxins regulations did not apply to specific genes or nucleic acids 
in isolation or non-select agent viruses. The Guidance document 
includes information on complying with the regulations for regulated 
genetic material, not for unregulated material or the genetic 
components of unregulated material. Further, a guidance document does 
not have the force and effect of law.
    The basis for listing SARS-CoV/SARS-CoV-2 chimeric viruses 
resulting from any deliberate manipulation of SARS-CoV-2 to incorporate 
nucleic acids coding for SARS-CoV virulence factors as an HHS select 
agent is that:
     Virulence factors from SARS-CoV including, but not limited 
to, those involved in inflammasome activation during infection could be 
introduced into SARS-CoV-2 and create a chimeric virus with increased 
virulence.
     There is significant potential risk of merging a select 
agent virus and pandemic virus and creating a chimeric virus with the 
transmissibility of SARS-CoV-2 and the pathogenicity of SARS-CoV.
    Comment: Two commenters, one from academia and one from industry, 
requested more robust definitions or guidance to clarify ``virulence 
factor'' and ``chimera'' to explicitly define ``virulence factors of 
concern.''
    Response: HHS/CDC agreed with the commenters.
    Virulence factors are genes or gene modifications that are 
associated with virulence. Virulence factors determine a pathogen's 
ability to replicate, modify host defenses, spread within the host and 
to other individuals, and produce products that are toxic to the host. 
These factors may impact infectivity, transmissibility, immunity, 
vaccine sensitivity, pathogenicity, and disease severity.
    SARS-CoV/SARS-CoV-2 chimeric viruses result from any intentional 
manipulation of SARS-CoV-2 to include nucleic acids coding for SARS-CoV 
virulence factors. They are select agents and entities are required to 
obtain prior approval from CDC's Division of Select Agents and Toxins 
(DSAT) to possess, use, or transfer these agents. Additionally, 
experiments to create these chimeric viruses must be submitted to the 
Federal Select Agent Program for prior approval.
    Additional Guidance has also been developed that provides examples 
of virulence factors found in SARS-CoV/SARS-CoV-2 and provides examples 
of experiments that may meet the definition of a restricted experiment. 
Guidance can be found at the Supporting Materials tab of the docket and 
at www.selectagents.gov.

II. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    HHS/CDC has examined the impacts of the final rule under Executive 
Order 12866, Regulatory Planning and Review (58 FR 51735, October 4, 
1993) and Executive Order 13563, Improving Regulation and Regulatory 
Review, (76 FR 3821, January 21, 2011). Both Executive Orders direct 
agencies to evaluate any rule prior to promulgation to determine the 
regulatory impact in terms of costs and benefits to United States 
populations and businesses. Further, together, the two Executive Orders 
set the following requirements: quantify costs and benefits where the 
new regulation creates a change in current practice; qualitatively 
describe costs and benefits; choose approaches that maximize net 
benefits; and support regulations that protect public health and 
safety. HHS/CDC has analyzed the final rule as required by these 
Executive Orders and has determined that it is consistent with the 
principles set forth in the Executive Orders and the Regulatory 
Flexibility Act, as amended by the Small Business Regulatory 
Enforcement Fairness Act (SBREFA). We anticipate that the rule will 
create minimal cost impact, but it could potentially result in benefits 
to the extent that it could reduce the probability of an accidental or 
intentional release of the SARS-CoV/SARS-CoV-2 chimeric viruses 
resulting from any deliberate manipulation of SARS-CoV-2 to incorporate 
nucleic acids coding for SARS-CoV virulence factors. Such an event is a 
low probability but potentially an extremely high-cost outcome. This 
rule has been determined to be a ``significant regulatory action'' as 
defined by Executive Order 12866, section 3(f). However, this rule is 
not an economically significant regulatory action, as it will not have 
an annual effect on the economy of $100 million or more or adversely 
affect in a material way the economy, a sector of the

