Biological protection level

Exemplary construction plan of a laboratory of protection level 4 with systems for air filtering and wastewater sterilization

The biological protection level (borrowed from the English biosafety level , BSL for short ) is a hazard classification of biological agents , especially microorganisms . This is standardized for the European Union by the EU Directive 2000/54 / EC on the protection of workers against risks from biological agents at work and introduced in the Biological Agents Ordinance in Germany. A similar classification is also used by the Centers for Disease Control and Prevention in the USA . Laboratories in which biological agents are handled must take certain protective measures. Accordingly, the laboratories are divided into four defined protection levels, with protection level 4 having the highest requirements. The protection levels build on each other so that the regulations of the lower protection levels also apply to the higher levels.

Laboratories that work with genetically modified organisms are classified according to the Genetic Engineering Act and the Genetic Engineering Safety Ordinance into four biological safety levels , which are referred to in laboratory jargon as S1 laboratories to S4 laboratories.

Legal basis in Germany

The Biological Agents Ordinance (BioStoffV) is used to implement several EC directives , the aim of which is to protect workers from the risks posed by biological agents at work. Since the update of the Biological Agents Ordinance in July 2013, the biological agents are also known as biomaterials called. Section 2 BioStoffV defines the terms that are important for understanding the legal text and differentiate between targeted and non-targeted activities . This distinction is important for choosing the right protection level. Section 3 BioStoffV regulates the classification of biological agents into four risk groups. The classification is based on the risk of infection . In simple terms, this means that the more dangerous a biological substance is, the higher the risk group. According to § 4 BioStoffV, a risk assessment is carried out, on the basis of which the appropriate protective measures are determined. However, according to § 5 BioStoffV, only certain activities are defined that are assigned to a protection level. These are activities in laboratories , in laboratory animal husbandry , in biotechnology and in health service facilities . For other activities, according to § 6 BioStoffV, the activities are not assigned to a protection level.

risk groups

Section 3 of the Biological Agents Ordinance (BioStoffV) defines four risk groups for biological agents . In Directive 90/679 / EEC of the Council of 26 November 1990 were assigned to risk groups different biological agents. However, since the number of biological substances is increasing steadily, an extended list was published with Directive 2000/54 / EC of the European Parliament and Council of September 18, 2000. The disadvantage of these lists is that they do not include biological agents in risk group 1, so that for a biological agent that is not on the list, it is unclear whether it belongs to this risk group or has not yet been classified. Biological agents not listed there must be classified by the member states in accordance with Article 18 of Directive 2000/54 / EC if they represent or could pose a risk to human health and this has not yet been done jointly, i.e. by the bodies of the European Union is.

For this reason, a committee for biological agents (ABAS) was formed in Germany in accordance with Section 19 BioStoffV , which was set up at the Federal Institute for Occupational Safety and Health (BAuA). His tasks include, among other things, the scientific evaluation of biological agents and their classification into risk groups. This is done by issuing the technical rules for biological agents (TRBA). The TRBA are subdivided into rules that classify prokaryotes ( bacteria and archaea ), viruses , fungi , parasites and cell cultures . The relevant TRBA is therefore the appropriate source of literature for the specific classification. Since the TRBA is only revised at longer intervals, a classification can also be made known in the Joint Ministerial Gazette for current biological substances . If a biological substance was not listed in all of these sources, it has not yet been classified. In this case, "the employer who intends to work specifically with this biological substance has to classify it in one of the risk groups according to paragraph 1." ( § 3 Biological Substances Ordinance)

Risk group 1

"Organic substances that are unlikely to cause disease in humans." ( § 3 Biological Substances Ordinance)

This applies, among other biological agents to which the food industry are used as the baker's yeast Saccharomyces cerevisiae , or in the production of yoghurt bacteria used Lactobacillus delbrueckii subsp. bulgaricus or Lactobacillus acidophilus and other lactic acid bacteria . Bacteria that normally occur as harmless commensals on human skin (e.g. Corynebacterium xerosis ) or in the air (e.g. Micrococcus luteus ) are also found in risk group 1.

