Executive summary

This article addresses biosafety and biosecurity in high-containment level laboratories (BSL-3 and BSL-4) in Latin America, with a focus on classification, current status, and regulatory frameworks. In the region, the lack of uniformity in data collection makes it difficult to accurately understand the infrastructure of high-containment laboratories. Regulatory frameworks vary across the region and present challenges in terms of standardization. Although countries like Colombia have made progress in this area, there is a need to establish updated and centralized regulatory frameworks in each country.

To improve biosafety and biosecurity, we make a series of recommendations such as the implementation of biological risk management systems in laboratories, the promotion of non-punitive incident reports, the standardization of supervision processes, collaboration between institutions, and the exchange of best practices.

Introduction

Biosafety and biosecurity in high-containment level laboratories (BSL-3 and BSL-4) are of vital importance for the protection of public health. These laboratories work with dangerous biological agents, so it is essential to ensure that practices, equipment, and security measures are adequate and rigorous. In this context, this article focuses on analyzing the current situation of BSL-3, BSL-3+, and BSL-4 laboratories in Latin America. We explore the increase in the construction of these laboratories at a global level, the regulatory frameworks by which they are governed, and the challenges that some Latin American countries face in their implementation. In addition, we propose several recommendations to improve biosafety and biosecurity in these laboratories. 

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Classification of laboratories by biosafety levels

In 1974, the United States Centers for Disease Control and Prevention (CDC) published a document titled "Classification of etiologic agents on the basis of hazard", proposing the classification of pathogens into four risk groups. Subsequently, both the National Institutes of Health (NIH) of the United States and the World Health Organization (WHO) updated this system, thus establishing the bases for the classification of laboratories according to the risk group of the pathogens they handle (Villegas et al. al., 2007). Out of the classification of risk groups, four levels of biosafety in laboratories have been established. These levels are determined taking into account several factors, such as the infectious capacity of the pathogen, the existence of treatments or vaccines for it, the severity of the disease it causes, its transmissibility, whether it is of exotic origin or not, and the nature of the work carried out in the laboratory (Lara-Villegas et al., 2008).

• Level 1 (BSL-1) laboratories use elemental equipment and practices for teaching purposes. They work with well-defined and characterized strains of microorganisms that do not cause disease in healthy people. The use of special protective equipment is not required.
• Level 2 (BSL-2) laboratories adopt appropriate practices, equipment, and measures to realize clinical analysis, diagnoses, and pathology. These laboratories handle microorganisms of moderate risk that are present in the community and are associated with human diseases of variable severity.
• Level 3 (BSL-3) laboratories implement appropriate practices, equipment, and measures to realize clinical analysis, diagnoses, and research. These laboratories handle known or unknown agents that have the potential to be transmitted by aerosol or splash and that can cause life-threatening infections but for which treatments or therapies are available.
• Level 4 (BSL-4) laboratories apply appropriate practices, equipment, and measures to realize analysis, diagnoses, and research that involve handling dangerous exotic agents. These agents represent a high risk by causing lethal diseases and can be transmitted by air. For these agents, there is no known vaccine or therapy.

In addition to these four groups is an additional category called 'BSL-3+' or 'Enhanced BSL-3', which are BSL-3 laboratories that take extra precautions of equipment and protocols when conducting particularly risky research that does not necessarily require BSL-4 precautions. There is no international guidance establishing what constitutes a BSL-3+ and there is little research showing that these enhancements actually provide additional safety for the riskier research carried out in these laboratories (King's College London, 2023).

Typically, the requirements of this scenario involve handling biological agents that would normally be studied in BSL-3 laboratories. However, certain types of pathogens are specifically contemplated here, such as highly pathogenic avian influenza and the 1918 pandemic influenza virus. In addition, some practices involve an increase in the number of samples handled, higher concentrations of cultures, and an increased production of aerosols (King's College London, 2023).
 

This research note focuses on biocontainment laboratories at BSL-3, BSL-3+ and BSL-4 levels since they handle potentially dangerous pathogens.

