Module_B_Biological_Agents_Pathogens.pdf

Professional Course in Biorisk Management Module B – Risk Assessment and hazards of Biological Materials The risks to human health is likely to be the major consideration in a risk assessment for work with biological agents. However, risks to the environment, including animal & plant life, must be...

Professional Course in Biorisk Management Module B – Risk Assessment and hazards of Biological Materials The risks to human health is likely to be the major consideration in a risk assessment for work with biological agents. However, risks to the environment, including animal & plant life, must be included. The risk to human health may be through infection, toxicity, carcinogenicity or allergy whereas the threat to the environment is likely to be via unintentional release, either through a breakdown in containment or a failure in the waste disposal route. Biological agents include bacteria, viruses, fungi, the agents which cause Transmissible Spongiform Encephalopathies, microscopic endoparasites, amoebae, trypanosomes and the microscopic forms of larger endoparasites such as the ova and larvae of helminths. There are many different species of each type and these can present different risks to laboratory personnel in terms of routes of infection, severity of disease, spread to the community, availability of treatment etc. and therefore it’s important that the risk assessment is carried out by those knowledgeable about the biological agent. Guidance for working with Biological Agents The principle guidance on the control of work with biological agents is the WHO Laboratory Biosafety Manual (LBSM) which is used in research, clinical and public health laboratories serving as a de facto global standard that presents best practices. The LBSM is supported by detailed monographs covering Risk assessment, Biosafety cabinets and other containment devices, Laboratory Design & maintenance, Personal protective equipment, Outbreak preparedness and resilience, Decontamination & waste requirements and Biosafety programme & management. The WHO also provides separate guidance pertaining to the security of pathogens in the WHO Biorisk Management Laboratory Biosecurity Guidance and on the transport of biological materials and infectious substances in the WHO Guidance on Regulations for Transport of Infectious Substances. In many countries there is national legislation for working safely with biological agents. The WHO guidance does not supersede any existing regulations and if used, it should be in conjunction and compliance with any national, local and/ or institutional biosafety requirements. © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 1 Risk-based approach for work with Biological agents In the WHO Laboratory Biosafety Manual control measures are selected using a strict risk and evidence-based approach informed by the consequence and likelihood of exposure to a biological agent. The approach is flexible, enabling each biological facility to implement the most feasible and effective combination of risk control measures. The goal of this approach is that laboratory facilities, safety equipment and work practices are locally relevant, proportionate and sustainable. Gathering information There are many different types of work involving biological agents such as laboratory, clinical and field work and the first step is to gather information on the biological agent known or suspected to be present and the types of procedures that will be carried out. Information on a biological agent key to the risk assessment process includes the route(s) of infection, pathogenicity, infectious dose, availability of prophylaxis or a vaccine, disease severity and mortality, contagiousness and endemicity. Most biological agents have a preferred route of infection, although infection can take place by multiple routes. These routes of infection are shown below: All possible routes of infection should be identified so that the control measures necessary to block these routes can be put in place. It is important to consider both natural and potential routes of laboratory transmission. For example an agent that is © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 2 transmitted naturally via an insect vector could be transmitted in the laboratory via a penetrating sharps injury. The dose of a biological agent that is required to cause an initial infection in the host is termed the minimal infectious dose. This dose varies from agent to agent, but for each agent it tends to be reasonably consistent in immuno-competent individuals. The minimal infectious dose for HIV is high, which means that it is relatively difficult to become infected with HIV. In contrast, Hepatitis B virus has a low minimal infectious dose, so very few viral particles are needed to cause an infection. The infectious dose is an important consideration particularly when handling propagated biological agents. Therefore exposure to biological agents should be controlled to as low as reasonably practicable taking account of the risk. The risk assessment should describe the nature of the work. For example whether the work is in vitro, in vivo or large scale. It’s important to determine the quantity of pathogen being handled and on what scale. Diagnostic samples typically contain a lower concentration of pathogens than cultures where pathogens can be propagated to high titres. Procedures or equipment that could provide a route of infection for the biological agent should be identified. For example, procedures such as pipetting, sonication, homogenisation & centrifugation can generate infectious aerosols which can be inhaled or ingested if droplets settle. Similarly, the use of sharps in laboratory procedures could provide a route of entry for any agents that are infectious by the blood-borne route. The competence of laboratory personnel and their ability to follow established biosafety practice and procedure is of particular importance since most LAIs are due to training, management & communication rather than the failure of engineering controls. Evaluating the risk of work with Biological agents Information on the biological agent & activities is collated and the risk evaluated. A risk matrix can be employed to help with this and an example is shown below: Factors associated with biological agents which can result in a greater consequence if an incident were to occur include: airborne transmission, high pathogenicity, low infectious dose, high communicability, high severe disease & mortality, lack of © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 3 endemicity and if there is limited availability of vaccination or treatment. Factors associated with activities that increase the likelihood of an incident occurring include: the formation of aerosols during sonication, homogenisation or centrifugation; the use of sharps; poor personnel competency; handling animals and poor maintenance of equipment. There are factors associated with both a high likelihood of and greater consequences from a potential incident. Biological agents with an airborne route of transmission can remain airborne for prolonged periods of time and disseminate widely in the laboratory environment, increasing the likelihood that personnel may be exposed to the agent. The use of high titres or culture volumes results in more infectious agent being present for exposure if there is a spill for example. Risk Control Measures Risk control measures should be compliant with any national or international regulations requiring prescribed risk control measures. The risk control measures in the 4th edition of the WHO laboratory Biosafety Manual include not only the laboratory facility and equipment but also procedures and appropriately trained and competent staff. The measures in the LBSM are designed to be continuous between lower risk and higher risk work. Depending on the overall risk assessment for the activity the work may need core or heightened, or maximum containment measures or a flexible approach (e.g. core plus selected heightened measures). Core Requirements Most laboratory activities have risks which are very low to low and can be safely carried out using core requirements. The core requirements are a combination of common biosafety control measures and set the minimum standard for safe work and © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 4 are expected to be used for the majority of procedures. The control measures reflect international standards and best practice in biosafety that are necessary to work safely with biological agents, even where the associated risks are minimal. The measures include the laboratory facility and equipment but also procedures and appropriately trained and competent staff. Core requirements includes Good microbiological practice and procedures, GMPP, which are essential risk control measures because human error and poor laboratory technique or poor use of equipment have been shown to be responsible for the majority of laboratory infections and injuries. Core requirements also include trained and competent staff, requirements for the laboratory facility, control measures for receiving, storing and inactivating specimens, processes for decontamination & waste management, the provision of PPE, an emergency response for biological spills and the provision of Occupational Health including preventative measures such as vaccination. Heightened Control Measures If the risk assessment indicates that the biological agents being handled and/or the proposed activities are associated with a risk that cannot be brought below an acceptable risk using the core requirements only, heightened additional control measures are required. So if the consequence of exposure is high, for example if the work involves a serious pathogen, or the likelihood is high due to the procedures involved, for example there is a risk of aerosol generation, heightened control measures are required. Control measures will therefore consist of the core requirements plus any specific heightened risk control measure or measures identified in the risk assessment. For example, for biological agents that are infectious via the airborne route, such as Mycobacterium tuberculosis, a biological safety cabinet should be used as a heightened control measure. For blood-borne agents, such as Hepatitis B virus, infection is via the bloodstream so heightened measures will include the avoidance of the use of sharps and protection of any damage or cuts to the skin. However, blood-borne agents can access the bloodstream via the mucous membranes so a microbiological safety cabinet and eye protection may also be required as heightened control measures. Maximum Containment Measures Laboratories using maximum containment measures give the highest level of protection to laboratory personnel, the community and/or the environment. This type of facility is only required where biological agents with the very highest consequences are used in work that has a high likelihood of exposure. Therefore only very rarely is a maximum containment laboratory required. Examples are for eradicated diseases such as small pox or for a pathogen with pandemic potential. Maximum containment comprises of a set of highly detailed and stringent risk control measures and a high level competence & training is required. The facility is usually located in a separate building and two laboratory designs are used. The first employs a © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 5 cabinet line facility, where all work is carried out in a closed system of class III BSCs, within a negative-pressure laboratory. In the second type of facility operators work in in a negative-pressure laboratory wearing positive-pressure suits whilst carrying out the work in open-fronted BSCs. There is very strict air handling arrangements, a complete change of clothes is required, all equipment is located in the facility and all waste and effluent is sterilised in a double ended autoclave. More information can be found in the LBSM Monograph, laboratory design and maintenance. Classification of biological agents into Risk Groups Many countries classify biological agents into Risk Groups according to particular criteria. Each Risk Group has a corresponding containment laboratory for work with the agent, termed Biosafety Levels. This approach is embodied in the national legislation of many countries, including the UK. In these countries, national legislation take precedence over WHO guidance. The classification is based on four key questions: Based on the following criteria: 1. ability to cause disease to humans or harm to the environment 2. severity of the harm that may result 3. likelihood of spread 4. availability of vaccines and effective treatment Risk Group Classification for human pathogens Risk Group 1 A biological agent unlikely to cause human disease Risk Group 2 A biological agent that can cause human disease and may be a hazard to employees; it is unlikely to spread to the community and there is usually effective prophylaxis or treatment available Risk Group 3 A