High-Containment Laboratories: Recent Incidents of Biosafety Lapses
Published: 2014-07-16T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Recent biosecurity incidents—such as the June 5, 2014, potential exposure of staff in Atlanta laboratories at the Centers for Disease Control and Prevention (CDC) to live spores of a strain of anthrax—highlight the importance of maintaining biosafety and biosecurity protocols at high-containment laboratories. This statement summarizes the results of GAO's past work on the oversight of high-containment laboratories, those designed for handling dangerous pathogens and emerging infectious diseases. Specifically, this statement addresses (1) the need for governmentwide strategic planning for the requirements for high-containment laboratories, including assessment of their risks; (2) the need for national standards for designing, constructing, commissioning, operating, and maintaining such laboratories; and (3) the oversight of biosafety and biosecurity at high-containment laboratories. In addition, it provides GAO's preliminary observations on the potential exposure of CDC staff to anthrax. For this preliminary work, GAO reviewed agency documents, including a report on the potential exposure, and scientific literature; and interviewed CDC officials.
section_title: What GAO Found
paragraphs: No federal entity is responsible for strategic planning and oversight of high-containment laboratories. Since the 1990s, the number of high-containment laboratories has risen; however, the expansion of high-containment laboratories was not based on a government-wide coordinated strategy. Instead, the expansion was based on the perceptions of individual agencies about the capacity required for their individual missions and the high-containment laboratory activities needed to meet those missions, as well as the availability of congressionally approved funding. Consequent to this mode of expansion, there was no research agenda linking all these agencies, even at the federal level, that would allow for a national needs assessment, strategic plan, or coordinated oversight. As GAO last reported in 2013, after more than 12 years, GAO has not been able to find any detailed projections based on a government-wide strategic evaluation of research requirements based on public health or national security needs. Without this information, there is little assurance of having facilities with the right capacity to meet the nation's needs.
GAO's past work has found a continued lack of national standards for designing, constructing, commissioning, and operating high-containment laboratories. As noted in a 2009 report, the absence of national standards means that the laboratories may vary from place to place because of differences in local building requirements or standards for safe operations. Some guidance exists about designing, constructing, and operating high-containment laboratories. Specifically, the Biosafety in Microbiological and Biomedical Laboratories guidance recommends various design, construction, and operations standards, but GAO's work has found it is not universally followed. The guidance also does not recommend an assessment of whether the suggested design, construction, and operational standards are achieved. As GAO has reported, national standards are valuable not only in relation to new laboratory construction but also in ensuring compliance for periodic upgrades.
No one agency is responsible for determining the aggregate or cumulative risks associated with the continued expansion of high-containment laboratories; according to experts and federal officials GAO interviewed for prior work, the oversight of these laboratories is fragmented and largely self-policing.
On July 11, 2014, the Centers for Disease Control and Prevention (CDC) released a report on the potential exposure to anthrax that described a number of actions that CDC plans to take within its responsibilities to avoid another incident like the one in June. The incident in June was caused when a laboratory scientist inadvertently failed to sterilize plates containing samples of anthrax, derived with a new method, and transferred them to a facility with lower biosecurity protocols. This incident and the inherent risks of biosecurity highlight the need for a national strategy to evaluate the requirements for high-containment laboratories, set and maintain national standards for such laboratories' construction and operation, and maintain a national strategy for the oversight of laboratories that conduct important work on highly infectious pathogens.
section_title: What GAO Recommends
paragraphs: This testimony contains no new recommendations, but GAO has made recommendations in prior reports to responsible agencies.

section_title: Letter
paragraphs: I am pleased to be here today to participate in today’s hearing to address  recent biosecurity incidents. On June 5, 2014, staff in Atlanta laboratories  at the Centers for Disease Control and Prevention (CDC) were potentially  exposed to live spores of the Ames strain of anthrax (Bacillus anthracis or  B. anthracis). On July 1, 2014, at the Bethesda, Maryland, National  Institutes of Health (NIH), vials of potentially live smallpox (variola) virus  were unexpectedly discovered. Public attention is once again focused on  the importance of maintaining biosafety and biosecurity protocols at high- containment laboratories.