Current state

During the last few years, there has been an increase in the number of BSL-4 laboratories around the world. This increase is attributed to the growing need to investigate emerging and re-emerging infectious diseases. BSL-4 laboratories are mostly located in North America, Europe and Asia, although an increase in the number of BSL-4 laboratories in developing countries has also been observed. In 2021, the Global Biolabs Report (2023) identified 59 biosafety level 4 (BSL-4) laboratories operating, under construction, or planned in 23 countries. By early 2023, that number had increased by 10, reaching 69 labs. There are 51 BSL-4 laboratories in operation, three under construction, and 15 planned, distributed in 27 countries (See Table 1).

The total number of BSL-4 laboratories globally has increased steadily after the 2001 anthrax incidents in the United States and the 2003 outbreak of SARS in Asia, due to growing concern about natural and man-made biological hazards (King's College London, 2023). The COVID-19 pandemic has triggered another boom in building BSL-4 labs. Since the start of the pandemic, nine countries have announced plans to build 12 new BSL-4 labs (King's College London, 2023).

The largest concentration of BSL-4 laboratories continues to be in Europe, with 26, one of which is under construction in the United Kingdom and another one planned in Spain. Asia has 20 BSL-4 laboratories; North America has 15; Oceania has four, all operational and located in Australia; Africa has three; and South America has one planned in Brazil.

Regarding BSL-3+ laboratories, according to the information in the Global Biolabs report (2023), 57 laboratories have been located that self-identify as BSL-3+. Approximately three-quarters of these laboratories are located in Europe, with 21 laboratories, and in North America, with 19. The remaining BSL-3+ laboratories are located in Asia (ten laboratories), South America (four), Africa (two) and Oceania (one). All of these labs are up and running, except for one in the United States that is still under construction and one in Brazil that is planned (King's College London, 2023).

Table 1. Global distribution of BSL-4 and BSL-3+ laboratories, Source: King’s College London (2023)

In addition to the registry of laboratories in Latin America carried out by Global Biolabs, which includes a planned BSL-4 laboratory in Brazil and four BSL-3+ laboratories located in Brazil and Argentina, we have identified one additional BSL-4 laboratory in Argentina (Government of Argentina, 2019) and one in Brazil specialized in the investigation of foot-and-mouth disease. In turn, there are records of a BSL-3+ laboratory located at the Autonomous University of Nuevo León, in Mexico. Likewise, several sources indicate the existence of BSL-3 laboratories in Brazil, Argentina, Mexico, Chile, Colombia, Peru and Panama.

It is important to clarify that the collection of data on the number and type of high-containment laboratories (BSL-3, BSL-3+ and BSL-4) in Latin America represents a great challenge due to the lack of standardized information. Various sources have been identified for each country and the data provided by these sources often conflicts with the data from the only centralized document that seeks to gather information on the various biocontainment laboratories in the world, which is the King's College London Global Biolabs report. This lack of uniformity and coherence in the data makes it difficult to obtain an accurate picture of the infrastructure dedicated to the investigation of dangerous pathogens in Latin America, which suggests the possibility that there are unknown laboratories under construction or others whose information is not available or is difficult to access.

Considering this, below we will present the regulatory frameworks of the Latin American countries in which at least one high-containment laboratory has been registered.

Regulatory frameworks of the BSL-3 and BSL-4 laboratories in Latin America

At a global level, the World Health Organization (WHO) together with the United States Department of Health and Human Services have designed regulations and strategies to control adverse events in laboratories (Binder et al., 2023). Among them, the most prominent is the WHO Biosafety Manual (2004), which establishes techniques and procedures to strengthen safe work with infectious agents. Likewise, it classifies laboratory facilities into four levels of biological safety, each with specific microbiological practices, specialized equipment, and rigorous security measures, as shown in Table 2.

Table 2. Technical requirements for high-containment laboratories, Source: World Health Organization (2004)

Although BSL-3 and BSL-4 laboratories are internationally regulated according to WHO guidelines, BSL-3+ laboratories lack similar international guidelines. In practice, improvements in BSL-3+ laboratories compared to BSL-3 often require additional training for personnel, more rigorous emergency response plans, better respiratory protection against aerosols, use of personal protective equipment, exhaust air HEPA filters, autoclaves, effluent decontamination systems, and reinforced access and monitoring controls. However, these improvements are not formalized and may vary from case to case (King's College London, 2023).

