"High-level laboratories are precisely designed at the beginning of construction, and the buildings are generally dedicated to biosafety laboratories, and many of the equipment is integrated into the building, which is rarely relocated. ”
"In the process of individual relocation, all the pollutants in the original laboratory can be treated, the equipment can be disinfected, and the risk of infection can be removed; mainly the samples or strains and strains with the risk of infection, these resources should be prevented from leakage on the one hand, and inactivation on the other hand, and the overall relocation is generally carried out by moving refrigerators or liquid nitrogen tanks. ”
Written by | Ji Jingjie (surging news reporter)
P2 and P3 laboratories (P is Pathogen/Protection level) refer to laboratories with level 2 and 3 biosafety protection. As scientists study pathogens such as viruses and microorganisms, protective and safe accommodation measures are necessary to protect researchers from infection and to prevent pathogens from leaking out and affecting surrounding areas and residents. There are four levels of biosafety, and the more dangerous the pathogen, the higher the level of safety required for the laboratory.
How are biosafety levels defined, what are the differences in the facilities of laboratories with different biosafety levels, how do Chinese universities and institutions allocate laboratories to research teams, and how do laboratories be renovated and relocated?
In order to answer these questions, on the evening of April 29, The Paper interviewed Li Qingchao, a lecturer in the Department of Microbiology of the School of Life Sciences of Shandong Normal University, who graduated from the Shanghai Pasteur Institute of the Chinese Academy of Sciences (now known as the Shanghai Institute of Immunology and Infection) with a Ph.D. in microbiology, and is now responsible for the teaching of microbiology and experiments and microbial engineering and experiments.
【Conversation】
Biosafety Laboratory: A frontline for the study of dangerous pathogens
The Paper: Can you tell us about the concept of the Biosafety Lab and the purpose of setting it up?
Li Qingchao (Lecturer, Department of Microbiology, School of Life Sciences, Shandong Normal University): According to the Regulations on the Management of Biosecurity in Pathogenic Microbiology Laboratories promulgated and implemented by the State Council in 2004, research, teaching, testing, diagnosis and other activities related to pathogenic microbial bacteria (viruses) and samples shall be carried out in biosafety laboratories that meet the requirements. The purpose of setting up a biosafety laboratory is to carry out activities such as research, teaching, testing, and diagnosis of pathogenic microorganisms, and in the process, to protect the staff, people, animals and plants in the environment where the laboratory is located from pathogens.
The Paper: What are the main classifications of laboratory safety levels at present? Some documents refer to it as "Biosafety Level" (BSL), while others call it "Protection Level", are they the same? There is also a reference to animal biosafety level (ABSL) in the guide, do laboratories have safety level classifications in many specific aspects?
Li Qingchao: According to the level of biosafety protection of pathogenic microorganisms in laboratories, and in accordance with the provisions of the national standards for laboratory biosafety, laboratories are divided into level 1, level 2, level 3, and level 4.
Biosafety level (BSL) or Pathogen/Protection level refers to different levels of biocontainment precautions. The two can be used in common, but with some emphasis. The former emphasizes the overall safety design, operation specifications, safety facilities and equipment requirements of the biosafety laboratory. The latter emphasizes the responsiveness of pathogens and protective measures handled by biosafety laboratories.
Animal biosafety level (ABSL) is the sum of biosafety level plus animal bio-security, which not only meets biosecurity requirements, but also facilitates the operation of experimental animals, avoids staff being scratched and bitten, and avoids pathogen transmission between animals and humans and animals.
According to the degree of danger of using or storing hazards in the laboratory, the laboratory safety risk level is divided into four levels: level 1 (high risk level), level 2 (high risk level), level 3 (medium risk level), and level 4 (general risk level). For example, laboratories with a level 1 safety risk level involve the use or storage of highly toxic, explosive, precursor, explosive chemicals, narcotics and psychotropic substances, highly pathogenic pathogenic microorganisms, radioactive sources, etc., and are the laboratories with the highest security level.