[[Page 13324]]

economy, productivity, competition, jobs, the environment, public 
health or safety, or State, local, or tribal governments or 
communities. This rule has been reviewed by the Office of Management 
and Budget (OMB) pursuant to Executive Orders 12866 and 13563.
    This regulatory impact section presents the anticipated costs and 
benefits that are quantified where possible. Where quantification is 
not possible, a qualitative discussion is provided of the costs and/or 
benefits that HHS/CDC anticipates from this regulation.
Analysis of Costs and Benefits
Costs
    As of September 7, 2022, CDC has not received any requests from 
already registered entities to amend their registration to work with 
this agent. In addition, CDC has not received any applications from new 
entities to register with CDC and work with this agent. Thus, as of 
this date, CDC has not observed any costs associated with the IFR or 
for this final rule. If an entity chooses to work with this agent in 
the future, the below estimates of costs and benefits would apply.
    In the following analysis, HHS/CDC looked at two different types of 
entities that may incur additional costs because of this rulemaking. 
They are described below as: (1) A registered entity that applies to 
amend its registration to add the agent; or (2) An unregistered entity 
that seeks to register to work with the agent. HHS/CDC also estimated 
the costs for CDC to work with an entity to amend its registration or 
to register because of this final rule. All costs and benefits for this 
analysis are reported in 2020 U.S. dollars. Further, HHS/CDC assumed 
that all costs would be incurred within a one-year time period 
corresponding to the expected period of time in which experiments with 
these chimeric viruses would be performed.
    (1) A registered entity that applies to amend its registration for 
the agent.
    As of September 7, 2022, none of the entities already registered 
with CDC to work with select agents and toxins have amended their 
registries to work with this agent. This final rule requires an entity 
to amend its registration using relevant portions of APHIS/CDC Form 1 
(Registration for Possession, Use, and Transfer of Select Agents and 
Toxins). The estimated time to apply for an amendment using this form 
is one hour for one select agent (Table 1). To account for uncertainty 
in the estimate, a range of 75% to 125% of this estimate is used as the 
lower bound and the upper bound estimates, respectively. HHS/CDC used a 
median hourly respondent labor rate of $49.83 for managerial staff 
(occupation code 11-1021 general and operations manager) as the upper 
bound estimate and $16.98 for clerical staff (occupation code 43-9061 
office clerks, general) as the lower bound estimate. These rates were 
obtained from the Bureau of Labor Statistics, 2020 Occupational 
Employment Statistics Survey by Occupation (http://www.bls.gov/oes/). 
HHS/CDC assumed that the hourly burden would be evenly split between 
managerial staff and clerical staff as a base case. The hourly 
respondent labor rate for the base case was the average of these two 
figures ($33.41 per hour). The base salary is multiplied by an overhead 
multiplier of 100% to account for non-wage benefits and other overhead 
costs for supporting each employee. The estimated cost per already 
registered entity to amend their registration for this agent was $66.81 
(range: $25.47 to $124.58).
    The additional time for HHS/CDC's review of the amended 
registration for the already registered entities will also generate 
additional costs. HHS/CDC estimated that one staff at the GS-13 (step 
5) level is required to review the amended registration application. 
The hourly wage of a Federal Employee at GS-13 (step 5) from the 2020 
General Schedule (GS) locality pay table for Atlanta (where CDC has its 
headquarters), $52.20 per hour, was used to estimate the hourly base 
salary (Table 1). The base salary is multiplied by an overhead 
multiplier of 100% to account for non-wage benefits and other overhead 
costs for supporting each employee. HHS/CDC estimated that the review 
of the amendment application takes two hours (range: 1.5 hours to 2.5 
hours) for HHS/CDC. The cost of having HHS/CDC amend an entity's 
registration for the agent is estimated to be $209 (range: $157 to 
$261).

        Table 1--Estimated Costs per Already Registered Entity To Amend Their Registration for the Agent
                                               [2020 U.S. dollars]
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                                                                     Base case      Lower bound     Upper bound
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Entity
    Number of employees working on the amendment (A)............               1               1               1
    Hourly wage (B).............................................          $33.41          $16.98          $49.83
    Overhead multiplier (C).....................................            100%            100%            100%
    Time required per staff (hours) (D).........................               1            0.75            1.25
    Estimated costs per entity (E) = (A) x (B) x ((C) + 1) x (D)          $66.81          $25.47         $124.58
HHS/CDC
    Number of staff required for the review of the amendment                   1               1               1
     application (F)............................................
    Hourly wage (G).............................................          $52.20          $52.20          $52.20
    Overhead multiplier (H).....................................            100%            100%            100%
    Time required for the amendment per staff (hour) (I)........               2             1.5             2.5
    Estimated costs per entity (J) = (F) x (G) x ((H) + 1) x (I)            $209            $157            $261
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    (2) An unregistered entity will apply to register in order to work 
with the agent (The entity is NOT currently registered).
    As of September 7, 2022, no unregistered entities notified CDC, as 
required by the IFR, that they plan to work with select agents and 
toxins and have amended their registries to work with this agent. For 
unregistered entities, which will register for working with the agent, 
HHS/CDC expects per facility costs to vary based on the entity type, 
laboratory size, and biosafety level (BSL). The first-year cost per 
facility for a medium-size BSL-\2/3\ research institute to register to 
work with the agent is estimated at $59,600. This estimate from the 
Regulatory Impact Analysis for the 2005 Select Agent Regulations Final 
Rule \2\ was adjusted to 2020 U.S. dollars value using the Consumer 
Price Index

