Biosafety level

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A biosafety level is the level of the biocontainment precautions required to isolate dangerous biological agents in an enclosed facility. The levels of containment range from the lowest biosafety level 1 (BSL-1) to the highest at level 4 (BSL-4). In the United States, the Centers for Disease Control and Prevention (CDC) have specified these levels.[1] In the European Union, the same biosafety levels are defined in a directive.[2]

History[edit]

The first prototype Class III (maximum containment) biosafety cabinet was fashioned in 1943 by Hubert Kaempf Jr., then a U.S. Army soldier, under the direction of Dr. Arnold G. Wedum, Director (1944–69) of Industrial Health and Safety at the United States Army Biological Warfare Laboratories, Camp Detrick, Maryland. Kaempf was tired of his MP duties at Detrick and was able to transfer to the sheet metal department working with the contractor, the H.K. Ferguson Co.[3]

On 18 April 1955, fourteen representatives met at Camp Detrick in Frederick, Maryland. The meeting was to share knowledge and experiences regarding biosafety, chemical, radiological, and industrial safety issues that were common to the operations at the three principal biological warfare (BW) laboratories of the U.S. Army[4][5] Because of the potential implication of the work conducted at biological warfare laboratories, the conferences were restricted to top level security clearances. Beginning in 1957, these conferences were planned to include non-classified sessions as well as classified sessions to enable broader sharing of biological safety information. It was not until 1964, however, that conferences were held in a government installation not associated with a biological warfare program.[6]

Over the next ten years, the biological safety conferences grew to include representatives from all federal agencies that sponsored or conducted research with pathogenic microorganisms. By 1966 it began to include representatives from universities, private laboratories, hospitals, and industrial complexes. Throughout the 1970s, participation in the conferences continued to expand and by 1983 discussions began regarding the creation of a formal organization.[6] The American Biological Safety Association (ABSA) was officially established in 1984 and a constitution and bylaws were drafted the same year. As of 2008, ABSA includes some 1,600 members in its professional association.[6]

Rationale[edit]

CDC technician dons an older-model positive-pressure suit before entering one of the CDC’s earlier maximum containment labs.

Biocontainment can be classified by the relative danger to the surrounding environment as biological safety levels (BSL). As of 2006, there are four safety levels. These are called BSL1 through BSL4, with one anomalous level BSL3-ag for agricultural hazards between BSL3 and BSL4. Facilities with these designations are also sometimes given as P1 through P4 (for Pathogen or Protection level), as in the term P3 laboratory. Higher numbers indicate a greater risk to the external environment. See biological hazard.

At the lowest level of biocontainment, the containment zone may only be a chemical fume hood. At the highest level the containment involves isolation of an organism by means of building systems, sealed rooms, sealed containers, positive pressure personnel suits (sometimes referred to as "space suits") and elaborate procedures for entering the room, and decontamination procedures for leaving the room. In most cases this also includes high levels of security for access to the facility, ensuring that only authorized personnel may be admitted to any area that may have some effect on the quality of the containment zone. This is considered a hot zone.

Levels[edit]

Biosafety level 1[edit]

This level is suitable for work involving well-characterized agents not known to consistently cause disease in healthy adult humans, and of minimal potential hazard to laboratory personnel and the environment (CDC,1997).[7]

It includes several kinds of bacteria and viruses including canine hepatitis, non-pathogenic Escherichia coli, as well as some cell cultures and non-infectious bacteria. At this level, precautions against the biohazardous materials in question are minimal and most likely involve gloves and some sort of facial protection. The laboratory is not necessarily separated from the general traffic patterns in the building. Work is generally conducted on open bench tops using standard microbiological practices. Usually, contaminated materials are left in open (but separately indicated) waste receptacles. Decontamination procedures for this level are similar in most respects to modern precautions against everyday microorganisms (i.e., washing one's hands with anti-bacterial soap, washing all exposed surfaces of the lab with disinfectants, etc.). In a lab environment all materials used for cell and/or bacteria cultures are decontaminated via autoclave. Laboratory personnel have specific training in the procedures conducted in the laboratory and are supervised by a scientist with general training in microbiology or a related science.

