Inactivation: a process to render infectious material (e.g., pathogens) unable to cause disease,  but retain characteristics of interest for future use. The Total Number of Incidents Involving Incomplete Inactivation of Pathogens Is Unknown

The total number of incidents involving incomplete inactivation that  occurred from 2003 through 2015 is unknown for several reasons,  including the inability to easily identify such incidents in existing  databases. Because the Select Agent Program and  NIH cannot easily identify which incidents involve incomplete inactivation  on reporting forms and within incident databases, they do not know the  frequency or reason these incidents occur, making it difficult to develop  guidance to help prevent future incidents. Eight of the 21 identified incidents involving incomplete inactivation that  occurred from 2003 through 2015 involved Bacillus anthracis. Gaps in Science and Limited Guidance Affect the Implementation of Inactivation in High- Containment Laboratories

Several challenges affect the implementation of inactivation in high- containment laboratories including (1) gaps in the scientific knowledge of  protocol development and implementation, (2) limited federal guidance for  the development of inactivation protocols, (3) inconsistent implementation  of safeguards to help ensure inactivation is properly conducted, and  (4) varied documentation requirements for the shipment of inactivated  material. Due to limited  guidance, high-containment laboratories we visited varied in their  interpretation of what constitutes a validated method of inactivation,  resulting in researchers applying differing levels of rigor to validation of  inactivation protocols. An expert from our meeting and laboratory  officials we interviewed identified concerns with the Select Agent  Program’s criteria for what constitutes the validation of a protocol. 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 of some protocols not always achieving  inactivation. The Select Agent Program Inconsistently Referred Violations and Enforced Regulations Related to Incidents Involving Incomplete Inactivation

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 (OIG) or APHIS’s Investigative and Enforcement  Services for violations of select agent regulations. For example, the  APHIS component of the program did not refer two 2014 incidents it was  investigating at CDC laboratories involving incomplete inactivation, while  the CDC component of the program referred a number of incidents that it  investigated at federal, private, and academic laboratories. Recommendations for Executive Action

To mitigate the risk to human and animal health due to incidents involving  incomplete inactivation of dangerous pathogens used in high-containment  laboratories, we are making the following six recommendations:  To understand the extent to which incomplete inactivation occurs and  whether incidents are being properly identified, analyzed, and addressed,  we recommend that the Secretary of Health and Human Services direct  CDC and NIH and that the Secretary of Agriculture direct APHIS to: develop clear definitions of inactivation for use within their respective  guidance documents that are consistent across the Select Agent  Program, NIH’s oversight of recombinant pathogens, and the  Biosafety in Microbiological and Biomedical Laboratories manual; and  revise reporting forms within their respective areas of oversight 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. Appendix I: Objectives, Scope, and Methodology

This report evaluates (1) the extent to which incidents involving  incomplete inactivation occurred from 2003 through 2015; (2) any  challenges that may affect the implementation of inactivation in high- containment laboratories; and (3) the extent to which the Select Agent  Program referred violations and enforced regulations related to incidents  involving incomplete inactivation.
Why GAO Did This Study

Several incidents involving the shipment of live pathogens, thought to be inactivated, have recently occurred, potentially exposing people to dangerous pathogens that cause infectious diseases, such as the bacterium that causes anthrax.
GAO was asked to evaluate issues related to inactivation of pathogens in high-containment laboratories. This report examines (1) the extent to which incidents involving incomplete inactivation occurred from 2003 through 2015, (2) any challenges that may affect the implementation of inactivation in high-containment laboratories, and (3) the extent to which the Select Agent Program referred violations and enforced regulations related to incidents involving incomplete inactivation. GAO convened an expert meeting with the assistance of the National Academy of Sciences to discuss various issues surrounding inactivation. GAO also reviewed relevant laws, regulations, and guidance, and interviewed officials at laboratories that conduct inactivation.

What GAO Found

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.

What GAO Recommends

GAO is making six recommendations to HHS and USDA to, among other things, improve the Select Agent Program’s oversight of inactivation by revising reporting forms, improving guidance for development and validation of inactivation protocols, and developing consistent criteria for enforcement of incidents involving incomplete inactivation. HHS and USDA agreed with GAO’s recommendations.
or John Neumann at (202) 512-3841 or neumannj@gao.gov .