Risk Assessment & Risk Management

1. Risk Assessment &Risk Management EMD 545b Lecture #2

2. Risk Assessment US Airways Magazine, October 1991

3. Risk Management US Airways Magazine, October 1991

4. Risk Assessment/Risk Management • Risk Identification • Adverse events? • Risk Estimation • Probability of adverse event? • Risk Management • Control measures?

5. Risk (Definitions) • “Possibility of loss, injury, disease, or death.” Webster's Medical Desk Dictionary (1986) • “The probability that exposure to a hazard will lead to a negative consequence.” David Ropeik, George Gray (2002) • “To risk living is to risk dying.” Anonymous

6. Risk Assessment • The emergent science based on toxicology, epidemiology and statistics that utilizes qualitative and quantitative hazard analysis to provide the public with a reasonable estimate of probability of harm. • “Not a scalpel, but a crude tool that allows you to make estimates.” Peter Preuss, US EPA

7. Risk Assessment • Difficult process (expertise of many fields needed) • Involves uncertainty • Range provided (not a specific number) • Estimates for society (individual risk may vary) • “Reasonable worst-case estimate” (better to overestimate than underestimate risk) • Costs and benefits of proposed actions helpful

8. 4 Steps in Risk Assessment (Jeff Wheelwright, 1996) • 1) Identify health hazard • 2) Quantify hazard • 3) Exposure assessment (from source to at risk person) • 4) Determine probability of disease (based on exposure estimate and potency of agent)

9. Biohazard Epidemiology • Incidence of Hepatitis among Danish clinical chemistry workers 7X higher than general population (Skinholj, 1974) • Risk of acquiring TB 5X greater among medical lab workers in England than general population (Harrington & Shannon, 1976)

10. Hierarchy of Controls • Anticipation • Recognition • Evaluation • Control • substitution • administrative • engineering • work practices • personal protective clothing • facility features

11. Biohazard Risk Assessment • Qualitative exercise (inexact) • General guidelines to assess/control risk: • agent in use, volumes, concentration • proposed practices/procedures • proposed location • training, experience, health status of worker

12. Biohazard Risk Assessment • Use to determine appropriate combination of containment • lab practices • safety equipment • facility design • Primary Containment • protects handlers and those in immediate vicinity • Secondary Containment • protects environment and those outside the lab

13. Biohazard Risk Assessment Pathway • Principal Investigator (initiates risk review) • Biosafety Officer (assists PI) • Institutional Biosafety Committee (must review and approve PI’s submission) • Assistance through • published listings, guidelines (U.S. and abroad) • other experts at host institution, local public health • other institutions working with same agents • Government entities (CDC, NIH, USDA, FDA, etc.)

14. Risk Assessment Pathway • Principal Investigator initiates process • Qualitative process • Agent • Virulence, pathogenicity, communicability, environmental stability, dose, route of exposure, availability of therapy • Use Risk Group Lists • Consider proposed procedures • Operations, quantity (volume/concentration), generation of aerosols, sharps, animals

16. Inhalation of aerosols Through intact or non-intact skin (needlestick, injury (broken glass), animal bites or scratches, vector (mosquito, tick, parasite), eczema, dermatitis Mucous membranes of eyes, nose or mouth Ingestion (mouth pipetting) Contact (indirect transfer from hands or contaminated surfaces) Routes of Exposure to Infectious Agents

17. Infectious Agents are Classified by Level of Hazard 4 Agent Risk Group Classifications • RG1 RG2 RG3 RG4 Low individual risk Moderate individual risk High individual risk High risk to community No risk to community Low risk to community

18. Risk Groups (RG) • RG1 • Not infectious to healthy adults • e.g. E. coli K12 strains, B. subtilis, S. cerevisiae • RG2 • Infectious agents of varying severity, treatment usually available, predominantly bloodborne, ingestion, and mucous membrane routes of exposure • e.g. Salmonella, Shigella, Vibrio, Plasmodium, Hepatitis B Virus, Cryptococcus neoformans • Both RG1/RG2 can be used in a basic lab • containment equipment to contain aerosols

19. Risk Groups (RG) • RG3 • potential to cause serious or lethal disease, airborne route of exposure (and others), treatment generally not available, lower infectious dose. • Containment Lab 2 doors off general corridor, dedicated air handler, controlled airflow, all work contained • e.g. TB, Vesicular Stomatitis Virus, Yellow Fever Virus, Coxiella burneti, Francisella tularensis

20. Risk Groups (RG) • RG4 • Dangerous, exotic agents with high risk to individual and community. Aerosol transmission along with all other routes. Very low infectious dose, high mortality rates. • Building within building approach for research purposes. • e.g. Ebola virus, Marburg virus, Junin, Lassa, Machupo, Sabia, Equine Morbillivirus (Hendra-like viruses), Tick-Borne Encephalitis Viruses

21. Risk Assessment Pathway • Principal Investigator responsible for completing initial risk assessment • Start with risk group for parent organism • Consider the proposed procedures • Identify Risk Management Procedures • Facility design elements • Safety or containment equipment • Work practices

22. Laboratory Safety Containment Levels • 4 Laboratory Biosafety Levels • BSL1 BSL2 BSL3 BSL4 Basic laboratory, confine aerosols in biosafety cabinet if needed Containment lab, 2 door separation from general traffic, negative air flow, alarms Maximum containment lab, building w/in building, all features isolated, pos. pressure suits, glove box type isolation

