KEY FACTORS FOR BUILDING AND SUSTAINABLY OPERATING HIGH-CONTAINMENT LABS IN LOW-RESOURCE CONTEXTS: AN OVERVIEW
Dr. Nancy Connell, a member of the organizing committee, gave a presentation on key factors for building and sustainably operating high-containment labs in low-resource settings to highlight what determines success. She began with a list of desirable factors, all of which were mentioned during previous presentations or discussions:
- Appropriate infrastructural components and adequate budgets and supply chain for power, water, equipment, reagents, labor, and maintenance services;
- Management and administrative controls and culture;
- Mechanisms to counter safety and security threats;
- Regulatory framework, standards, and enforcement mechanisms;
- Effective regular inspections;
- Affiliation with biosafety and biosecurity organizations, curricula, and training to ensure professional competency; and
- Multidisciplinary design and execution.
Dr. Connell then explained that in 2015, the U.S. government submitted a document to the Meeting of Experts for the Biological Weapons Convention (BWC) titled “The United States of America High Containment Laboratory Policy.” This document, which was included in the meeting book for participants, laid out five guiding principles:
- Establish a demonstrated need for high-containment biocontainment facility in the country.
- Establish that the recipient has demonstrated the commitment and ability to operate and maintain the facility upon completion.
- Establish that the recipient country demonstrates commitment to nonproliferation.
- Foreign policy considerations are addressed.
- Factors related to biological risk management are considered (biosafety, security, training, local codes, and regulations).
Dr. Connell summarized the key points of the U.S. policy document as follows and elaborated on each of these elements.
Sustainability: The operation and maintenance of a high-containment laboratory is an extraordinarily expensive process. Moreover, although required, reliable, high-quality infrastructure (e.g., power, water, waste handling), replacement parts, and trained maintenance and repair personnel may not be readily available in some areas.
“Fit”: “Fit” should be interpreted in terms of national priorities and needs. The report Biosecurity Challenges of the Global Expansion of High-Containment Biological Laboratories (National Research Council, 2012) noted that “when contributing to a new laboratory, donor groups and national governments do not . . . always ascertain how the new facility will complement other existing and planned infrastructure” (page 9).
Safety: High-containment laboratories may increase safety, but only when accompanied by ongoing training, adherence to appropriate protocols, procedures, regulations, and guidelines, and oversight.
Nonproliferation (biosecurity): Although there is a legitimate need for biocontainment facilities worldwide, the inherent dual-use potential of these facilities and related equipment, as well as the pathogens they contain and the skills developed through hands-on work, merit scrutiny in a world where terrorism and the proliferation of weapons-relevant materials, technologies, and expertise pose genuine threats.
The purpose of this brief discussion of the U.S. policy document was to prepare the plenary group for a breakout session to discuss the basis for developing a candidate set of “norms” for funding high-containment laboratories. Dr. Connell shared the following list of “factors to consider,” which combine the key factors and policy considerations, to focus the breakout discussions:
- Assessment of site-specific challenges and needs
- Obtaining commitments of support from in-country government officials
- Soundness and availability of necessary infrastructure: power, water, transportation network, waste treatment, and communications
- Presence or absence of country- or region-specific regulatory framework guidelines and/or standards
- Availability of appropriately trained and credentialed local workforce
- Access to a national or regional biosafety organization
- Biosecurity and nonproliferation considerations.
The group divided into two breakout groups in separate rooms. Breakout Group 1 was chaired by Ann Arvin, with Fran Sharples as the rapporteur. Breakout Group 2 was chaired by David Franz, with Nancy Connell as the rapporteur.
When the groups returned to the plenary room, Group 1 reported out first, with Dr. Sharples summarizing the group’s discussion. Starting with the establishment of needs, participants believe that the selection process is very important, and funders could consider narrowing their focus to fewer but better projects to stretch resources, because not every project can be funded. However, to establish needs, must one follow a specific process of just answering questions? The crucial question is “What is the lab for and why is it needed?” It is also important to understand what is driving the request, that is, “which scientists want to perform research or other work in the laboratory? Who is committed to the project, and are in-country national government officials committed?” If the answer to the last question is “no,” can funders help to motivate them to commit to the project? One participant said that a strong commitment from the local authorities, who may have some control over finances or infrastructure, is also essential. Finally, does the laboratory have a champion, that is, someone who can effectively gather support for the project?
