Chapter 4: Risk Assessments, Risk Groups, and Containment Levels (CLs)

1. Biorisk An Engineering Safety ModulePrepared by Valentin MalenkovReviewed by Prof. Marc AucoinSponsored by: MINERVA (www.safetymanagementeducation.com/)and MITACS Chapter 4: Risk Assessments, Risk Groups, and Containment Levels (CLs)

2. Course Outline Chapter 1: Introduction to Biorisk Chapter 2: Microorganisms, Pathogens, and Toxins Chapter 3: Regulation of Biohazardous Materials and Risk Management Systems Chapter 4: Risk Assessments, Risk Groups, and Containment Levels Chapter 5:Biohazardous Material Containment

3. Learning Objectives Understand the purpose and steps involved in different types of risk assessments Learn the factors which dictate the Risk Group of a micro-organism Understand how Risk Group relates to CL required for it Summarize the characteristics of facilities at each CL Introduce PPE and protocols required at each Containment Level

4. Risk Assessments

5. Risk Assessment Goal/Purpose “Risk Assessments are the basis of all of the components of a biosafety program;...” Canadian Biosafety Standards and Guidelines, pg 136 Extent dependant on scope • “Overarching” • Multiple organisms, protocols, laboratories • Involves most facility staff • “Local” • Laboratory/protocol-specific • Less involved, more specific

6. Risk Assessment Goal/Purpose (cont’d) Determine requirements for biosafety • Equipment, containment, SOPs • BSO-driven • Other stakeholders involved (Laboratory Staff, Management, Engineers, Health & Safety, etc) • Risk mitigation • Elimination/substitution • Engineering Controls • Administrative controls • PPE

7. Pathogen Risk Assessments One for every pathogen used • Conducted before it is brought in • Determines Risk Group • Required by law based on main host/target (CBSG) Covers all aspects of use • Storage, containment, handling PPE • SOPs for entire lifecycle Pathogen Safety Data Sheet (PSDS) created • Pathogenicity, route of infection, infectious dose, survival in the environment

8. Genetically Modified Organisms Risk can increase or decrease • Depends on transformation and gene(s) affected • Original organism and source of genes considered first Reassessment of risk required with alteration of: • Pathogenicity/virulence • Pharmacological activity (resistance) • Genes related to hazardous properties • Production of toxins, oncogenes • Survivability outside containment zone • Ability to replicate • Attenuation • Change in host range

9. Genetically Modified Organisms Factors to consider in GMO risk assessments • Containment level of organisms • Gene recipient and gene donor • Replication competency • Potential pathogenic factors of genetic info • Possible novel hazards • Behaviour of donor genetic info in recipient

10. Viral Vectors Engineered viruses • Can create GMOs • Transient or permanent gene modification Considerations similar to GMO “Safety features” included in design • Reduced risk • Replication deficiency Additional risk from retroviral vectors • Modify host DNA permanently • Potential for oncogenesis (mutation causing cancer)

11. Synthetic Biology Genes/sequences created synthetically • Not found in nature • More novel approach Risk difficult to assess • Effects not always predictable • Careful assessment and testing required Interaction with existing genes/gene products • Unexpected risks

12. Infectious RNA RNA infection causing production of whole virus • Positive-sense RNA required • Can be translated into protein • Ex: Polio, West Nile, Dengue Viruses Reduced routes of infection • Not found in nature • No natural delivery methods Can carry increased risks • RNA more stable than proteins • Unaffected by virus-targeting antibodies • Increased host range

13. Toxin Risk Assessment Not infectious material or toxic chemical • Separate risk assessment required • Common regulated toxins listed in HPTA • Schedule 1 and Part I of Schedule 5 Considerations • Toxicity (lethal dose and/or effective dose) • Risk and routes of exposure • Concentration and amount used • Rate of action • Neurotoxins effective in minutes/hours • Cytotoxins effective in hours/days • Availability of treatment

14. Biosecurity Risk Assessment Can be incorporated into overarching Biological Risk Assessment • Preliminary for biosecurity plan Steps to the assessment: • Identify and prioritize assets • Define threats • Determine risks and mitigation strategies Covers information as well as biological materials

15. Microorganism Risk Groups

16. Pathogen Risk Groups Applied to pathogens based on risk assessment • Applies to microorganisms, nucleic acid, or protein • Risk dictated by circumstances (can change) • Strain virulence • Genetic modification • Inactivation • Apply higher group when in doubt Dictate level of regulation and containment Pathogens listed by risk group • Schedules 2-4 of Human Pathogens and Toxins Act (HPTA)

17. Risk Group 1 Low individual and community risk • Incapable/unlikely to cause disease in humans • May cause opportunistic infections • Immunocompromised individuals No special regulation of containment Good micro-biological practises recommended Not listed in HPTA

18. Risk Group 2 Moderate individual risk • Can cause disease in exposed humans/animals • Disease unlikely or not serious Low community risk • Low transmission potential • Effective treatment available Regulated containment and handling • Applies to all higher Risk Groups as well Ex: Avian Influenza, Cowpox Virus, Hepatitis A

19. Risk Group 3 High individual risk • Cause serious disease on exposure Low community risk • Low human transmission risk • Low to high livestock/poultry risk • Effective treatment available Highly regulated containment/handling Ex: Chlamydia, Influenza A H2N2, Rabies