[[Page 13325]]

(CPI) Inflation Calculator.\3\ This results in an adjusted value of 
$78,994 for each additional registered, medium-size BSL-\2/3\ research 
institute laboratory (range: $41,087 to $936,528) (Table 2).
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    \2\ Regulatory Impact Analysis, 42 CFR part 73: Possession, Use, 
and Transfer of Select Agents and Toxins Final Rule, Centers for 
Disease Control and Prevention, February 3, 2005.
    \3\ https://www.bls.gov/data/inflation_calculator.htm.
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    Two HHS/CDC staff, GS-12 (step 5) would perform the initial review 
of the application with the final review conducted by GS-13 (step 5). 
HHS/CDC estimated the upper bound hourly wage for a Federal Employee at 
the GS-13 (step 5) from the 2020 General Schedule (GS) locality pay 
table for Atlanta, $52.20 per hour. The lower bound was estimated using 
the hourly wage for a GS-12 (step 5) employee, $43.90 per hour (Table 
2). The mean of these two wage rates was used as the base case. The 
base salary is multiplied by an overhead multiplier of 100% to account 
for non-wage benefits and other overhead costs for supporting each 
employee. HHS/CDC estimated that the review of an application would 
take two hours (range: 1.5 hours to 2.5 hours). The estimated HHS/CDC 
cost per entity to review an application was $384 (range: $263 to 
$522).
    Registration also will require an inspection by CDC to assess the 
applicant's ability to comply with the select agents and toxins 
regulations. HHS/CDC assumed that two CDC investigators, GS-12 (step 5) 
or GS-13 (step 5) would travel to the laboratory and that the visit 
would require 3 days (1 day for outbound trip to the laboratory, 1 day 
for the investigation, and 1 day for the return trip) and 8 work hours 
per day inclusive of report writing. The estimated travel costs were 
$1,200 per trip for two CDC investigators. The total estimated costs 
associated with laboratory investigation per entity are $5,183 (range: 
$5,414 to $6,211). The estimated total costs for CDC per registered 
entity are $6,197 (range: $5,678 to $6,733) for application review and 
laboratory investigation.
    HHS/CDC assumed that all costs associated with the final rule will 
occur during the first year after the final rule is published and that 
the final rule will not affect costs for registered entities in 
following years. This may result in an over-estimate of the costs to 
register an entity if that entity were to decide to continue to work 
with select agents and toxins in future years.

