Source: https://www.federalregister.gov/articles/2011/10/03/2011-25427/possession-use-and-transfer-of-select-agents-and-toxins-biennial-review
Timestamp: 2015-08-30 19:54:59
Document Index: 475221971

Matched Legal Cases: ['§ 73', '§ 73', 'art 73', 'art 73', '§ 73', '§ 73', 'art 73', '§ 73', 'arts 100', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', '§ 121', '§ 331', '§ 73', 'art 73', 'ART 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73', '§ 73']

Federal Register | Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review
Dates: Comments should be received on or before December 2, 2011.
Comments Close: 12/02/2011
-61226 (22 pages)
Document Number: 2011-25427
Shorter URL: https://federalregister.gov/a/2011-25427 Related Topics
Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List 5 actions from October 3rd, 2011 to October 2012
76 FR 61206
The Public Health Security and Bioterrorism Preparedness and Response Act of 2002, Subtitle A (Department of Health and Human Services) of Title II (Enhancing Controls on Dangerous Biological Agents and Toxins) of Public Law 107-188 (June 12, 2002) (42 U.S.C. 262a) (the Bioterrorism Response Act), requires the HHS Secretary to establish by regulation a list of each biological agent and each toxin that has the potential to pose a severe threat to public health and safety. In determining whether to include an agent or toxin on the list, the HHS Secretary considers 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; the potential for an agent or toxin to be used as a biological weapon; and the needs of children and other vulnerable populations. The current list of HHS select agents and toxins can be found at 42 CFR 73.3 (HHS select agents and toxins) and 42 CFR 73.4 (Overlap select agents and toxins). The list of HHS and Overlap select agents and toxins is available at: http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html. The Bioterrorism Response Act requires that the HHS Secretary review and republish the list of select agents and toxins on at least a biennial basis. See 42 U.S.C. 262a(a)(2).
The HHS Secretary last republished the HHS select agents and toxins list in the Federal Register on October 16, 2008 (73 FR 61363). The HHS select agents and toxins list is divided into two sections. The select agents and toxins listed in § 73.3 (HHS select agents and toxins) are those regulated only by HHS under the authority of the Bioterrorism Response Act. The select agents and toxins listed in § 73.4 (Overlap select agents and toxins) are those regulated by HHS under the authority of the Bioterrorism Response Act and regulated by the USDA under the authority of the Agricultural Bioterrorism Protection Act of 2002 (7 U.S.C. 8401).
On July 2, 2010, President Obama signed Executive Order (E.O.) 13546: “Optimizing the Security of Biological Select Agents and Toxins in the United States” that directed the Secretaries of HHS and USDA to (1) designate a subset of the select agents and toxins list (Tier 1) that presents the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure; or public confidence; (2) explore options for graded protection of Tier 1 agents and toxins to permit tailored risk management practices based upon relevant contextual factors; and (3) consider reducing the overall number of agents and toxins on the select agents and toxins list. E.O. 13546 also established the FESAP to advise the HHS and USDA Secretaries on the designation of Tier 1 agents and toxins, reduction in the number of agents on the Select Agent List, establishment of personnel reliability standards for those having access to Tier 1 select agents and toxins, and establishment of physical security and information security standards for Tier 1 select agents and toxins. E.O. 13546 is available at: http://edocket.access.gpo.gov/2010/pdf/2010-16864.pdf. The FESAP provided its recommendations to the HHS and USDA Secretaries on November 2, 2010. The FESAP recommendations addressed the reduction of the list of select agents and toxins, the identification of a subset of the list that includes those that presents the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure; or public confidence; and the optimization of security programs at registered entities. In drafting its recommendations to modify and stratify the list of select agents and toxins, the FESAP utilized expert knowledge of the agents, combined with information from the DHS's Material Threat Determinations of biological agents and toxins. Care was used to balance risks identified with the Congressional mandate to ensure the availability of select agents and toxins for research and educational activities.
II. Proposed Changes to 42 CFR Part 73 Back to Top
Proposed Changes to 42 CFR Part 73 Back to Top
Applicability and related requirements
Definitions added: Adjudicated as a mental defective; alien; committed to any mental institution; controlled substance; crime punishable by imprisonment for a term exceeding 1 year; indictment; information security; lawfully admitted for permanent residence; mental institution; occupational exposure; recombinant and synthetic nucleic acids; restricted person; unlawful use of any controlled substance.
Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the HHS list.
Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the overlap list.
Exemptions for HHS select agents and toxins
Amends the immediate notification list to Tier 1 agents.
Exemptions for overlap select agents and toxins
Redesignates paragraphs; adds new paragraphs (a)(3), (a)(6).
Restricting access to select agents and toxins; security risk assessments
Redesignates paragraphs; adds new paragraph (e); adds clarifying language.
Revises regulatory text—paragraph (b), (c)(2). Redesignates paragraphs; adds new paragraphs (c)(8), (c)(9), (c)(10), (e).
Revises paragraphs (a) and (c)(1); replaces “url” in paragraph (c)(3); redesignates paragraph (d); adds new paragraph (d).
Redesignates paragraphs; adds new paragraphs (d) and (e).
Revises paragraph (a); redesignates paragraphs; adds new paragraph (b).
Redesignates paragraphs; adds new paragraphs (f), (h), (l).
Revises paragraph (a)(1); redesignates paragraphs; adds new paragraph (a)(2).
Revises paragraphs.
The ISATTAC and the FESAP also recommended the removal of Cercopithecine herpesvirus 1 (Herpes B virus) from the HHS list of select agents and toxins. We agreed with the commenters, ISATTAC, and FESAP and propose to remove Cercopithecine herpesvirus 1 (Herpes B virus) from the HHS list of select agents and toxins. Our rationale for this proposal is based on the facts that this virus is not easily transmitted to humans, the person-to-person transmission risk is small, the numbers of recorded human infections are low, and multiple licensed antiviral treatments for Herpes B infections are available.
We examined the current scientific data and noted that there is an increased incidence of Monkeypox virus in humans as well as studies identifying the virus being easily transmitted in Gambian rats. A recent study on an outbreak in Sudan indicates there is much strain variation in level of infectivity and severity of disease. Concern over the detection of new lineages with increased pathogenesis has been expressed. Another recent outbreak of Monkeypox virus in the United States suggested numerous animals could become infected complicating the understanding of zoonotic maintenance of the virus (Ref 29-33).
Commenters to the July 21, 2010 ANPRM suggested that the regulations needed a clear statement concerning staphylococcal enterotoxins (SEs) and staphylococcal enterotoxin-like toxins (SEls). Commenters stated that SEs and SEls have been distinguished from each other on the basis of emetic activity (Ref 12). Commenters were confused regarding whether the intent of the select agent regulations is to acknowledge this difference and not regulate SEls or to regulate both SEs and SEls. ISATTAC recommended that we amend the HHS list of select agents and toxins to specifically include Staphylococcal enterotoxins A, B, C, D, and E in the HHS list of select agents and toxins. We agree with the commenters and the ISATTAC recommendation, and propose to amend the select agents and toxins list from “Staphylococcal enterotoxins” to specifically include “Staphylococcal enterotoxins A, B, C, D, and E” in the HHS list of select agents and toxins (Ref 7-14). Serotypes G, H, and I should not added to the HHS list of select agents and toxins because serotypes G, H, and I are at least 10 fold less of a risk than SEE and SEA (Ref 15-16.) According to the International Nomenclature Committee for Staphylococcal Superantigens, emesis in a primate model within five hours post-feeding must be observed to classify an exotoxin as an enterotoxin (Ref 12). If emesis is not observed in this period of time, the exotoxin should be classified as enterotoxin-like rather than enterotoxin. Based on this internationally accepted standard, we are proposing serotypes J, K, L, M, N, O, P, Q, T, U, U2 and V should be designated staphylococcal enterotoxin-like rather than enterotoxin because these serotypes have been shown to either not cause emesis in a primate model or have not been tested for emesis (Ref 17-26). Therefore, we are proposing serotypes J, K, L, M, N, O, P, Q, T, U, U2 and V should not added to the HHS list of select agents and toxins.
The FESAP and ISATTAC recommended that Burkholderia mallei and Burkholderia pseudomallei remain on the Overlap list of select agents and toxins. We made no changes based on these comments because we agreed with these expert panels that Burkholderia mallei and Burkholderia pseudomallei should remain on the Overlap list of select agents and toxins based on our scientific determination that the bacteria can be produced in large quantity; transmitted via aerosol; and Burkholderia pseudomallei is highly stable in the environment. The mortality rate for untreated cases of both melioidosis and glanders is high, and given the rarity of these diseases in the United States, experience in their diagnosis and treatment is limited.