The viruses assigned to risk group 1 include, for example, canine adenovirus  1 (CAdV-1, causative agent of canine hepatitis ) and canine adenovirus 2 (CAdV-2, causative agent of kennel cough ). Most of the cell lines used in cell culture are also assigned to this risk group, unless they are used together with viruses, which may then belong to a higher risk group. According to Annex III of Directive 2000/54 / EC, all biological agents that are not included in risk groups 2 to 4 do not automatically belong to risk group 1, as the list only reflects the state of knowledge at the time it was drawn up.

Risk group 2

“Biological substances that can cause disease in humans and pose a risk to employees; it is unlikely to spread to the population ; an effective prevention or treatment is normally possible. "( § 3 Biostoffverordnung)

Here you will find biological agents that are considered pathogens , but whose risk of infection is low due to effective measures or for which the infectious disease caused does not have as serious consequences as is the case with biological agents in risk group 3 or 4. In risk group 2, gram-positive bacteria include u. a. Clostridium TYPES such as Clostridium botulinum , Clostridium perfringens and Clostridium tetani , Staphylococcus TYPES such as Staphylococcus aureus and Staphylococcus epidermidis , or Streptococcus TYPES as Streptococcus mutans , Streptococcus pneumoniae and Streptococcus pyogenes as well as Corynebacterium diphtheriae . Among the gram-negative bacteria there are Salmonella species or serovars , such as Salmonella enterica , Salmonella Typhimurium and Salmonella Enteritidis or z. B. Borrelia burgdorferi , Escherichia coli (wild type), Legionella pneumophila , Pseudomonas aeruginosa or Vibrio cholerae .

Viruses in risk group 2 include, for example, the herpes simplex viruses HHV-1 and HHV-2, the varicella zoster virus (human herpes virus 3, HHV-3), the human hepatitis A virus HHAV, the measles virus MeV, the mumps virus MuV, most noroviruses or human rhinoviruses A and B (HRV-A and HRV-B). Some of the influenza viruses are also found in risk group 2, e.g. B. the influenza A virus H1N1 , but this does not apply to the influenza A virus 1918 (H1N1), it was upgraded in 2006. Among the fungi in this risk group are, for example, Aspergillus flavus , Candida albicans , Cryptococcus neoformans , Microsporum canis or Trichophyton rubrum . Among the parasites there are representatives of the genera Acanthamoeba , Ancylostoma , z. B. Ancylostoma caninum and Ancylostoma tubaeforme , Ascaris , e.g. For example, the roundworm ( Ascaris lumbricoides ) and Ascaris suum ( Ascaris suum ) or Babesia . Further examples are Cryptosporidium parvum , the fish tapeworm ( Diphyllobothrium latum ) or the great liver fluke ( Fasciola hepatica ).

Risk group 3

“Biological substances that can cause serious illness in humans and pose a serious risk to employees; there may be a risk of spreading to the population, but effective prevention or treatment is usually possible. "( § 3 Biological Agents Ordinance)

Biological agents are found here that are considered to be pathogens and for which the infectious disease caused has more serious consequences than those in risk group 2 and is also easier to transmit . As with risk group 2, however, there are effective measures against it. Certain biological agents in risk group 3, which are normally not transmitted by air, have been given two asterisks in the context of the classification of biological agents (risk group 3 **). In the case of specific activities with these biological agents, some of the protective measures provided for protection level 3 can be dispensed with.

In risk group 3, gram-positive bacteria include e.g. B. Bacillus anthracis and Mycobacterium tuberculosis , among the gram-negative bacteria enterohaemorrhagic Escherichia coli (EHEC, the strains O157: H7 or O103), Salmonella Typhi or Yersinia pestis .