One participant said that funders should distinguish between the scientific, political, and financial factors underlying a request for a laboratory. Another participant added that the “branding” of laboratories with BSL-2 or -3 labels can cause problems, stimulating requests that over-reach needs and capabilities. A third participant commented that funders should shift from thinking “donation” to thinking “investment.” Funders should view a project in terms of a cooperative agreement from the beginning and should engage potential multi-sectoral partners as early as possible—for example, local universities and companies. Funders could
also think in terms of how a new or enhanced laboratory could serve as a “nucleation point” in a national or regional network.
Having the necessary infrastructure is a guiding principle. Infrastructure includes not only water supply and quality, power, waste treatment (including incinerators), and transportation resources, but also telecommunications and internet connectivity. For a new laboratory, electricity is perhaps the most important resource. The frequency of past outages and voltage fluctuations should be checked before any design plans are made, and backup generators and regulators should be provided if necessary, a participant said. Water quality is also very important, and a sound transportation network is critical for moving samples and supplies. This last need may be the hardest to deal with because there are not many good solutions if the existing network is inadequate. Another person familiar with a number of labs did indicate, however, that there are successful solutions that could be examined as potential models. Waste treatment, including incinerators, is also essential.
Once built, a laboratory’s operational needs are diverse and include funding, equipment, reagents, and human resources. A partnership among many funding organizations might be required to sustain operations. Realistically, recipient countries are rarely positioned to assume responsibility after the 3- to 5-year planning, construction, and startup period, and partnerships can help here. A shift among funders to plan for the longer term (e.g., 10-15 years) might facilitate longer and broader commitments. Japan created some successful partnerships with Zambia, for example, that have been sustained over decades because of Japan’s continued commitment to financial and technical assistance. A participant suggested that comprehensive transition plans, rather than simple handoffs, are needed. Continued involvement by funders or other supporters could also help to protect against proliferation threats. Co-ownership of labs could be more widely applied—if not interpreted as infringing on the sovereign rights of recipient countries.
The group recommended that funders have a “risk list” to review when making funding decisions. This list includes laboratory needs that could result in bad consequences if they were unreliable, including operations (e.g., power, water, security); training (i.e., is there a minimum standard for clinical labs or universal precautions?); retention and a pipeline for new hires to replace trained employees who leave;1 financial sustainability; internal monitoring and assessment; buy-in and ownership from the
1 Training and experience often result in more opportunities for the staff to work elsewhere.
national government (e.g., is there a clear commitment, such as a line item in the national budget?); and potential for collaboration (e.g., are the negotiators and lab officials able to work well with the local community and who is involved?). Participants said that strategies to address all of these risk items must be flexible and adapted to circumstances. Funders might want to “map” these risks.
The relationship between the funder and recipient should be based on trust. Many recipient countries may be sensitive to words such as “audit,” which is used by some funders to mean project evaluation and progress checks. Financial audits are expected, but audits of the relationship between the funder and the recipient may construed as offensive. Some funders call these types of evaluations “supervisory assessments” and use a checklist to determine compliance with contracts. Development banks and other funding organizations require both internal and external audits because they give money to recipient governments to spend, and there have been too many past examples of funds being diverted. One participant mentioned that cooperative agreements from the U.S. Centers for Disease Control and Prevention (CDC) require both technical and financial audits, which are generally welcomed because they protect the lab director. CDC also works with the recipient’s staff, teaching and improving biosafety and standard operating procedures. One participant mentioned, however, that donors are not homogeneous as to how they operate. Providing funds for the recipient country to contract, build, and operate a laboratory is very different from providing both funds and all the other necessary capabilities to a project.
One participant stated that many funders know what to consider in the other domains, but they need guidance on biosecurity and nonproliferation. A meeting on governance of dual-use research in the life sciences held by the U.S. National Academies of Sciences, Engineering, and Medicine (the National Academies) in June 2018 in Croatia highlighted that this area of governance is a very low priority, if at all, for many countries. Another participant agreed the BWC receives very low priority, if any, in many recipient countries, who do not deem bioterrorism to be a risk. In response to the need to raise awareness, the attendees of the recent (June 2018) governance workshop identified training on biosecurity issues as one answer. Another participant expressed more concern about insider threats, which are not addressed in many donation agreements. Dealing with potential insider threats requires good management, leadership, knowledge of the laboratory personnel, and development of a culture of responsibility among laboratory personnel. High-containment laboratories built by Japan in other countries are provided “maximum
measures” for physical security, and personnel are trained in Japan on both biosafety and biosecurity while they are given other training for other issues for other procedures and operations. Personnel are asked to develop biosecurity guidelines and then implement them at the facility.