E.O. 13546 specifies that a subset of the Select Agent List be categorized as “Tier 1” because these agents and toxins present the greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. All but one of the commenters to the July 21, 2010 ANPRM who addressed the idea of a tiering system based on the relative bioterrorism risk of each agent or toxin favored the use of tiers. Several commenters mentioned specific criteria for tiering. A few commenters expressed the concern that tiering could create confusion, especially for facilities with multiple Biological Select Agents and Toxins (BSAT) and had concerns about additional requirements that would be placed on some laboratories. Some commenters identified specific Tier 1 candidates from the BSAT listed in 42 CFR 73.3 and § 73.4. Most of these commenters included Variola major virus and Variola minor virus, as well as Reconstructed 1918 Influenza virus, Ebola viruses, and Marburg virus in their Tier 1 list. Two commenters also suggested Bacillus anthracis and Lassa fever virus. Other commenters suggested Francisella tularensis, South America hemorrhagic fever viruses, Brucella species, Coxiella burnettii, Botulinum neurotoxin, and Ricin as candidates for Tier 1.
With respect to the remainder of the sections outlined below, we are proposing the following changes based on comments received in response to the July 21, 2010 ANPRM and recommendations from the FESAP. We are proposing to update the Web address throughout the document as all information concerning the Federal Select Agent Program is now centralized on the National Select Agent Registry Web site at http://www.selectagents.gov/. We also are proposing non-substantive changes throughout the regulations for purposes of clarity. In addition, HHS/CDC and USDA/APHIS made the language similar to ensure consistency between the regulations.
We are proposing to define a “crime punishable by imprisonment for a term exceeding 1 year” as “any Federal, State, or foreign offense for which the maximum penalty, whether or not imposed, is capital punishment or imprisonment in excess of 1 year. What constitutes a conviction of such a crime shall be determined in accordance with the law of the jurisdiction in which the proceedings were held. Any conviction that has been set aside or nullified as a matter of law or for which a person has been pardoned shall not be considered a conviction for purposes of this part.” Contrary to definition of this term used under the Gun Control Act, we have decided that foreign offenses should be considered a disqualifier. In doing so we are aware of the Supreme Court's decision in Small v. United States, 544 U.S. 385 (2005) in which the court, interpreting the provisions of 18 U.S.C. 922(g)(1), held that phrase “convicted in any court” refers only to U.S. courts, not to foreign courts. In its opinion interpreting the Gun Control Act, the court stated that “the statute itself and its history offer only congressional silence” as to whether Congress considered whether the statutory language included foreign convictions. In the case of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Bioterrorism and Response Act), we believe Congress spoke clearly about their desire to limit or deny access to select agents and toxins for those who have committed serious crimes regardless of where committed.
Sections in §§ 73.3 and 73.4 of 42 CFR contain provisions for toxins regulated by HHS under part 73. In 42 CFR 73.3(e) and 73.4(e), we are proposing to clarify that the “inactive form of a select toxin” may be excluded from regulation since the current term, “attenuated strain of toxin” is scientifically inaccurate. “Attenuated” is a term that is applied to living organisms and toxins are not living organisms. Since “Inactive form of a select toxin” is a more accurate term, we are proposing to amend the regulations to include the correct terminology.
Section 42 CFR 73.3(d)(3) specifies the permissible select toxin amounts under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor that are excluded from the requirements of the select agent regulations. We are proposing to require that the person transferring toxins in amounts which would otherwise be excluded from the provisions of the select agent regulations would be excluded only if the transferor: (1) Can show that the transferor used due diligence (i.e., reasonably justified by a prophylactic, protective, bona fide research, or other peaceful purpose) to assure that the recipient has a legitimate need to handle or use such toxins; and (2) reports to CDC if they detect a known or suspected violation of Federal law or become aware of suspicious activity related to the toxin. The HHS Secretary would also retain the authority to, without prior notification, inspect and copy or request the submission of the due diligence documentation. It should be noted that this proposed requirement would not apply to toxins exempted under Section 42 CFR 73.5(c).
The regulations in 42 CFR 73.11 establish the requirements for developing and implementing a security plan sufficient to safeguard select agents or toxins against unauthorized access, theft, loss, or release. The regulations currently require that the security plan must be submitted by all regulated entities upon request. We are proposing to amend § 73.11 to require that the security plan be submitted for initial registration and renewals of registration.