My statement summarizes the results of our past work on the oversight of  high-containment laboratories and our preliminary assessment of the  recent incident in Atlanta. Since 2007, we have reported on several  issues associated with the proliferation of high-containment laboratories  and risks posed by past biosafety incidents. The public is concerned  about these laboratories because exposing workers and the public to  dangerous pathogens, whether deliberate or accidental, can have  disastrous consequences. Highly publicized laboratory errors and  controversy about where high-containment laboratories should be located  have raised questions about whether the governing framework,  standards, and oversight for biosafety and biosecurity measures are  adequate.
This testimony is primarily based on GAO’s past work on high- containment laboratories. The issues in this work covered (1) the need for  governmentwide strategic planning for the requirements for high- containment laboratories, including assessment of their risks; (2) the need  for national standards for designing, constructing, commissioning,  operating, and maintaining such laboratories; and (3) the oversight of  biosafety and biosecurity at high-containment laboratories. Each report  cited in this statement provides detailed information on our work’s  objectives, scope, and methodology (the reports are listed at the end of  this statement). For our preliminary observations, on the June 5–13, 2014  biosafety incident at CDC’s laboratories we interviewed CDC officials and  reviewed agency documents and scientific literature. We provided a draft  of this statement to CDC for technical review and addressed their  comments in the body of our statement where appropriate. We also  reviewed CDC’s July 11, 2014, Report on the Potential Exposure to  Anthrax. The work this statement is based on was conducted 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 provided a reasonable basis for our findings and  conclusions based on our audit objectives.
subsections: section_title: No Federal Entity Is Responsible for Expansion and Oversight of High- Containment Laboratories
paragraphs: The number of biosafety level (BSL)-3 and BSL-4 laboratories (high- containment laboratories) began to rise in the late 1990s, accelerating  after the anthrax attacks throughout the United States. The laboratories  expanded across federal, state, academic, and private sectors.  Information about their number, location, activities, and ownership is  available for high-containment laboratories registered with CDC’s Division  of Select Agent and Toxins (DSAT) or the U.S. Department of  Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS)  as part of the Federal Select Agent Program. These entities register  laboratories that work with select agents that have specific potential  human, animal, or plant health risks.
Other high-containment laboratories work with other pathogens that may  also be dangerous but are not identified as “select agents” and therefore  these laboratories are not required to register with DSAT or APHIS. We  reported in 2009 that information about these non-select agent  laboratories is not known.
Our work has found that expansion of high-containment laboratories was  not based on a government-wide coordinated strategy. The expansion  was based on the perceptions of individual agencies about the capacity  required for their individual missions and the high-containment laboratory  activities needed to meet those missions, as well as the availability of  congressionally approved funding. Decisions to fund the construction of  high-containment laboratories were made by multiple federal agencies  (e.g., Department of Health and Human Services (HHS), Department of  Defense, USDA), in multiple budget cycles. Federal and state agencies,  academia, and the private sector (such as drug companies) considered  their individual requirements, but as we have previously reported a robust  assessment of national needs was lacking.
Since each agency or organization has a different mission, an  assessment of needs, by definition, was at the discretion of the agency or  organization. We have not found any national research agenda linking all  these agencies, even at the federal level, that would allow for a national  needs assessment, strategic plan, or coordinated oversight. As we last  reported in 2013, after more than 12 years, we have not been able to find  any detailed projections based on a government-wide strategic evaluation  of research requirements based on public health or national security  needs. Without this information, there is little assurance of having facilities  with the right capacity to meet our national needs. This deficiency may be  more critical today than 5 years ago when we first reported on this  concern because current budget constraints make prioritization essential.
