Biosafety level

Biosafety level

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]

Contents

History

The first prototype Class III 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 was 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 has includes some 1,600 members in its professional association.[6]

Rationale

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 the organism by means of building systems, sealed rooms, sealed containers, personal isolation equipment commonly 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

Biosafety level 1

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, 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) 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

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, influenza A, Lyme disease, dengue fever, Salmonella, mumps, measles, HIV,[8] scrapie, MRSA, and VRSA. Genetically modified organisms have also been classified as level 2 organisms[citation needed], even if they pose no direct threat to humans. This designation is used to limit the release of modified organisms into the environment. Approval by the FDA is required to release these organisms. An example is genetically modified food crops. 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

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 Leishmania donovani, Mycobacterium tuberculosis, Bacillus anthracis, Chlamydophila psittaci, West Nile virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Hendra virus, SARS coronavirus, Salmonella typhi, Coxiella burnetii, Rift Valley fever virus, Rickettsia rickettsii, and yellow fever 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

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 fever, Crimean-Congo hemorrhagic fever, smallpox, and various other 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 (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 is 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-3 and BSL-4 facilities

Name Location Level Established Discontinued Description
University of Queensland - Sir Albert Sakzewski Virus Research Centre (SASVRC) Royal Womens Hospital Brisbane P3 (BL3) Australia, Queensland, Herston 3+4
University of Queensland - St Lucia Microbiology Building 76 P3 (BL3) Australia, Queensland, St Lucia 3
Virology Laboratory of the Queensland Department of Health Australia, Queensland, Coopers Plains 4
Australian Animal Health Laboratory Australia, Victoria, Geelong 4
National High Security Laboratory Australia, Victoria, North Melbourne 4 National High Security Laboratory Operates under the auspice of the Victoria Infectious Diseases Reference Laboratory.
University of Auckland, School of Medical Sciences New Zealand, Auckland 3 Construction completed June 2011 -awaiting MAF approval
Republican Research and Practical Center for Epidemiology and Microbiology Belarus, Minsk 4 Laboratory for Biotechnology and Immunodiagnosis of Highly Dangerous Infections
British Columbia Centre for Disease Control Canada, British Columbia 3 The British Columbia Centre for Disease Control, operates three biosafety level 3 labs.
National Microbiology Laboratory Canada, Manitoba, Winnipeg 4 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.
Saskatchewan Disease Control Laboratory Canada, Saskatchewan, Regina 3 Officially opened in May 2010, the new building for the Saskatchewan Disease Control Laboratory is located at Innovation Place Research Park, on the campus of the University of Regina. It is operated by the Saskatchewan Ministry of Health.
International Vaccine Center Canada, Saskatchewan, Saskatoon 3 2011 (under construction) Located on the University of Saskatchewan campus, part of the Vaccine and Infectious Disease Organization
Centre National de Biologie Expérimentale Canada, Quebec, Quebec 3 Located at the Institut national de la recherche scientifique.
Canada, Ontario, Toronto 4 This facility never opened due to community opposition in the 1990s.[9]
Biological Defense Center Czech Republic 4 Located at the Centrum biologické ochrany Těchonín (Biological Defense Center)[10]
National Institute for Health and Welfare Finland, Hermanni, Helsinki 3 Document from National Institute for Health and Welfare that mentions the facility.[11]
National Institute for Health and Welfare Finland, Tilkanmäki, Helsinki 3 Document from National Institute for Health and Welfare that mentions the facility.[11]
Laboratoire P4 Jean Mérieux France, Rhône-Alpes, Lyon 4 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.[12]
Centre International de Recherches Médicales de Franceville Gabon 4 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).[13]
Robert Koch Institute Germany, Berlin 4 The facility was licenced for construction by City of Berlin on November 30, 2008.
Bernhard Nocht Institute for Tropical Medicine Germany, Hamburg 4
Philipps University of Marburg Germany, Marburg 4 2008 The facility is licenced to work with genetically modified organisms
Friedrich Loeffler Institute on the Isle of Riems Germany, the Isle of Riems (Greifswald) 4 2010 Deals especially with virology
National JALMA Institute for Leprosy & Other Mycobacterial Diseases (NCJILOMD), Agra India, Agra 3 2002 This facility deals with the Mycobacterial strains & their pathogenicity & epidemiology.
Laboratory of Epidemiology and Public Health (LEPH), Yale United States, New Haven, CT 3 This facility deals with pathogenicity & epidemiology.
High Security Animal Disease Laboratory (HSADL) India, Bhopal 4 1998 This facility deals especially to zoonotic organisms and emerging infectious disease threats.
All India Institute of Medical Sciences India, New Delhi 1-4 1993 Conducts studies on major pathogenic organisms. Has contributed in discovering new strains & vaccines.
Institute of Tropical Disease (ITD) Indonesia, East Java, Surabaya 3 2008 Operated by Institute of Tropical Disease - Airlangga University, Build Cooperation with Japan.
Azienda Ospedaliera Ospedale Luigi Sacco Italy, Lombardy, Milano 4 A university hospital in Polo Universitario; it contains two special vehicles for transporting infectious persons.
Istituto Nazionale Malattie Infettive Italy, Rome, Rome 4 This facility, (trans.) National Institute of Infectious Diseases, operates within the Lazzaro Spallanzani Hospital.
Institute for Medical Research (IMR), Ministry of Health Malaysia, Kuala Lumpur 3 This facility is able to conduct research and tests on acarology, bacteriology, medical entomology, parasitology and virology.
National Institute for Infectious Diseases Japan, Kantō, Tokyo 3 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 3 - 4 2009 Currently under construction, it is planned to be finished by the end of 2009. It is planned to operate as a BSL 3 and a BSL 4 facility.
Erasmus Medical Center Netherlands, Rotterdam 3
Biological Threats Identification and Countermeasure Centre of the Military Institute of Hygiene and Epidemiology Poland, Puławy 3 [14]
Sanitary and Epidemiological Station Poland, Warsaw 3 25.03.2010 [15]
Molecular Medicine Institute Portugal, Lisbon 3 [16]
Wuhan Institute of Virology of the Chinese Academy of Sciences People's Republic of China, Hubei, Wuhan 3 - 4 2010 (P4) 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.[17][18] It will be the first at level 4 in China, under the direction of Shi Zhengli.[19]
State Research Center of Virology and Biotechnology VECTOR Russia, Novosibirsk Oblast, Koltsovo 1 - 4 It is one of two facilities in the world that officially hold smallpox. The other Russian BSL-4 facilities have been dismantled.
Defence Science Organization (DSO) Singapore 4 Defence Science Organization goal is to conduct autopsies during a potential deadly epidemic outbreak. Singapore also has a mobile BSL-4 autopsy facility.[20]
National Institute for Communicable Diseases South Africa, Johannesburg 4 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.
University of Iceland, The Department of Medical Virology Iceland, Reykjavik 3 1990 The Department of Medical Virology at the University of Iceland serves as a