We are proposing to codify current practices for shipping, receiving, and storage of select agents and toxins to ensure that the entity has documented processes for securing and monitoring the shipment, receipt, and storage of these items. These changes would serve to decrease the chance that such materials would be made available to an unauthorized individual or an individual without a legitimate use for the material.
The regulations in 42 CFR 73.13 concern restricted experiments that may not be performed unless approved by the HHS Secretary. We are proposing to add language in order to expand the current “restricted experiment” approval requirement to include all experiments involving the creation of drug resistant select agents that are not known to acquire the resistance naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture and not just those involving recombinant DNA. The regulations in 42 CFR 73.13 concern restricted experiments which may not be performed unless approved by the HHS Secretary. Furthermore, we are proposing to state that, in addition to the existing prohibition on conducting restricted experiments without express approval, entities may not possess the products (i.e., creation of drug resistant select agents that are not known to acquire the resistance naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture, or recombinant and or synthetic DNA containing genes for the biosynthesis of select toxins lethal for vertebrates at an LD[50] 100 ng/kg body weight resulting from restricted experiments) resulting from restricted experiments without the express approval of the HHS Secretary. We are also proposing to remove recombinant technology as the only determining factor for a restricted experiment. Current regulations regarding restricted experiments focus solely on the use of recombinant technology in the generation of drug resistant select agents or biosynthesis of toxins lethal to vertebrates. Since synthetic DNA technology or selection in sublethal exposures may also be used to generate such products, we are proposing to expand the category of restricted experiments to include passive selection, recombinant and/or synthetic DNA.
The transportation in commerce of hazardous materials, including select agents and toxins, is governed by the United States Department of Transportation's Hazardous Material Regulations found in Title 49 of the Code of Federal Regulations, parts 100-185. The regulations in 42 CFR 73.16 do not impose requirements on the transportation in commerce of select agents or toxins. We are proposing to clarify when “transportation in commerce” begins and ends to better allow registered individuals and entities to adequately address those situations when a select agent or toxin is (1) ready to be packaged for transportation, (2) packaged for shipment, or (3) received and handled by a person with approval to access select agents and toxins. In addition, we are proposing language to codify policies and practices into a standard for shipping, receiving, and storage of select agents and toxins to ensure that the entity has documented processes for securing and monitoring the shipment, receipt, and storage of select agents and toxins that make it extremely unlikely that such materials would be made available to an unauthorized individual or an individual without a legitimate use for the material. We note the concerns identified in two HHS Office of Inspector General (OIG) audits regarding vulnerabilities that may occur during the shipment of select agents and toxins. HHS/CDC reviewed how entities ship select agents and toxins and evaluated ways to improve this process to ensure they are not only safeguarded against unauthorized access, but also against theft, loss, or release. We believe that the proposed amendments will help address OIG's concerns.
III. Required Regulatory Analyses Back to Top
We have prepared an economic analysis for this rule. The economic analysis provides a cost-benefit analysis, as required by E.O. 12866, and an initial regulatory flexibility analysis (See III.b.) that examines the potential economic effects of this proposed rule on small entities, as required by the Regulatory Flexibility Act. The economic analysis is summarized below. Copies of the full analysis are available by contacting the person listed under FOR FURTHER INFORMATION CONTACT or on the Federal Select Agent Program Web site at: http://www.selectagents.gov/ or on the public docket at http://www.regulations.gov.
This proposed rule would update the APHIS, CDC, and overlap select agent and toxin lists. The regulation of select agents and toxins is intended to prevent their misuse and thereby reduce the potential for those pathogens to harm humans, animals, animal products, plants or plant products in the United States. Should any select agent or toxin be intentionally or unintentionally released into the environment, the consequences would be significant. Consequences could include disruption of markets, difficulties in sustaining an adequate food and fiber supply, and the potential spread of disease infestations over large areas. The entities most likely to be affected by this rule would be those laboratories and other institutions conducting research and related activities that involve the use of the newly categorized Tier 1 select agents and toxins. The impact of the changes to the regulations is expected to be minimal, however. Based on information obtained through site-specific inspections, indications are that very few entities would incur significant costs for compliance. Many of the proposed changes to the regulations would impose an added cost of the time spent on documenting measures already required for compliance, with respect to security, biocontainment/biosafety, and incident response plans, information security, and ongoing background checks. While the total costs imposed by the proposed regulations are estimated to range between $5.30 million and $6.95 million, including costs to government, we believe many of these costs are incurred through observance of generally recognized industry standards. Costs actually incurred would depend upon the extent to which current facility practices will need to be enhanced based on the proposed requirements. The expected benefits of strengthened safeguards against the costs associated with unintentional or deliberate release of select agents or toxins would greatly exceed the estimated costs of the proposed measures. The cost associated with a single outbreak have been known to exceed $100 million as outlined in the Regulatory Impact Analysis. Deliberate introduction greatly increases the probability of a select agent or toxin becoming established and causing wide-ranging and devastating impacts on an economy, loss of market access for consumer goods and services, disruption to society, and diminished confidence in public and private institutions.
