The total number of incidents involving incomplete inactivation that occurred from 2003 through 2015 is unknown for three reasons: (1) the inability to easily identify incidents involving incomplete inactivation in incident databases; (2) the absence of reporting requirements for pathogens that are not select agents; and (3) the absence of a clear, consistent definition of inactivation. First, we found that the Select Agent Program and NIH do not have the ability to easily identify incidents involving incomplete inactivation because their incident reporting forms are not structured to specifically identify this type of incident. As a result, neither the Select Agent Program nor NIH (for the oversight of recombinant pathogens) was able to provide us with an accurate number of all incidents involving incomplete inactivation that occurred from 2003 through 2015. We identified additional incidents that the Select Agent Program and NIH did not initially identify. Second, we found that federal incident reporting, in general, is required only for (1) incidents that involve select agents, which are reportable to the Select Agent Program, and (2) incidents that involve recombinant pathogens, which are reportable to NIH. Thus, incidents involving incomplete inactivation of pathogens that are neither select agents nor recombinant pathogens, such as West Nile virus or the bacteria that causes tuberculosis, are generally not required to be reported to any federal agency. Third, we found that there is currently no clear and consistent definition of inactivation in guidance or regulations issued by the Select Agent Program and NIH. As a result, researchers may not consistently define inactivation, which potentially affects how and when they report incidents involving incomplete inactivation. Moreover, experts at our meeting noted that this can make it difficult to understand when an incident occurs. These experts stated that there is a need for a clear, consistent definition of inactivation across key federal guidance documents, and our past work has also shown that the use of standardized definitions is key to ensuring that information is reported consistently. Without the ability to easily identify incidents involving incomplete inactivation on reporting forms, the Select Agent Program and NIH are unable to easily search their respective databases to determine the frequency and causes of incidents related to the pathogens they regulate. In addition, without a clear and consistent definition of inactivation across key federal guidance, researchers may not know when to include incomplete inactivation in an incident report, potentially affecting the number of incidents reported. We concluded that, collectively, these issues prevent the Select Agent Program and NIH from knowing the extent to which incomplete inactivation occurs and whether incidents are properly identified, analyzed, and addressed. Not knowing the magnitude of the problem may inhibit agencies’ ability to achieve program missions of investigating any incidents in which noncompliance may have occurred. In our report, we recommended that the agencies develop clear definitions of inactivation for use within their respective guidance documents. We also recommended that they revise reporting forms to help identify when incidents involving incomplete inactivation occur and analyze the information reported to help identify the causes of incomplete inactivation to mitigate the risk of future incidents. HHS and USDA agreed with our recommendations and noted steps they were taking to address them. For example, CDC and APHIS are proposing revisions to the select agent regulations to include a definition of inactivation and are planning to update their reporting forms. Several challenges affect the implementation of inactivation in high- containment laboratories, including (1) limited scientific information for developing and implementing inactivation protocols, (2) limited federal guidance for developing inactivation protocols, (3) inconsistent implementation of safeguards to help ensure inactivation is properly conducted, and (4) varied documentation requirements for shipping inactivated material. Experts in our meeting stated that such challenges may affect laboratories’ ability to mitigate the risk of incomplete inactivation. First, we found that insufficient scientific information exists for developing and implementing inactivation protocols. This could result in incomplete inactivation, according to peer-reviewed literature and our group of experts. Examples of insufficient scientific information include a lack of understanding about (1) mechanisms of inactivation, (2) the ability of some pathogens to repair themselves after inactivation, and (3) viability testing (a procedure to determine the extent to which viable pathogens remain in a sample after an inactivation process). Second, we found that federal guidance for developing and validating inactivation protocols is limited. Major sources for technical guidance that researchers commonly use—such as NIH guidelines and Select Agent Program guidance—provide little detailed information on development and validation of inactivation protocols. In lieu of guidance, we found that researchers in laboratories we visited often developed inactivation protocols at a laboratory level and that protocols sometimes varied within the same department, agency, or laboratory, which may increase the risk of incomplete inactivation. We concluded that without more comprehensive and consistent federal guidance on the development and validation of inactivation protocols, protocols will vary in their scientific soundness and effectiveness, increasing the risk that inactivation may not be achieved. Third, we found that the high-containment laboratories that we visited did not consistently apply safeguards when conducting inactivation, and there is limited federal guidance on doing so. Examples of safeguards that were inconsistently applied at these laboratories included conducting viability testing following inactivation procedures, implementing verification mechanisms to ensure inactivation protocols are followed, and sharing lessons learned. Fourth, according to experts from our meeting, documenting the shipment of inactivated pathogens provides an important safeguard if the pathogen is determined to be still viable and needs to be destroyed to prevent potential exposures or release. However, we found through our review of agency documents and interviews with agency officials that laboratories vary in their documentation requirements for shipping inactivated pathogens. Without guidance for documenting the shipment of inactivated pathogens, laboratories are at risk of being unable to locate shipped pathogens in a timely manner, which is important if material thought to be inactivated is determined to still be viable. In our report, we recommended that the agencies take several steps to address these findings. First, we recommended that the Secretaries of Health and Human Services and Agriculture coordinate research efforts and take actions to help close gaps in the science of inactivation and viability testing. Second, we recommended that the agencies create comprehensive and consistent guidance for the development, validation, and implementation of inactivation protocols, including the application of safeguards. Third, we recommended that guidance on documenting the shipment of inactivated material be developed. HHS and USDA agreed with these recommendations and described steps they are taking to address them. For example, HHS and USDA stated that they are developing a federally supported program to improve