According to the degree of danger of using or storing hazards in the laboratory, the laboratory safety risk level is divided into four levels. Courtesy of the interviewee
The Paper: Who proposed this classification? We often see that some universities and institutions have their own laboratory standards, does it mean that there are differences in the laboratories of different institutions? Are there differences in the standards of these classifications at home and abroad?
Li Qingchao: The iconic equipment of the biosafety laboratory is the biosafety cabinet, the prototype of which was first seen in the U.S. Army Biological Warfare Laboratory in 1943, and the discussion about the biosafety laboratory also began with the needs of biological warfare. With the participation of representatives from universities, hospitals, and enterprises, the American Biosafety Association was finally established in 1984 and relevant rules and regulations were drafted. On November 5, 2004, China promulgated and implemented the Regulations on the Management of Biosafety in Pathogenic Microbiology Laboratories.
In addition to national regulations, there is also an international consensus on biosafety levels and related regulations. There are differences in the details of the laboratory specifications issued by universities or institutions, but they should all comply with national laws and regulations and the consensus of the academic community. China's 2008 General Requirements for Laboratory Biosafety (GB 19489-2008) contains detailed provisions.
The Paper: Is the safety level of a laboratory related to the complexity of the experiments it does, the number of personnel, and the perfection of the equipment? Is it true that the higher the security level, the larger and more "advanced" the laboratory?
Li Qingchao: The higher the biosecurity level, the more dangerous the pathogens studied, the stricter the protective measures required, and the more complete the safety equipment will inevitably be. However, there is no inevitable relationship between the level of the biosafety laboratory and the complexity of its experiments and the number of personnel. Laboratories with high biosafety levels have high training and use costs, and it is impossible for a large number of people to participate in the laboratory, and the number of people working in the same laboratory is generally two people (mutual watch).
It should be said that the higher the biosafety level, the more "advanced" the biosafety level and the more expensive the cost. Among them, only a few countries have the capacity to build a fourth-level laboratory. In 2003, the Chinese Academy of Sciences approved the construction of the first BSL-4 laboratory in Chinese mainland at the Wuhan Institute of Virology. After a decade of hard work, the National Biosafety Laboratory of the Wuhan Institute of Virology was built in 2014 at a cost of 300 million yuan (US$44 million).
The higher the biosafety level, the tighter the protective measures
The Paper: What types of experimental subjects do laboratories with different biosafety levels usually handle, and what are the differences in laboratory design, equipment, and regulatory measures?
Qingchao Li: The BSL-1 lab can work with microorganisms that don't normally pose a threat to human or animal health. The operation needs to comply with the technical specifications of microbiology operation, does not require special isolation measures, and can be used for basic teaching and research.
BSL-2 laboratories are suitable for microorganisms that can cause human or animal diseases, but do not pose serious hazards, have a limited risk of transmission, have controllable post-infection diseases, and have effective treatment and prevention measures. In addition to complying with the technical specifications for microbiological operations, it is necessary to wear personal protective clothing, be equipped with a biological safety cabinet, and hang a biohazard mark. Can be used for primary health services, diagnostics, or research.
BSL-2 Laboratory. Courtesy of the interviewee
BSL-3 laboratories are suitable for pathogens that can cause serious illness in humans or animals and have a high risk of transmission, but vaccines are usually available to prevent infection. At the level of secondary biosafety protection, special protective clothing is added, laboratory air pressure and airflow control (air cannot leak out), personnel training and access system.
BSL-3 Laboratory. Courtesy of the interviewee
BSL-4 laboratories are used for pathogenic microorganisms that cause very serious illness in humans or animals, transmitted by aerosol route or by unknown transmission route, for which there is currently no effective vaccine or treatment, and for microorganisms that have not been discovered or have been declared eradicated in China. Add air locks, entrance and exit showers, special treatment of contaminated items, and wear positive pressure protective clothing at the level of three-level biosecurity protection.