Viruses in risk group 3 include, for example, the dengue virus (DENV-1 to DENV-4), the yellow fever virus YFV, the Hantaan virus HTNV from the genus Hantavirus , the hepatitis C virus HCV and the hepatitis virus E-virus HEV, the human immunodeficiency virus (HIV-1 and HIV-2), the influenza A virus H1N1 from 1918 that caused the Spanish flu , the influenza A virus H2N2 ( Asian flu virus ) , the influenza A virus H5N1 ( bird flu virus ) and the West Nile virus WNV. The coronavirus SARS-CoV-2 is currently classified in this group. The prions that cause bovine spongiform encephalopathy (BSE) are also assigned to risk group 3. Among the fungi there are only a few in this risk group, for example Blastomyces dermatitidis , Cladophialophora bantiana and Histoplasma capsulatum . Among the parasites there are representatives of the genus Leishmania , e.g. B. Leishmania braziliensis and Leishmania donovani , and Plasmodium falciparum .

Risk group 4

“Biological substances that cause serious illness in humans and pose a serious risk to employees; the risk of spreading to the population may be great; normally an effective prevention or treatment is not possible. "( § 3 Biostoffverordnung)

Biological agents are found here that are considered pathogens and for which the infectious disease caused has more serious consequences compared to those of risk group 2. The disease is more easily transmitted compared to risk group 3. Unlike risk groups 2 and 3, there are usually no effective measures against it. Only viruses are listed in risk group 4. Examples are hemorrhagic fever pathogens such as Ebola , Lassa , Crimean-Congo hemorrhagic fever and Marburg virus, and the variola virus (smallpox pathogen).

Protection levels

The Biological Agents Ordinance assigns four protection levels to the four risk groups. The regulations are referred to as levels because the regulations of the lower protection levels also apply to the higher levels. If it is a specific activity (compare definitions - § 2 BioStoffV ), the protection level corresponds to the risk group. If the activity is not targeted , the further procedure is regulated by § 5 BioStoffV. The protective measures for protection levels 2, 3 and 4 are listed in Appendix II BioStoffV. These are either marked as recommendations or made mandatory. Annex III BioStoffV also lists protective measures for activities in biotechnology that affect the apparatus, the bioreactor . The following examples of measures of the biological protection levels give an overview but are not complete.

Protection level 1

Washing facilities and the possibility of hand disinfection , typical for protection level 1

In laboratories of protection level 1, only the general hygiene measures must be observed. These include structural, technical and organizational requirements, for example workplaces and work equipment must be cleaned regularly, there must be washing facilities for employees and changing facilities separate from the workplace . In addition, the special hygiene measures must be observed for activities with assigned protection levels . These are contained in the technical rules for biological agents issued by the ABAS , for example in TRBA 500: Basic measures for activities involving biological agents . This means, among other things, that it is not allowed to eat or drink at the workplace and that the break room is not allowed to be entered with microbially contaminated work clothes . The employer must create options for storing food outside the workplace. If pests ( rodents , pigeons , insects and other animals) appear in the work area, regular pest control must be carried out. Furthermore, according to the rules of good microbiological technology, the formation of bioaerosols must be avoided or reduced; for this purpose, state-of-the-art working methods are to be used.

For work in the laboratory, the TRBA 100: Protective measures for activities with biological agents in laboratories must also be observed. Here it is specified, for example, that the work should be carried out in demarcated and sufficiently large rooms or areas. Every employee must be provided with a sufficiently large workplace. The surfaces in the work area should be easy to clean and resistant to the cleaning agents used. The laboratory doors should open outwards, in the direction of escape, and have a viewing window. The laboratory rooms should be kept clean and only the necessary equipment should be on the work surfaces. Windows and doors should be closed during the activity and waste containing biological agents must be collected and disposed of properly. The use of an autoclave is not required for this.