biological agent that can cause severe human disease and presents a serious hazard to employees; it may present a risk of spreading to the community, but there is usually effective prophylaxis or treatment available Risk Group 4 A biological agent that causes severe human disease and is a serious hazard to employees; it is likely to spread to the community and there is usually no effective prophylaxis or treatment available. © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 6 Whilst it is unlikely that biological agents in Risk Group 1 will cause disease, many have the potential to cause opportunistic infections and this should always be borne in mind. If a biological agent is not listed it should not be automatically categorised into Risk Group 1. Where an agent does not have an approved classification, the agent should be provisionally categorised using the risk group classification criteria. If there is doubt as to which of two groups is most appropriate, the higher risk group should be chosen. All viruses which have been isolated from humans, but which do not have an approved classification should be classified as Risk Group 2 as a minimum unless and until there is evidence that there are unlikely to cause disease in humans. The risk group categorisation only gives an indication of the inherent hazard of the biological agent and the risk assessment should identify additional risk factors associated with the biological agent as well as how exposure and/or release could occur. Biosafety Levels There are four different levels of laboratory containment, called Biosafety Levels, directly related to each Risk Group. The number of the risk group indicates the minimum level of containment under which a biological agent must be handled. For example, Risk Group 3 agents are handled at Biosafety Level 3. In matching risk group with containment level the pathogenic potential, host susceptibility, epidemiological consequence and availability of effective treatment have all been taken into account. The matching of risk group to Biosafety level works well wherever the identity, and thus the pathogenicity, of an agent is known. Containment requirements where the identity or presence of a biological agent is not known, for example diagnostic samples or tissue samples, is summarised below: © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 7  Minimum Biosafety levels when biological agents may be present Biological agent(s) Containment Where uncertainty exists over the Minimum of Biosafety presence of pathogenic biological Level 2 agents but the intention is not to deliberately propagate or concentrate such agents Where the presence of a pathogenic Minimum of Biosafety biological agent is known or suspected Level appropriate to the agent Where the risk assessment is Minimum of Biosafety inconclusive Level 3 but where the activity might involve a serious health risk Biosafety level requirements At Biosafety Level 1 there should be general control measures to minimise exposure to substances hazardous to health. Examples include prohibiting eating and drinking in the laboratory. Biosafety Level 2 is probably the most commonly used containment level and is suitable for a broad range of research, clinical and diagnostic work with biological agents which, although capable of causing disease, only present a low-to-moderate risk to employees and are unlikely to spread to the community, with effective treatment or prophylaxis being available. Indeed, most modern laboratories are now constructed to meet the requirements for Biosafety Level 2 because there are few additional costs in constructing a Biosafety Level 2 facility over and above those for Level 1 and it provides greater flexibility for future use. The basic construction requires a sealed coved flooring, easily washable work surfaces that are chemically resistant, separate facilities for hand washing and the laboratory door to be closed during the work. © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 8 Summary of requirements – Biosafety level 2 a) Access is to be restricted to authorised persons only b) Infected material to be handled in a safety cabinet or isolator or other suitable containment c) Safe storage of biological agents d) Specified disinfection procedure e) Benches impervious to water and easy to clean f) Benches resistant to acids, alkalis, solvents, disinfectants g) Separate hand-washing facilities (hands free) Summary of requirements – Biosafety level 3 (additional to level 2) a) The workplace is to be separated from any other activities in the same building b) Maintained at an air pressure negative to atmosphere b) Extract air from the workplace is to be filtered using HEPA or equivalent c) Sealable to permit disinfection e) Benches and floors impervious to water and easy to clean f) Benches and floors resistant to acids, alkalis, solvents, disinfectants g) An observation window, or alternative, is to be present, to view occupants h) A laboratory is to contain its own equipment so far as is reasonably practicable Additional controls The specified measures at each Biosafety Level are a minimum and additional control measures may be necessary to those prescribed for each Biosafety level. The risk group does not take into account the following factors: © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 9  Route of infection Additional hazardous properties e.g. allergenicity or toxicity Minimal infectious dose of the agent Types of procedures that will be conducted Ability of the agent to survive in the environment and susceptibility to disinfectants and heat inactivation  Groups of individuals who may be more susceptible to infection The risk group classification is based on the level of risk of infection in immuno- competent individuals. No account is taken of particular effects on those whose susceptibility to infection may be compromised by: pre-existing disease; medication; compromised immunity (temporarily or more permanently); pregnancy or breastfeeding. The risk assessment should therefore consider whether these factors present any additional risks and whether additional control measures are necessary. Using less than full CL3 containment measures Although there are minimum containment requirements for each Biosafety level, there are certain circumstances when not all measures normally required at Biosafety level 3 need to be applied because of either the nature of the work and/or the nature of the biological agent. Derogation is permitted for specified RG3 agents that are not normally infectious by the