An exposure control plan is only as effective as the understanding and compliance of the personnel who implement it, so biosafety reviews are crucial
By Ted A. Myatt, Sc.D., Environmental Health & Engineering
In the past year, there have been a number of high-profile incidents at high-containment biological laboratories (biolabs). At Texas A&M University, a laboratory worker was exposed and infected with Brucella during an aerosolization experiment. This incident was not reported to the Centers for Disease Control and Prevention (CDC) as required by federal regulations. Research with “select agents” at the university was terminated and the university was levied a $1 million fine as result of not properly reporting the incident. At the CDC, a power outage in the Biosafety Level 4 (BSL-4) laboratories made headlines. In the United Kingdom, a faulty wastewater drain at a laboratory facility resulted in an outbreak of foot-and-mouth disease. Ongoing controversy surrounding the planned construction of a new, federally funded BSL-4 laboratory in Boston, MA, has increased the media coverage of these (and other) events. This increased media focus has fueled concern among the public about the potential for a release of infectious microorganisms from biolabs regardless of their containment level.
Primarily due to these publicized events, the U.S. Government Accountability Office (GAO) was asked to investigate oversight at BSL-3 and -4 laboratories in the U.S.1 The GAO investigators identified six lessons from the incidents that are relevant not only for work in high-containment laboratories but all biolabs:
- Identifying and overcoming barriers to reporting in order to enhance biosafety through shared learning from mistakes and to assure the public that accidents are examined and contained.
- Training lab staff in general biosafety, as well as in specific agents being used in the labs to ensure maximum protection.
- Developing mechanisms for informing medical providers about all the agents that lab staff work with to ensure quick diagnosis and effective treatment.
- Addressing confusion over the definition of exposure to aid in the consistency of reporting.
- Ensuring that laboratory safety and security measures are commensurate with the level of risk these labs present.
- Maintenance of laboratories to ensure integrity of physical infrastructure over time.
All of these lessons can be applied to any biolab, including biotechnology and pharmaceutical laboratories. Development of new products from cells and tissues for therapeutic use, isolation and identification of genes, and introduction of genes into microorganisms, plants, animals, and human cells are all current and expanding biotechnologies. However, these procedures can present health risks for infections in laboratory workers during the handling of bacteria, fungi, viruses, viral vectors, recombinant DNA (rDNA), and organisms containing rDNA. Careful consideration of safety guidelines and regulations is warranted.
The CDC and the National Institutes of Health (NIH) have developed guidelines for the four levels of biosafety. These guidelines, which are designed to protect not only laboratory personnel but also individuals in the surrounding community, are described in two publications: Biosafety in Microbiological and Biomedical Laboratories (BMBL) and the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). In addition, the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens Standard (Title 29 Code of Federal Regulations Part 1910.1030) applies to laboratory workers who come in contact with the human blood, bodily fluids, and tissues frequently used in research laboratories.
Companies and institutions with biolabs understand that complying with biosafety guidelines and regulations is critical to maintaining the safety of their workforce and to sustaining a solid relationship with the community in which they conduct business. Yet remaining in compliance can be demanding and complex as research and development efforts continue to expand into new areas. As a proactive approach, these companies and institutions are recognizing the value of investing in a laboratory review to ensure compliance with the existing guidelines and standards.
Review process is key to control plan
For many years, we have seen how a laboratory review process can be successful in mitigating potential gaps in biosafety, whether in biotechnology, pharmaceutical, or research laboratory environments. The review process typically begins with a meeting with lab representatives to understand overall activities in the laboratory. This is followed by a walkthrough to evaluate compliance with applicable biosafety guidelines and the OSHA standard, as well as a review of laboratory equipment and relevant documents, such as a biosafety manual.
A fundamental element of the laboratory review process is recognition that working safely in laboratories requires integration of safe laboratory practices and the design and operation of laboratory buildings. This integration of approaches, termed containment in the BMBL, includes primary containment provided by the use of good microbiological techniques and safety equipment as well as secondary containment provided by the design and operational procedures used by the laboratory facility.
Fgure 2. The pipetting work seen here requires a worker to be garbed with a lab coat, protective gloves, and safety glasses. Photo courtesy of EH&E.
The biosafety guidelines summarized in the BMBL can be simply defined as a group of practices and procedures designed to provide safe environments for individuals who work in laboratories with potentially hazardous biological agents. Work with biological agents is classified into four distinct biosafety levels, BSL-1 to BSL-4, based on the potential health risks for both individuals who work in the laboratory environment and for members of the surrounding community. Each of these biosafety levels is matched with increasingly restrictive practices and facilities that are designed to reduce the risk of exposures to potentially hazardous biological agents.
