The American Society for Microbiology (ASM) would like to submit the following points to consider to the Centers for Disease Control and Prevention (CDC) and the Interagency Work Group on Select Agents as it develops the proposed Interim Final Rule to implement Title II, Enhancing Controls on Dangerous Biological Agents and Toxins, in the Public Health Security and Bioterrorism Preparedness Response Act of 2002 (Public Law 107-188).
The ASM stands ready to assist the CDC and the Select Agent Work Group in any way possible.
Points to Consider and Recommendations for Implementation of Title II, Enhancing Controls on Dangerous Biological Agents and Toxins, of the Public Health Security and Bioterrorism Preparedness Act of 2002 (P.L. 107-188)
- Title II expands the current select agent registration program to include mandatory registration of possession of select agents. The July 12, 2002 Federal Register includes a list of HHS Select Agents, USDA-HHS Overlap Agents, and USDA High Consequence of Livestock Pathogens and Toxins on the Draft Notification of Possession of Select Agents or High Consequence Livestock pathogens and toxins form. (copy of draft form from page 46365 attached). The form appears to incorporate the current list of select agents in Appendix A of 42 CFR Part 72.
Title II provides a new comparable authority to the USDA for the possession, use and transfer of biological agents and toxins that the USDA Secretary determines have the potential to pose a severe threat to animal or plant health or to animal or plant products. Therefore, a new list of agricultural agents must be generated in consultation with scientific experts.
Title II mandates a biennial review and republication of the select agent list. A federal advisory board should be created to periodically review the list. Scientific societies such as the American Society for Microbiology should be consulted, as mandated in the legislation, to review the select agent list as often as needed.
Within the current list the Interagency Select Agent Work Group should remove the fungus Coccidioides because of its wide distribution and limited potential for use as a biothreat agent.
The review of the select agent list should reexamine the inclusion of avirulent strains and genetic elements encoding virulence factors from select agents which is discussed in point 7 below.
The HHS and USDA regulations need to be harmonized and there should be a unified approach to regulatory requirements across government agencies. The regulations should not duplicate regulations that are already in place and all federal agencies should be consulted. It will be critical for the HHS and USDA to coordinate activities for overlap agents and toxins to minimize the administrative burden on facilities subject to both programs and to provide for the development and implementation of a single system of registration.
The scientific community would best be served by having one integrated list of select agents regardless of whether the select agents on the list are promulgated by the Secretary of HHS or the Secretary USDA.
- Requirements for limited access to select agents for security reasons should ensure the need for the appropriate availability of select agents for research and public health purposes as mandated in the legislation. Policy measures and regulations to prevent terrorists from acquiring pathogens and technical information could affect legitimate activities outside of the ones they are intended to address if not carefully crafted.
Registered facilities must determine and ensure limited access to select agents and follow a clearance procedure for those individuals with a need to have access to ensure exclusion of restricted persons under the Patriot Act and persons "reasonably suspected" of committing certain crimes or knowing involvement in terrorism. This provision cross references the Patriot Act and gives specific authority to the Secretary for personnel security measures to be implemented in the regulations. Registered facilities must promptly submit to the Attorney General and HHS Secretary the names and "other identifying information" of individuals who have a legitimate need to handle or use listed agents and toxins.
Given that Title II is intended to increase security against bioterrorism without hindering legitimate research and diagnostic testing, the clearance procedure should be nonburdensome. Names should be submitted to the Attorney General and HHS and a process for timely notification must be established. Attention must be paid to the transitional provision regarding current research and applicability of timeframes in the rule that minimize disruption of research that is underway as of the effective date of the rule.
- A secure national database of the names and locations of registered facilities and select agents must be established that includes information, when available, that will allow the organisms to be traced. There should be one national database for both the select agents of human health relevance and agricultural relevance.
There should be a secure notification procedure and a central clearinghouse for receiving and inputting the information. The database should include strain specific information including source and if available sequence of key physiological data.