Estimated total annual burden on respondents: 10,947 hours. (Due to averaging, the total annual burden hours may not equal the product of the annual number of responses multiplied by the reporting burden per response.) Section
9 CFR 121.5 and 6, 7 CFR 331.5, 43 CFR 73.5 and 6
Report of Identification of a Select Agent or Toxin
§ 121.7, § 331.7, § 73.7
Amendment to a Certificate of Registration
§ 121.11, § 331.11, § 73.11
§ 121.12, § 331.12, § 73.12
Biosafety/Biocontainment Plan
§ 121.13, § 331.13, § 73.13
Request Regarding a Restricted Experiment
§ 121.14, § 331.14, § 73.14
§ 121.15, § 331.15, § 73.15
§ 121.16, § 331.16, § 73.16
§ 121.17, § 331.17, § 73.17
§ 121.19, § 331.19, § 73.19
24. Ono, H.K., K. Omoe, et al., 2008. Identification and characterization of two novel staphylococcal enterotoxins, types S and T. Infect Immun 76(11): 4999-5005. 25. Letertre, C., S. Perelle, et al., 2003. Identification of a new putative enterotoxin SEU encoded by the egc cluster of Staphylococcus aureus. J Appl Microbiol 95(1): 38-43.
List of Subjects in 42 CFR Part 73 Back to Top
PART 73—SELECT AGENTS AND TOXINS Back to Top
42 U.S.C. 262a; sections 201-204, 221 and 231 of Title II of Public Law 107-188, 116 Stat 637 (42 U.S.C. 262a).
§ 73.1 Definitions.
(3) Except as required in § 73.16(l), HHS toxins under the control of a principal investigator, treating physician or veterinarian, or commercial manufacturer or distributor, if:
(i) The aggregate amount does not, at any time, exceed the following amounts: 100 mg of Abrin; 0.5 mg of Botulinum neurotoxins; 100 mg of Clostridium perfringens epsilon toxin; 100 mg of Conotoxins; 1,000 mg of Diacetoxyscirpenol; 100 mg of Ricin; 100 mg of Saxitoxin; 100 mg of Shiga-like ribosome inactivating proteins; 100 mg of Shigatoxin; 5 mg of Staphylococcal enterotoxins; 1,000 mg of T-2 toxin; or 100 mg of Tetrodotoxin.
§ 73.5 [Amended]
§ 73.6 [Amended]
§ 73.8 [Amended]
§ 73.10 Restricting access to select agents and toxins; security risk assessments.
§ 73.11 Security.
(f) In developing a security plan, an individual or entity should consider the documents entitled, “Select Agents and Toxins Security Information Document” and “Select Agents and Toxins Security Plan Template.” These documents are available on the Internet at http://www.selectagents.gov/.
c. In paragraph (c)(3), by removing the URL “http://www.cdc.gov/&rdquo; and adding in its place “http://www.selectagents.gov&rdquo;.
§ 73.12 Biosafety.
§ 73.13 [Amended]
a. In paragraph (a), in the introductory text, by adding the phrase “, or possess products (i.e. select agents that are not known to acquire the resistance naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture, or recombinant and or synthetic DNA containing genes for the biosynthesis of select toxins lethal for vertebrates at an LD[50] < 100 ng/kg body weight) resulting from,” after the word “conduct” both times it appears.
§ 73.14 Incident response.
(a) An individual or entity required to register under this part must develop and implement a written incident response plan based upon a site specific risk assessment.
The incident response plan must be coordinated with any entity-wide plans, kept in the workplace, and available to employees for review.
§ 73.15 Training.
§ 73.16 Transfers.
(l) A registered individual or entity transferring an amount of a HHS toxin otherwise excluded under the provisions of § 73.3(d) of this part must:
§ 73.20 Administrative review.