High-Containment Laboratories:

Improved Oversight of Dangerous Pathogens Needed to Mitigate Risk

GAO-16-642: Published: Aug 30, 2016. Publicly Released: Sep 21, 2016.

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  • GAO Interactive Graphic
    Risk of Incomplete Inactivation of Pathogens - Anthrax Example

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Contact:

Timothy M. Persons, Ph.D.
(202) 512-6412
personst@gao.gov

 

John Neumann
(202) 512-3841
neumannj@gao.gov

 

Office of Public Affairs
(202) 512-4800
youngc1@gao.gov

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.

Figure: Twenty-one Identified Incidents Involving Incomplete Inactivation that Occurred from 2003 through 2015 by Pathogen and Laboratory Type

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.

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 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.

For more information, contact Timothy M. Persons, Ph.D. at (202) 512-6412 or personst@gao.gov or John Neumann at (202) 512-3841 or neumannj@gao.gov.

Recommendations for Executive Action

  1. Status: Closed - Implemented

    Comments: In January and March 2017, the U.S. Department of Agriculture, in collaboration with the Department of Health and Human Services, issued updated select agent regulations and guidance that included clear definitions of inactivation and a validated inactivation procedure that are consistent across the Federal Select Agent Program.

    Recommendation: To understand the extent to which incomplete inactivation occurs and whether incidents are being properly identified, analyzed, and addressed, the Secretary of Agriculture should direct the Animal and Plant Health Inspection Service (APHIS) to develop clear definitions of inactivation that are consistent across the Select Agent Program.

    Agency Affected: Department of Agriculture

  2. Status: Open

    Comments: As of July 2017, the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) within the Department of Health and Human Service (HHS) are taking steps to address this recommendation. Specifically, in January and March 2017, HHS, in collaboration with the United States Department of Agriculture (USDA), issued updated select agent regulations and guidance that included clear definitions of inactivation and a validated inactivation procedure that are consistent across the Federal Select Agent Program. Additionally, HHS stated in December 2016 that NIH will consider providing clear and consistent definitions of inactivation in future guidance that is harmonized with the select agent regulations. Moreover, NIH and CDC told us they plan to include a new appendix in the revised Biosafety in Microbiological and Biomedical Laboratories manual that specifically addresses the development, validation, and implementation of inactivation protocols, which they anticipate releasing in 2 to 3 years.

    Recommendation: To understand the extent to which incomplete inactivation occurs and whether incidents are being properly identified, analyzed, and addressed, the Secretary of Health and Human Services should direct the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) 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.

    Agency Affected: Department of Health and Human Services

  3. Status: Open

    Comments: In March 2017, officials from the Federal Select Agent Program told us that they are in the process of modifying the program?s incident reporting form to include reporting of inactivation failures, with completion anticipated by summer 2017.

    Recommendation: To understand the extent to which incomplete inactivation occurs and whether incidents are being properly identified, analyzed, and addressed, the Secretary of Agriculture should direct APHIS to 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.

    Agency Affected: Department of Agriculture

  4. Status: Open

    Comments: In March 2017, officials from the Federal Select Agent Program told us that they are in the process of modifying the program?s incident reporting form to include reporting of inactivation failures, with completion anticipated by summer 2017. In addition, in August 2016, the National Institutes of Health (NIH) revised its template for reporting incidents subject to the NIH Guidelines to include a specific checkbox for entities to identify incidents that involve incomplete inactivation.

    Recommendation: To understand the extent to which incomplete inactivation occurs and whether incidents are being properly identified, analyzed, and addressed, the Secretary of Health and Human Services should direct CDC and NIH to 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.

    Agency Affected: Department of Health and Human Services

  5. Status: Open

    Comments: In March 2017, United States Department of Agriculture (USDA) officials stated that the department, in coordination with the Department of Health and Human Services (HHS), has examined current gaps related to inactivation and are in the process of taking steps to increase research on applied biosafety, in part to improve scientific understanding of processes for inactivation in high-containment laboratories. We are waiting for documentation and timeframes for implementation.

    Recommendation: To increase scientific information on inactivation and viability testing, the Secretaries of Health and Human Services and Agriculture should coordinate research efforts and take actions to help close gaps in the science of inactivation and viability testing across high-containment laboratories.

    Agency Affected: Department of Agriculture

  6. Status: Open

    Comments: In March 2017, Department of Health and Human Services (HHS) officials stated that the department, in coordination with the United States Department of Agriculture (USDA), has examined current gaps related to inactivation and are in the process of taking steps to increase research on applied biosafety, in part to improve scientific understanding of processes for inactivation in high-containment laboratories. We are waiting for documentation and timeframes for implementation.

