A Call for a National Agency for Biorisk Management

Background

As cases of a mysterious pneumonia led to a global pandemic, scientists around the world led the charge against COVID-19. Researchers quickly identified the etiological agent of COVID-19 and shared the full sequence of its genome days later. Key transmissibility, pathogenicity, and stability studies were conducted with unprecedented levels of data sharing to inform evidence-based public health measures on personal protective equipment, disinfection, engineering controls, and social distancing to “flatten the curve.” In less than a year, an impressive feat of scientific research produced a highly effective vaccine ready for manufacturing and distribution. These accomplishments would not have been achieved without the ability to conduct this research safely; underlying these enormous achievements is a crucial component of the vaccine development process: biorisk management, the field that seeks to prevent biological materials from causing harm via an accident or intentional misuse.

When done well, biorisk management ensures that work done with the world's most dangerous pathogens—research that is crucial to preparing for the next pandemic—is of minimal risk to the communities in which it occurs. At the same time, however, the enormity of the pandemic's human and economic toll underscores that highly transmissible pathogens must be carefully controlled so that the benefits of the research enterprise are not completely undone by a single incident. This fact remains true even if the pandemic was a result of natural phenomena.

Unlike research on pathogens, other enterprises with the potential for accidents that could harm communities are highly regulated in the United States, including nuclear power (regulated by the Nuclear Regulatory Commission), transportation of hazardous materials (regulated by the Pipeline and Hazardous Materials Safety Administration under the Hazardous Materials Regulations), ¹ and chemical manufacturing (regulated under the Toxic Substances Control Act of 1976² and the Pollution Prevention Act of 1990 ³ ). Yet today in the United States, many biological laboratories have no outside authority tasked with oversight and regulation, and no federal entity has biorisk management as its core mission. Notably, life science laboratories currently are subject to regulations with the force of law regarding research involving human subjects, vertebrate animals, radioisotopes, and hazardous waste, but they are not subject to regulations with the force of law regarding biorisk management.

Current oversight of biorisk management is determined by a patchwork of guidance, policies, ordinances, and regulations that depend on the pathogen being studied, funding source, and laboratory location. For example, the US Centers for Disease Control and Prevention and the US Department of Agriculture can regulate laboratories that possess select agents but have little control over laboratories that research other transmissible pathogens. ⁴ Funders can dictate how a researcher must operate to receive funding, but a shrinking proportion of funding in the life sciences originates from the federal government. ⁵ The Biden administration has explicitly recognized that improving biosafety and biosecurity is an essential measure to prevent future pandemics and that the return on these investments is well worth their potential cost. ⁶ The Biden administration should be lauded for these efforts, yet the action plan elaborated does not address all gaps in biorisk management.

Currently, the US government does not know the location of laboratories working with pathogens, what pathogens are being studied within these laboratories, or the conditions under which these laboratories are operating—something the US Government Accountability Office itself has repeatedly recognized as a serious issue. ⁷ This lack of oversight and awareness undermines efforts to understand risk and to ensure that work is being conducted safely and securely. Moreover, the United States cannot make strategic investments in pathogen research to address gaps if the country has an incomplete understanding of the current facilities, personnel, and research programs already undertaking this work.

The most robust US governance for work on pathogens derives from the authority under the Select Agent Regulations, ⁸ although its sole focus on select agents leaves glaring holes. Hypothetically, for example, a privately funded laboratory in the United States that studies the influenza A subtype H2N2, which caused a pandemic in the early 20th century that left 1 million people dead, ⁹ would require no federal oversight even if that laboratory was attempting to make strains more transmissible or more pathogenic than the wild strain. No federal entity could stop this research or ensure its safe conduct, and in many locales, no state or local entity could either. In addition, no one is mandated to determine if the researchers with access to this pathogen in these laboratories have a criminal background or are known to associate with terrorists.

Without independent oversight, ultimate biorisk management authority resides in the same institution that is conducting or funding the research; therefore, conflicts of interest abound. ¹⁰ In the private sector, the biosafety authority reports to the management of the facility. In the government, the biosafety authority reports to the director of the center, institute, or agency. The decision not to conduct research that is too risky—or to manage risk by changing protocols or investing in more safety measures—pits safety concerns against the desire for funding and prestige.

Additionally, identifying safety and security weaknesses can damage the reputation of the home organization, potentially disincentivizing personnel within the organization to report issues. This is a real concern we have heard expressed by biosafety professionals. Only by empowering an outside organization that has biorisk management authority can these inherent conflicts of interest be addressed. Importantly, this reporting should be used only to improve safety practices and must not trigger additional regulatory action or other penalties, as a nonpunitive system is vital to fostering open and honest reporting. Such nonpunitive reporting of safety lapses has been cited as an essential factor in the vast improvements in aviation safety observed over the last century.^11,12

Furthermore, the lack of a national body with responsibility for biorisk management results in inefficiencies, waste, and duplication of efforts due to a lack of standardization. Currently, research entities each create their own independent approaches to reduce biological risks and no one is tasked with empirically determining if the various risk mitigation efforts instituted are sufficiently effective. Biorisk management strategies and training are redeveloped repeatedly across different entities, which is an inefficient use of time and resources. Some entities require completion of extensive live training sessions before staff are permitted to work with the most dangerous pathogens, while other entities merely require attendance at lectures. Many entities perform extensive risk assessment, but some take a minimalist approach.

