Lack of Consideration for Full Array of BSL-4 Activities
The uSSRA focuses exclusively on risks associated with handling of large animals in BSL-4 containment and neglects risks posed by other activities in BSL-4 containment. Work in a BSL-4 laboratory that does not house large animals is not risk-free as implied by the uSSRA. Due to the nature of BSL-4 pathogens, work that would normally be conducted in BSL-3 special procedure or BSL-3 Enhanced areas of the facility are required to be conducted in BSL-4 if it involves live virus. The 20-year record for safe operation of major BSL-4 laboratories in the United States is excellent (Johnson, 2003) and the use of biosafety cabinets and other biosafety measures in the BSL-4 laboratory setting can reduce the risk of release from non-animal-related activities, but it does not reduce the risk to zero. Consequently, by omitting the risk of activities in non-large-animal BSL-4 space, the uSSRA does not address “overall risks” as this committee had expected because it ignores these risks.
Magnitude of Risks Associated with Unknown or Uncharacterized Pathogens
The uSSRA notes that NiV and HeV are not the only pathogens that would be examined in the BSL-4 laboratory. As part of its mission to serve as a world-class laboratory, the NBAF is expected to conduct essential and cutting-edge research both on known BSL-4 agents and on unknown and uncharacterized pathogens. There is a possibility that experiments would involve large animals for hemorrhagic fever agents, variant influenza viruses, or pox viruses, and work on these pathogens will pose risks. As the microbiological and epidemiological features of these agents differ from those of henipaviruses, it is likely the risks associated with working on these agents would also be different from those of henipaviruses. The committee concurs that it is difficult, if not impossible, to model the risks associated with unknown agents. However, the uSSRA provides only a minimal risk estimate, and the present committee echoes the previous committee’s concern that the risk assessment did not adequately discuss “the magnitude of risk and the strategy or process flow to identify and mitigate risk in future research areas” (NRC, 2010, p. 94).
Scenarios Not Fully Developed or Characterized
The uSSRA modeled 109 scenarios in the BSL-4 assessment, but the risks associated with some of them were not fully developed. For example, the necropsy scenario does not consider what the procedure entails with regard to livestock, including the use of knives, saws, rib cutters, and various