diagnostic unit for virus diseases for hospitals and practising physicians.

Swedish Institute for Communicable Disease Control Sweden, Solna 4 Swedish Institute for Communicable Disease Control is Scandinavia's P4 facility.
Institute of Virology and Immunoprophylaxis (IVI) Switzerland, Mittelhäusern 4 2007-02-01 This facility only deals with animal diseases which do not transmit to humans, and is the only P4 facility where complete isolation suits are not used.
High Containment Laboratory DDPS (SiLab) Switzerland, Spiez 4 Under construction, it will start operations in 2010. This laboratory will comply with BSL-4 standards.
Preventive Medical Institute of ROC Ministry of National Defense (Taiwan) 4
Kwen-yang Laboratory (昆陽實驗室) Center of Disease Control (Taiwan) 4 Part of the Department of Health Republic of China.
Institute for Animal Health United Kingdom, Pirbright 4
National Institute for Medical Research United Kingdom, London 4 [21]
Health Protection Agency's Centre for Infections United Kingdom, Colindale 4 Located in the Viral Zoonosis unit.
Defence Science and Technology Laboratory United Kingdom, Porton Down 4
Health Protection Agency United Kingdom, Porton Down 4 Special Pathogens Reference Unit.
Health Protection Agency United Kingdom, Porton Down 4 Botulism.
University of Florida Medical Entomology Laboratory United States of America, Florida, Vero Beach 3 Also an arthropod containment facility, used to study mosquito-borne viruses including West Nile Virus, dengue virus, and chikungunya virus.
Centers for Disease Control and Prevention United States of America, Georgia, Atlanta 4 Currently operates in two buildings. One of two facilities in the world that officially hold smallpox.
Georgia State University United States of America, Georgia, Atlanta 4 Is an older design "glovebox" facility.
Integrated Research Facility United States of America, Maryland, Fort Detrick 4 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 of America, Maryland, Fort Detrick 4 Under construction, it will be operated for the Department of Homeland Security.
National Institutes of Health (NIH) United States of America, Maryland, Bethesda 4 Located on the NIH Campus, it currently only operates with BSL-3 agents.
US Army Medical Research Institute of Infectious Diseases (USAMRIID) United States of America, Maryland, Fort Detrick 4 Old building
US Army Medical Research Institute of Infectious Diseases (USAMRIID) United States of America, Maryland, Fort Detrick 4 New building, currently under design construction
National Emerging Infectious Diseases Laboratory (NEIDL) United States of America, Massachusetts, Boston 4 Under construction by Boston University, building and staff training complete, waiting for regulatory approval.
Tufts Cummings School of Veterinary Medicine United States of America, Massachusetts, Grafton 3-4
NIAID Rocky Mountain Laboratories United States of America, Montana, Hamilton 4 National Institute of Allergy and Infectious Diseases
Albert Einstein College of Medicine of Yeshiva University United States of America, New York, The Bronx 3 2008 The Michael F. Price Center for Genetic and Translational Medicine in the Harold and Muriel Block Research Pavilion operated by Einstein.[22]
Stony Brook University Centers for Molecular Medicine Center for Infectious Diseases United States of America, New York, Stony Brook 3 1999 Operated by State University of New York at Stony Brook, a BSL-3 facility studying Borrelia burgdorferi (Lyme Disease), Yersinia pestis (Bubonic plague) and Francisella tularensis (Rabbit fever)
Institute for Food Safety and Health United States of America, Illinois, Bedford Park 3 2010 Located off-campus of the Illinois Institute of Technology[23]