23. Hybrid Biosafety Level • BSL2/BSL3 (BL2+) • Creutzfeld Jacob • HIV • High risk clinical specimens • BSL3-Enhanced (HEPA filtered exhaust Lab) • Yellow Fever, Rift Valley Fever Virus, VEE • Rickettsia rickettsii

24. Unknown Specimens • Facility Evaluation (highest level of protection available) • “B.A.R.E” • Block All Routes of Exposure

25. Containment achieved with: • Good microbiological practices • Safety Equipment • Facility Design

26. Risk Assessment Pathway • Institutional Biosafety Committee verifies and approves PI Risk Assessment • Review of written risk assessment • Verification of personnel training and experience • Biosafety courses • Hands-on experience/proficiency • Safety record • Inspection of facility and work practices • Formal approval of protocol

27. Brucella canis Chlamydia trachomatis diagnostic work high concentrations Francisella tularensis diagnostic/clinical work cell culture experiments Coccidioides immitis clinical specimens cultures Prions human prions animal prions Rabies virus HIV/SIV research scale Vesicular Stomatitis virus lab adapted strains Isolates from livestock rDNA, Insertion of oncogene into human cells Vesicular Stomatitis virus-NJ with HIV gp 120 Botulinum toxin Find Assigned Risk Group for:

28. Risk Assessment & Risk Management • Prior Planning Prevents Poor Performance

29. Risk Assessment & Risk Management • Pathogen (Agent) • Procedures (Protocol) • Personnel • Protective Equipment • Place (Proposed lab facility)

30. P-1: Pathogen • Should this agent be used in this experiment? On this campus? • Note: concentration or amplification in lab may present greater hazard than in nature.

31. PATHOGEN • Agent Classification (Prior LAI’s) • Source of agent • Routes of Exposure • Infectious Dose (LD50’s for toxins) • Pathogenicity • Virulence • Antibiotic resistance

32. Agent Ebola virus TB Tularemia Anthrax Cholera Salmonella typhi E. coli Shigella Dose 1 1 - 10 10 >1300????? 10^8 10^5 10^8 10^9 Infectious Dose

33. PATHOGEN • Quantity/Concentration • Incidence in the Community • Immunization/Treatment • Communicability • Presence of Vectors • Environmental Concerns (stability) • Data from animal experiments • Clinical specimens

34. Immunizations • Vaccinia • Tetanus • Meningococcal Immunization • Typhoid • Botulinum • Hepatitis B virus, Hepatitis A virus • Yellow Fever, EEE • Rabies

35. rDNA Molecules • Classification of parent agent • Toxins • Antibiotic resistance genes • Altered host range or tropism • Replication competency • Integration into host genome • Toxicity, allergenicity, other

36. P-2: Personnel • Are the proposed researchers capable of safely conducting these experiments?

37. PERSONNEL • Host Immunity • neoplastic disease/infectionimmunosuppressive therapyage, race, sex, pregnancysurgery (splenectomy, gastrectomy)diabetes, lupus • Reproductive age • Contraindications for therapy

38. PERSONNEL • Medical Surveillance • prophylactic immunizations • serum storage • post-exposure prophylaxis/treatment • screening

39. PERSONNEL • aware of hazards • prior documented work experience • microbiological proficiency (observed) • comfort/choice

40. PERSONNEL • Safety Attitude • Those who have fewer accidents: adhere to safety regulations respect infectious agents defensive work habits able to recognize potential hazards • Women • Older employees (age 45-64)

41. PERSONNEL • Safety Attitude • Those who have more accidents: low opinion of safety take excessive risks work too fast less aware of risks • Men • Younger employees (age 17-24)

42. P-3: Protective Equipment • Has the Principal Investigator selected the appropriate combination of personal protective clothing and safety equipment for the safe conduct of research?

43. Protective Equipment • Personal Protective Equipment (clothing) • Containment Equipment • Biological safety cabinets • Safety centrifuges • Sealed sonicators, blenders, homogenizers • Sealed tubes, transport carriers • Safe sharps, needleboxes, medical waste bags, tongs, forceps, etc.

44. PERSONAL PROTECTIVE EQUIPMENT • Protect: skin clothing mucous membranes respiratory system • Use: gloves (double, kevlar) lab coats, solid-front gowns sleeve covers full face protection respiratory protection

45. PERSONAL PROTECTIVE EQUIPMENT • Disposable • Decontamination • Dedicated to area • Donning/Doffing • Compromised (wet/contaminated/torn) • Respiratory Protection Program

46. P-4: Place (Facility Design) • Does this research group have (or have access to) a laboratory with the requisite containment features this work?

47. PLACE – FACILITY DESIGN • Restricted access/Door sign • Easily cleanable • Hand washing sinks (near exit door) • Eye wash • Autoclave • Vacuum system protection • Biosafety Cabinet

48. PLACE – FACILITY DESIGN • Anteroom • Negative pressure gradient • Airflow monitor • Air changes per hour (10-15) • Sealed penetrations, coved flooring • Facility alarms/interlocks • Communication outside the lab

49. P-5: Procedures • Has the Principal Investigator outlined all of the proposed steps in the protocol? • Has the lab outlined sufficient protective work practices to minimize the risk to those working and those outside the lab?

50. PROCEDURES • Develop standard written practices (SOP’s) for handling pathogens • Job Safety Analysis (JSA) • identify each task • describe all steps • hazard assessment at each step • incorporate safety • Focus on containing aerosol generating procedures and equipment