The lack of harmonization across institutions is further revealed by the fact that there is no standard for the number of biorisk management professionals needed by a facility. Some facilities have no dedicated person assigned to this task (or that person has minimal experience), undermining safety efforts; for example, less than 40% of clinical laboratories have an employee with a full-time responsibility for biorisk management. ¹³ Perhaps worse, this lack of standardization means that an institution could suffer from a risk already discovered and mitigated by another—the very scenario that motivated the airline industry to better share data on accidents and near misses. The airline industry began to share data only after discovering that an accident that killed 92 people could have been prevented if the information on a flight that nearly crashed 2 months earlier under nearly identical circumstances had been shared more broadly. ¹⁴ The biological enterprise can—and should—do better.

Moreover, no authority has the mission of improving biorisk management and overseeing research. Currently, we lack data on factors that contribute to accidents and the effectiveness of measures meant to prevent or mitigate them. Because no government agency has the responsibility to improve biosafety and biosecurity, no federal funding is available for this crucial work. Encouragingly, the Biden administration's American Pandemic Preparedness plan calls for such funding, ⁶ but it has yet to be implemented.

The lack of scientific data in biorisk management hampers the research community's ability to ensure that mitigation measures are adequate for new experiments and modified pathogens. The lack of these data prevents smart investments in biorisk management because we cannot determine if we are spending enough, not enough, or too much. ¹⁵ The administration's plan includes a call for the establishment of a “mission control” within the US Department of Health and Human Services to oversee progress toward the goals to respond to and prevent pandemics, including improvements in biosafety and biosecurity research. ⁶ While the administration should be lauded for recognizing the importance of biorisk management research, the mission control, as outlined, would encompass only one of the critical roles that is necessary for effective biorisk management in the United States. Conversely, this mission control also has many missions beyond that of laboratory biorisk management; these missions would be beyond the scope of a national authority focused on mitigating biorisks. Moreover, the current plan does not clarify if this mission control would coordinate research conducted at other organizations—currently, there is little coordination—or if it would hire the technical, administrative, financial, and managerial talent needed to manage the research directly. Unless housed in a new federal entity, this mission control would not resolve the conflict of interest caused by assigning oversight responsibility to a federal entity that performs or funds research, or both.

The Solution

We propose the creation of a new, independent federal entity, which we are calling the National Agency for Biorisk Management (NABM), that will sit outside of any existing agency, ensuring that NABM would have the ability to provide oversight for safety in laboratories operating within or funded by the US Centers for Disease Control and Prevention, US National Institutes of Health, US Department of Agriculture, US Department of Defense, US Department of Energy, US Environmental Protection Agency, US Food and Drug Administration, and others, without conflicts of interest. NABM would oversee all US laboratories working on pathogens; the risk group of the pathogen roughly corresponds with the biosafety level (BSL) of the lab that works on it, so Risk Group 2 agents are manipulated in BSL-2 laboratories. ¹⁶ By providing oversight to all pathogen laboratories, NABM would help certify that private laboratories are operating safely and securely, thereby reducing industry's exposure to liability. The oversight powers of NABM will largely focus on providing advice and guidance—much like biosafety officers inside institutions do today—but will also include the ability to prevent or halt research that is not being conducted safely because researchers refuse to implement necessary mitigation actions.

NABM will not supplant existing institutional or federal risk assessments or research review, but instead will provide oversight and review of existing efforts to ensure that no review falls below a set standard. As NABM would have visibility across all laboratories, it would have the data necessary to enable our government to make strategic decisions related to the funding of pathogen research. It would also retain the data on accidents and near misses in laboratories.

To improve laboratory safety in the long term, the mission of NABM will include coordinating and funding basic and applied research in biorisk management. This research would span a variety of disciplines (eg, life sciences, engineering, social sciences, human systems), and its funding would foster a community of practice committed to biosafety. This research is essential to ensure that the science of biorisk management keeps pace with the advancing science of biology. Also, additional data underpinning biorisk management could help determine which mitigations are effective and identify the appropriate levels of funding for biorisk management, resulting in no more and no less being spent than required.

By promoting and implementing standards for biorisk management, including training guidance, NABM will improve the efficiency of the pathogen research enterprise. Moreover, because most—but not all—institutions are investing substantial time and funding in implementing training and biorisk assessment systems, these standards will ensure that all members of the community are meeting a baseline level of biorisk management, thus eliminating the advantage that laboratories implementing a slapdash approach have over the vast majority of laboratories that invest heavily in biorisk management. The standards will not be prescriptive, acknowledging that flexibility in managing biorisks is necessary to accommodate unique aspects of each facility, experiment, environment, staff member, and physical plant. The standards, however, will provide a set of minimum biorisk management practices that all institutions must have when working with pathogens.