airborne route and may only apply to diagnostic but not intentional work with the specified agent. The list includes certain enteric bacteria, mycobacteria, parasites (including Plasmodium falciparum and some Leishmania spp.), certain blood-borne viruses, and agents for human TSEs. The derogation permits dispensing of some of the physical requirements which protect from airborne infection at Biosafety Level 3. This includes the requirements for: a) net inward flow of air b) the use of microbiological safety cabinets c) the laboratory to be sealable for fumigation They do not however permit significant derogation from management requirements, e.g., record keeping, staff training (including knowledge of emergency procedures) or access control. © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 10 Biosafety Level equipment requirements It is good practice to have key equipment readily accessible in all laboratories, as long as crowding does not compromise safety. The precise requirements for ‘self-contained’ equipment increases with the level of containment. Therefore: BSL2 - not absolutely necessary to have all the equipment in the laboratory BSL3 - equipment should be provided so far as is reasonably practicable BSL4 - mandatory to have all the equipment located in the facility Safe procedures Information and instruction should be provided to those working with biological agents for them to be able to carry out their work safely. This should include local codes of practice, standard operating procedures, the procedures to be taken in the event of accidents and incidents, and details of the risk assessment explaining both the nature of the hazards and the use of control measures. It is sufficient for the procedures in Laboratories with Core Requirements or Biosafety Level 1 to be based upon accepted good microbiological practice & procedures (GMPP). However, procedures should be more rigorous as the level of risk or level of containment increases. In order to facilitate consistency and compliance it is recommended that all containment laboratories have local rules setting out the basic standards that should be adopted. Model rules should be developed and for higher risk work these rules should be part of a more detailed Code of Practice. The requirement to provide information and instruction also extends to contractors such as servicing engineers who made require access to the containment facility. Safe People: Training and competence requirements Training programmes should be developed for work with biological agents, identifying key competencies to be achieved and demonstrated. Training should be given on safe working practices and how to effectively apply routine and emergency control measures. These competencies should be first be demonstrated for lower risk work before an individual is permitted to work carry out higher risk work. The achievement of these competencies should be recorded at least for higher risk work (high risk work using heightened control measures; Maximum Containment measures; BSL3 or BSL4). Refresher training should also be carried out to demonstrate continued competency for the specified work/biosafety level. The key competencies should relate to the codes of practice and examples of these are illustrated below: © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 11  Training and competence requirements Risk level Key competencies Core requirements  Awareness and understanding of all procedures and risk assessments Core requirements plus  Technical competence for all aspects of the work* heightened measures  Knowledge and understanding of disinfection policy  Knowledge and understanding of waste disposal BSL1 arrangements†  Knowledge and understanding of emergency spillage BSL2 procedures All those included for above plus - Higher risk work requiring Core  Full understanding of emergency procedures, requirements plus including – heightened measures  safe evacuation and sealing of the facility prior to emergency room fumigation  securing and sealing a cabinet prior to emergency BSL3 cabinet fumigation  Full training, where applicable, on fumigation procedures * specific training should be given if use of a microbiological safety cabinet is required † specific training should be given if operation of an autoclave is required Review Once the laboratory work begins, the risk assessment should be reviewed and reassessed periodically to address any procedural changes or newly available information. Record keeping Employers should maintain a list of employees who work with pathogens that can cause serious disease (Risk Group 3 or Risk Group 4 biological agents). The record must list the type of work carried out, the biological agents to which they have been exposed, records of exposure and any accidents and incidents. A record is required where there is the likelihood of exposure, not just when there has been a known incident or accident. In containment facilities, where partial enclosure is used, i.e., Class I and Class II safety cabinets, then protection is not complete and thus exposure must be assumed. For those who may be incidentally exposed, such as healthcare workers, the risk assessment will determine whether or not an exposure record is required. For © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 12 example, records may not need to be kept for normal patient management, but may be required if staff are handling infected patients in isolation facilities and/or involved in invasive procedures. Although there is no absolute requirement to keep written risk assessments, it would be beneficial if these were retained by an employer for a certain period, particularly in situations where exposure records have also been kept. Permission for work with pathogens Many countries have national legislation for working with biological agents and permission is required from the authorities for first use of biological agents. Work with serious pathogens, for example in Risk Groups 3 & 4, requires permission for every use. An application is sent to the competent national authority in advance of the agent being brought onto the premises and typically requires the following information: Premises where biological agent will be stored/used, details of personnel with specific responsibility for health and safety, name of biological agent & the risk group assigned, risk assessment and the control measures that will be used. © University of Edinburgh Professional Course in Biorisk Management Biosafety Training Institute Module B – Biological agents/Pathogens 13