                 Table 2--Estimated Costs per Entity, Which Will Register To Work With the Agent
                                               [2020 U.S. dollars]
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                                                                     Base case      Lower bound     Upper bound
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Entity
    Estimated costs for registration per entity (A) \4\.........         $78,994         $41,087        $936,528
HHS/CDC
    Application review (time) costs per entity..................
        Number of staff required for the review of the                         2               2               2
         application (B)........................................
        Hourly wage (C).........................................          $48.05          $43.90          $52.20
        Overhead multiplier (D).................................            100%            100%            100%
        Time required for the application per staff (hour) (E)..               2             1.5             2.5
        Estimated costs associated with a registration                      $384            $263            $522
         application review (F) = (B) x (C) x ((D) + 1) x (E)...
    Lab investigation costs per entity..........................
        Number of staff required for the lab investigation (G)..               2               2               2
        Hourly wage (H).........................................          $48.05          $43.90          $52.20
        Overhead multiplier (I).................................            100%            100%            100%
        Time required for the amendment per staff (hour) (J)....              24              24              24
        Estimated time costs for lab investigation per entity             $4,613          $4,214          $5,011
         (K) = (G) x (H) x ((I) + 1) x (J)......................
        Number of trips required per lab investigation (L)......               1               1               1
        Travel-associated costs per trip (M)....................          $1,200          $1,200          $1,200
        Travel-associated costs per lab investigation (N) = (L)           $1,200          $1,200          $1,200
         x (M)..................................................
        Estimated costs associated with lab investigation (O) =           $5,813          $5,414          $6,211
         (K) + (N)..............................................
                                                                 -----------------------------------------------
    Estimated total costs for HHS/CDC per entity (P) = (F) + (O)          $6,197          $5,678          $6,733
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    As of September 7, 2022, none of the entities already registered 
with CDC to work with select agents and toxins have amended their 
registries to work with this agent. The base case is the assumption for 
the final rule that only one registered entity would amend their 
registration for the agent and no unregistered entities would undergo 
the registration process to work with this agent. The lower bound is 
the same as the base case. For the upper bound, HHS/CDC assumed that 
two registered entities would amend their registration to work with 
this agent and one unregistered entity would undergo the registration 
process to work with this agent (Table 3).
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    \4\ The estimates from the Regulatory Impact Analysis for the 
2005 Select Agent Regulations Final Rule (Regulatory Impact 
Analysis, 42 CFR Part 73: Possession, Use, and Transfer of Select 
Agents and Toxins Final Rule, Centers for Disease Control and 
Prevention, February 3, 2005) was adjusted to 2020 U.S. dollars 
value using the Consumer Price Index (CPI) Inflation Calculator 
(https://www.bls.gov/data/inflation_calculator.htm).

                      Table 3--Numbers of Entities That Will Be Affected by the Final Rule
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                                                                     Base case      Lower bound     Upper bound
----------------------------------------------------------------------------------------------------------------
Registered entities, which want to amend the registration for                  1               1               2
 the agent......................................................
Unregistered entities, which want to be registered for the agent               0               0               1
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[[Page 13326]]

    The total costs associated with the final rule for the entities 
working with this agent are estimated at $67 (range: $25 to $936,777) 
(Table 4).

  Table 4--Total Estimated Costs for Entities To Work With the SARS-CoV/SARS-CoV-2 Chimeric Viruses Associated
                                               With the Final Rule
                                               [2020 U.S. dollars]
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                                                                     Base case      Lower bound     Upper bound
----------------------------------------------------------------------------------------------------------------
Registered entities, which want to amend their registrations to
 work with the agent
    Number of entities (A)......................................               1               1               2
    Estimated costs per entity (B)..............................             $67             $25            $125
    Estimated costs (C) = (A) x (B).............................             $67             $25            $249
Unregistered entities, which would pursue registration to work
 with this agent
    Number of entities (D)......................................               0               0               1
    Estimated costs per entity (E)..............................         $78,994         $41,087        $936,528
    Estimated costs (F) = (D) x (E).............................              $0              $0        $936,528
                                                                 -----------------------------------------------
        Total estimated costs for entities to comply with HHS/               $67             $25        $936,777
         CDC requirements to work with this agent (G) = (C) +
         (F)....................................................
----------------------------------------------------------------------------------------------------------------

    The total estimated costs for HHS/CDC to review applications to 
amend registrations or to register unregistered entities to work with 
this agent, which are associated with the final rule are $209 (range: 
$156 to $7,255) (Table 5).

 Table 5--Total Estimated Costs for HHS/CDC To Review Entities' Applications To Amend Their Registrations or To
 Register Unregistered Entities To Work With the SARS-CoV/SARS-CoV-2 Chimeric Viruses Associated With the Final
                                                      Rule
                                               [2020 U.S. dollars]
----------------------------------------------------------------------------------------------------------------
                                                                     Base case      Lower bound     Upper bound
----------------------------------------------------------------------------------------------------------------
Registered entities, which want to amend the registration for
 the agent
    Number of entities (A)......................................               1               1               2
    Estimated costs per entity (B)..............................            $209            $157            $261
    Estimated costs (C) = (A) x (B).............................            $209            $157            $522
Unregistered entities, which want to be registered for the agent
    Number of entities (D)......................................               0               0               1
    Estimated costs per entity (E)..............................          $6,197          $5,678          $6,733
    Estimated costs (F) = (D) x (E).............................              $0              $0          $6,733
                                                                 -----------------------------------------------
        Total estimated costs for HHS/CDC (G) = (C) + (F).......            $209            $156          $7,255
----------------------------------------------------------------------------------------------------------------

Summary of Costs
    In summary, the total estimated costs associated with the final 
rule are $276 (range: $182 to $944,032) (Table 6). All costs are one-
time costs, and the follow-up costs are assumed to be minimal. The 
upper bound cost estimate includes the cost to register an unregistered 
entity to work with select agents and toxins, which may not be pursued. 
Even this upper bound estimate is less than $1 million.