    Recommendation: To increase scientific information on inactivation and viability testing, the Secretaries of Health and Human Services and Agriculture should coordinate research efforts and take actions to help close gaps in the science of inactivation and viability testing across high-containment laboratories.

    Agency Affected: Department of Health and Human Services

  7. Status: Closed - Implemented

    Comments: In March 2017, the United States Department of Agriculture (USDA), in collaboration with the Department of Health and Human Services (HHS), issued Federal Select Agent Program guidance on the inactivation of select agents and toxins. According to USDA, this guidance is intended to assist entities with development and implementation of inactivation procedures and viability testing. Our review found the guidance to generally be comprehensive, consistent, and applicable across the Federal Select Agent Program. This fulfills the intent of the recommendation.

    Recommendation: To help ensure that inactivation protocols are scientifically sound and are effectively implemented, the Secretary of Agriculture should direct APHIS to create comprehensive and consistent guidance for the development, validation, and implementation of inactivation protocols--to include the application of safeguards--across the Select Agent Program.

    Agency Affected: Department of Agriculture

  8. Status: Open

    Comments: In March 2017, the Department of Health and Human Services (HHS), in collaboration with the United States Department of Agriculture (USDA), issued Federal Select Agent Program guidance on the inactivation of select agents and toxins. According to HHS, this guidance is intended to provide additional information to regulated entities to assist them in meeting new requirements for rendering samples with select agents as non-viable. HHS also stated that the Federal Select Agent Program will continue to work with other federal agencies to ensure that the federal government is addressing inactivation in a consistent manner. In addition, according to HHS, the National Institutes of Health (NIH) will consider providing clear and consistent guidance related to inactivation that is harmonized with the Federal Select Agent Program as appropriate. As of March 2017, NIH and the Centers for Disease Control and Prevention (CDC) were in the process of revising the Biosafety in Microbiological and Biomedical Laboratories manual to include a new appendix that addresses the development, validation, and implementation of inactivation protocols. HHS plans to release the updated manual in 2 to 3 years.

    Recommendation: To help ensure that inactivation protocols are scientifically sound and are effectively implemented, the Secretary of Health and Human Services should direct CDC and NIH to create comprehensive and consistent guidance for the development, validation, and implementation of inactivation protocols--to include the application of safeguards--across the Select Agent Program, NIH's oversight of recombinant pathogens, and the Biosafety in Microbiological and Biomedical Laboratories manual.

    Agency Affected: Department of Health and Human Services

  9. Status: Open

    Comments: The Department of Health and Human Services (HHS) stated in March 2017 that the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) are in the process of revising the Biosafety in Microbiological and Biomedical Laboratories manual to include a new appendix that addresses inactivation methods, including guidance on documenting the shipment of inactivated material by 2020. HHS plans to release the updated manual in 2 to 3 years.

    Recommendation: To help ensure that dangerous pathogens can be located in the event there is an incident involving incomplete inactivation, the Secretary of Health and Human Services should direct the Directors of CDC and NIH, when updating the Biosafety in Microbiological and Biomedical Laboratories manual, to include guidance on documenting the shipment of inactivated material.

    Agency Affected: Department of Health and Human Services

  10. Status: Open

    Comments: In July 2017, officials from the Federal Select Agent Program stated that the program is in the process of developing categories of inspection departures, grouped by level of risk, along with enforcement options that may be applied for each category, which it was still in the process of finalizing. GAO will review the revised program documents once finalized.

    Recommendation: To help ensure more consistent enforcement for violations involving incomplete inactivation of select agents, the Secretary of Agriculture should direct APHIS to develop and implement consistent criteria and documentation requirements for referring violations to investigative entities and enforcing regulations related to incidents involving incomplete inactivation.

    Agency Affected: Department of Agriculture

  11. Status: Open

    Comments: In July 2017, officials from the Federal Select Agent Program told us that the program is in the process of developing categories of inspection departures, grouped by level of risk, along with enforcement options that may be applied for each category, which it was still in the process of finalizing. GAO will review the revised program documents once finalized. In addition, the Centers for Disease Control and Prevention worked with the Department of Health and Human Services (HHS) Office of Inspector General (OIG) to develop a policy document that outlines criteria for referring violations to the HHS OIG. One of the criterion for referral is ?any departure from the select agent regulations that creates a danger to public health and safety.? This policy document was finalized in June 2017.

    Recommendation: To help ensure more consistent enforcement for violations involving incomplete inactivation of select agents, the Secretary of Health and Human Services should direct CDC to develop and implement consistent criteria and documentation requirements for referring violations to investigative entities and enforcing regulations related to incidents involving incomplete inactivation.

    Agency Affected: Department of Health and Human Services

 

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