Risk Assessment Risk Management EMD 545 b Lecture
Risk Assessment & Risk Management EMD 545 b Lecture #2
Risk Assessment US Airways Magazine, October 1991
Risk Management US Airways Magazine, October 1991
Risk Assessment/Risk Management n Risk Identification – Adverse events? n Risk Estimation – Probability of adverse event? n Risk Management – Control measures?
Risk (Definitions) n “Possibility of loss, injury, disease, or death. ” Webster's Medical Desk Dictionary (1986) n “The probability that exposure to a hazard will lead to a negative consequence. ” David Ropeik, George Gray (2002) n “To risk living is to risk dying. ” Anonymous
Risk Assessment n 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. n “Not a scalpel, but a crude tool that allows you to make estimates. ” Peter Preuss, US EPA
Risk Assessment n n n 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
4 Steps in Risk Assessment (Jeff Wheelwright, 1996) n n 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)
Biohazard Epidemiology n Incidence of Hepatitis among Danish clinical chemistry workers 7 X higher than general population (Skinholj, 1974) n Risk of acquiring TB 5 X greater among medical lab workers in England than general population (Harrington & Shannon, 1976)
Hierarchy of Controls n n Anticipation Recognition Evaluation Control – substitution – administrative – engineering – work practices – personal protective clothing – facility features
Biohazard Risk Assessment n n 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
Biohazard Risk Assessment n Use to determine appropriate combination of containment – lab practices – safety equipment – facility design n Primary Containment – protects handlers and those in immediate vicinity n Secondary Containment – protects environment and those outside the lab
Biohazard Risk Assessment Pathway n n 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. )
Risk Assessment Pathway n 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
Routes of Exposure to Infectious Agents n Inhalation of aerosols n Through intact or non-intact skin (needlestick, injury (broken glass), animal bites or scratches, vector (mosquito, tick, parasite), eczema, dermatitis n n n Mucous membranes of eyes, nose or mouth Ingestion (mouth pipetting) Contact (indirect transfer from hands or contaminated surfaces)
Infectious Agents are Classified by Level of Hazard 4 Agent Risk Group Classifications RG 1 Low individual risk No risk to community RG 2 Moderate individual risk RG 3 RG 4 High individual risk Low risk to community High risk to community
Risk Groups (RG) n RG 1 • Not infectious to healthy adults • e. g. E. coli K 12 strains, B. subtilis, S. cerevisiae n RG 2 • 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 RG 1/RG 2 can be used in a basic lab • containment equipment to contain aerosols
Risk Groups (RG) n RG 3 • 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
Risk Groups (RG) n RG 4 • 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 (Hendralike viruses), Tick-Borne Encephalitis Viruses
Risk Assessment Pathway n 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
Laboratory Safety Containment Levels 4 Laboratory Biosafety Levels BSL 1 BSL 2 BSL 4 Basic laboratory, confine aerosols in biosafety cabinet if needed BSL 3 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
Hybrid Biosafety Level n BSL 2/BSL 3 (BL 2+) – Creutzfeld Jacob – HIV – High risk clinical specimens n BSL 3 -Enhanced (HEPA filtered exhaust Lab) – Yellow Fever, Rift Valley Fever Virus, VEE – Rickettsia rickettsii
Unknown Specimens n Facility Evaluation (highest level of protection available) n “B. A. R. E” – Block All Routes of Exposure
Containment achieved with: n Good microbiological practices n Safety Equipment n Facility Design
Risk Assessment Pathway n 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
Find Assigned Risk Group for: n n Brucella canis Chlamydia trachomatis – diagnostic work – high concentrations n Prions – human prions – animal prions Rabies virus HIV/SIV – research scale n Vesicular Stomatitis virus – lab adapted strains – Isolates from livestock n Coccidioides immitis – clinical specimens – cultures n n Francisella tularensis – diagnostic/clinical work – cell culture experiments n n r. DNA, Insertion of oncogene into human cells Vesicular Stomatitis virus -NJ with HIV gp 120 Botulinum toxin
Risk Assessment & Risk Management n Prior Planning Prevents Poor Performance
Risk Assessment & Risk Management n n n Pathogen (Agent) Procedures (Protocol) Personnel Protective Equipment Place (Proposed lab facility)
P-1: Pathogen n Should this agent be used in this experiment? On this campus? n Note: concentration or amplification in lab may present greater hazard than in nature.