Table 6--Summary of Total Estimated Costs Associated With the Final Rule To Add the SARS-CoV/SARS-CoV-2 Chimeric
 Viruses Resulting From Any Deliberate Manipulation of SARS-CoV-2 To Incorporate Nucleic Acids Coding for SARS-
                       CoV Virulence Factors to HHS/CDC's List of Select Agents and Toxins
                                               [2020 U.S. dollars]
----------------------------------------------------------------------------------------------------------------
                                                                     Base case      Lower bound     Upper bound
----------------------------------------------------------------------------------------------------------------
Total estimated costs to entities working with the agent (A)....             $67             $25        $936,777
Total estimated costs to HHS/CDC (B)............................             209             157           7,255
Total estimated costs (C) = (A) + (B)...........................             276             182         944,032
----------------------------------------------------------------------------------------------------------------

    Benefits:
    The agents and toxins placed on the HHS/CDC select list have the 
potential to pose severe threats to public health and safety. The 
benefits of the HHS/CDC rule derive from the strengthened prevention 
against the accidental or intentional release of SARS-CoV/SARS-CoV-2 
chimeric viruses resulting from any deliberate manipulation of SARS-
CoV-2 to incorporate nucleic acids coding for SARS-CoV virulence 
factors. The provisions of this rule will reduce the risk of human 
exposure to these chimeric viruses by ensuring that laboratory 
facilities employ adequate security and safety measures including:
    (1) Develop and implement a written biosafety plan and measures in 
place that are commensurate with the risk of the agent given its 
intended use,

[[Page 13327]]

    (2) Develop and implement a written security plan and measures in 
place that are sufficient to safeguard the agent against unauthorized 
access, theft, loss, or release,
    (3) Develop and implement a written incident response plan based 
upon a site-specific risk assessment,
    (4) Have an adequate training program for handling select agents, 
and
    (5) Maintain an inventory of select agents.
    The benefits to public health and safety from the implementation of 
the rule result from the strengthened prevention of either accidental 
or intentional release of the modification of a non-select agent with 
nucleic acids from a select agent, however, the benefits are difficult 
to quantify. The cost of such an event in morbidity and mortality could 
be very high. In addition, a release of such a chimera or chimeric 
virus that is composed of the modification of a non-select agent with 
nucleic acids from a select agent may require a complicated and 
expensive emergency response effort. This effort could include 
extensive public health measures, such as quarantine, preventative 
treatment, and diagnostic testing for large numbers of potentially 
exposed persons, and extensive decontamination. Substantial costs could 
be incurred by hospitals and other medical facilities and institutions 
of government at all levels. A release, or widespread fear of one, also 
would create significant secondary effects. It could disrupt business, 
transportation, and many other aspects of normal behavior, on both a 
short-term and potentially a long-term basis.
    HHS/CDC is unable to predict the potential infectiousness or 
virulence of the SARS-CoV/SARS-CoV-2 chimeric viruses that are 
regulated according to the provisions of this final rule. However, 
implementation of the final rule will provide a means of determining 
where the modification of a non-select agent with nucleic acids from a 
select agent is taking place; ensure that transfer, storage, and use of 
the agent can be tracked; provide for the screening of personnel with 
access to such agent; and require that entities in possession of such 
agent develop and implement effective means of biosafety and physical 
security. The benefit of these provisions is a reduced likelihood of 
either an accidental or intentional release of the agent and the 
consequent avoidance of costs associated with such a release.
    This final rule addresses a risk associated with substantial 
economic consequences. The likelihood of these negative outcomes under 
a baseline scenario of no further regulatory action are low but also 
highly uncertain and difficult to characterize. Based on this analysis, 
HHS/CDC believes the expected benefits of this final rule are likely to 
exceed the estimated costs associated with this final rule.