University of New Mexico United States of America, New Mexico, Albuquerque 3 University of New Mexico operates several BSL-3 and ABSL-3 labs as part of the School of Medicine.
Galveston National Laboratory, National Biocontainment Facility United States of America, Texas, Galveston 4 Opened in 2008, facility is operated by the University of Texas Medical Branch.[24]
Shope Laboratory United States of America, Texas, Galveston 4 Operated by the University of Texas Medical Branch (UTMB).
Texas Biomedical Research Institute United States of America, Texas, San Antonio 4 The only privately-owned BSL-4 lab in the US.
George Mason University Biomedical Research Laboratory United States of America, Virginia, Manassas 3 This facility is currently under construction on a 10-acre (40,000 m2) site adjacent to George Mason University's Prince William Campus. It is scheduled to be fully operational in the Spring of 2010.
Division of Consolidated Laboratory Services United States of America, Virginia, Richmond 4 This facility is part of the Department of General Services of the Commonwealth of Virginia. It is so called "surge" BSL-4 capacity.
National Bio and Agro-Defense Facility (NBAF) United States of America, Kansas State University, Manhattan, Kansas 4 Facility to be operated by the Department of Homeland Security, and replace the Plum Island Animal Disease Center. Planned to be operational by 2014.
Plum Island Animal Disease Center United States of America, New York, Plum Island 3-ag Facility scheduled to be replaced by the National Bio and Agro-Defense Facility. Researches zoonotic pathogens only.
Saint Louis University Doisy Research Building United States of America, Missouri, St. Louis 3 Saint Louis University's new center for biomedical research. Monkeypox is the primary BSL-3 agent studied.
University of California, Berkeley United States of America, California, Berkeley 3 The UC Berkeley BSL3 Facility is currently housed in a single location but will be expanded in 2011 to include a second site (in a building under construction).
Instituto Nacional de Tecnologia Agropecuaria, Buenos Aires Argentina, Buenos Aires, Castelar 3-A Instituto de Virologia (CICVyA)
Veterinary Research Institute (VRI), Department of Veterinary Services Malaysia, Ipoh, Perak 3 This facility created a breakthrough in identifying the Nipah virus,[citation needed] which is classified internationally as a BSL-4 agent.
International Vaccine Institute Republic of Korea, Seoul 3+ 2009 Opened in 2009. This facility is operated by International Vaccine Institute supported by UNDP, WHO and Republic of Korea Government.[25]
Ministry of Health's National Institute of Hygiene and Epidemiology Socialist Republic of Vietnam, Hanoi 3 2006 Built in Hanoi with the assistance of the Japanese International Cooperation Agency, World Health Organization, and other international players. Japan and the WHO would provide financial and technical assistance in building a BSL-3 standards lab for four years (2006–2010) in order to help combat emerging infectious diseases.[26] The aid was in response to criticism of Vietnam's handling of recent disease outbreaks.[27]
CISA-INIA / Animal Health Research Center Valdeolmos, Madrid , Spain 3 - 3+ [28]
Gauhati Medical College and Hospital Guwahati, Assam , India 2011
Global Bio Lab United States of America, California, Los Angeles 3 2011 Under Construction Pending certification, under construction, joint project between UCLA School of Public Health and Los Alamos National Laboratory[29]
Kent State University, Kent Campus United States of America, Ohio, Kent 3-4 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.
Biotechnology Research Institute (BRI), Universiti Malaysia Sabah Malaysia, Sabah, Kota Kinabalu 3 2011 This facility is an enhanced ABSL3 and BSL3. The first in the island of Borneo.

