Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins

<RULE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <CFR>42 CFR Part 73</CFR> <DEPDOC>[Docket No. CDC-2020-0024]</DEPDOC> <RIN>RIN 0920-AA71</RIN> <SUBJECT>Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). <HD SOURCE="HED">ACTION:</HD> Final rule. <SUM> <HD SOURCE="HED">SUMMARY:</HD> This rule finalizes updates to the HHS list of select agents and toxins that could pose a severe threat to public health and safety. These updates were proposed along with other changes to the select agent and toxin regulations, which will be addressed in a separate regulatory action. In a companion document published in this issue of the <E T="04">Federal Register</E> , the U.S. Department of Agriculture (USDA) is making parallel regulatory changes. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This final rule is effective January 16, 2025. </EFFDATE> <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Daniel A. Singer, MD, Acting Director, Division of Regulatory Science and Compliance, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop H21-4, Atlanta, Georgia 30329. Telephone: (404) 553-8266. </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> The final rule is organized as follows: <EXTRACT> <FP SOURCE="FP-2">I. Background</FP> <FP SOURCE="FP1-2">A. Legal Authority</FP> <FP SOURCE="FP1-2">B. 2024 Proposed Rule</FP> <FP SOURCE="FP-2">II. Responses to Comments and Provisions of the Proposed Rule</FP> <FP SOURCE="FP1-2"> A. Removal of <E T="03">Brucella abortus, Brucella melitensis,</E> and <E T="03">Brucella suis</E> </FP> <FP SOURCE="FP1-2">B. Nomenclature and Other Changes in the Select Agent and Toxin List</FP> <FP SOURCE="FP1-2">C. Additional Comments Received</FP> <FP SOURCE="FP1-2"> D. Retaining Tier 1 Designation of Botulinum Neurotoxin Producing Species of <E T="03">Clostridium</E> </FP> <FP SOURCE="FP1-2">E. No Addition of Hantaviruses</FP> <FP SOURCE="FP1-2">F. Toxin Review: Changes to Exclusion Limits for Short, Paralytic Alpha Conotoxins</FP> <FP SOURCE="FP1-2">G. Designation of Nipah Virus as a Tier 1 Select Agent</FP> <FP SOURCE="FP1-2">H. Addition of a Footnote to the HHS Select Agent and Overlap Select Agent List</FP> <FP SOURCE="FP1-2">I. Summary of Final Rule Provisions</FP> <FP SOURCE="FP-2">III. Alternatives Considered</FP> <FP SOURCE="FP-2">IV. Required Regulatory Analyses</FP> <FP SOURCE="FP1-2">A. Executive Orders 12866, 13563, and 14094</FP> <FP SOURCE="FP1-2"> B. The Regulatory Flexibility Act (RFA), as Amended by the Small Business Regulatory Enforcement Fairness Act (SBREFA) </FP> <FP SOURCE="FP1-2">C. Paperwork Reduction Act of 1995</FP> <FP SOURCE="FP1-2">D. E.O. 12988: Civil Justice Reform</FP> <FP SOURCE="FP1-2">E. E.O. 13132: Federalism</FP> <FP SOURCE="FP1-2">F. Plain Language Act of 2010</FP> <FP SOURCE="FP-2">V. References</FP> </EXTRACT> <HD SOURCE="HD1">I. Background</HD> <HD SOURCE="HD2">A. Legal Authority</HD> Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Bioterrorism Response Act), the HHS Secretary must, by regulation, establish and maintain a list of biological agents and toxins that have the potential to pose a severe threat to public health and safety (42 U.S.C. 262a(a)(1)). In determining whether to include a biological agent or toxin on the list, the Bioterrorism Response Act requires that the HHS Secretary consider the following criteria: • the effect on human health of exposure to an agent or toxin; • the degree of contagiousness of the agent and the methods by which the agent or toxin is transferred to humans; • the availability and effectiveness of pharmacotherapies and immunizations to treat and prevent illnesses resulting from an agent or toxin; and • any other criteria, including the needs of children and other vulnerable populations, that the HHS Secretary considers appropriate (42 U.S.C. 262a(a)(1)(B)). Under 42 U.S.C. 262a(a)(2), the HHS Secretary must review and republish the list of HHS select agents and toxins at least biennially. In the preparation of this rulemaking, HHS/CDC considered the statutory criteria and evaluated each agent and toxin based on the following: • <E T="03">Effect on human health:</E> ○ the degree of pathogenicity (ability of an organism to cause disease); ○ long-term health effects; ○ severity of illness; ○ case fatality rate; ○ status of host immunity ( <E T="03">e.g.,</E> whether an individual has already been exposed to the agent and generated an immune response); ○ vulnerability of special populations; • <E T="03">Degree of contagiousness:</E> ○ dissemination efficacy; ○ aerosol stability; ○ rate of transmission; • <E T="03">Availability and effectiveness of pharmacotherapies:</E> ○ available treatment; • <E T="03">Other Criteria:</E> ○ decontamination and restoration (the extent remediation efforts are needed due to agent persistence in the environment and population); ○ matrix stability; ○ ease of production; ○ ability to genetically manipulate or alter; ○ the burden or impact on the health care system. The Federal Select Agent Program (FSAP) is the collaboration of the CDC, Division of Regulatory Science and Compliance (previously known as the Division of Select Agents and Toxins), and the USDA Animal and Plant Health Inspection Service (APHIS), Division of Agricultural Select Agents and Toxins. These two agencies administer the HHS and USDA select agent and toxin regulations and coordinate Federal oversight of select agents and toxins in a manner to minimize the administrative burden on the regulated community. The list of HHS select agents and toxins is divided into two sections—agents and toxins regulated solely by HHS and agents that are regulated by both HHS and USDA. The biological agents and toxins listed in 42 CFR 73.3 (HHS select agents and toxins) have the potential to pose a severe threat to human health and safety and are regulated only by HHS. The biological agents listed in § 73.4 (overlap select agents and toxins) have the potential to pose a severe threat to human health and safety, as determined by HHS, and a severe threat to animals and animal products, as determined by the USDA, pursuant to USDA's authority under the Agriculture Bioterrorism Protection Act of 2002 (7 U.S.C. 8401). Accordingly, these biological agents are jointly regulated by HHS and USDA as “overlap” select agents. The Bioterrorism Response Act defines the term “overlap agents and toxins” to mean biological agents and toxins that are listed pursuant to 42 U.S.C. 262a(a)(1) and listed pursuant to 7 U.S.C. 8401(a)(1). If HHS/CDC removes any overlap select agents from its list, these agents might still be regulated as USDA select agents dependent on the outcome of the USDA biennial review. <HD SOURCE="HD2">B. 2024 Proposed Rule</HD> On March 17, 2020, CDC published an advance notice of proposed rulemaking (ANPRM) (85 FR 15087) seeking public comments on potential changes to the current list of HHS and overlap select agents and toxins that are regulated by both HHS and USDA. The received comments broadly supported removal of the <E T="03">Brucella</E> species—of the 335 comments received, 325 supported removal of one or more species of <E T="03">Brucella.</E> Only two commenters were in favor of retaining the <E T="03">Brucella</E> species. HHS/CDC engaged the Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC) to review and consider the public comments. The committee reviewed the public comments over a series of seven meetings held between June 12, 2020, and December 11, 2020. Other Federal subject-matter experts were invited to the meetings to address questions from the committee. The ANPRM also requested input on removal of other agents from the list ( <E T="03">e.g., Coxiella burnetii, Rickettsia prowazekii, Bacillus anthracis</E> [Pasteur strain]). After considering public comments, ISATTAC advisory input, and Federal subject-matter experts' input, CDC proposed changes to the select agent and toxin list and removal of three species of <E T="03">Brucella.</E> On January 30, 2024, HHS issued a proposed rule entitled “Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins” (89 FR 5823). The proposed rule included two sets of proposals: (1) regulatory changes related to the select agents and toxins on the list ( <E T="03">i.e.,</E> remove three species of <E T="03">Brucella</E> from the list of overlap select agents and toxins, raise one toxin's exclusion amounts, rename three viruses, designate a current agent as a Tier 1 agent, and remove the designation of Tier 1 status from one agent), and (2) regulatory changes related to the administration of FSAP. This second set of proposals included adding definitions and provisions to clarify inactivation of select agents, adding requirements to report discoveries of select agents and toxins, and codifying policies regarding effluent decontamination systems and biosafety provisions for facility verification requirements for registered biosafety level 3 and animal biosafety level 3 laboratories. HHS/CDC has elected to finalize the January 30, 2024, proposed rule in two separate rulemakings—one final rule focused on changes to the select agents and toxins list (this final rule), and a second final rule focused on regulatory changes to the administration of the FSAP discussed above. This final rule will focus solely on removing three select agents, raising one toxin's exclusion limit, updating nomenclature, and designating an agent as Tie ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 82k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━