- Federal Register Notice: Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review
- Select Agent Information
Centers for Disease Control and Prevention
Select Agent Program
1600 Clifton Road, NE
Atlanta, GA 30333
Re: Regulatory Information Number (RIN) 0920-AA34; Document ID CDC-2011-0012-0001
The American Society for Microbiology (ASM) is submitting the following comments on the October 3, 2011, Department of Health and Human Services (DHHS) Notice of Proposed Rulemaking (NPRM), which requests input on the proposed changes to the DHHS list of biological agents and toxins that have potential as severe threats to public health and safety. The USDA has published similar proposed rule changes coincident with the DHHS Notice. This letter responds to both notices.
The ASM is the largest single life science Society, with approximately 38,000 members, dedicated to the study and advancement of scientific knowledge to benefit the public. Research in diverse fields of microbiology supports the discovery of new vaccines, therapeutic drugs, diagnostic technologies, and prevention strategies. The study of microorganisms, including those pathogens on the DHHS and USDA select agent and toxin lists, is crucial to preserve public health and ensure national security. The ASM continues to stress the importance of balancing research and diagnostic testing on the listed select agents and toxins with careful oversight and regulation to protect both public health and national security.
The ASM has submitted responses to previous agency requests for input on proposed select agent rules and changes, including comments on the July 21, 2010, DHHS and USDA Advance Notices of Proposed Rulemaking (ANPR). The ASM suggestions, submitted August 19, 2010, included creation of a tiered list of agents and toxins based on relative risk, with corresponding increased biosecurity measures for agents that pose the greatest danger (Tier 1) and reduced levels of biosecurity recommended for agents designated as Tier 2 and 3 (August 19, 2010 - ASM Comments on the Changes to the HHS List of Select Agents and Toxins). The ASM also offered detailed suggestions for placing agents and toxins within the tiered levels.
The ASM appreciates that the DHHS and the USDA have solicited recommendations and observations from external stakeholders during their biennial reviews of select agent regulations. We agree with the assessments by both agencies (summarized in their respective October 3 documents) that the tiering of the select agents and toxins list will help optimize security measures against threats that pose the higher risk to public health and safety. The ASM supports a risk based approach to biosecurity requirements and supports tiering select agents and toxins commensurate with risk.
However, the ASM has the following concerns about several proposed changes to 42 CFR Part 73, in particular those related to sections 73.11 (security) and 73.17 (records).
Security Requirements (Section 73.11)
Smallpox Virus. We note that the proposed DHHS rule does include additional physical security measures for Variola major and Variola minor viruses, over and above those for other Tier 1 agents, under Section 73.11 (e)(5) (Security). This addition recognizes that these viruses pose a significantly higher public health risk than the other agents and toxins proposed for the Tier 1 list. We also note, and agree with, the DHHS conclusion that it would be inappropriate to require these special security procedures be used with the other agents or toxins on the Tier 1 list. The ASM is concerned, however, about listing the smallpox virus as a Tier 1 agent, given the stringent conditions already in place for its handling and tracking. An alternative approach might be to designate smallpox (and perhaps rhinderpest) as pathogens with very special handling requirements, given that they have now been officially eradicated worldwide.
Additional Minimum Security Standards for Tier 1 Agents and Toxins. The proposed rule includes more specific minimum security standards for Tier 1 select agents and toxins. The additional regulations for Tier 1 agents and toxins will mandate more federal agency oversight, institutional responsibilities, and increased resources. These requirements include pre-access suitability evaluation of all persons with access to Tier 1 agents and toxins. Some institutions and investigators might not be willing to undertake much needed research on Tier 1 agents and toxins because of the increased layers of regulation. The ASM requests that the full impact of these added requirements be carefully assessed prior to implementation. The ASM also seeks clarification on the unspecified timeline for implementation of the new requirements. While eleven agents would be classified in Tier 1 under the new rules, these agents will become more difficult to use in the laboratory and the proposed rule will negatively impact research as a result.
Non-Tier 1 Agents and Toxins. The ASM notes that the proposed rule does not relax physical security requirements for the non-Tier 1 select agents and toxins. There are no Tier 2 or Tier 3 levels of agents and toxins proposed as suggested by the ASM. As stated in its previously submitted comments, the ASM supports reducing the regulatory burden for non-Tier 1 agents and believes that the current proposed rule has not sufficiently addressed this important issue. Reduced levels of security requirements for facilities should be strongly considered for non-Tier 1 agents to the degree that such reductions are consistent with existing federal legislation.
List of Select Agents and Toxins (Section 73.3)
The ASM agrees with the proposed removal of Coccidioides posadasii/Coccidioides immitis, Cercopithecine herpesvirus 1 (Herpes B virus), and Flexal from the South American Haemorrhagic Fever Viruses. However, we disagree with the proposed retention of Rickettsia rickettsii and recommend further assessment of whether Rickettsia prowazekii should be retained as a select agent. The ASM has previously provided justification for removal of agents from the select agent list. The ASM also continues to recommend that the following toxins be eliminated from the select agent list: Saxitoxin, Shiga-like ribosome inactivating proteins, Shigatoxin, T-2 toxin, Tetrodotoxin, Conotoxins, Diacetoxyscirpenol, and Clostridium perfringens epsilon toxin. Continuing to include these toxins on the select agent list has unintended consequences such as the US Department of Transportation (USDOT) policies regarding shipment of infectious substances that extends the list to agents, such as E. coli that produce these toxins, which results in limiting shipments to public health laboratories.