See also

References

  1. ^ Richmond JY, McKinney RW (editors) (1999). Biosafety in Microbiological and Biomedical Laboratories (4th ed. ed.). ISBN 0-7881-8513-6. http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm. 
  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. ^ "A History of the American Biological Safety Association". American Biological Safety Association. http://www.absa.org/abohist1.html. Retrieved 2008-08-14. 
  5. ^ "Biosafety History,Recombinant DNA Molecules,Hybrid Organisms,NIH Guidelines,Bacillus Subtilis". Molecular-Plant-Biotechnology.info. http://www.molecular-plant-biotechnology.info/biosafety/biosafety-history.htm. 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. http://riley.nal.usda.gov/nal_display/index.php?info_center=8&tax_level=4&tax_subject=158&topic_id=1982&level3_id=6419&level4_id=10967&level5_id=0&placement_default=0&test. 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. ^ Lofstedt R (2002). "Good and bad examples of siting and build biosafety level 4 laboratories: a study of Winnipeg, Galves and Etobicoke.". J Hazard Mater 93 (1): 47–66. doi:10.1016/S0304-3894(02)00038-9. PMID 12062953. 
  10. ^ Ministerstvo obrany - Centrum biologické ochrany Těchonín
  11. ^ a b National Institute for Health and Welfare (2009-03-25) (in Finnish) (JPEG), Kulutukseen luovutuslupa (application to the National Agency of Medicines), p. 2, http://www.infosota.fi/wp-content/uploads/2009/12/thl-h5n1-m%C3%A4%C3%A4r%C3%A4aikainen-erityislupa1.jpeg , published in Välimäki, Teemu (2009-12-07), "Suomi testaamaan uutta lintuinfluenssarokotetta" (in Finnish), Infosota, http://www.infosota.fi/2009/12/07/suomi-testaamaan-uutta-lintuinfluenssarokotetta/, retrieved 2011-11-20 .
  12. ^ English presentation of Jean Mérieux P4 laboratory
  13. ^ CIRMF
  14. ^ Peter Stopa BSL-3 laboratory, Pulawy, Poland
  15. ^ Kurier Elektroniczny Medycyny Praktycznej - Otwarto laboratorium BSL-3 w Warszawie [en: The On-Line Journal of Practical Medicine - A BSL-3 lab opened in Warsaw]
  16. ^ [1]
  17. ^ French subcontractor release and programme profile page
  18. ^ Information on Wuhan Institute of Virology and timeline
  19. ^ Don Burke's Global Health Blog - Wuhan, China
  20. ^ Chong, Peter (2006). ""Mobile Biosafety Level-4 Autopsy Facility - An Innovative Solution" - Conference Paper Abstract". http://www.absa.org/conf49abstracts.html#22. 
  21. ^ Deadly secrets of the pathogen labs - Times Online
  22. ^ http://www.buildings.com/Magazine/ArticleDetails/tabid/3413/ArticleID/8946/Default.aspx
  23. ^ IFSH home Retrieved 2011-10-31
  24. ^ Galveston National Laboratory Fact Sheet
  25. ^ The IVI Newsletter Issue 20, Jan.2009
  26. ^ http://www.jica.go.jp/vietnam/english/activities/activity06.html
  27. ^ http://www.sciencemag.org/content/309/5733/368.full?sid=c05960c3-1571-4340-b6e0-e475ad763781
  28. ^ [2]
  29. ^ [3]

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