In a complementary effort to global regulations, each country has developed its own regulations. However, most of these regulatory frameworks are not specifically oriented to high-containment laboratories, but rather cover laboratories with different levels of risk.

A significant challenge in the identification of national regulations has been the lack of clear information on the institutions responsible for applying and supervising these regulations in each country, which makes it difficult to search for and obtain the corresponding regulations at the institutional level. In many cases, the information is dispersed among various government entities, institutions in charge of the laboratories, and regulatory bodies, which complicates the identification of the sources from which to obtain updated and reliable information. Considering these limitations, the information on laboratory biosafety regulations and standards available in Brazil, Argentina, Mexico, Colombia, Chile and Panama is presented below.

Brazil

In Brazil, government regulation only applies to laboratories that conduct research related to public health, agriculture, and genetically modified organisms (GMOs). There is no oversight or evaluation mechanism for laboratories, whether high-containment or otherwise, that operate in public or private universities and that work with biological agents other than GMOs (Committee on Anticipating Biosecurity Challenges of the Global Expansion of High-Containment Biological Laboratories, National Academy of Sciences, & National Research Council, 2011).

The Ministry of Health is responsible for supervising public health laboratories, while the Ministry of Agriculture is in charge of agricultural laboratories. However, for university laboratories, except for those working with GMOs, there is no designated oversight body. In the case of laboratories that work with GMOs, the National Biosafety Committee (CTNBio) assumes responsibility.

In terms of laboratory engineering and construction standards, the Ministries of Public Health and Agriculture have produced some manuals and documentation. However, there is a gap in the regulation of university laboratories that do not work with GMOs. In case of incidents, some laboratories inform the Institutional Biosafety Committees or the Commission for the Prevention of Hospital Infections. There are no specific guidelines for laboratories that do not work with GMOs, nor is there a regular and mandatory system for the notification of accidents or liability measures. Although some voluntary guidance is available, a more structured and normative approach in this area is lacking (Committee on Anticipating Biosecurity Challenges of the Global Expansion of High-Containment Biological Laboratories, National Academy of Sciences, & National Research Council, 2011).

Argentina

In Argentina, the norms and regulations of laboratories are dispersed and not easily accessible. There are specific manuals from various research institutes that regulate their own biosafety practices in laboratories (National Institute of Parasitology, 2007; Kusznierz et al., 2019), which makes it hard to obtain a complete and coherent vision of the regulations in the country.

To complement these manuals, government regulations have been established for each sector, such as the regulations of the National Testing and Diagnostic Network linked to the area of animal health (Government of Argentina, 2021), which has a manual of good laboratory practices. In the area of human health, the Ministry of Health established the Regulations for the Organization and Operation of the Laboratory Area in Health Care Establishments (Ministry of Health and Social Action, 1997).

It is noteworthy that it was not possible to find an official source listing the type and number of existing biosafety laboratories in Argentina.

Mexico

In Mexico, several BSL-3 laboratories have been identified in different institutions. These include the Institute of Epidemiological Diagnosis and Reference of the Ministry of Health (InDRE), the Biosafety Unit of the Institute of Biomedical Research of the UNAM, the Center of Research and Assistance in Technology and Design of the State of Jalisco, the Biomedical Sciences Unit of the Regional Research Center, the University of Monterrey, and the Autonomous University of Nuevo León. This information was extracted from unofficial sources (Diario de Yucatán, 2023; UNAM Biomedical Research Institute, 2023; Ruiz-Jaimes, 2013). As in the case of Argentina, it was not possible to access an official public list of existing biosafety laboratories in the country.

For the national regulation of laboratories, Mexico has a total of 32 official standards. These standards were published by the InDRE of the Ministry of Health. Its content covers various aspects, from laboratory infrastructure, such as lighting and thermal conditions in workplaces, to safe materials handling and storage practices, labeling of containers of hazardous substances, and proper management of hazardous waste (Government of Mexico, 2023). However, there is no clear information regarding the responsibilities of laboratory supervision or the protocols to follow in case of incidents.