section_title: National Standards for Designing, Constructing, Commissioning, Operating, and Maintaining High- Containment Laboratories Are Needed
paragraphs: Our work on this issue has found a continued lack of national standards  for designing, constructing, commissioning, and operating high- containment laboratories. These laboratories are expensive to build,  operate, and maintain. For example, we noted in our 2009 report that the  absence of national standards means that the laboratories may vary from  place to place because of differences in local building requirements or  standards for safe operations. In 2007, while investigating a power outage  at one of its recently constructed BSL-4 laboratory, CDC determined that  construction workers digging at an adjacent site had some time earlier cut  a critical grounding cable buried outside the building. CDC facility  managers had not noticed that cutting the grounding cable had  compromised the electrical system of the facility that housed the BSL-4  laboratory. It became apparent that the building’s integrity as it related to  the adjacent construction had not been adequately supervised. In 2009,  CDC officials told us that standard procedures under local building codes  did not require monitoring of the new BSL-4 facility’s electrical grounding.
This incident highlighted the risk of relying on local building codes to  ensure the safety of high-containment laboratories in the absence of  national standards or testing procedures specific to those laboratories.
Some guidance exists about designing, constructing, and operating high- containment laboratories. The Biosafety in Microbiological and Biomedical  Laboratories guidance, often referred to as BMBL recommends various  design, construction and operations standards, but our work has found it  is not universally followed. of whether the suggested design, construction, and operations standards  are achieved. As we have recommended, national standards would be  valuable for not only new laboratory construction but also periodic  upgrades. Such standards need not be constrained in a “one-size fits all”  model but could help specify the levels of facility performance that should  be achieved.
section_title: Risks Associated with Expanding High- Containment Laboratories and Oversight Challenges
paragraphs: Department of Health and Human Services (Washington, D.C., 2007), Biosafety in  Microbiological and Biomedical Laboratories, 5th ed. HHS has developed and provided  biosafety guidelines outlined in this manual. developed by the funding or regulatory agencies. In 2013, we reported  that another challenge of this fragmented oversight is the potential  duplication and overlap of inspection activities in the regulation of high- containment laboratories. We recommended that CDC and APHIS work  with the internal inspectors for Department of Defense and Department of  Homeland Security to coordinate inspections and ensure the application  of consistent inspection standards.
According to most experts that we have spoken to in the course of our  work, a baseline risk is associated with any high-containment laboratory.  Although technology and improved scientific practice guidance have  reduced the risk in high-containment laboratories, the risk is not zero (as  illustrated by the recent incidents and others during the past decade).  According to CDC officials, the risks from accidental exposure or release  can never be completely eliminated and even laboratories within  sophisticated biological research programs—including those most  extensively regulated—has and will continue to have safety failures. Many  experts agree that as the number of high-containment laboratories has  increased, so the overall risk of an accidental or deliberate release of a  dangerous pathogen will also increase.
Oversight is critical in improving biosafety and ensuring that high- containment laboratories comply with regulations. However, our work has  found that aspects of the current oversight programs provided by DSAT  and APHIS depend on entities’ monitoring themselves and reporting  incidents to the regulators. For example, with respect to a certification that  a select agent had been rendered sterile (that is, noninfectious), DSAT  officials told us, citing the June 2014 updated guidance, that “the burden  of validating non-viability and non-functionality remains on the individual  or entity possessing the select agent, toxin, or regulated nucleic acid.”