The Paper: What are the special requirements for personnel protection in high-level laboratories (such as BSL-3 and BSL-4)?
Li Qingchao: First of all, you must go through strict biosafety training before you can enter the BSL-3 or BSL-4 laboratory.
BSL-3 operators wear personal protective equipment (PPE) such as hoods, goggles, masks, gloves (multi-layer), foot covers, and lab coats (multi-layer) that do not directly expose the laboratory space to any mucous membranes, and that all skin does not come into direct contact with lab equipment, samples, or supplies, and is effective in preventing droplets from contaminating the face.
BSL-4 operators can effectively prevent aerosol-induced transmission by isolating their entire body from the laboratory space by wearing a positive pressure suit (a fully sealed suit that delivers fresh air through a pipe and keeps the air pressure inside the suit higher than the laboratory air pressure to ensure that in the event of a leak, the air only leaks from the suit to the lab).
The Paper: How do laboratories deal with accidental spills and infections? What are the negligence or defects in these problems? What are some famous examples?
Li Qingchao: Biosafety laboratories need to be operated in strict accordance with regulations, and accidental exposure or even infection is a very serious accident. The main reason for the problem is the non-strict adherence to biosafety practices.
There have been many accidents caused by laboratory safety problems in history, such as the 1967 Marburg virus laboratory infection incident in Germany, in which 37 laboratory personnel were infected with the virus in the monkeys used in the laboratory. In 2019, an accident at the laboratory of the Lanzhou Veterinary Research Institute in China infected 65 staff members with brucellosis, and more than 10,000 residents were subsequently infected. The outbreak was reportedly caused by incomplete sterilized exhaust gas from a nearby biopharmaceutical plant.
In the event of a biosecurity accident, the on-site personnel must calmly observe and take scientific and reasonable rescue measures, and all personnel should not blindly carry out mutual rescue on the premise of ensuring their own safety. Measures include: immediately shutting down laboratories, effectively disinfecting contaminated areas, properly isolating, treating, and relocating infected persons, and cooperating with higher-level authorities to respond to emergencies (e.g., disinfection, isolation, investigation, etc.).
Biosafety norms should cover the entire experimental research process, from the biosafety laboratory training and access system, to the disposal of biosafety waste, the disposal of contaminated gloves and lab coats after the experiment, etc., not only responsible for their own safety, but also responsible for the safety of colleagues and the area where the laboratory is located, so as to prevent personal infection and environmental leakage.
Biosecurity management should be legal and compliant, "foolproof"
The Paper: How exactly is the laboratory graded, and what organization will evaluate it?
Li Qingchao: The state has clear regulations on the establishment and responsibilities of pathogenic microbiology laboratories, especially the establishment of tertiary and quaternary laboratories. The Regulations on the Management of Biosafety in Pathogenic Microbiology Laboratories stipulate that institutions certified by the State Council may accredit Level 3 and Level 4 laboratories. If the laboratory is accredited, a biosafety laboratory certificate of the corresponding level will be issued. The certificate is valid for 5 years.
In addition, the regulations also stipulate that primary and secondary laboratories shall not engage in experimental activities on highly pathogenic pathogenic microorganisms. Level 3 and Level 4 laboratories must be nationally recognized, have qualified staff and building conditions in order to engage in experimental activities on highly pathogenic pathogenic microorganisms.
Laboratory safety requires its establishment unit to be responsible for its filing, filing and management. China's Biosecurity Law stipulates that the legal representative and the person in charge of the laboratory shall be responsible for the biosecurity of the laboratory, establish and improve the safety and security system, and take safety and security measures to ensure the safety of the laboratory and its pathogenic microorganisms.
The Paper: Does the fact that the laboratory has a higher level of security mean that it can be "backward compatible" and do less dangerous experiments? Can a low-level laboratory be "upgraded" by adding equipment and modifications?