laboratory biological safety that will include examination of gaps related to inactivation. In addition, for the Select Agent Program the agencies said they plan to develop guidance to assist with the development and implementation of inactivation protocols and viability testing. The two agencies that comprise the Select Agent Program—CDC and APHIS—did not consistently refer incidents involving incomplete inactivation for further investigation and enforcement to the HHS Office of Inspector General or APHIS’s Investigative and Enforcement Services. For example, the CDC component of the program referred a number of incidents involving incomplete inactivation that it investigated at high- containment laboratories between 2004 and 2015 to the Office of Inspector General. In contrast, the APHIS component of the program investigated two 2014 incidents at CDC laboratories involving incomplete inactivation that it did not refer to its Investigative and Enforcement Services. We found that it was unclear why some incidents were referred and enforced and not others. According to an interagency memorandum of understanding regarding the Select Agent Program, CDC and APHIS should maintain consistency in the application and enforcement of the select agent and toxin regulations. We found, however, that CDC and APHIS did not use the same set of criteria for referring violations for investigation by the HHS Office of Inspector General or APHIS’s Investigative and Enforcement Services. Moreover, they did not clearly document the bases for referring or not referring violations. In addition, it was unclear why the Select Agent Program took certain administrative actions, such as revoking or suspending an entity’s registration to possess select agents or requiring a corrective action plan, in response to some violations and not others. The Select Agent Program recently took some steps to increase consistency in the application and enforcement of the select agent regulations. However, the extent to which these steps will improve the understanding and transparency of the program’s enforcement is not yet clear. Without consistent criteria and documentation of decisions for referring violations and enforcing regulations related to incidents involving incomplete inactivation, the Select Agent Program will not have reasonable assurance that its regulatory approach to overseeing high-containment laboratories is applied consistently. In our report, we recommended that CDC and APHIS develop and implement consistent criteria and documentation requirements for referring violations to investigative entities and enforcing regulations related to incidents involving incomplete inactivation. HHS and USDA agreed with this recommendation and described steps they recently took, or are planning to take, to increase consistency in the application and enforcement of the select agent regulations. For example, they said that for the Select Agent Program they have developed a draft document that provides guidance on when to refer violations and options for enforcement actions but they did not provide a time frame for finalizing and implementing the draft document. In conclusion, these inconsistencies, in conjunction with our past work, also raise larger questions about the potential limitations of the Select Agent Program as a whole to effectively and independently oversee high- containment laboratories, both within HHS and across other federal agencies. Select Agent Program officials and an expert from our group noted that the Select Agent Program is independent in its oversight of HHS labs since it organizationally exists in a separate part of the department from the HHS agencies that have high-containment laboratories. However, as we have noted in our prior work, existing federal oversight of high-containment laboratories is fragmented and largely self-policing, raising questions about whether the government framework and oversight are adequate. Chairman Murphy, Ranking Member DeGette, and Members of the Subcommittee, this concludes our prepared statement. We would be pleased to respond to any questions that you may have at this time. For further information on this testimony, please contact Timothy M. Persons, Chief Scientist, at (202) 512-6522 or personst@gao.gov or John Neumann, Director, Natural Resources and Environment, at (202) 512-3841 or neumannj@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. Key contributors to this testimony include Mary Denigan- Macauley (Assistant Director), Sushil Sharma (Assistant Director), Amy Bowser, Caitlin Dardenne, Ashley Grant, Lesley Rinner, and Paola Tena. This is a work of the U.S. government and is not subject to copyright protection in the United States. The published product may be reproduced and distributed in its entirety without further permission from GAO. However, because this work may contain copyrighted images or other material, permission from the copyright holder may be necessary if you wish to reproduce this material separately.

Summary: This testimony summarizes the information contained in GAO's September 2016 report, entitled ( GAO-16-642 ). or John Neumann at (202) 512-3841 or neumannj@gao.gov . The total number of incidents involving incomplete inactivation--a process to destroy the hazardous effects of pathogens while retaining characteristics for future use--that occurred from 2003 through 2015 is unknown for several reasons. One key reason is that the Select Agent Program--operated by the Departments of Health and Human Services (HHS) and Agriculture (USDA) to oversee certain dangerous pathogens, known as select agents--does not require laboratories to identify such incidents on reporting forms. According to the program, 10 incidents occurred from 2003 through 2015. However, GAO identified an additional 11 incidents that the program did not initially identify. Because the program cannot easily identify incidents involving incomplete inactivation, it does not know the frequency or reason they occur, making it difficult to develop guidance to help mitigate future incidents. The 21 identified incidents involved a variety of pathogens and laboratories, as shown below. Several challenges affect the implementation of inactivation in high-containment laboratories, including gaps in scientific knowledge and limited guidance. For example, there is limited federal guidance for researchers on the development and validation of inactivation protocols. Validation helps ensure protocols are scientifically sound and produce consistent results. Due to limited guidance, laboratories varied in their interpretation of validated methods of inactivation, resulting in researchers applying differing levels of rigor. Without more comprehensive guidance, as called for by experts, protocols will vary in their scientific soundness, increasing the risk of incomplete inactivation. The Select Agent Program did not consistently refer incidents involving incomplete inactivation for further investigation and enforcement for violations of select agent regulations. For example, the program referred incidents involving incomplete inactivation at various laboratories, but did not refer two incidents in 2014 that occurred at HHS. A memorandum of understanding between HHS and USDA states that the program should handle incidents consistently. GAO found, however, that the program does not have a consistent, written set of criteria for handling incidents. Without such criteria, the program risks inconsistent enforcement of select agent regulations. This further highlights GAO's previous finding that existing federal oversight of high-containment laboratories is fragmented and self-policing.