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POTENTIAL NORMS FOR FUNDERS OF BIOLOGICAL LABORATORIES IN LOW-RESOURCE COUNTRIES

In the final plenary session, the group discussed suggestions from many participants for “norms” for donors. As noted in the introduction to these proceedings, the views contained herein are those of individual workshop participants and do not represent the views of all workshop participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine.

ESTABLISHING NEEDS

No participant suggested that high-containment laboratories should not be constructed in low-resource settings. High-containment labs may be needed for many reasons, including performing diagnostics, supporting clinical care, supporting epidemiology, identifying cases and chains of transmission, supporting and carrying out ecological investigations, and conducting applied and basic research.

However, participants emphasized the need to match the facility type with the country’s needs as well as its competency to operate and maintain the facility. Donors, a participant said, should be wary of ambitions that exceed capabilities. Funders must ask as many of the “right” questions as possible to determine the true requirements. Recipient countries must be able to justify the need for a laboratory and to explain the work that will be performed there. Conversations to establish answers to these questions may take a long time and may never reach resolution.

Several participants also strongly believe that if the “right” facility for a country is less than a BSL-3, then that is all that a funder should provide. Matching the appropriate type, design, and level of facility to the needs of the recipient is the focus of a joint effort by the government of Canada, the

World Organisation for Animal Health, and Chatham House. Some participants noted that countries where very hazardous pathogens, such as Ebola virus, are endemic may not need high-containment facilities to do diagnostic and clinical work because the organisms are already present in the surrounding environment.

CONSTRUCTING NEW LABS VERSUS REPURPOSING EXISTING ONES

Phased approaches that increase lab capability as competency increases might be a beneficial approach when a recipient asks for a high-containment laboratory that exceeds its needs and capabilities at that time. This would avoid the issue of donors committing to provide a high-containment laboratory before the recipient is ready to handle it. However, it is technically difficult to renovate a laboratory designed for BSL-2 into a BSL-3 laboratory. If a donor wishes to encourage tiering or repurposing, then the original lower-level laboratory should be designed with the intent to add on to it to facilitate repurposing success.

LABORATORY NETWORKS

Donors might also want to consider how a new laboratory might expand or complement existing national and/or regional capabilities, some participants noted. What capabilities are already in place? Have existing laboratories been operated as intended and sustained over time? Are there ways in which a new or enhanced facility could complement the capabilities of existing labs or leverage resources by sharing?

RISK ASSESSMENT

Risks for donors: Serious issues arise when funding is insufficient to support ongoing operations, the necessary infrastructure is inadequate, no regulatory framework exists, government officials fail to provide support, the availability of an appropriately trained and skilled workforce is questionable, and awareness of biosecurity and nonproliferation concerns is insufficient. Due diligence on the part of donors requires that an accurate picture of the situation in each of these areas be obtained before committing funding or approving a particular facility design.

Risks for workers and the local community: Personnel must learn, understand, and follow all laboratory safety protocols to ensure that infectious live pathogens do not cause illness for themselves, their

colleagues, and members of the local community outside the laboratory walls. Donors cannot simply fund the construction of a lab and then walk away, assuming that sustainment of safety, security, and effectiveness will take care of themselves; there is ample evidence that this is not the case. The degree of risk and the containment level needed to ameliorate that risk depend on the types of pathogens being handled, their mode of transmission, whether effective countermeasures exist, and the factors discussed by Drs. Ksiazek and Kojima and summarized in Chapter 2. Although most donors may not be responsible for day-to-day lab operations and maintenance, they must perform due diligence and create contracts or other funding agreements that recognize these crucial concerns.

ALTERNATIVE TECHNOLOGIES

The new molecular diagnostic approaches now under development hold the promise of being able to substitute faster and safer surveillance and diagnostic testing for the more classical approaches that require handling of viable infectious organisms (see Chapter 4). Unfortunately, participants observed, very few of these technologies are ready for use even in sophisticated laboratories in wealthy countries, much less in low-resource settings. Their specificity is a key strength in positively identifying a particular strain. However, the specificity is also a weakness in that their utility is compromised when strains of a pathogen are different or mutating. In addition, few of the new technologies have been standardized or validated, especially under field conditions, and their effectiveness and accuracy must be demonstrated before they can be widely used in medical diagnostics. In addition, their costs must be reduced if they are to be used in low-resource settings. Finally, none has received regulatory approval. Dr. Chiu stated that it might take 5 to 10 years before the new test types are accepted as a basis for patient treatment. It is, therefore, unrealistic at this time to dismiss the need for biological containment facilities based on a belief that alternative technologies will obviate the need for handing of live infectious organisms, at least in some circumstances.

HUMAN VERSUS ANIMAL HEALTH

Although participants recognized that One Health is a good approach to protect both human and animal health, there are few examples in developing countries of human and animal pathogens being handled at the

same facilities. In the United States, however, facilities such as the Galveston, Texas, BSL-4 lab may host work on both, in different spaces. When this is the case, the human and animal organisms are generally kept well separated. This precaution is intended to reduce the chances of organisms, such as avian influenza, coming into contact with human flu strains and undergoing reassortment to become infectious to humans. The World Health Organization (WHO) prohibits handling both animal and human strains of influenza in the same laboratories. Aside from such specific exceptions, however, a facility suited for work on Level 3 human pathogens is generally also suitable for work on Level 3 animal pathogens, which could be useful for surge capacity.