Li Qingchao: In principle, high-level security labs can be "backward compatible", but no one does that because it's a huge waste. Low-level laboratories can be upgraded with additional equipment and retrofits, but they need to comply with legal and regulatory requirements.
The Paper: How do domestic universities and institutions generally manage and allocate laboratories, how do scientific research teams generally apply for the use of laboratories of different levels, and do they need to go through safety training?
Li Qingchao: Generally, at the beginning of the introduction of talents or the establishment of the laboratory, it is divided into experimental and office space under the name of the talent or laboratory. In addition to this, some units may have public spaces such as cryogenic refrigerator storage rooms, germ rooms, etc. For some large-scale equipment or public facilities, they are generally open to all teachers and students in schools or research institutes.
For high-level biosafety labs, there may be a dedicated lab space, or a shared lab space for appointments. This depends on the needs of the team: if you specialize in the study of pathogenic microorganisms, there is a high demand for the use of biosafety laboratories, and if conditions permit, you may have your own biosafety laboratory space (usually a room in a centrally located biosafety laboratory located in the same building or floor), and if the demand is not large, you can make an appointment to use a laboratory on a public biosafety platform.
In either case, access to the laboratory must be approved by a training and safety supervisor. If you borrow someone else's laboratory, in addition to biosafety training and approval, you need to get the consent of the person in charge of the laboratory before you can enter someone else's biosafety laboratory.
The Paper: What are the steps that need to be taken when a high-level laboratory needs to be relocated for various reasons?
Li Qingchao: The high-level laboratory has been precisely designed at the beginning of the construction of the building, and the building is generally dedicated to the biosafety laboratory, and many equipment is integrated into the building, which is rarely relocated.
More often than not, it is "moving in with bacteria and viruses", carrying the samples required for the experiment and entering the biosafety laboratory with perfect conditions for experiments. The transportation of pathogenic microbial samples shall comply with the "Regulations on the Management of Biosecurity in Pathogenic Microbiology Laboratories".
In the process of individual relocation, all the pollutants in the original laboratory can be treated, the equipment can be disinfected, and the risk of infection can be removed; mainly the samples or strains and strains with the risk of infection, these resources should be prevented from leakage on the one hand, and inactivation on the other hand, and the overall relocation is generally carried by moving refrigerators or liquid nitrogen tanks.
The Paper: According to your observations, what problems exist in the management of biological laboratories in China, and what can be improved?
Li Qingchao: For biosafety laboratories in universities or research institutes, due to the graduation of students, the resignation of employees, and the addition of new students and new employees, personnel changes are relatively rapid, and in the process of "master with apprentice", the level of masters is uneven, which is easy to cause a decline in training quality, so it is necessary to continue to carry out standardized training and assessment. Laboratory managers should be familiar with the changes in personnel and subject trends in the group, so as to avoid the occurrence of private experiments by junior students or interns without standardized training.
The Paper: With the development of biotechnology, what are the possible changes in the classification and management of laboratory safety levels?
Li Qingchao: With the study of known pathogens, experiments that can only be carried out by individual high-level biosafety laboratories can be gradually turned to low-security laboratories through alternatives such as pseudovirus particles, defective viruses, irreversible attenuated strains, and one-time infection models. It is even said that certain dangerous pathogens can be overcome so that they no longer become a security threat to human beings, and there is no need to conduct research in high-level biosafety laboratories.
However, it should also be noted that there will be new pathogens that need to be studied in high-level biosafety laboratories, such as unanticipated emerging viral diseases. Scientific research itself requires innovation, but the classification and management of laboratory safety levels focuses on a "no accidents, no mistakes", and stability and safety are the first.
Source of this article: The Paper Life Sciences, Editor: Lu Yan, Photo Editor: Chen Feiyan, Proofreader: Liu Wei.
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