High-Containment Laboratories: Actions Needed to Mitigate Risk of Potential Exposure and Release of Dangerous Pathogens
Published: 2016-09-23T00:00:00

Fast Facts:
In 2015, the Department of Defense discovered that one of its labs had inadvertently sent live anthrax to almost 200 other labs worldwide over 12 years. The lab's "inactivation" (removal of hazardous effects) of the pathogen was incomplete.
Both the science and the federal guidance around pathogen inactivation are limited and inconsistently implemented. No one knows how many incomplete inactivation incidents have occurred because labs don't have to identify them in incident reports, and are only required to report incidents involving certain pathogens. The report related to this testimony recommends ways to address incomplete inactivation risks.

Highlights:
section_title: Why GAO Did This Study
paragraphs: 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 .
section_title: What GAO Found
paragraphs: 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.

section_title: Letter
paragraphs: We are pleased to be here today to discuss our work on high-containment  laboratories, with a particular focus on the inactivation of pathogens,  which is the removal of a pathogen’s hazardous effects while retaining  characteristics of interest for future use. A number of concerns have  been raised in recent years about the biological safety and security of  pathogens in high-containment laboratories, and we have previously  reported on these issues. For example, in 2009, we found that oversight  of high-containment laboratories is duplicative and fragmented and relies  on self-policing. Agencies have made some progress in implementing  many of our past recommendations, but the United States still does not  have a single entity charged with overseeing the implementation of a  national strategy to identify the aggregate risks associated with the  expansion of the number of high-containment laboratories and the nature  and extent of oversight needed.
Our testimony today summarizes our August 2016 report entitled High- Containment Laboratories: Improved Oversight of Dangerous Pathogens  Needed to Mitigate Risk. In May 2015, the Department of Defense  discovered that one of its laboratories had inadvertently sent live Bacillus  anthracis, the bacterium that causes anthrax, to almost 200 laboratories  worldwide over the course of 12 years. Several other incidents involving  incomplete inactivation of pathogens have occurred in the United States  in recent years, potentially exposing people to dangerous pathogens that  can cause infectious diseases.
Researchers in high-containment laboratories may perform inactivation  for a variety of reasons, such as to develop vaccines or perform  diagnostic testing, and may perform inactivation on a variety of  pathogens, including pathogens classified as select agents. Select agents  are pathogens, such as bacteria, viruses, and toxins, that have the  potential to pose a severe threat to human, animal, or plant health and  safety, or to animal or plant products. The Federal Select Agent Program  (Select Agent Program) regulates the possession, use, and transfer of  select agents and is comprised of the Department of Health and Human  Services’ (HHS) Centers for Disease Control and Prevention’s (CDC)  Division of Select Agents and Toxins and the Department of Agriculture’s  (USDA) Animal and Plant Health Inspection Service’s (APHIS) Agriculture  Select Agent Services. These agencies are responsible for providing  oversight and ensuring that high-containment laboratories that work with  select agents comply with relevant regulations. In addition, the National  Institutes of Health (NIH) provides oversight and guidance for working  with pathogens that contain recombinant or synthetic nucleic acid  molecules.
This testimony addresses (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.
For our August 2016 report, we examined the implementation of  inactivation at federal, academic, and private high-containment  laboratories in the United States, including incidents involving incomplete  inactivation. We convened, with the assistance of the National Academy  of Sciences, a meeting with experts to discuss issues related to the  inactivation of pathogens in high-containment laboratories. To evaluate  the extent to which incidents involving incomplete inactivation occurred,  we analyzed documentation on incidents reported to the Select Agent  Program and NIH from 2003 through 2015 and interviewed agency  officials. During interviews with agency officials and our expert meeting,  we asked about challenges and safeguards associated with the  implementation of inactivation in high-containment laboratories. We also  reviewed Select Agent Program guidance and inspection documents and  interviewed agency officials regarding the steps the program had taken to  refer violations and enforce regulations related to incidents involving  incomplete inactivation. Additional information on our scope and  methodology is available in our report. The work upon which this  testimony is based was performed in accordance with generally accepted  government auditing standards.
subsections: section_title: The Total Number of Incidents Involving Incomplete Inactivation of Pathogens Is Unknown
paragraphs: 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.
section_title: Gaps in Science and Limited Guidance Affect the Implementation of Inactivation in High-Containment Laboratories
paragraphs: 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.
section_title: The Select Agent Program Inconsistently Referred Violations and Enforced Regulations Related to Incidents Involving Incomplete Inactivation
paragraphs: 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.
section_title: GAO Contact and Staff Acknowledgments
paragraphs: 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.
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