Figure 3. Centrifuge work requires careful attention to load balance, proper cleaning of the equipment, and consistent use of personal protective equipment. Photo courtesy of EH&E.
BSL-1 and BSL-2 practices and containment are applicable for the majority of work conducted in today’s biotechnology and pharmaceutical laboratories. BSL-1 is suitable for work with well-characterized biological agents that are not known to consistently cause disease in healthy adults; they pose minimal potential health hazards for laboratory personnel and the environment. BSL-2 is applicable for work with biological agents that present moderate potential health hazards to laboratory personnel and the environment. BSL-2 indicates that individuals working directly with the biological materials are at moderate risk for infection through skin and eye exposure, skin puncture, and ingestion.
Human cells, tissues, and body fluids may contain bloodborne pathogens (BBPs); therefore, work with any of these materials should be conducted at BSL-2. Although no specific federal regulations apply to the majority of cell and tissue culture activities in laboratories, the Bloodborne Pathogens Standard does apply to laboratory workers who come in contact with human blood, bodily fluids, or tissues. This standard was issued in 1991 based on health concerns related to increased risks for exposures to certain BBPs, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and other infectious agents that may be present in human materials. In addition to HIV and the hepatitis viruses, the standard covers a wide variety of bloodborne diseases. Sources of potential exposures to BBPs include a variety of potentially infectious materials, including all human blood, blood products, certain body fluids, any body fluids in which visible blood is present, and any unfixed tissue or organ from a human (living or dead).
The Bloodborne Pathogens Standard requires that an exposure control plan be written and implemented. The exposure control plan includes several required elements and policies and procedures to eliminate or minimize BBP exposures. These elements include identifying all individuals in a laboratory group who may be at risk for BBP exposures, annual training, and providing appropriate personal protective equipment. Unlike the biosafety guidelines, the OSHA BBP Standard has the force of law and non-compliance can result in serious financial penalties.
To minimize potential exposures to aerosols or splashes of infectious biological agents, designated procedures are conducted in biological safety cabinets (BSCs) or other physical containment equipment. As recognized by the GAO, workers should be trained to recognize potential exposure events and the proper procedures for conveying information regarding the agents they work with to medical staff in the event of an exposure. BSCs provide the primary means of containment for working safely with potentially hazardous biological materials. However, training on how BSCs operate, which should be included in general biosafety training, and good microbiological practices are necessary to protect laboratory personnel, the environment, and the sterility of the product.
While the risks of releasing infectious agents out of a BSL-1 or BSL-2 facility are not as great as a release from a high-containment laboratory, the GAO recommendation for proper maintenance of a biolab is important. For example, filtration mechanisms are an essential laboratory design feature for reducing levels of infectious agents in the air entering a laboratory and for removal of these agents from air exiting the laboratory. Filtration is critical for biotechnology and pharmaceutical companies to ensure product sterility. High-efficiency particulate air (HEPA) filters are also integral components for optimal operation of BSCs. To ensure optimal operation, it is very important that BSCs are tested and certified annually, preferably by someone accredited by the National Sanitary Foundation (NSF). BSCs should also be certified when they are first installed and whenever they are moved, even to a nearby laboratory.
In addition to complying with OSHA regulations and CDC-NIH guidelines, another challenge for companies using biological agents is the transfer or shipping of biological agents. To lawfully send samples, specimens, or other research-related materials via aircraft or by ground transportation, companies must comply with standards from the U.S. Department of Transportation (DOT), the International Civil Air Association (ICAO), or the International Air Transport Association (IATA). Before any “dangerous goods” packages are offered for transport, specific training must occur, and training is required for all employees involved in the shipping process. The phrase “dangerous goods” refers to a diverse list of materials that can include dry ice, cell lines, fixed tissue specimens, and pathogenic microorganisms.
In summary, compliance with the biosafety guidelines recommended by the CDC and NIH and with the BBP Standard requirements mandated by OSHA provides clear advantages for biotechnology and pharmaceutical companies. The laboratory review process can ensure compliance and address a company’s ethical responsibilities to its employees as well as reduce potential liability concerns related to exposures to infectious agents. This approach can support companies in meeting the CDC-NIH goal of providing safe environments for both laboratory personnel and the surrounding community.
Ted A. Myatt, Sc.D., is a senior scientist for Environmental Health & Engineering, Inc. (www.eheinc.com), a consulting and engineering services company based in Needham, MA. He also serves as the biological safety officer at Brigham and Women’s Hospital in Boston, MA, as well as a biosafety officer at several other high profile institutions. Myatt can be reached at [email protected] or 800-825-5343.
- U.S. Governmental Accountability Office (GAO), Testimony before the Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, House of Representatives, “High-Containment Biosafety Laboratories