20. Risk Group 4 High individual risk, high community risk • Lack of effective treatment • High risk of human transmission • Low to high risk of livestock transmission • Usually causes deadly disease Highly regulated containment and handling • Many prohibited except by special permits All listed pathogens are viruses Ex: Ebola, Herpes B Virus, Marburg Virus

21. Facility Containment Levels

22. Facility Containment Levels (CLs) Set minimum containment requirements • Physical containment and practises Determined alongside Risk Groups in risk assessment • Usually same levels • More based on usage/protocols • Can change with modification/mitigation • Inactivation • Non-infectious strains • Vaccination

23. Factors Affecting CLs Aerosol generation • Liquid particulate transmission • Pipetting, centrifugation, mixing, etc. Quantity of material • Scale of work conducted • State of storage/use Concentration of material • Risk increases with concentration

24. Factors Affecting CLs (cont’d) Type of work (usage) • In vitro vs in vivo • Protocols heightening risk • Use of sharps/needles • Dangerous animals used Animal shedding of pathogen • Replication of pathogen in live animals • Increased threat of containment breech • Pathogen in waste and bodily fluid • Animal containment breech (escape or loss)

25. Containment Regulations Regulations for CL2 and above • PHAC and CFIA regulations • Specific requirements in CBSG • Requirements in Chapter 3 (all levels) • Representative diagrams in Appendix A Administrative Requirements • Biosafety Management, Medical Surveillance, and Training Programs • Decontamination and waste management • Emergency response plan • Certification and Performance testing

26. Containment Regulations (cont’d) Physical requirements • Structure and location • Containment barriers • Access • Surface finishes and casework • Air handling • Essential equipment • Effluent treatment Certification standards must be met

27. Containment Level 1 Sets baseline for biological safety • Basic laboratory containment • Higher levels add to CL1 requirements Unregulated Risk Group 1 Pathogens only • Low risks for any kind of infection/disease • Standards not listed in CBSG • Requirements set by risk assessment and policy

28. Containment Level 1 (cont’d) Recommended elements (CBSG): • Good microbiology practises • Cleanable and functional space • Proper cleaning/decontamination • Good hygienic practises • Required hand washing, no food or drink, no makeup application • Appropriate PPE available and used • Gloves, lab coats, closed foot-wear

29. Containment Level 2 Pathogens of Risk Group 2 or less handled • No mitigating circumstances • animal shedding, high volumes • Airborne transmission not likely • Assumes immuno-competent personnel Standards mitigating personal risk • Low risk to general population • Aerosol generation • Biological safety cabinets • Respirators in high-risk work

30. Containment Level 3 Pathogens of Risk Group 3 or less handled • Airborne transmission likely • Serious/lethal disease if infected • Increased threat with animal work and aerosols Higher standards for personal protection • Gowning/degowning procedures • Immunization • Respirator fit testing • All personnel trained/equipped with PPE • Janitorial staff, engineering, etc

31. Containment Level 3 (cont’d) Additional facility design and engineering controls • HEPA filtration on all exhaust air • Negative pressure air handling with alarms • Separate gowning areas • Full decontamination possible • Air handling, ceilings, etc Additional commissioning and certification • Full commissioning/inspection before starting • Annual re-certification

32. Containment Level 4 Pathogens of Risk Group 4 can be handled • Serious/lethal disease on infection • Effective treatment unavailable • Airborne transmission Further engineering controls (addition to CL3) • Two-stage HEPA filters on exhaust air • Structurally indep. labs • Additional access control • Containment zone storage for pathogens

33. Containment Level 4 (cont’d) Extensive PPE requirements • Positive pressure suits required • Decontamination prior to de-gowning • Emergency response considerations • Positive pressure suit dysfunction • Emergency services access/PPE Federally controlled research facilities • Only 1 facility in Canada • Highest possible security

34. Biorisk An Engineering Safety ModulePrepared by Valentin MalenkovReviewed by Prof. Marc AucoinSponsored by: MINERVA (www.safetymanagementeducation.com/)and MITACS Chapter 4: Quiz

35. True or False: Risk Assessments are something the BSO conducts on their own, and other personnel must follow. A facility rated for CL2 work is in operation and a new research project calls for a new Risk Group 2 pathogen to be brought in. Is a local or overarching risk assessment at the facility required based on the situation described. Explain why. A facility rated for CL1 work is in operation and a new research project calls for a new Risk Group 2 pathogen to be brought in. Is a local or overarching risk assessment at the facility required based on the situation described. Explain why. A pathogen is being removed from storage which you’re never worked with. Where can you find information to work with it safely? An infectious material is being assessed and found to be infective only by direct contact. Unfortunately, it also bypasses viral antibodies making it more dangerous to work with. What is this material? A risk assessment for a new pathogen. This pathogen is genetically engineered and is being used to deliver genes into host cells. It has been designed to not replicate in regular animal cells. What type of pathogen is this?

36. You are interested in research involving a particular human pathogen. Where is the first place to look to determine its Risk Group? A human pathogen causes severe illness and is transmitted only by the fecal-oral route. What is its most likely Risk Group? What are the five factors affecting the required CL at a facility which were listed? True or False: The CL will always match up with the highest Risk Group which is present at the facility. A facility is equipped with a few Biosafety Cabinets in which aerosol-producing work is done. However, no biosafety officer is assigned and no pathogens are of Risk Group above 1. What CL is the facility? At which CL does the facility house pathogens dangerous to the general population?