While DSAT does not approve each entity’s scientific procedure, DSAT  strongly recommends that “an entity maintain information on file in  support of the method used for rendering a select agent non-viable . . . so  that the entity is able to demonstrate that the agent . . . is no longer  subject to the select agent regulations.” Biosafety select agent regulations  and oversight critically rely on laboratories promptly reporting any  incidents that may expose employees or the public to infectious  pathogens. Although laboratories have been reasonably conscientious  about reporting such incidents, there is evidence that not all have been  reported promptly.
section_title: The June 2014 Incident at the CDC Laboratories and GAO’s Preliminary Observation
paragraphs: The June 2014 incident in which live anthrax bacteria were transferred  from a BSL-3 contained environment to lower-level (BSL-2) containment  laboratories at CDC in Atlanta resulted in the potential exposure of tens of  workers to the highly virulent Ames strain of anthrax. According to CDC’s  report, on June 5, a laboratory scientist in the BSL-3 Bioterrorism Rapid  Response and Advanced Technology (BRRAT) laboratory prepared  protein extracts from eight bacterial select agents, including Bacillus  anthracis, under high-containment (BSL-3) conditions.were being prepared for analysis by matrix-assisted laser  desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, a  relatively new technology that can be used for rapid bacterial species  identification. Also, according to CDC officials that we spoke to this  protein extraction procedure was being evaluated in a preliminary  assessment of whether MALDI-TOF mass spectrometry could provide a  cheaper and faster way to detect a range of pathogenic agents, including  anthrax, compared to conventional methods and thus could be used by  emergency response laboratories. According to CDC officials, the  researchers intended to use the data collected in this experiment to  submit a joint proposal to CDC’s Office of Public Health Preparedness  and Response to fund further evaluation of the MALDI TOF method   These samples  because MALDI TOF is increasingly being used by clinical and hospital  laboratories for infectious disease diagnostics.
The protein extraction procedure was chemically based and intended to  render the pathogens noninfectious, which alternative extraction  procedures would have done using heat, radiation, or other chemical  treatments that took longer. The procedure that was used to extract the  proteins was not based on a standard operating procedure that had been  documented as appropriate for all the pathogens in the experiment and  reviewed by more senior scientific or management officials. Rather, the  scientists used a procedure identified by the MALDI TOF equipment  manufacturer that had not been tested for effectiveness, in particular, for  rendering spore-forming organisms such as anthrax noninfectious.  Following that procedure, the eight pathogens were exposed to chemical  treatment for 10 minutes and then plated (spread on plates to test for  sterility or noninfectious status) and incubated for 24 hours. According to  CDC, on June 6, when no growth was observed on sterility plates after 24  hours, the remaining samples, which had been held in the chemical  solution for 24 hours, were moved to CDC BSL-2 laboratories for testing  using the MALDI TOF technology. Importantly, the plates containing the  original sterility samples were left in the incubation chamber rather than  destroyed as would normally occur because of technical problems with  the autoclave that would have been used for destruction.
According to CDC officials, on June 13, a laboratory scientist in the  BRRAT laboratory observed unexpected growth on the anthrax sterility  plate, possibly indicating that the sample was still infectious. (All the other  pathogen protein samples showed no evidence of growth.) That scientist  and a colleague immediately reported the discovery to the CDC Select  Agent Responsible Official (RO) in accordance with the BRRAT  Laboratory Incident Response Plan. That report triggered a response that  immediately recovered the samples that had been sent to the BSL-2  laboratories and returned them to BSL-3 containment, and a response  effort that lasted a number of days was implemented to identify any CDC  employees who might have been affected by exposure to live anthrax  spores. (The details of the subsequent actions and CDC’s lessons  learned and proposed actions are described in CDC’s July 11, 2014,  Report on Potential Exposure to Anthrax. That report indicates that none  of the potentially affected employees experienced anthrax-related  adverse medical symptoms.)
Our preliminary analysis indicates that the BRRAT laboratory was using a  MALDI-TOF MS method that had been designed for protein extraction but  not for the inactivation of pathogens and that it did not have a standard  operating procedure (SOP) or protocol on inactivation. We did not find a  complete set of SOPs for removing agents from a BSL-3 laboratory in a  safe manner. Further, neither the preparing (BRRAT BSL-3) laboratory  nor the receiving laboratory (BRRAT BSL-2) laboratory conducted sterility  testing. Moreover, the BRRAT laboratory did not have a kill curve based  on multiple concentration levels.