This Concept Is Not New

Many of these issues were noted in 2014 by the Federal Experts Security Advisory Panel, which recommended establishing a robust biosafety research program and a nonpunitive and anonymous system for reporting biosafety lapses and accidents where the institution is not subject to additional regulation. ¹⁷ NABM would be the natural home for this reporting system and research, which would eliminate inherent conflicts of interest.

While creating a new federal entity may appear like an immense challenge, similar efforts have been undertaken before. The US Department of Homeland Security was created in the aftermath of the terrorist attacks of September 11, 2001. Regardless of the origin of the COVID-19 pandemic, the fact that a laboratory origin of this pandemic is feasible due to weaknesses in the oversight of pathogen research should provide enough justification for a similar government restructuring, given that the harm caused by the pandemic far exceeds that suffered on September 11, 2001.

Palmer et al ¹⁰ provide an interesting discussion of various federal bodies that could serve as a model for NABM. The Nuclear Regulatory Commission (NRC) is, perhaps, the most applicable model for NABM due to its independence, funding mechanism, and dual regulatory and research mission. NRC was created to reduce risks arising from the use of radiological and nuclear material and to ensure the safety and security of these materials nationwide without conflict of interest. ¹⁸ NRC is also the home of safety and security research in the field, which greatly reduced the risk of radiological and nuclear accidents over the long term. Most of its funding is derived from fees from users of radiological and nuclear materials. Ironically, the most stringent inspections most biological laboratories receive today occur due to the use of radiological materials in biological experiments, even though the risks of irresponsible use of radiological materials pale in comparison with the risks posed by irresponsible use of pathogens.

The funding of NABM could mirror that of NRC. Those who wish to conduct research with pathogens would pay a fee to NABM. This fee would be tailored to the amount of containment space needed, the number of different pathogens held, and the risk group of the pathogens held. The fee would, therefore, be proportional to the amount of oversight required and the amount of benefit the institution would obtain by the standards and templates offered by NABM. Currently, universities pay NRC a fee of several thousand dollars to use radiological material for research purposes. ¹⁹ A cost–benefit analysis is required to determine the optimum balance of direct federal funding versus funding of NABM through fees without putting an undue burden on the research community, while ensuring long-term sustainability of NABM.

Federal oversight of all (ie, private, academic, clinical, research) BSL-2 laboratories would be a major expansion beyond the Federal Select Agent Program ²⁰ because many more laboratories work with Risk Group 2 agents than Risk Group 3 agents (many Risk Group 3 agents are select agents, but not all). To prove the value of NABM prior to a major regulatory expansion, NABM could first oversee all BSL-3 and BSL-4 facilities while also conducting its other critical missions, including funding biorisk management research, developing standards, and collecting data on incidents.

Using data from this initial phase, a cost–benefit analysis should be conducted to determine if NABM should be expanded to oversee all BSL-2+ laboratories (eg, laboratories that have notable enhancements over most BSL-2 facilities such as those that work on the H3N2 pandemic flu strain) and then an expansion to all BSL-2 facilities. Funding must be sufficient to ensure that NABM is adequately staffed both to provide oversight of ongoing research and to review research protocols without delaying progress in the life sciences; because much of the risk of research is realized when experiments are begun, review of protocols is an essential step in mitigating potential risks. The Federal Select Agent Program typically can review new protocols in a few weeks to a few months, but the larger scope of NABM would require more reviewers to avoid further delays and perhaps shorten the current review times.

Compared with other nations, the United States lags in oversight and regulation of the life sciences. Canada's Centre for Biosecurity licenses all pathogen laboratories, verifies safety compliance in laboratories, regulates transfer of pathogens, receives incident reports, and provides biosafety standards, guidelines, training, and information. ²¹ This entity is funded by the government of Canada (not user fees) under the Health Security Infrastructure Branch of the Public Health Agency of Canada, which has a total budget of less than US$60 million. The United Kingdom's Health and Safety Executive receives notification of work with pathogens and centralizes all reporting of laboratory-acquired infections but has few other functions of the proposed NABM. ²² China and India also centralize reporting and approval for work on dangerous pathogens. ²³

Recognizing gaps in strengthening biosafety in the country, the US Government Accountability Office recommended the creation of a “single entity charged with […] evaluation of high containment laboratories” back in 2009. ⁷ This entity would have been charged with identifying all laboratories working on dangerous pathogens to understand if the United States has adequate or surplus capacity to address the risk of disease agents, estimate risks of further expansion of this capacity, recommend necessary oversight of these laboratories, and develop standards for the design, construction, and operation of these laboratories.

The American Pandemic Preparedness plan clearly shows the Biden administration has recognized that the potential human and economic toll of future pandemics justifies billion-dollar investments to prevent pandemics—and that biorisk management is a central pillar in this strategy. ⁶ NABM can be established and operated with a similar investment and is crucial to address persistent weaknesses in biorisk management in the United States that have not yet been addressed in any federal plan. By establishing NABM, the United States can strengthen biorisk management and ensure that scientific progress is not undone by a preventable accident.