Biosafety level

Laws and practice of several countries specify four levels of biocontainment precautions for biological agents, Biosafety Levels 1 through 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]

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Rationale

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. 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 fume hood that utilizes HEPA filters. At the highest level the containment involves isolation of the organism by means of building systems, sealed rooms, sealed containers, personal isolation equipment similar to "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.

The levels

Biosafety Level 1 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.^{[citation needed]} Includes several kinds of bacteria and viruses including Bacillus subtilis, canine hepatitis, Escherichia coli, varicella (chicken pox), as well as some cell cultures and non-infectious bacteria. At this level precautions against the biohazardous materials in question are minimal, most likely involving 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) trash receptacles. Decontamination procedures for this level are similar in most respects to modern precautions against everyday viruses (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 is similar to Biosafety Level 1 and is suitable for work involving agents of moderate potential hazard to personnel and the environment. 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 hepatitis A, B, and C, influenza A, Lyme disease, salmonella, mumps, measles, HIV^[3], scrapie.

It differs from BSL-1 in that

1. laboratory personnel have specific training in handling pathogenic agents and are directed by competent scientists;
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 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 as a result of exposure by the inhalation route. Includes various bacteria and viruses that can cause severe to fatal disease in humans, but for which vaccines or other treatment exist, such as anthrax, West Nile virus, Venezuelan equine encephalitis, Eastern Equine Encephalitis, SARS, smallpox, tuberculosis, typhus, Rift Valley fever, Rocky Mountain spotted fever, yellow fever.

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 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 facility, providing

1. the 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 are made only by the laboratory director.

Biosafety Level 4 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, dengue fever, Marburg virus, Ebola virus, hantaviruses, Lassa fever, Crimean-Congo hemorrhagic fever, and other various hemorrhagic diseases. When dealing with biological hazards at this level the use of a Hazmat suit and a self-contained oxygen 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 opening at the same time. All air and water service going to and coming from a Biosafety Level 4 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 competent 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 uses negatively pressurized facilities, which, 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. The Biosafety Level 4 laboratory has special engineering and design features to prevent microorganisms from being disseminated into the environment. The laboratory is kept at negative air pressure, so that air flows into the room if the barrier is penetrated or breached. Furthermore, an airlock is used during personnel entry and exit.

Biosafety Level 5 does not exist, given that the protocols followed by a Biosafety Level 4 facility are as strict as technically feasible. In popular culture, this level has been referenced. However, the protocols used are usually so extreme they seem focused on preventing the object of study from being inadvertently contaminated by the researchers studying it than preventing the researchers from being inadvertently contaminated by what they are studying. The novel The Andromeda Strain by Michael Crichton, along with the 1971 film of the same name, directed by Robert Wise reference a fictional Level 5 facility. The novel Mount Dragon by Douglas Preston and Lincoln Child also references such a facility, and its measures likely have a similar purpose.

Biocontainment practices and facilities by country

Australia

Australia operates three BSL-4 labs. These are

• The Australian Animal Health Laboratory in Geelong (VIC).

• The Virology Laboratory of the Queensland Department of Health at Coopers Plains (QLD).

• The National High Security Laboratory, operating under the auspices of the Victoria Infectious Diseases Reference Laboratory, in North Melbourne (VIC).

Brazil

Several research institutions such as University of São Paulo, Instituto Butantan and Instituto Adolf Lutz have BSL-3 laboratories to study infectious diseases or develop vaccines against Tuberculosis. It is not clear that Fundação Oswaldo Cruz actually operates a BSL-4 laboratoy in Rio de Janeiro. Original citation in this page: "The Fundação Oswaldo Cruz, a biomedical research institute of the Brazilian government, operates a BSL-4 in Rio de Janeiro".

Canada

Canada has one BSL4 facility, located at the National Microbiology Laboratory in Winnipeg. In the 1990s, a BSL-4 was constructed in Toronto, however, it never opened due to community opposition.

Czech Republic

Czech Republic has BSL4 lab at Centrum biologické ochrany Těchonín (Center of Biological Protection).^[4]

France

France maintains a P4 (for "pathogen" or "protection" level 4) laboratory, Laboratoire P4 Jean Mérieux in Lyon.

Gabon

The Centre International de Recherches Médicales de Franceville (CIRMF), a research organization supported by the French government, operates West Africa's only BSL-4 lab.

Germany

Germany currently has two L4 facilities: one located at the Philipps University of Marburg, Institute of Virology and the Bernhard Nocht Institute for Tropical Medicine in Hamburg. A new P4 lab is currently being built in Marburg and will take over the functions of the old L4 facility there. Also, another P4 lab is planned to be built at the Robert Koch Institute in Berlin.