Laboratory coats or other protective clothing must be worn in the workplace . When pipetting are pipettors to use. Pointed and sharp tools (e.g. cannulas or scalpels ) should only be used in exceptional cases. They then have to be collected and disposed of in lockable waste containers (e.g. a needle disposal box ). After the end of the activity or after contamination , the employees must clean and disinfect their hands and care for them according to the skin protection plan. For activities that require hand disinfection or the wearing of gloves, a "jewelry ban" applies, i. H. no rings, watches, bracelets or other jewelry may be worn. Furthermore, the fingernails must be trimmed short.

Protection level 2

The symbol for biohazard according to Appendix I of the BioStoffV identifies laboratories with protection levels 2 to 4.

First of all, the protection level area must be spatially defined and identified with the protection level designation and the biohazard symbol . Used pointed and sharp tools (e.g. hypodermic needles or scalpels ) must be disposed of safely. Access is to be restricted to employees named by name. Activities with aerosol formation must be carried out on a safety workbench or with the help of a technical device with an equivalent level of protection. The surfaces of the workbenches must be impermeable to water and easy to clean. In addition, they should be resistant to acids , alkalis and solvents as well as to disinfectants . Process exhaust air that contains biological agents must not be returned to the work area.

Disinfection procedures tailored to the organisms must be used. Contaminated solid and liquid waste must be inactivated using tried and tested physical or chemical processes before final disposal . An autoclave is usually used for this. Proper disposal by a contracted company is also permitted. Decontamination and washing facilities must be available for employees. On vectors that can contribute to the spread of disease, such as B. rodents and insects should be checked regularly (recommendation, regulation only for protection levels 3 and 4). The biological agents are to be stored safely. There must be a suitable facility in order to be able to see into the laboratories from the outside (windows, usually as portholes in the doors or cameras). In the case of animal experiments, an incinerator for experimental animal bodies or other suitable facility for the safe disposal of infected animal bodies must be available.

Laboratory worker at a safety workbench , a typical work place of protection level 2

For work in the laboratory, the TRBA 100 also provides that protective gloves must be worn in addition to the laboratory coat if the hands can come into contact with the biological agents. If the face can also be affected, for example from splashes, face protection (e.g. protective goggles , mask or face shield) must be worn. In addition to the options for washing and disinfecting the hands already prescribed for protection level 1, a facility for rinsing the eyes must now also be available, such as B. an eye shower or an eye wash bottle . Windows and doors must be closed during the activity (recommendation for protection level 1). After completion of the activity, the work surfaces must be disinfected and cleaned in accordance with the hygiene plan; this applies accordingly to contaminated work equipment after use. Accidental contamination must be properly removed immediately. For internal transport, the biological agents or materials that they may contain must be kept in closed, safe containers that can be disinfected from the outside. They must be permanently labeled. Before cleaning or repair work on contaminated equipment, work equipment or facilities, decontamination must be carried out by the laboratory staff or initiated by them.

Protection level 3

A CDC employee performing a protection level 3 activity, wearing a respiratory protection filter and using a safety cabinet.

According to § 10 BioStoffV, access to bio-substances of risk group 3 or 4 is to be restricted, only competent and reliable employees are allowed to carry out activities of protection level 3 or 4. To do this, they must have been instructed and trained beforehand using work instructions. Access is only to be granted to these designated employees with access control . Biological substances that are pathogenic for humans must be kept under lock and key.

If air- borne biological agents are used, the laboratory must be structurally separated and sealable for possible fumigation . The exhaust air must be filtered . A lock with two mutually lockable doors is required to access the protection level area . In addition, there must be negative pressure in the laboratory. The protection level area must have an autoclave or an equivalent sterilization unit . If the biological agents cannot be transferred via the air, these regulations are not necessary, but the protection level area must be spatially separated.

Checks for vectors regularly. It must not be possible to open the windows. The floor must be lined with a water-impermeable, easy-to-clean material and the surfaces must be acid, alkali and solvent-resistant, as well as resistant to disinfectants. Each laboratory must have its own equipment and work must be carried out on safety cabinets. Proper disposal by a commissioned company is only permitted in justified individual cases; it is common to use an autoclave directly in the protection level area. An emergency power supply is required for safety-relevant facilities . If an employee works alone , an emergency call facility must be available.