When we visited CDC on July 8, it became apparent to us, that a major  cause of this incident was the implementation of an experiment to prepare  protein extractions for testing using the MALDI TOF technology that was  not based on a validated standard operating procedure. acknowledged that significant and relevant studies in the scientific  literature about chemical procedures studied for preparing protein  samples for use in the MALDI TOF technology, were successful in  rendering tested pathogens noninfectious, except for anthrax. The  literature clearly recommends an additional filtering step before  concluding that the anthrax samples are not infectious. Our preliminary  work indicates that this step was not followed for all the materials in this  incident.
Validating a procedure or method provides a defined level of statistical confidence in the  results of the procedure or method. staff did not perform sterility testing on the suspension received in March  2004.
CDC’s 2004 report further stated that “Research laboratory workers  should assume that all inactivated B. anthracis suspension materials are  infectious until inactivation is adequately confirmed [using BSL-2  laboratory procedures].” These recommendations are relevant to the June  2014 incident in Atlanta but were not followed. The laboratories receiving  the protein extractions were BSL-2 laboratories, but the activities  associated with testing with the MALDI TOF technology were conducted  on open laboratory benches, not using biocontainment cabinets otherwise  available in such laboratories.
CDC’s July 11, 2014, Report on the Potential Exposure to Anthrax  describes a number of actions that CDC plans to take within its  responsibilities to avoid another incident like the one in June. However,  we continue to believe that a national strategy is warranted that would  evaluate the requirements for high-containment laboratories, set and  maintain national standards for such laboratories’ construction and  operation, and maintain a national strategy for the oversight of  laboratories that conduct important research on highly infectious  pathogens.
This completes my formal statement, Chairman Murphy, Ranking  Member DeGette and members of the committee. I am happy to answer  any questions you may have.
section_title: GAO Contact and Staff Acknowledgments
paragraphs: For future contacts regarding this statement, please contact Nancy  Kingsbury at (202) 512-2700 or at kingsburyn@gao.gov. Contact points  for our Offices of Congressional Relations and Public Affairs may be  found on the last page of this statement. Sushil Sharma, Ph.D., Dr.PH,  Assistant Director; and Elaine L. Vaurio also made key contributions to  this statement.
section_title: Related GAO Products
paragraphs: High-Containment Laboratories: Assessment of the Nation’s Need Is  Missing. GAO-13-466R. Washington, D.C.: February 25, 2013.
Biological Laboratories: Design and Implementation Considerations for  Safety Reporting Systems. GAO-10-850. Washington, D.C.: September  10, 2010.
High-Containment Laboratories: National Strategy for Oversight Is  Needed. GAO-09-1045T. Washington, D.C.: September 22, 2009.
High-Containment Laboratories: National Strategy for Oversight Is  Needed. GAO-09-1036T. Washington, D.C.: September 22, 2009.
High-Containment Laboratories: National Strategy for Oversight Is  Needed. GAO-09-574. Washington, D.C.: September 21, 2009.
Biological Research: Observations on DHS’s Analyses Concerning  Whether FMD Research Can Be Done as Safely on the Mainland as on  Plum Island. GAO-09-747. Washington, D.C.: July 30, 2009.
High-Containment Biosafety Laboratories: DHS Lacks Evidence to  Conclude That Foot-and-Mouth Disease Research Can Be Done Safely  on the U.S. Mainland. GAO-08-821T. Washington, D.C.: May 22, 2008.
High-Containment Biosafety Laboratories: Preliminary Observations on  the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in the  United States. GAO-08-108T. Washington, D.C.: October 4, 2007.
Biological Research Laboratories: Issues Associated with the Expansion  of Laboratories Funded by the National Institute of Allergy and Infectious  Diseases. GAO-07-333R. Washington, D.C.: February 22, 2007.
Homeland Security: CDC’s Oversight of the Select Agent Program  GAO-03-315R. Washington, D.C.: November 22, 2002.
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