Biosafety level 2[edit]

This level is similar to Biosafety Level 1 and is suitable for work involving agents of moderate potential hazard to personnel and the environment.[7] It includes various bacteria and viruses that cause only mild disease to humans, or are difficult to contract via aerosol in a lab setting, such as C. difficile, most Chlamydiae, hepatitis A, B, and C, orthopoxviruses (other than smallpox), influenza A, Lyme disease, Salmonella, mumps, measles,[8] scrapie, MRSA, and VRSA. BSL-2 differs from BSL-1 in that:

  1. laboratory personnel have specific training in handling pathogenic agents and are directed by scientists with advanced training;
  2. access to the laboratory is limited when work is being conducted;
  3. extreme precautions are taken with contaminated sharp items; and
  4. certain procedures in which infectious aerosols or splashes may be created are conducted in biological safety cabinets or other physical containment equipment.

Biosafety level 3[edit]

Researcher at US Centers for Disease Control, Atlanta, Georgia, working with influenza virus under biosafety level 3 conditions, with respirator inside a biosafety cabinet (BSC).

This level is applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents which may cause serious or potentially lethal disease after inhalation.[7] It includes various bacteria, parasites and viruses that can cause severe to fatal disease in humans but for which treatments exist, such as Yersinia pestis (causative agent of plague), Francisella tularensis, Leishmania donovani, Mycobacterium tuberculosis, Chlamydia psittaci, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, SARS coronavirus, Coxiella burnetii, Rift Valley fever virus, Rickettsia rickettsii, several species of Brucella, rabies virus, chikungunya, yellow fever virus, and West Nile virus.

Laboratory personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists who are experienced in working with these agents. This is considered a neutral or warm zone.

All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets, specially designed hoods, or other physical containment devices, or by personnel wearing appropriate personal protective clothing and equipment. The laboratory has special engineering and design features.

It is recognized, however, that some existing facilities may not have all the facility features recommended for Biosafety Level 3 (i.e., double-door access zone and sealed penetrations). In this circumstance, an acceptable level of safety for the conduct of routine procedures, (e.g., diagnostic procedures involving the propagation of an agent for identification, typing, susceptibility testing, etc.), may be achieved in a biosafety level 2 (P2) facility, providing

  1. the filtered exhaust air from the laboratory room is discharged to the outdoors,
  2. the ventilation to the laboratory is balanced to provide directional airflow into the room,
  3. access to the laboratory is restricted when work is in progress, and
  4. the recommended Standard Microbiological Practices, Special Practices, and Safety Equipment for Biosafety Level 3 are rigorously followed.

The decision to implement this modification of biosafety level 3 recommendations is made only by the laboratory director.

Biosafety level 4[edit]

The Galveston National Laboratory BSL-4 (P4) lab on the Campus of the University of Texas Medical Branch

This level is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections, agents which cause severe to fatal disease in humans for which vaccines or other treatments are not available, such as Bolivian and Argentine hemorrhagic fevers, Marburg virus, Ebola virus, Lassa virus, Crimean-Congo hemorrhagic fever, and various other hemorrhagic diseases. This level is also used for work with agents such as smallpox that are considered dangerous enough to require the additional safety measures, regardless of vaccination availability. When dealing with biological hazards at this level the use of a positive pressure personnel suit, with a segregated air supply, is mandatory. The entrance and exit of a level four biolab will contain multiple showers, a vacuum room, an ultraviolet light room, and other safety precautions designed to destroy all traces of the biohazard. Multiple airlocks are employed and are electronically secured to prevent both doors from opening at the same time. All air and water service going to and coming from a biosafety level 4 (or P4) lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release.

Agents with a close or identical antigenic relationship to biosafety level 4 agents are handled at this level until sufficient data are obtained either to confirm continued work at this level, or to work with them at a lower level.