The TRBA 100 also provides for work in the laboratory that the intended protective clothing and personal protective equipment must be put on in the protection level area and removed after completion of the activity. A vestibule that belongs to the protection level area is recommended. If work is carried out with air-borne biological substances, a lock is mandatory. In the anteroom or the lock there are collecting containers for the protective clothing intended for decontamination and cleaning. This includes a lab coat to be closed on the back, which must be marked with the protection level, closed shoes and suitable protective gloves. Depending on the result of the risk assessment, mouth and nose protection (e.g. a breathing mask) and protective goggles must also be worn.

Protection level 4

An employee of the USAMRIID during an activity of protection level 4, she wears a full protective suit with self-sufficient breathing air supply.

According to § 10 BioStoffV, access to bio-substances of risk group 3 or 4 is to be restricted, only competent and reliable employees are allowed to carry out activities of protection level 3 or 4. To do this, they must have been instructed and trained beforehand using work instructions. Access is only to be granted to these designated employees with access control. All biological materials are to be kept under lock and key.

The laboratory must be structurally separated and sealable for possible fumigation (containment). The supply air and exhaust air must be filtered and access may only take place via a three-chamber lock (pressure cascade) so that a defined negative pressure can be maintained. The laboratory must be hermetically sealed in order to carry out disinfection. Walls and ceilings must also be made of a water-impermeable, easy-to-clean material and the surfaces must be acid, alkali and solvent-resistant and resistant to disinfectants. Contaminated solid and liquid waste must be disposed of in the protection level area using an autoclave (as a pass-through autoclave ) or an equivalent sterilization unit. Infected animal bodies must also be disposed of in the protection level area, usually through thermal inactivation. All wastewater is chemically and thermally inactivated. The employees must shower before leaving the protection level area.

For work in the laboratory, the TRBA 100 stipulates that the lock system consists of four chambers: An outer lock chamber, where street clothing is removed and underwear is put on. This is followed by the personal shower, where the underwear is taken off and put on again after showering. The third chamber is used to put on and take off full protective suits , while the inner lock chamber is equipped with a chemical shower to enable decontamination. For activities in a laboratory of protection level 4, a fully ventilated protective suit must be worn, the breathing air of which is provided by an independent air supply line. The full protective suit must be abrasion-proof, tear-proof, impermeable to air and resistant to the disinfectant used during decontamination. The protective suits are ideally equipped with welded-on boots. To protect the hands, two pairs of gloves must be worn on top of each other, the outer pair e.g. B. is tightly attached to the sleeve cuffs of the protective suit by a clamp device.

List of BSL-4 laboratories

Because of the complex protective measures, there are only a small number of laboratories worldwide in which activities of protection level 4 ( biosafety level  4 or BSL-4 laboratory) may be carried out. They are also referred to as high-security laboratories or S4 laboratories, the latter allowing confusion with a laboratory of safety level 4 according to the genetic engineering safety regulation. In English, the term Biocontainment Laboratories or High Containment Facilities is also used. In French, the abbreviation P4 is common, the P stands for pathogène (pathogenic). The following list (as of 2020, but partly with older documents) gives an overview but is not complete.

