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documents, such as biological safety manuals, laboratory newsletters, and articles from peer-reviewed literature. We also discussed challenges that exist and safeguards applied to address these challenges in our interviews with agency officials and researchers from high-containment laboratories and during our expert meeting. We compared information from our interviews with that of officials and our review of federal documents on the development and validation of inactivation protocols and application of safeguards with key reports related to biological safety, expert comments, and our past work. We also compared information from our interviews with laboratory officials and our review of related documents on the shipment of inactivated material with expert comments and internal controls from Standards for Internal Control in the Federal Government. 14 To determine how the Select Agent Program referred violations and enforced regulations related to incidents involving incomplete inactivation in high-containment laboratories, we reviewed guidance, inspection reports, and other documents from the Select Agent Program. In our interviews with laboratory and Select Agent Program officials, we discussed steps the Select Agent Program has taken to refer violations and enforce regulations related to incidents involving incomplete inactivation. We compared information we learned from our interviews with Select Agent Program officials and our review of program documents on the enforcement of the select agent regulations with agency guidance on the program and internal controls from Standards for Internal Control 13The views of these officials are not generalizable to all laboratories, but they provide illustrative examples. 14GAO, Standards for Internal Control in the Federal Government, GAO/AIMD-00-21.3.1 (Washington, D.C.: November 1999). GAO has revised and reissued Standards for Internal Control in the Federal Government, with the new revision effective as of October 1, 2015. GAO-14-704G (Washington, D.C.: September 2014). Page 7 GAO-16-642 Inactivation of Pathogens in the Federal Government. 15 For further information on our objectives, scope, and methodology, see appendix 1. We conducted this performance audit from July 2015 to August 2016 in accordance with generally accepted government auditing standards. Those standards require that we plan and perform the audit to obtain sufficient, appropriate evidence to provide a reasonable basis for our findings and conclusions based on our audit objectives. We believe that the evidence obtained provides a reasonable basis for our findings and conclusions based on our audit objectives. Researchers use various methods in high-containment laboratories to inactivate pathogens, as shown in figure 1, which they select depending on the type of pathogen to be inactivated and intended use of the inactivated material. Once a method is selected, researchers develop a protocol that outlines a detailed plan for the scientific procedure. The frequency with which inactivation is performed in high-containment laboratories varies significantly, with some researchers conducting inactivation on a daily or weekly basis and others conducting inactivation only a few times each year. 15GAO/AIMD-00-21.3.1. Background Types of Inactivation Methods Page 8 GAO-16-642 Inactivation of Pathogens Figure 1: Methods Used to Inactivate Pathogens Pathogens can be inactivated using physical, irradiation, and chemical methods, each having advantages and disadvantages. For example, inactivating pathogens using heat—a physical method—is generally simple and inexpensive, but may destroy the pathogen’s protein structure, thus rendering the pathogen useless for certain research purposes. Inactivating pathogens using irradiation better maintains pathogens’ protein structure, but irradiators are costly for most laboratories and subject to additional regulations and security concerns. See table 1 for descriptions of selected types of inactivation methods and their advantages and disadvantages. Page 9 GAO-16-642 Inactivation of Pathogens Table 1: Description of Selected Inactivation Methods Used in High-Containment Laboratories Inactivation method Description Advantages Disadvantages Physical methods of inactivation Heat (dry or wet) Hot-air (dry) or steam under pressure (wet), are used to irreversibly destroy the pathogen’s protein structure. • Simple • Inexpensive • Nontoxic • Rapidly kills most pathogens • Can damage the pathogen’s ability to produce an immune response in its host and may render it useless for research purposes Filtrationa A filter traps intact pathogens while smaller parts of the pathogen pass through. • Separates pathogens that are not inactivated or are clumping • Works on a wide range of microorganisms • Not all particles that are smaller than the filter’s pore-size pass through, resulting in loss of research material Irradiation methods of inactivation Ionizing radiation Ionizing radiation causes DNA damage. Some forms of ionizing radiation require radioactive sources, while others do not. • Disrupts the nucleic acids of an organism while preserving the protein components for research • Gamma radiation has greater ability to penetrate samples than other types of radiation, allowing for successful application on denser materials •
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