EXECUTIVE SUMMARY

Final Document: Final_Report_of_the_Variola_Mishap-2017
In August of 2016, the National Institutes of Health (NIH) appointed a Blue Ribbon Panel to review the July 2014 discovery of six vials containing variola virus, the causative agent of smallpox, as well as over 300 other previously undiscovered biological samples on the NIH Bethesda, Maryland campus. The samples were found in an unsecured cold-storage room in a building occupied and managed by Food and Drug Administration (FDA) staff under NIH biosafety and biosecurity oversight.
The Panel includes a diverse group of seven external subject matter experts, and was constituted as a Working Group of the National Science Advisory Board for Biosecurity (NSABB), a federal advisory committee to the United States Government. The Panel began its work in August of 2016 and completed this final report in May of 2017. The Blue Ribbon Panel was charged with a number of tasks, including, 1) to determine how the smallpox virus vials came to be improperly stored and overlooked for years; 2) to identify any systemic issues that contributed to the lapse; and 3) to evaluate whether NIH had taken adequate corrective actions in response to this incident. It should be noted that this incident was one of several biosafety lapses involving federally regulated pathogens that occurred in the United States in 2014. These incidents caused considerable concern and led to substantial remedial activity throughout the United States Government.
Smallpox was a devastating, contagious disease that infected over 300 million people in the 20th century, killing up to 30% of those infected. It was declared eradicated by the World Health Organization in 1980, and by international agreement, the remaining acknowledged samples were to be placed under tight control and oversight in only two repositories: in the US, at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and in Russia, now at The State Research Center of Virology and Biotechnology (VECTOR), Novosibirsk.
While there are now smallpox vaccines available in the U.S. should they be needed, routine vaccination of Americans ceased in the mid-1970’s. As a result, nearly half of the population is unvaccinated, and, because vaccine effectiveness wanes over time, nearly the entire US population is potentially vulnerable to infection. The finding of viable smallpox virus samples outside of the established repositories was totally unanticipated and required an appropriate response and a rethinking of laboratory biosafety and biosecurity policy at NIH.
The Blue Ribbon Panel evaluation benefited from several prior comprehensive investigations of the smallpox virus incident, including by the Federal Bureau of Investigation jointly with the CDC, by the Government Accountability Office, and by Congress. The FDA also conducted an internal review. The Blue Ribbon Panel examined relevant federal and biosafety policy, regulation and guidance documents, as well as the many administrative actions taken by NIH in response to the 2014 smallpox virus discovery. The Panel visited pertinent sites on the NIH

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campus, and interviewed those who had knowledge of or responsibility for the response. The Panel assessed that the incident has been now adequately evaluated and documented. Some questions remain, however, including the identity of the original owner of the samples and how they may have come to be in the cold-storage room. Unless further new information surfaces to solve this mystery, it is unlikely to be resolved, due to the passage of time. In addition, storage of the samples likely occurred before the Select Agents Program was established, at a time when biosafety standards were very different from today.
The Blue Ribbon Panel identified several key factors that contributed to the smallpox virus incident: There was a lack of individual responsibility for infectious materials in the FDA occupied space where the vials were found. There were also numerous missed opportunities to find the samples prior to 2014, particularly in the 1980’s when all smallpox virus samples were required to be either destroyed or sent to CDC, and again in 2003 when laws governing the possession of regulated pathogens, called “select agents,” were implemented. In addition, a lack of policies for dealing with abandoned research materials and for regular inventory of potentially hazardous biological materials were major contributors to the occurrence of this incident.
The panel assessed the response to the incident as appropriate and thorough, with excellent inter-agency cooperation (including the FBI) to manage a highly unusual situation. However, the Panel noted several specific problematic issues relating to the immediate response after discovery of the smallpox virus and other samples. In particular, the Panel determined that given the potentially hazardous nature of the abandoned samples, there are significant concerns about how they were packaged and transferred between buildings on the NIH campus. Following the discovery by an FDA official, it was decided by NIH that the samples should be immediately transferred to a secure high-containment Biosafety Level 3 laboratory. The samples, in their original boxes, were packaged into a larger cardboard box, and then handcarried to the secure NIH laboratory. No negative consequences occurred — there were no infections or injuries — but packaging and transport of the samples were conducted in ways that presented both biosafety and security risks. Other concerns identified by the panel included inadequate chain-of-custody and logging of events directly after the discovery of the vials, and the use of cardboard in cold-storage rooms. Although secondary to the issues associated with this event, cardboard containers can contribute to mold and unsanitary conditions.
The Panel assessed efforts pursued by NIH following the incident that were intended to improve biosafety and biosecurity procedures and minimize the likelihood of such occurrences in the future. It was determined that most of the factors and causative issues have been addressed by NIH’s subsequent efforts and policy revisions and are detailed in the report. However, there are several remaining issues requiring attention.

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The Blue Ribbon Panel offers to NIH the following observations and recommendations. First, with regard to specific, detailed steps NIH should take to remedy remaining gaps in biosafety policies and procedures, the BRP recommends:  Revise several specific biosafety policies and procedures, as detailed in the report.  Rapidly finish the on-going space audit to ensure responsibility and oversight of all research materials is assigned to individuals by name, and updated as required by personnel changes.  Ensure that any shared research space arrangements have clear written agreements with responsibilities well defined.  The BRP noted that NIH policies and procedures use terms that are not in general use; such as “High consequence pathogens,” “and “potentially infectious materials. These categories need to be defined carefully or eliminated when not clearly necessary.

Second, regarding more general approaches to improving biosafety and biosecurity at NIH, the BRP considers the following to be important considerations:

 Effective and complete implementation of current policies, procedures, guidance and practices on an on-going basis over time will be critical to ensuring safety and security surrounding pathogen research at NIH.  The importance of leadership at the highest levels and continuous efforts to develop and maintain a culture of safety and responsibility among research staff cannot be overemphasized.  There would be significant benefits to having consistent biosafety and biosecurity policies across the Department of Health Human Services (HHS) and the entire USG; ideally, insofar as possible, these should be harmonized with efforts by governments and international institutions as well. The BRP recommends continuing on-going efforts to address these issues.  Response plans coordinated and exercised with agencies outside of HHS, including the Federal Bureau of Investigation, the Environmental Protection Agency and others, as needed, remain important.  The variola virus incident illustrates how changes in infectious disease epidemiology and biosafety practices over time can radically alter a situation from “standard lab practice” to a potential major public health event.
The Blue Ribbon Panel concludes its effort with the observation that the smallpox virus incident illustrates how biosafety practices and laboratory management need to be continually evaluated. There was a time that research with smallpox virus could be conducted in relatively routine containment settings because the virus presented no extraordinary danger to the US population, as most everyone was vaccinated. As other infectious diseases are eradicated or controlled in the future, similar situations to the events of 2014 may arise — for example, with polio virus, which is currently close to eradication. Research samples and collections not

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previously considered a significant biosecurity concern, need to be routinely re-evaluated to ensure proper biosafety and handling so that public health and safety are not compromised.