Colombia

In Colombia, the norms that regulate work in laboratories are centralized and easily accessible. In total, there are seven laws that govern activities in these environments.

In turn, Colombia has a solid set of regulations compiled in the document General Guidelines for Biosafety and Biocontainment for the laboratories of the National Laboratory Network (2022), which provides specific guidelines to ensure safe practices in these environments. This document represents a significant advance in the standardization of regulations compared to other countries in the region. The guidelines cover aspects such as regulations, laboratory risk assessment, biosecurity, emergency and incident response, and certifications, among other relevant aspects (Ministry of Health and Social Protection, 2022).

Chile

In Chile, laboratory regulations are based on a specific biosafety guide for clinical laboratories, which seeks to provide guidance on the implementation of the corresponding measures according to the level of biosafety (Instituto de Salud Pública de Chile, 2019). This document contains guidelines for the management of biological risk according to containment levels, the use of personal protection elements, waste management, and the transport of samples and infectious substances, among others.

In addition to the guide, laws related to the operation of bioclinical laboratories have been established (Instituto de Salud Pública de Chile, 2023). However, as in other countries in the region, the lack of clarity in supervisory responsibilities and the absence of a consolidated registry of laboratories represent a major obstacle to guarantee effective management and a comprehensive understanding of biosafety.

Panama

Although Panama hosts a BSL-3 laboratory in charge of the Gorgas Memorial Institute for Health Studies (ICGES), it was not possible to access detailed official sources that provide regulations for laboratories in this country.

Recommendations to improve biosafety and biosecurity in Latin American laboratories

Considering the difficulties identified in the regulation of BSL-3, BSL-3+ and BSL-4 laboratories in Latin America, we suggest the following recommendations to improve biosafety and biosecurity in the region:

Establish a centralized regulatory framework

Responsible institutions: Ministries of Health, in collaboration with biosafety experts and laboratory representatives from each country.

• Convene a multidisciplinary committee composed of biosafety experts, scientists, laboratory representatives, and health professionals from each country to develop the regulatory framework.
• Identify the different biosafety levels (BSL-3, BSL-3+ and BSL-4), define the infrastructure, equipment and training requirements necessary for each level, and align them with international biosafety standards and guidelines.
• Define, along with biocontainment levels and requirements, minimum adaptive requirements for crisis situations, allowing agile responses without compromising safety.
• Establish a periodic review and update process of the regulatory framework in collaboration with relevant stakeholders. This could be carried out from time to time, such as every 3 to 5 years, depending on the pace of scientific and technological development. It could also be triggered by significant changes in the understanding of biological threats or by experiences of health crises that reveal regulatory deficiencies.

Implement a structured framework for risk management (The Nuclear Threat Initiative, 2023)

For laboratories

Responsible institutions: Research institutions and laboratories.

• Design a structured risk management framework that includes the identification, assessment, mitigation, and monitoring of biological risks in laboratories.
• Form risk management teams in each high-containment laboratory, composed of biosafety experts, researchers, and technical personnel.
• Establish Standard Operating Procedures (SOP) to document risks, decisions, and actions taken to address risk situations.
• Conduct regular training for staff in the effective use of the framework and best practices in risk identification and management.

For supervision at the national level

Responsible institution: Ministry of Health, in collaboration with the designated biosafety regulatory agency.

• Evaluate the implementation of the risk management framework in high-containment laboratories through periodic audits.
• Verify the proper training of risk management teams and the adherence to the documentation and decision-making procedures. 
• Establish a periodic review and follow-up process.
• Provide guidance and advice to laboratories in the effective implementation of the framework.

Establish a non-punitive incident reporting system (Perkins et al., 2019)

For laboratories

Responsible institutions: Research institutions and laboratories.

• Design a reporting system accessible to all laboratory personnel.
• Guarantee the confidentiality of informants through an anonymous reporting option.
• Establish clear protocols for the investigation and resolution of reported incidents.