Members of the laboratory staff have specific and thorough training in handling extremely hazardous infectious agents and they understand the primary and secondary containment functions of the standard and special practices, the containment equipment, and the laboratory design characteristics. They are supervised by qualified scientists who are trained and experienced in working with these agents. Access to the laboratory is strictly controlled by the laboratory director.

The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Building protocols for preventing contamination often use negatively pressurized facilities, which, even if compromised, would severely inhibit an outbreak of aerosol pathogens.

Within work areas of the facility, all activities are confined to Class III biological safety cabinets, or Class II biological safety cabinets used with one-piece positive pressure personnel suits ventilated by a life support system.

List of BSL-4 facilities[edit]

According to the U.S. Government Accountability Office (GAO) report published on October 4, 2007, a total of 1,356 CDC/USDA registered BSL-3 facilities were identified throughout the United States (GAO-08-108T [9]). This represents a very conservative estimate of the number of facilities in the US in 2007. Approximately 36% of these laboratories are located in academia. Only 15 BSL-4 facilities were identified in the U.S. in 2007, including nine at federal labs.[9]

The following is a list of existing BSL-4 facilities worldwide.

Name Location Date
established
Description
Virology Laboratory of the Queensland Department of Health Australia, Queensland, Coopers Plains
University of Queensland - Sir Albert Sakzewski Virus Research Centre (SASVRC) Royal Women's Hospital Brisbane P3 (BL3) Australia, Queensland, Herston
Australian Animal Health Laboratory Australia, Victoria, Geelong
National High Security Laboratory Australia, Victoria, North Melbourne National High Security Laboratory Operates under the auspice of the Victoria Infectious Diseases Reference Laboratory.
Republican Research and Practical Center for Epidemiology and Microbiology Belarus, Minsk Department of Molecular Epidemiology & Innovational Biotechnologies
National Microbiology Laboratory Canada, Manitoba, Winnipeg Located at the Canadian Science Centre for Human and Animal Health, it is jointly operated by the Public Health Agency of Canada and the Canadian Food Inspection Agency.
Wuhan Institute of Virology of the Chinese Academy of Sciences China, Hubei, Wuhan 2003 Wuhan Institute of Virology already hosts a BSL-3 laboratory. A distinct BSL-4 facility is currently being built based on P4 standards, the original technology for confinement developed by France.[10][11] It will be the first at level 4 in China, under the direction of Shi Zhengli.[12]
Biological Defense Center Czech Republic, Pardubice, Těchonín Located at the Centrum biologické ochrany (Biological Defense Center)[13]
Laboratoire P4 Jean Mérieux France, Rhône-Alpes, Lyon 1999-03-05 Jean Mérieux laboratory is a co-operation between the Pasteur Institute and INSERM. Note that in France, it is P4 for Pathogen or Protection level 4.[14]
Centre International de Recherches Médicales de Franceville Gabon This facility is operated by a research organization supported by both Gabonese (mainly) and French governments, and is West Africa's only P4 lab (BSL-4).[15]
Robert Koch Institute Germany, Berlin The facility was licenced for construction by City of Berlin on November 30, 2008.
Bernhard Nocht Institute for Tropical Medicine Germany, Hamburg
Friedrich Loeffler Institute on the Isle of Riems Germany, Isle of Riems (Greifswald) 2010 Deals especially with virology
Philipps University of Marburg Germany, Marburg 2008 The facility is licenced to work with genetically modified organisms
High Security Animal Disease Laboratory (HSADL) India, Bhopal 1998 This facility deals especially to zoonotic organisms and emerging infectious disease threats.
Centre for Cellular and Molecular Biology India, Hyderabad 2009 National Bio-Safety Level-4 Containment Facility for Human Infectious Diseases & Clinical Research Facility in Regenerative Medicine [16][17]
All India Institute of Medical Sciences India, New Delhi 1993 Conducts studies on major pathogenic organisms. Has contributed in discovering new strains & vaccines.
Microbial Containment Complex India, Pune 2012 Bio-Safety Level-IV Laboratory established by ICMR with support from Department of Science & Technology
Azienda Ospedaliera Ospedale Luigi Sacco Italy, Lombardy, Milan A university hospital in Polo Universitario; it contains two special vehicles for transporting infectious persons.
Istituto Nazionale Malattie Infettive Italy, Rome, Rome This facility, (trans.) National Institute of Infectious Diseases, operates within the Lazzaro Spallanzani Hospital.