The ASM does not believe that Burkholderia mallei (formerly Pseudomonas mallei) or Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) should be included as Tier 1 agents. Meliodosis and glanders do not have the same level of concern as the other agents proposed as Tier 1. We strongly recommend that Burkholderia mallei and Burkholderia pseudomallei be designated as non-Tier 1 agents.
Record Keeping Requirements (Section 73.17)
Section 73.17 (a)(1) (Records). The ASM is disappointed that the revised rule continues to require accounting of individual vials and vial volumes of each select agent. Any research entity using pathogens should be accountable for the safety and security of each microorganism under its control, but counting individual vials of replicating biological agents is costly, burdensome, and a major source of frustration for investigators. The requirement to measure volumes within each vial is even more troubling, given the ease with which volumes can change through natural processes. There is widespread concern among microbiologists that neither counting vials nor measuring volumes of individual vials is an effective means of increasing biosecurity.
Section 73.17 (a)(2) (Records). The ASM also has serious misgivings about the implementation of, as well as the benefits from, the proposed new requirement for “an accurate, current inventory of any animals or plants intentionally or accidentally exposed to or infected with a select agent (including number and species, location, and appropriate disposition).” This concern is based on the following:
- Animals infected with a select agent are part of ongoing experimentation and are thus part of working stocks rather than a research institution’s current inventory.
- Those animals experimentally exposed to select agents are transiently infected and either succumb to their infection or recover, similar to the DHHS observations in the October 3 document about the transitory nature of toxins within affected animals. Harvested infectious tissues that become part of the select agent inventory at a research facility are already accounted for under existing regulations.
- Oversight of animals used in research facilities is already carefully monitored by institutional animal care and use committees, as well as by independent accreditation organizations like the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). Numbers and species used, location, and appropriate disposition already are recorded for accounting purposes through routine husbandry, either on an individual basis for larger animals or by cage for rodents. Arthropod vectors experimentally infected are individually counted.
- Given the transient nature of infected animals, it is unclear how oversight would be implemented or how records would be validated or confirmed independently during inspections.
- It also is unclear which biosecurity threat is being addressed through this proposed additional record-keeping requirement.
- The requested inventory of transiently held animals specifically to meet select agent requirements would represent a significant additional reporting and record-keeping burden placed on investigators and institutions.
The ASM believes the proposed requirement that the Responsible Official (RO) be physically located at the facility utilizing select agents and toxins needs clarification and evaluation. It is our understanding that a facility has to be contiguous and that laboratories separated on a campus constitute separate facilities. Having separate ROs for such laboratories would be problematic. We agree, however, that distant facilities should have an RO at each location. We request that the definition of a facility be clarified for this requirement and that the impact of the requirement be evaluated. There may not be a sufficient number of experienced, qualified individuals to meet this requirement and the result may be weaker oversight.
DHHS proposes “that the security plan include procedures for the Responsible Official to immediately notify the FBI of suspicious activity that may be criminal in nature and related to the entity, its personnel, or its select agents or toxins.“ Since the select agent program is administered by CDC and USDA, previously any potential theft or problems were to be reported to those agencies, not the FBI. We are uncertain why the regulations now require reporting directly to the FBI rather than to the regulatory agencies.
We do not understand the implications of the proposed additions to cyber-security requirements. This represents an added regulatory burden, and the impact of this added requirement should be evaluated.
Requirements have been added for an “occupational health program for individuals with access to Tier 1 select agents and toxins” that includes “review of medication or treatment that may affect security and safety.” This requirement appears ambiguous. Would someone on insulin be considered a safety risk, since they may have a hypoglycemic reaction while in the lab? Someone on steroids could be at increased risk of serious infection if exposed. The occupational health program requirements need to be clarified.
It is essential to have mandatory, periodic training of personnel working with and responsible for biosafety and biosecurity. We recommend that a national training center for training and education be considered to ensure the adequate training of personnel.
The proposed select agent revisions state that any experiment that introduces drug resistance to a select agent is restricted, although express approval can be requested from DHHS. We suggest aligning this language with the RDNA Guidelines language which restricts and requires approval for experiments with pathogens involving drug resistance for therapeutically useful agents against that pathogen. The wording in the proposed requirement is too expansive.
The ASM appreciates this opportunity to comment on the proposed DHHS/USDA rules regulating the DHHS list of select agents and toxins with biosecurity risk potential. It would welcome any request from the federal agencies for additional input on these agents and toxins, as well as their importance to biomedical research and recommendations on biosafety oversight.
Roberto Kolter, Ph.D., Chair, Public and Scientific Affairs Board
Ronald M. Atlas, Ph.D., Co-Chair, Committee on Biodefense
Kenneth I. Berns, M.D., Ph.D., Co-Chair, Committee on Biodefense
Stephen M. Ostroff, M.D., Chair, Committee on Public Health