Country	place	Facility
Australia	Geelong , Victoria	Australian Animal Health Laboratory (AAHL)
	Melbourne , Victoria	Victorian Infectious Diseases Reference Laboratory (VIDRL)
People's Republic of China	Wuhan	Wuhan Institute of Virology , Chinese Academy of Sciences
Germany	Hamburg	Bernhard Nocht Institute for Tropical Medicine (BNITM)
	Riems Island	Institute for new and novel animal disease pathogens (INNT) of the Friedrich-Loeffler-Institut (FLI) (In the context of the new building, the INNT will be responsible for the operation of the S4 area)
	Marburg	Philipps University of Marburg , Institute for Virology
	Berlin	Robert Koch Institute (RKI) (inaugurated on February 3, 2015)
France	Lyon	Laboratoire Jean Mérieux (Inserm Jean Mérieux BSL4 Laboratory and National Reference Center for VHF)
Gabon	Franceville	Center International de Recherches Médicales de Franceville (CIRMF)
India	Bhopal	National Institute of High Security Animal Diseases
	Hyderabad	Center for Cellular and Molecular Biology
	Pune	National Institute of Virology
Italy	Rome	Istituto nazionale per le malattie infettive Lazzaro Spallanzani
	Milan	Ospedale Luigi Sacco
Japan	Tokyo	National Institute for Infectious Diseases (NIID), Department of Virology I.
Canada	Winnipeg , Manitoba	National Microbiology Laboratory (NML) - Public Health Agency of Canada
Russia	Kolzowo , Novosibirsk Oblast	State Research Center of Virology and Biotechnology VECTOR (this institute is the only one besides the CDC in the USA where smallpox viruses are still kept)
	Sergiev Posad	Virological Center of the Research Institute of Microbiology (VC)
Sweden	Solna	Swedish Institute for Infectious Disease Control (the laboratory is the only one with protection level 4 in the Nordic countries )
Switzerland	Geneva	Hôpitaux universitaires de Genève (HUG, diagnostic laboratory)
	Middle houses	Institute for Virology and Immunology (IVI) of the Federal Food Safety and Veterinary Office
	Spiez	Labor Spiez , security laboratory of the Federal Office for Civil Protection (FOCP)
South Africa	Sandringham	National Institute for Communicable Diseases (NICD), Special Pathogens Unit
Taiwan	Taipei	Institute of Preventive Medicine, National Defense University ,
Czech Republic	Těchonín	Centrum biologické ochrany Těchonín (Center for Biological Protection), Czech Armed Forces
Hungary	Budapest	National Center for Epidemiology
United Kingdom	Porton Down , Wiltshire	Defense Science and Technology Laboratory , formerly Chemical and Biological Defense Establishment
		Health Protection Agency (HPA) Center for Emergency Preparedness and Response (CEPR) Public Health England
United States	Atlanta , Georgia	Centers for Disease Control and Prevention (CDC)
		Georgia State University Center for Biotechnology and Drug Design (smaller facility)
	Boston , Massachusetts	National Emerging Infectious Diseases Laboratory (NEIDL) at Boston University (final operating license issued at the end of 2017)
	Fort Detrick , Frederick , Maryland	Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases, (planned or under construction)
		National Biodefense Analysis and Countermeasures Center (NBACC), Department of Homeland Security, (planned or under construction)
		US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Department of Defense, (expansion planned)
	Galveston , Texas	Center for Biodefense and Emerging Infectious Diseases of the University of Texas Medical Branch (UTMB)
	Hamilton , Montana	Rocky Mountain Laboratories of the National Institute of Allergy and Infectious Diseases or Rocky Mountain Laboratory Integrated Research Facility (RML-IRF)
	Manhattan , Kansas	National Bio- and Agro-Defense Facility (NBAF) , Department of Homeland Security, (planned or under construction)
	Richmond , Virginia	Virginia Division of Consolidated Laboratory Services , Department of General Services of the Commonwealth of Virginia, (planned or under construction)
	San Antonio , Texas	Southwest Foundation for Biomedical Research or Texas Biomedical Research Institute
Belarus	Minsk	Republican Research and Practical Center for Epidemiology and Microbiology (RRPCEM)

Legal sources

• Council Directive 90/679 / EEC (PDF)of November 26, 1990 on the protection of workers from risks related to risks related to biological agents at work
• Directive 2000/54 / EC (PDF) ofthe European Parliament and of the Council of September 18, 2000 on the protection of workers from risks related to biological agents at work
• Biostoffverordnung ( Text of the Biostoffverordnung - BioStoffV (2013) from juris. Accessed on May 13, 2014.)