B. The Regulatory Flexibility Act (RFA), as Amended by the Small 
Business Regulatory Enforcement Fairness Act (SBREFA)

    We have examined the impacts of the final rule under the Regulatory 
Flexibility Act (5 U.S.C. 601-612). The Regulatory Flexibility Act 
(RFA), as amended by the Small Business Regulatory Enforcement Fairness 
Act (SBREFA), requires agencies to analyze regulatory options that 
would minimize any significant economic impact of a rule on small 
entities. Based on our current knowledge of who may possess this agent, 
we certify that this final rule will not have a significant economic 
impact on a substantial number of small entities within the meaning of 
the RFA.
    This regulatory action is not a major rule as defined by section 
804 of the SBREFA. This final rule will not result in an annual effect 
on the economy of $100,000,000 or more; a major increase in cost or 
prices; or significant adverse effects on competition, employment, 
investment, productivity, innovation, or on the ability of United 
States-based companies to compete with foreign-based companies in 
domestic and export markets.

C. Paperwork Reduction Act of 1995

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), the information collection or 
recordkeeping requirements included in the current regulations are 
approved by the Office of Management and Budget (OMB) under OMB Control 
Number 0920-0576, expiration date 1/31/2024. This rulemaking includes a 
request for a nonmaterial/non-substantive change to account for small, 
potential increases in burden for a limited number of entities to 
submit amendments to their registrations.
    We estimate that only one to five registered entities may add the 
select agent to their registration or transfer the select agent to 
another registered entity. Therefore, we calculate that there is no 
increase in the number of respondents that need to apply for 
registration. This represents a non-material/non-substantive change in 
burden for respondents to this approved information collection. The 
burden is outlined in the table below.

----------------------------------------------------------------------------------------------------------------
                                                                     Number of    Average burden
            Section                 Form name        Number of     responses per   per response    Total burden
                                                    respondents     respondent      (in hours)         hours
----------------------------------------------------------------------------------------------------------------
Section 7.....................  Application for                3               1               5              15
                                 Registration.
----------------------------------------------------------------------------------------------------------------

D. E.O. 12988: Civil Justice Reform

    This rule has been reviewed under E.O. 12988, Civil Justice Reform. 
Once the rule was in effect, HHS/CDC notes that: (1) All State and 
local laws and regulations that are inconsistent with this rule will be 
preempted; (2) No retroactive effect will be given to this rule; and 
(3) Administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

E. E.O. 13132: Federalism

    HHS/CDC has reviewed this final rule in accordance with Executive 
Order 13132 regarding Federalism and has determined that it does not 
have ``federalism implications.'' The rule does not ``have substantial 
direct effects on the States, on the relationship between the national 
government and the States, or on the distribution of power and 
responsibilities among the various levels of government.''

F. Plain Language Act of 2010

    Under the Plain Language Act of 2010 (Pub. L. 111-274, October 13, 
2010), executive Departments and Agencies are required to use plain 
language in documents that explain to the public how to comply with a 
requirement the Federal Government administers or enforces. HHS/CDC has 
attempted to use plain language in announcing this rule consistent with 
the Federal Plain Writing Act guidelines.

[[Page 13328]]

List of Subjects in 42 CFR Part 73

    Biologics, Packaging and containers, Penalties, Reporting and 
Recordkeeping requirements, Transportation.


0
For the reasons stated above in the preamble, HHS/CDC adopts the 
interim final rule which was effective November 17, 2021 (86 FR 64075) 
as final without change. In accordance with the interim final rule, 
SARS-CoV/SARS-CoV-2 chimeric viruses resulting from any deliberate 
manipulation of SARS-CoV-2 to incorporate nucleic acids coding for 
SARS-CoV virulence factors are an HHS select agent. Any individual or 
entity that possesses SARS-CoV/SARS-CoV-2 chimeric viruses on or after 
November 17, 2021 must provide notice to CDC regarding their possession 
and must secure the agent against theft, loss, release, or unauthorized 
access; and by November 17, 2021, an individual or entity that intends 
to continue to possess, use, or transfer this agent is required to 
either register in accordance with 42 CFR part 73 or amend their 
current registration in accordance with 42 CFR 73.7(h) and meet all of 
the requirements of select agent regulations (42 CFR part 73). Further, 
experiments that involve the creation of SARS-CoV/SARS-CoV-2 chimeric 
viruses resulting from any deliberate manipulation of SARS-CoV-2 to 
incorporate nucleic acids coding for SARS-CoV virulence factors or vice 
versa are restricted experiments and require prior approval in 
accordance with 42 CFR 73.13(a)(3).

    Dated: February 27, 2023.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2023-04323 Filed 3-2-23; 8:45 am]
BILLING CODE 4163-18-P