A participant noted that physical security protects a lab from outside threats, while “biosecurity” focuses more on internal threats. In addition, “biosecurity” means different things to different people. Another participant mentioned that funders could use current bio-risk management frameworks as guidelines for awareness training. However, a participant noted that context also matters. A regional laboratory working with Ebola virus must worry about biosecurity. In comparison, a field laboratory dealing with rat urine contaminated by Lassa fever in an area where 10 percent of the rats carry the disease will not worry about biosecurity, although biosafety is a concern. Security and safety are not always linked and should not always be linked, a participant said. The presence of hazardous pathogens in a particular location influences not only how biosecurity is defined for that locale, but also how the need for a laboratory is defined.
According to Dr. Connell, the two breakout groups had similar discussions and observations. Group 2 also discussed the importance of establishing the need for a lab—what does a recipient need and why? A laboratory’s purpose may be for diagnostics, for surveillance, as a repository for preserving or banking strains, or for research. Are the recipient’s diagnostic needs related to day-to-day health and medicine and/or outbreak response? Do the scientists plan to use traditional microbiology or newer molecular techniques? Do they understand the potential costs and complexity? What about the proposed requirements for training? Are local candidates available to fill the positions? The answers to these questions will dictate the type of laboratory needed. All of these things influence what kind of lab capabilities might be required to meet recipient needs.
Group 2 produced a list of various “models” of assistance for biological laboratories for low-resource countries based on the experience of the participants:2
U.S. Department of Defense model: Construction of large and fully equipped high-containment laboratories and peripheral laboratory
2 These are simplified sketches created to communicate overall approaches and are not meant to characterize everything that a particular nation or organization does.
networks (e.g., Tbilisi and Almaty); may encompass work on both human and animal pathogens.
Canadian Custom Package model: New or repurposed modular units; two have been created in Nigeria and Sierra Leone; they provide safety with reduced complexity and are peer designed using core lab specifications plus or minus specific functions.
Japanese model: Upgrade of existing high-containment laboratories (not new construction) as part of creating a network; they also provide extensive training and education over the decades-long duration of the partnership.
French model (Pasteur): Maintain long-term (Pasteur Institutes date back 130 years) established labs; provide their own skilled personnel as well as relatively long education/training of local personnel.
Zambia model: Six agent-specific BSL-3s, each devoted to a different specific pathogen; these “Container Labs” are managed by the Zambia AIDS Related Tuberculosis Project, which is affiliated with the University of Zambia’s School of Medicine and the London School of Hygiene and Tropical Medicine.
World Bank model: The following areas are important for consideration by donors, with the ones in bold of highest importance.
- Political and governance (including corruption)
- Sector strategies and policy
- Technical design of project
- Institutional capacity and sustainability
- Fiduciary risk
- Environmental and social risk
- Stakeholder commitment (are they on board?)
There was considerable discussion of obtaining “buy in” from both local and national government officials. Two participants said that involvement of the recipient country’s minister of health may no longer be sufficient. Decision making now rests with the vice president or the Cabinet in some places.
Participants discussed the pros and cons of One Health. Laboratories that work on human and animal health are “double track,” providing resources for two purposes with a single investment. This can be important
for dealing with zoonotic threats, but stored agents should be kept separate. However, a participant stated that human health and animal health compete for resources when scarce.
Breakout Group 2 also produced a list of “Donor Operational Risk Analysis Factors:”
- Human resources: staff, training and education
- Ownership/buy in
- Collaboration and how well a country works with others
- Finance and financial history
- Regulatory framework
The importance of training and education received a lot of attention from both groups. One participant suggested that a donor agreement should require a training program that continuously serves the needs of a laboratory and its host country. Donors, local or foreign educational institutions, or national or regional biosafety professional organizations can provide training. Training should also encompass mechanisms for employee retention, motivation, and mapping of career paths. Donors need to consider alternative ways to deal with these needs.
Breakout Group 2’s takeaway messages were as follows:
- The conversation about the different models should have started 20 years ago.
- The donor risks that were identified were not surprising.
- Forcing the use of culture-free techniques is infeasible.