Web links

• Biological substances - systematic protection for activities with biological substances. In: Website of the Federal Institute for Occupational Safety and Health (BAuA). Retrieved March 12, 2018 . 
• Recognizing the Biosafety Levels (Quick-Learn Lessons). In: Website of the Centers for Disease Control and Prevention (CDC). Retrieved May 14, 2014 . 
• Biosafety level information. In: Website Federation of American Scientists (FAS) . Retrieved May 16, 2014 . 
• A virtual visit to the high security laboratory BSL 4, Prof. Dr. Stephan Günther from the Bernhard Nocht Institute for Tropical Medicine shows how research is carried out with deadly viruses (video). March 8, 2012, accessed March 12, 2018 . 
• Karlsruhe Institute of Technology (KIT) - Research center for fire protection technology: Research on fire protection and extinguishing systems in microbiological and genetic engineering laboratories. Volume I (PDF; 6.4 MB); Volume II (PDF; 8.5 MB).

Individual evidence

1. ↑ ^{a b c} TRBA (Technical Rules for Biological Agents) 466: Classification of prokaryotes (bacteria and archaea) into risk groups. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . August 25, 2015, accessed on March 12, 2018 (last update March 31, 2017).  
2. ↑ ^{a b c d} TRBA (Technical Rules for Biological Agents) 462: Classification of viruses in risk groups. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . April 25, 2012, accessed on March 12, 2018 (last updated March 31, 2017).  
3. ↑ TRBA (Technical Rules for Biological Agents) 468: List of cell lines and activities with cell cultures. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . April 25, 2012, accessed on March 12, 2018 (last change on July 21, 2015).  
4. ↑ ^{a b} TRBA (Technical Rules for Biological Agents) 460: Classification of fungi in risk groups. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . July 22, 2016, accessed on March 12, 2018 (last change on October 17, 2016).  
5. ↑ ^{a b} TRBA (Technical Rules for Biological Agents) 464: Classification of parasites into risk groups. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . July 19, 2013, accessed March 12, 2018 .  
6. ↑ ^{a b c d e f} TRBA (Technical Rules for Biological Agents) 100: Protective measures for activities with biological agents in laboratories. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . October 17, 2013, accessed on March 12, 2018 (last update March 31, 2017).  
7. ^ German statutory accident insurance registered association: DGUV - Prevention - Topics A to Z - Biological hazards - Coronavirus. Retrieved on March 20, 2020 (German).  
8. ↑ TRBA (Technical Rules for Biological Agents) 500: Basic measures for activities with biological agents. In: Website of the Federal Institute for Occupational Safety and Health (BAuA) . April 25, 2012. Retrieved March 12, 2018 .  
9. ↑ ^{a b} Institute of Virology - General Information. In: Website Institute for Virology at the University of Marburg . December 16, 2011, accessed March 12, 2018 .  
10. ↑ ^{a b} The S4 laboratory in the Robert Koch Institute. In: Website Robert Koch Institute . August 17, 2017. Retrieved March 12, 2018 .  
11. ↑ ^{a b c d e f g h i j k l} BSL-4 Laboratories in the United States. In: Website Federation of American Scientists . 2013, accessed February 1, 2020 .  
12. ↑ Kelly Cole, Daniel J. Fisher, Steve Westfall (Eds.): Management Principles for Building and Operating Biocontainment Facilities . Dockside Consultants In, Newport, CA 2013, OCLC 904606385 ( limited preview in Google Book Search).
13. ↑ ^{a b} presentation. (No longer available online.) In: Website Le laboratoire P4 Jean Mérieux . 2010, archived from the original on April 6, 2014 ; Retrieved May 17, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.   