For supervision at the national level

Responsible institution: Designated biosafety regulatory agency, in collaboration with the Ministry of Health.

• Establish an independent incident review committee composed of biosafety and ethics experts.
• Evaluate the effectiveness of the incident reporting system through periodic audits and reviews.
• Ensure the confidentiality of reports and protect whistleblowers from retaliation. 
• Ensure that reported incident investigation and resolution protocols are followed.
• Provide feedback to laboratories on improvements following the reports.

Strengthen and standardize supervision in laboratories (Haines & Gronvall, 2023)

Responsible institutions: Supervisory entities, research institutions or biosafety regulatory agencies designated by the Ministries of Health.

• Designate qualified biosafety professionals as supervisors of high-containment laboratories.
• Establish a biosafety committee with representatives from different disciplines to supervise and validate compliance with regulations and protocols.
• Carry out periodic audits to evaluate the implementation of biosafety measures in public and private laboratories.
   

Map laboratories rigorously

Responsible institutions: Ministries of Health

• Create a regional working group composed of representatives of laboratories and public health agencies, led by the Ministries of Health.
• Define information criteria to be shared for mapping, including details of investigations and biocontainment capabilities. Considering that this information may include data on pathogens and work in progress, which in turn may have a dual use, it is necessary to evaluate the disclosure of public information to prevent misuse.
• Review possible dual uses to assess which information should be public when sharing data on pathogens and research papers. 
• Establish a mandatory reporting system for activities relevant to mapping (such as the design, construction, and commissioning of laboratories).
• Publish and update an interactive map showing the distribution and characteristics of high-containment laboratories in the region.

Develop a database of biorisk management experts (The Nuclear Threat Initiative, 2023).

Responsible institutions: Ministry of Health, in collaboration with academic institutions

• Create an online platform where experts can register and provide details about their experience and expertise.
• Verify the credibility of experts through references and work history.
• Offer online training and webinars led by experts to strengthen the community and knowledge in risk management.
• Use the database to access specialized knowledge in situations that require it, such as technical consultations, protocol reviews and specific risk analysis.

Implement a dual-use scanning tool (Vennis et al., 2021)

Responsible Institutions: Biosafety organizations and safety experts.

• Develop an online platform with a dual-use rapid scan tool, allowing researchers and experts to evaluate emerging technologies and research based on their dual-use potential.
• Provide examples and guidelines to interpret the responses and assess the level of dual risk.
• Make this tool available to evaluate new projects and substantial modifications in existing high-risk projects.

Develop mechanisms for the exchange of practices (The Nuclear Threat Initiative, 2023).

Responsible institutions: Networks of international institutions and organizations such as PAHO/WHO

• Establish an online platform where institutions in the region can share case studies, lessons learned, and best practices in biosafety.
• Organize regular workshops and conferences where professionals from different regions and areas of expertise can present and discuss their experiences.
• Promote the creation of collaborative working groups to address specific challenges in the region.
• Facilitate collaboration between laboratories and experts through trusted networks and constant communication.

Conclusion

In this article, we have explored biosafety in high-containment laboratories in Latin America, considering their classification, current status, and regulatory frameworks. We have identified a lack of uniformity and consistency in data collection on laboratories, making it hard to understand the infrastructure dedicated to dangerous pathogen research. Regulatory frameworks for high-containment laboratories vary in Latin America, with challenges regarding lack of centralization, standardization, and clarity in oversight responsibilities.

To improve biosafety and biosecurity in Latin America, we propose to establish a centralized and standardized regulatory framework in each country. In addition, the implementation of biorisk management systems, the promotion of non-punitive incident reporting, and the standardization of supervision in laboratories are critical steps towards improving safety. Building databases of biorisk management experts and implementing dual-use scanning tools can also strengthen prevention and mitigation efforts.

Ultimately, collaboration between institutions, transparency in communication, and sharing of best practices are essential to build a strong network of high-containment laboratories in the region. These laboratories not only play a crucial role in scientific research, but are also guardians of public health and engines of response to potential biological threats in the region.

We thank Michelle Bruno and Jaime Sevilla for their comments on this article.