August 30, 2010 - ASM Comments on the Proposed Changes to the APHIS List of Select Agents and Toxins

APHIS Agriculture Select Agent Program
Regulatory Analysis and Development
PPD, APHIS, Station 3A-03.8
4700 River Road Unit 118
Riverdale, MD 20737-1238

Subject: Docket No. APHIS-2009-0070

The American Society for Microbiology (ASM) is submitting the following comments on the July 29, 2010, U.S. Department of Agriculture Animal Plant Health Inspection Service (APHIS) Advance Notice of Proposed Rulemaking (ANPR) request for comments on the biennial review of the USDA list of select agents and toxins, including whether any agent or toxin should be removed from the list, whether the list should be tiered based on the relative bioterrorism risk of the agent or toxin, and corresponding changes to security requirements. The ASM is the largest single life science society with approximately 40,000 members dedicated to the study and advancement of scientific knowledge of microbiology for the public benefit.

The study of pathogenic microorganisms, including select agents, is essential for the biosecurity of the United States. Research is needed to find protective vaccines and therapeutic drugs and diagnostic activities are critical for protecting individual and public health. The legislation that led to the select agent regulations recognizes that some select agents may pose a greater threat to the public health and safety than others and specifically states that security requirements should be “commensurate with the risk of the agent and toxin, including the risk of use in terrorism.”

Stratification of the HHS and USDA Select Agent List and Biosecurity Requirements

The ASM believes that biosecurity requirements, including personnel clearance requirements, could be stratified to be commensurate with risk. The ASM recommends that the select agent regulations be tiered at 3 levels so that biosecurity requirements are commensurate with the risk that a particular agent could be misused to do significant harm.  Changing to a tiered system would allow the focus to be on agents that pose the greatest danger. It could reduce the regulatory burden and thus permit critical research activities that will provide real protection to proceed. Additionally, tiering and reducing the number of agents requiring the highest levels of biosecurity could increase the likelihood for international harmonization that would greatly increase biosecurity.

The ASM believes that the current oversight mechanisms for select agents, including biosecurity and personnel clearance requirements, are best suited for those agents that are included in Tier 2 in the ASM proposal.   Higher levels of biosecurity and personnel clearance would be appropriate for facilities that handle the agents listed in Tier 1 in the ASM proposal.  In contrast, reduced levels of biosecurity and personnel responsibility should be strongly considered for the agents designated as Tier 3 to the degree that such reductions are consistent with existing federal legislation. 

The ASM believes that those who work with select agents are responsible for the safe and secure handling of pathogens under their control. However, the requirement to account for individual vials of pathogens is inappropriate for a replicating agent and is burdensome and costly for laboratories. The single exception is for Tier 1 agents where there is limited access to agents not readily available in nature or where there are other restrictions that severely limit the laboratories where those agents may be housed.  For Tier 2 and 3 agents, we recommend elimination of the requirement for counting individual vials of agents.

We also recommend that the current Security Risk Assessment screening process should include an appeal process to consider the circumstances surrounding otherwise disqualifying factors as recommended by the NAS report Responsible Research with Biological Select Agents and Toxins.

Tiering of the   USDA Select Agent List Including Overlap agents

The ASM recommends retaining an agent based list for tiering. Biosecurity requirements should be aligned with the public health risk categories established by the Centers for Disease Control and Prevention (CDC) and with special international agreements.  The CDC Category A and B agent lists would capture all biological agents for which material threat assessments have been made and all agents reported by the US Government to have been weaponized except for T2 Toxin.

Consideration should be given to adding a highest category for major threat agents that have been extinguished from nature and which require special consideration due to international agreement.
For agricultural agents the ASM recommends inclusion of:

  • FMD virus
  • Rinderpest virus  

The second tier should be aligned with the CDC Category A agents for overlap agents, which include organisms that pose a risk to national security because they can be easily disseminated or transmitted from person to person; result in high mortality rates and have the potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness.   Overlap agents in this second tier would include:

  • Bacillus anthracis
  • Francisella tularensis
  • Yersinia pestis.

A third tier, which should have lower biosecurity requirements, would include agents that are moderately easy to disseminate and result in moderate morbidity rates and lower mortality rates. Overlap agents that would be included as Category 3 agents are:

  • Brucella abortus
  • Brucella melitensis
  • Brucella suis
  • Burkholderia mallei (formerly Pseudomonas mallei)
  • Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)
  • Hendra virus
  • Nipah virus
  • Rift Valley Fever Virus
  • Venezuelan Equine Encephalitis virus

With the exception of Rathaytibacter toxicus, the plant pathogens on the current USDA-APHIS select agent list do not pose a direct human or animal health risk. Even R. toxicus has such a complex life cycle for significant animal disease to occur that it should not be considered a deterrent to its use in research for its ability to cause plant disease.  Thus, for most of the plant pathogen select agents that are listed, we recommend a fourth tier be established to place them in a category below that of the lowest tier for human pathogens.  This fourth tier that would include agents that do not result in human or animal morbidity or mortality.  These agents would require significant effort to disseminate (particularly, those that are not transmitted by insects), would not have the potential for major public health impact, would not cause public panic or social disruption or require special action for public health preparedness.  Agents currently on the list that would fall in this category are:

Peronosclerospora philippinensis (Peronosclerospora sacchari)
Phoma glycinicola (formerly Pyrenochaeta glycines)
Ralstonia solanacearum race 3, biovar 2
Sclerophthora rayssiae var zeae
Synchytrium endobioticum
Xanthomonas oryzae
Xylella fastidiosa
(citrus variegated chlorosis strain)                                   

We recommend that a panel of expert scientists in the fields of agriculture and veterinary medicine be consulted to assess the specific agents and toxins on the USDA APHIS list of select agents that have been determined to have the potential to pose a severe threat to animal or plant health or animal and plant products. 

The ASM also recommends that the expert panel be charged with recommending which agents should be eliminated from the select agent list due to their wide distribution in nature, lack of ease of production, and/or limited pathogenicity. Experts within the ASM Committee on Agricultural and Food Microbiology have recommended removing equine encephalitis because the viruses are endemic and are not transmitted without a vector.  The Committee has also recommended removing exotic bluetongue viruses.  Many of these viruses have been isolated within the United States during multiple years and the term “exotic” is meaningless.  The present designation greatly complicates research and even routine diagnostic work especially related to serology (where live virus is currently needed).  The exotic part of this designation is the stumbling block and in my mind the viruses (at least the United States isolates) should be removed from this list when detected in our back yards. Since 1999, “exotic” bluetongue viruses in the US have included BTV 1, 3, 5, 6, 12, 14, 19, and 22. We also have had at least two introductions of BTV-2 (now established) in the US prior to the select agent rules. None of these introductions were associated with any morbidity or mortality above background and in many cases were isolated as part of routine diagnostics associated with export.

Thank you for the opportunity to comment.

Sincerely,

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

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