National Institute for Infectious Diseases Japan, Kantō, Tokyo Located at National Institute for Infectious Diseases, Department of Virology I; this lab has the potential of operating as a BSL-4, however it is limited to perform work on only BSL-3 agents due to opposition from local residents and communities.
Institute of Physical and Chemical Research Japan, Kantō, Tsukuba This is a non-operating BSL-4 facility.
Netherlands National Institute for Public Health and the Environment (RIVM) Netherlands, Bilthoven 2009
Cantacuzino Microbiological Research Institute (INCDMI) Romania, Bucharest [18]
"Dr. Carol Davila" Central Military Hospital Romania, Bucharest [19]
State Research Center of Virology and Biotechnology VECTOR Russia, Novosibirsk Oblast, Koltsovo It is one of two facilities in the world that officially hold smallpox. The other Russian BSL-4 facilities have been dismantled.
National Institute for Communicable Diseases South Africa, Johannesburg National Institute for Communicable Diseases of Special Pathogens Unit is one of only two BSL-4 facilities in Africa but the only suit laboratory on the continent.
Swedish Institute for Communicable Disease Control Sweden, Solna Swedish Institute for Communicable Disease Control is Scandinavia's P4 facility.
University Hospital of Geneva Switzerland
Spiez Laboratory Switzerland, Spiez This laboratory comply with BSL4 standards.
Kwen-yang Laboratory (昆陽實驗室) Center of Disease Control Taiwan Part of the Department of Health, Taiwan.
Preventive Medical Institute of ROC Ministry of National Defense Taiwan
Health Protection Agency's Centre for Infections United Kingdom, Colindale Located in the Viral Zoonosis unit.
National Institute for Medical Research United Kingdom, London [20]
Institute for Animal Health United Kingdom, Pirbright
Institute for Animal Health Compton Laboratory United Kingdom, Compton [21]
Defence Science and Technology Laboratory United Kingdom, Porton Down
Health Protection Agency United Kingdom, Porton Down Special Pathogens Reference Unit.
Health Protection Agency United Kingdom, Porton Down Botulism.
Francis Crick Institute[22] United Kingdom, London Under construction. The UKCMRI will not work on Human Hazard Group 4 agents.
Centers for Disease Control and Prevention United States, Georgia, Atlanta Currently operates in two buildings. One of two facilities in the world that officially hold smallpox.
Georgia State University United States, Georgia, Atlanta Is an older design "glovebox" facility.
National Bio and Agro-Defense Facility (NBAF), Kansas State University United States, Kansas, Manhattan Under construction. Facility to be operated by the Department of Homeland Security, and replace the Plum Island Animal Disease Center (which is not a BSL-4 facility). Planned to be operational by 2015, but likely delayed.
National Institutes of Health (NIH) United States, Maryland, Bethesda Located on the NIH Campus, it currently only operates with BSL-3 agents.
Integrated Research Facility United States, Maryland, Fort Detrick Under construction. This facility will be operated by National Institute of Allergy and Infectious Diseases (NIAID), it is planned to begin operating at 2009 at the earliest.
National Biodefense Analysis and Countermeasures Center (NBACC) United States, Maryland, Fort Detrick Under construction, it will be operated for the Department of Homeland Security.
US Army Medical Research Institute of Infectious Diseases (USAMRIID) United States, Maryland, Fort Detrick 1969 Old building
US Army Medical Research Institute of Infectious Diseases (USAMRIID) United States, Maryland, Fort Detrick 2017? New building, currently under construction
National Emerging Infectious Diseases Laboratory (NEIDL), Boston University United States, Massachusetts, Boston Under construction by Boston University, building and staff training complete, waiting for regulatory approval.
NIAID Rocky Mountain Laboratories United States, Montana, Hamilton National Institute of Allergy and Infectious Diseases
Kent State University, Kent Campus United States, Ohio, Kent Operates as a clean lab at level 3 for training purposes. Scheduled for conversion to a hot level 4 lab in response to a bioterrorism event in the USA.
Galveston National Laboratory, National Biocontainment Facility United States, Texas, Galveston Opened in 2008, facility is operated by the University of Texas Medical Branch.[23]
Shope Laboratory United States, Texas, Galveston Operated by the University of Texas Medical Branch (UTMB).
Texas Biomedical Research Institute United States, Texas, San Antonio The only privately owned BSL-4 lab in the US.
Division of Consolidated Laboratory Services United States, Virginia, Richmond This facility is part of the Department of General Services of the Commonwealth of Virginia. It is so called "surge" BSL-4 capacity.