Japan

Japan has a BSL4 lab at the National Institute for Infectious Diseases, Department of Virology I, Tokyo; however, currently work in this lab is only performed with BSL3 agents. Japan has also a non-operating BSL4 lab at the Institute of Physical and Chemical Research in Tsukuba. Both labs face community opposition.

India

India's BSL4 lab is High Security Animal Disease Laboratory (HSADL) located in Bhopal, India. It deals with all kinds of zoonotic organisms and emerging infectious disease threats.

Italy

Italy's BSL4 lab are at: - Istituto Nazionale Malattie Infettive, Ospedale Lazzaro Spallanzani, Rome. (National Institute of Infectious Diseases, Lazzaro Spallanzani Hospital.) - Azienda Ospedaliera Ospedale Luigi Sacco - Polo Universitario - (Milano). In that hospital there are also two special vehicles in BSL4 for transportation of infectious persons

Russia

VEKTOR State Research Center of Virology and Biotechnology, Koltsovo, Novosibirsk region. Other BSL4 facilities available during the Soviet era have been dismantled.

Singapore

The Defence Science Organization(DSO) National Laboratories operates a BSL-4 facility. With the announced^[5] goal of conducting autopsies during a potential deadly epidemic outbreak, Singapore also has a mobile BSL-4 autopsy facility, perhaps the only one of its kind in the world.

South Africa

The National Institute for Communicable Diseases, Special Pathogens Unit in Johannesburg, South Africa is one of two BSL4 labs in Africa.

Sweden

The Swedish Institute for Infectious Disease Control runs Scandinavia's only P4 laboratory in Solna.

Switzerland

The Institute of Virology and Immunoprophylaxis (IVI) in Mittelhäusern is the only publicly known laboratory in Switzerland to be classed as having biosafety level (BSL) 4. This laboratory only deals with animal disease which do not transmit to humans, and is the only P4 facility where complete isolation suits are not used.

A P4 laboratory was inaugurated on February 01, 2007 in the Teaching Hospital of Geneva.

Since November 12, 2007 the new High Containment Laboratory DDPS (SiLab) in Spiez is under construction and will start operations in 2010. This laboratory will comply with biosafety level (BSL) 4.

Taiwan

In Taiwan, two laboratories have BSL4. One is Preventive Medical Institute of ROC Ministry of National Defense, another is Kwen-yang Laboratory (昆陽實驗室) Center of Disease Control, Department of Health ROC.

United Kingdom

The United Kingdom currently has three BSL-4 laboratories, with another under construction. One is under construction at the National Institute for Medical Research in London, and the other has been built by the Ministry of Defence at Porton Down and is called the Chemical and Biological Defence Establishment. There is also a BSL-4 Laboratory in the Viral Zoonosis unit at the Health Protection Agency's Centre for Infections in Colindale.

United States of America

The U.S. maintains at least eight Biosafety Level 4 facilities, and is currently planning at least seven more:

Operational Facilities:

• USAMRIID in Fort Detrick, MD ("old building")
• CDC in Atlanta, GA (two buildings operational)
• NIH's BSL-4 lab on the NIH Campus in Bethesda, MD (sometimes operates at BSL-3), never operated as a "hot" BSL4
• NIH's BSL-4 lab at the Twinbrook III building, Rockville, MD (sometimes operates at BSL-3)
• Southwest Foundation for Biomedical Research in San Antonio, TX
• UTMB's Shope Laboratory in Galveston, TX
• Georgia State University in Atlanta, GA (smaller "glovebox" facility)
• The Division of Consolidated Laboratory Services lab (part of the Department of General Services of the Commonwealth of Virginia) in Richmond, VA (so-called "surge" BSL-4 capacity)

Facilities Under Construction and Planned:

• USAMRIID in Fort Detrick, MD ("new building", in design)
• Boston University's National Emerging Infectious Diseases Laboratory (NEIDL) in Boston, MA (under construction)
• UTMB's National Biocontainment Facility in Galveston, TX (under construction)
• DHS's National Biodefense Analysis and Countermeasures Center (NBACC) in Fort Detrick, MD (under construction)
• DHS's National Bio and Agro-Defense Facility (NBAF), shortlisted July 2007; final site selection mid to late 2008
• NIAID's Integrated Research Facility in Fort Detrick, MD (in construction- earliest operational date 2009)
• NIAID's Rocky Mountain Laboratories in Hamilton, MT (in construction - earliest operational date 2009)

See also

• Biological hazard
• Safety engineering
• Security engineering

References