14. ↑ PC4 Zoonosis Suite & Bioimaging Facility. In: csiro.au. Accessed April 24, 2017 .  
15. ↑ ^{a b c d e f g h i j k l m n o p q r s t} JH Kuhn, Y. Bao u. a .: Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae . In: Archives of Virology . tape 158 , no. 6 , June 2013, ISSN  1432-8798 , p. 1425-1432 , doi : 10.1007 / s00705-012-1594-2 , PMID 23358612 , PMC 3669655 (free full text).
16. ↑ About VIDRL. In: website VIDRL . Retrieved May 16, 2014 .  
17. ^ Wuhan Institute of Virology. In: China Information Network of Industrial Biotechnology website . Retrieved May 17, 2014 .  
18. ↑ About the institute. In: Website Bernhard Nocht Institute for Tropical Medicine . 2018, accessed March 12, 2018 .  
19. ^ Institute for New and Novel Animal Disease Pathogens (INNT). In: The FLI . Friedrich Loeffler Institute , 2018, accessed on March 12, 2018 .  
20. ↑ ^{a b c d e f} Chantal B. Reusken, Ramona Mögling, Pieter W. Smit, Roland Grunow, Giuseppe Ippolito, Antonino Di Caro, Marion Koopmans: Status, quality and specific needs of Ebola virus diagnostic capacity and capability in laboratories of the two European preparedness laboratory networks EMERGE and EVD-LabNet . In: Eurosurveillance . tape 23 , no. 19 , May 10, 2018, p. 1–10 , doi : 10.2807 / 1560-7917.ES.2018.23.19.17-00404 ( online ).
21. ↑ National Instiute of High Security Animal Diseases. Retrieved April 29, 2019 .  
22. ^ India gets high security lab for human diseases . In: Nature . tape  449 , no. 7163 , October 11, 2007, ISSN  0028-0836 , p. 649–649 , doi : 10.1038 / 449649e ( online [accessed April 29, 2019]).
23. ↑ India Completes First Biodefense Level 4 Lab. March 11, 2013. Retrieved April 29, 2019 (American English).  
24. ^ Establishment of BSL IV Laboratory. Retrieved April 29, 2019 .  
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26. ^ Department of Virology I. In: Website National Institute for Infectious Diseases . Retrieved May 17, 2014 .  
27. ^ Canadian Science Center for Human and Animal Health. In: Website Public Health Agency of Canada . February 28, 2008, accessed May 17, 2014 .  
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29. ↑ High-containment laboratory. In: Website About Folkhälsomyndigheten - The Public Health Agency of Sweden . February 17, 2016, accessed March 12, 2018 .  
30. ↑ Laboratoire ultra securisé contre virus dangereux. In: Website Hôpitaux Universitaires de Genève . February 26, 2013, accessed May 17, 2014 .  
31. ↑ Institute for Virology and Immunology IVI. In: Website Institute for Virology and Immunology (IVI) . Retrieved March 12, 2018 .  
32. ↑ Virology. In: Website Labor Spiez . Retrieved March 12, 2018 .  
33. ↑ Emerging and Zoonotic Diseases. In: Website National Institute for Communicable Diseases . 2014, accessed May 17, 2014 .  
34. ↑ Eurosurveillance editorial team: Case of SARS reported in a laboratory research worker in Taiwan . In: Weekly releases (1997-2007) . tape 7 , no. 51 , December 18, 2003, ISSN  9999-1233 , p. 2347 , doi : 10.2807 / esw.07.51.02347-en ( online [accessed January 30, 2020]).
35. ↑ Biological Defense Department at Techonin. In: Website Ministry of Defense & Armed Forces of the Czech Republic . April 14, 2014, accessed May 17, 2014 .  
36. ^ CDC Laboratories: Where contagions meet their match. In: Web site of the Centers for Disease Control and Prevention (CDC). March 19, 2014, accessed May 14, 2014 .  
37. ↑ https://www.bostonglobe.com/metro/2017/12/06/biolab-gets-final-approval-begin-reseach-deadly-microbes/lhodHjQkuLXOKZHtlLJ9QM/story.html
38. ↑ Researchers Cite Experts' Findings of NEIDL Safety. In: National Emerging Infectious Diseases Laboratories website . April 18, 2014, accessed May 14, 2014 .  

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