See also[edit]

Notes and references[edit]

  1. ^ Richmond JY, McKinney RW (editors) (1999). Biosafety in Microbiological and Biomedical Laboratories (4th ed. ed.). ISBN 0-7881-8513-6. 
  2. ^ Council Directive 90/679/EEC of 26 November 1990 on the protection of workers from risks related to exposure to biological agents at work, OJ No. L 374, p. 1.
  3. ^ Covt, Norman M. (1997), “A History of Fort Detrick, Maryland”, 3rd edition. Kaempf retired from Fort Detrick in 1994, having completed more than 50 years service. He was chief of the mechanical branch, Directorate of Engineering and Housing.
  4. ^ Manuel S. Barbeito; Richard H. Kruse. "A History of the American Biological Safety Association". American Biological Safety Association. Retrieved 2008-08-14. 
  5. ^ "Biosafety History,Recombinant DNA Molecules,Hybrid Organisms,NIH Guidelines,Bacillus Subtilis". Molecular-Plant-Biotechnology.info. Retrieved 2008-08-14. 
  6. ^ a b c "American Biological Safety Association Collection : NAL Collections : National Agricultural Library". United States Department of Agriculture: National Agricultural Library. 2009-02-11. Retrieved 2009-02-11. 
  7. ^ a b c The 1, 2, 3's of Biosafety Levels
  8. ^ "Routine diagnostic work with clinical specimens can be done safely at Biosafety Level 2, using Biosafety Level 2 practices and procedures. Research work (including co-cultivation, virus replication studies, or manipulations involving concentrated virus) can be done in a BSL-2 (P2) facility, using BSL-3 practices and procedures. Virus production activities, including virus concentrations, require a BSL-3 (P3) facility and use of BSL-3 practices and procedures", see Recommended Biosafety Levels for Infectious Agents.
  9. ^ a b http://www.gao.gov/new.items/d08108t.pdf
  10. ^ French subcontractor release and programme profile page
  11. ^ Information on Wuhan Institute of Virology and timeline
  12. ^ Don Burke's Global Health Blog - Wuhan, China
  13. ^ Ministerstvo obrany - Centrum biologické ochrany Těchonín
  14. ^ English presentation of Jean Mérieux P4 laboratory
  15. ^ CIRMF
  16. ^ http://web.mit.edu/ssp/news/event_presentations/kuhn-biosecurity.pdf
  17. ^ Stone laid for stem cell research lab in Hyderabad | Business Line
  18. ^ http://www.embarc.eu/7-ODracea.pdf
  19. ^ Spitalul Militar Central – Bucuresti - harta, adresa, contact, panorama
  20. ^ "Deadly secrets of the pathogen labs". The Times (London). 
  21. ^ "Jobs March 2014 SAPO 3-4 Officer". Pirbright (Compton). 
  22. ^ http://www.publications.parliament.uk/pa/cm201012/cmselect/cmsctech/727/72710.htm
  23. ^ Galveston National Laboratory Fact Sheet

External links[edit]