If new strains are acquired, notification is required (i.e. information submitted to the data base through secure means). Given that clinical labs have 48 hours to register and notify or destroy and transfer (with notification) to a registered facility, rapid notification, e.g. 48 hours may be warranted. This would correspond to the clinical exemption timeframe.
- The ASM believes that the core elements of a regulatory regime are already in place in 42 CFR Part 72 and in the BMBL. Appendix F includes guidelines for Laboratory Security and Emergency Response for Microbiological and Biomedical Laboratories. Although it is currently nonspecific, it is a reasonable basis for the development of biosecurity requirements. It should be possible for HHS to modify its current regulatory regime to govern registration for possession and build on the BMBL guidance to provide for threat and risk based regulations.
- Because toxins and live organisms are different, separate regulations are needed for toxins and for living agents. Toxins that are select agents could be treated as controlled substances.
Secure records could be kept so that all quantities can be accounted for, i.e., there should be an accurate log of use. The toxins that are select agents should be kept in secure locked storage facilities and access restricted to those individuals who have been cleared. Toxins may be used in labs that are not above BL1 and as such special procedures must be put in place to limit access to exclude restricted individuals.
Consideration should be given to having restricted access to the lab under the control of the principal investigator (lab supervisor) when toxins are removed from the locked storage facility--this would be consistent with BMBL biosafety procedures for dangerous agents.
Toxins being used for research should be kept separate from those used in medical practice since the latter are exempt.
Clarification should be given regarding the quantities of toxins that are select agents which are exempt (the current system of relying on LD 50s is not at all clear to investigators and there are conflicting views as to whether some of the select agent toxins are totally exempt based upon LD 50 data).
- Additional requirements for physical security and personnel security should have some reasonable expectation of improving public safety and be based on a risk assessment of the select agents with the highest consequence agents receiving the highest security. Some select agents pose a greater threat to public health than other and Title II provides flexible authority to the Secretary of HHS to impose different levels of security requirements on different agents.
Smallpox (Variola) should be treated as a special case given that it is not present in nature and that its possession in the US is restricted to the CDC. Very high security measures are warranted, including stringent personnel screening procedures, for access to smallpox virus. Given the enormous security needs work with smallpox virus should be at the BL-3 or even BL-4 or a new BL-2 secure facility classification should be established that meets the same security and restricted access of a BL-4 facility.
Most of the viruses that are select agents and that are virulent strains, including the South American Hemorrhagic Fever Viruses, Marburg, and Ebola, must be restricted to BL-4 facilities. This permits full control of access. Given the limited number of BL-4 facilities, additional security measures--such as guards and surveillance cameras should not represent an unreasonable burden. Currently the BMBL has specifications for BL-4 facilities that will provide for controlled access.
Most of the bacteria that are select agents and that are virulent strains are restricted to BL-3 facilities. Controlled (secure) access to BL-3 facilities can readily be established. Consideration should be given to requiring work with all bacteria that are select agents be conducted within BL-3 facilities or that a new BL-2 secure facility classification be established. Currently the BMBL has specifications for BL-3 facilities that will provide for controlled access.
Avirulent strains and genetic elements that are considered select agents represent special problems. Avirulent forms or the genetic elements that are select agents have the potential for being used to create dangerous pathogens through genetic engineering. Thus, they have been treated as select agents under the select agent transfer act. This position should be reevaluated although it seems to still be scientifically justified.
Avirulent strains do not require the same levels of biosafety containment as the virulent forms. Thus, they will not have the same biosecurity unless a new BL-2 secure facility classification is established and required.
Because of the number of strains that may be created with genetic elements that are select agents, there may be an excessive reporting burden if all such strains have to be registered. Therefore special reporting processes, perhaps simply a secure log maintained at the site should be used to record the existence of such strains.
- There is an inherent conflict between the measures intended for security and those required for biosafety that must be resolved. Institutional biosafety committees generally are public and require community participation to ensure transparency and assurance of biosafety for the wider community-however, biosecurity requires opacity. Biosafety procedures in the BMBL specify procedures for posting the names of dangerous pathogens in laboratories where they are in use. Biosecurity precludes the public posting of such information.