Several participants noted that developing countries are usually more interested in public health and that the agricultural sector does not receive nearly the same level of funding and attention. Typically, the lines of authority for human and animal health are separate, which is a complicating factor.

REGULATORY FRAMEWORK

The International Health Regulations (IHR) are legally binding on 196 Member States worldwide. They impact governmental functions and responsibilities across many ministries, sectors, and governmental levels in many countries. However, WHO does not specify how the legal and regulatory requirements imposed by the IHR are to be implemented. It is up to each State Party to do so in the context of its own legislation, governmental structures, and policies (WHO, 2009). The effective implementation of IHR obligations, however, requires that an adequate legal framework be in place. In some Member States, the relevant authorities adopt implementing legislation. Although new or revised legislation, regulations, or other instruments may not be explicitly required under the State Party’s legal system, a country may still consider adopting them to facilitate performance of IHR activities in a more efficient and effective way.

However, approximately only one-half of the 196 Member States met the 2016 deadline for IHR implementation. Consequently, many low-resource countries still lack formal legal and regulatory frameworks that apply to the operation and management of the biocontainment laboratories they need to protect public health. In these cases, prospective donors should seek alternatives, such as requiring the recipient country to use existing guidelines or best practices, such as the WHO Laboratory Biosafety Manual or CDC’s Biosafety in Microbiological and Medical

Laboratories manual. The recipient country’s willingness to commit to this requirement should factor into the donor’s decision-making process.

The various biosafety manuals also require regular inspections of equipment and other aspects of lab operation and management to ensure that safety and security measures are given appropriate attention. One participant noted, however, that the newer types of equipment are modular and may require maintenance by the manufacturer, rather than the lab. A surveillance system to detect infections among lab workers is also required. Finally, some participants noted that financial audits are needed to prevent corruption and diversion of funds to unacceptable purposes. Supervisory assessments using checklists can be used to “audit” operations. Verification and enforcement of whatever rules are in place will be necessary and might require contracting to a third party.

INFRASTRUCTURE

As noted by many participants, reliable power, water, transportation, resupply, waste treatment, telecommunications, and internet connectivity are all needed, if not absolutely required, to ensure that biological laboratories operate for the purposes for which they were constructed. Donors should ensure that these resources are available, and funding agreements should specify how these resources will be provided and by whom. Furthermore, donors should gather data on the reliability of these resources, perhaps by spending time on site and devising corrective measures if needed. How well the issues of availability and reliability are addressed elsewhere in the country could signal what to expect at a new laboratory site.

Donors should also determine in-country support for infrastructure. That is, Will the regional or national government contribute to the success of the project by contributing new or improved infrastructure components? Will the government accept some financial responsibility for maintaining new infrastructure paid for by the donor?

BIOSAFETY AND BIOSECURITY AND NONPROLIFERATION

Biosecurity has received little attention in low-resource countries. It is, nevertheless, a crucial and element in the operation and maintenance of biological laboratories as is biosafety. The legal framework for biosecurity includes the requirements imposed by the Biological Weapons Convention, the Australia Group, and U.N. Resolution 1540. The WHO, CDC, and other manuals provide guidance on implementing biosafety and

biosecurity requirements. The June 2018 National Academies workshop in Zagreb, Croatia, on governance concluded that addressing biosecurity and the need to prevent access to hazardous pathogens by people with malicious intent requires awareness and procedural training for laboratory management and staff. A participant said that donors must ensure that the recipient recognized these topics are important and has a plan to implement the required measures. Some participants suggested the use of bio-risk management plans, which integrate safety and security. Donors should look for evidence that lab management and governmental authorities are aware of all safety and security needs and, if not, seek commitments from recipients to create awareness in all persons who need it.

WORKFORCE AND TRAINING

The need for trained workers who are competent to handle pathogenic organisms was mentioned numerous times during the workshop. Key points made in the discussions included:

• Education and training are not the same thing. Low levels of education in the locality of a proposed new laboratory may make it difficult to ensure that local people can be adequately trained to competently carry out laboratory procedures.
• Local sources of training for lab workers may not be readily available depending on the location. Donors could contract with third parties to provide training, or, if a technical organization itself, could provide training by its own personnel. In some cases, personnel may receive training in facilities in the donor nation, which enables them to experience the entire operation, including its culture. Professional societies and international biosafety organizations are other potential sources of training.
• The management of a lab workforce involves more than just training employees to carry out their responsibilities. Measures to assist employees with acquiring leadership skills and with career planning, as well as providing promotion opportunities, can reduce attrition and prevent experienced workers from accepting higher level jobs at other facilities.
• A pipeline to counteract attrition among workers should be developed. Programs such as internships could create a pool of potential employees who are prepared to enter a lab’s workforce. Collaborative relationships with local colleges and universities could provide a

• source of staff with relevant experience. Such relationships can also improve access to training by educational institutions.

• Collaboration with foreign universities is a potential means to provide training, including in more advanced scientific and technological subject matters. Some low-resource countries already have relationships with such foreign institutions (e.g., Zambia).

Dr. Arvin closed the workshop with thanks from the National Academies.

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