PATHOGEN n n n n Agent Classification (Prior LAI’s) Source of agent Routes of Exposure Infectious Dose (LD 50’s for toxins) Pathogenicity Virulence Antibiotic resistance
Infectious Dose n Agent – – – – Ebola virus TB Tularemia Anthrax Cholera Salmonella typhi E. coli Shigella n Dose – – – – 1 1 - 10 10 >1300? ? ? 10^8 10^5 10^8 10^9
PATHOGEN n n n n Quantity/Concentration Incidence in the Community Immunization/Treatment Communicability Presence of Vectors Environmental Concerns (stability) Data from animal experiments Clinical specimens
Immunizations – Vaccinia – Tetanus – Meningococcal Immunization – Typhoid – Botulinum – Hepatitis B virus, Hepatitis A virus – Yellow Fever, EEE – Rabies
r. DNA Molecules n n n n Classification of parent agent Toxins Antibiotic resistance genes Altered host range or tropism Replication competency Integration into host genome Toxicity, allergenicity, other
P-2: n Personnel Are the proposed researchers capable of safely conducting these experiments?
PERSONNEL n n Host Immunity neoplastic disease/infection immunosuppressive therapy age, race, sex, pregnancy surgery (splenectomy, gastrectomy) diabetes, lupus Reproductive age Contraindications for therapy
PERSONNEL n n n Medical Surveillance prophylactic immunizations serum storage post-exposure prophylaxis/treatment screening
PERSONNEL n n aware of hazards prior documented work experience microbiological proficiency (observed) comfort/choice
PERSONNEL n n 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)
PERSONNEL n n 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)
P-3: n Protective Equipment Has the Principal Investigator selected the appropriate combination of personal protective clothing and safety equipment for the safe conduct of research?
Protective Equipment n n 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.
PERSONAL PROTECTIVE EQUIPMENT n Protect: n Use: skin clothing mucous membranes respiratory system gloves (double, kevlar) lab coats, solid-front gowns sleeve covers full face protection respiratory protection
PERSONAL PROTECTIVE EQUIPMENT n n Disposable Decontamination Dedicated to area Donning/Doffing – Compromised (wet/contaminated/torn) – Respiratory Protection Program
P-4: n Place (Facility Design) Does this research group have (or have access to) a laboratory with the requisite containment features this work?
PLACE – FACILITY DESIGN n n n n Restricted access/Door sign Easily cleanable Hand washing sinks (near exit door) Eye wash Autoclave Vacuum system protection Biosafety Cabinet
PLACE – FACILITY DESIGN n n n n Anteroom Negative pressure gradient Airflow monitor Air changes per hour (10 -15) Sealed penetrations, coved flooring Facility alarms/interlocks Communication outside the lab
P-5: n n 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?
PROCEDURES n n 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 n Focus on containing aerosol generating procedures and equipment
Aerosols – Procedures that impart energy into a microbial suspension are a potential source of aerosol (Chatigny, 1974) – Many common lab procedures and accidents have capability of releasing aerosols – homogenization, sonication, blending, mixing, grinding, shaking, vortexing, spills, opening vials, pipetting, animals excreting agent, opening vials under pressure, etc.
Viable Particles Recovered from Air (Chatigny, 1974) n Procedure – – – sonic oscillator mixing w/ pipette overflow from mixer opening lyophilized vial top removed after blending – dropping flask of culture – dropping lyophilized culture n # Particles/ft 3 of air – – – 6 7 9 135 1500 – 1551 – 4839
Procedures - Sharps Hazards n Syringe/Needle – adjusting volume – withdrawal from stopper – separation from syringe – leaking syringe – leakage from injection site – inappropriate disposal – poor work practices
Procedures - Sharps Precautions n Syringe/Needle – use needle-locking syringes – cover with disinfectant soaked gauze – animal restraints – cleanse inoculation site – safe needle practices – immediate collection/disposal
Procedures - Sharps Precautions n Needle/syringe – removal of needle from syringe (hemostat) – no recapping, bending, breaking, etc. – immediate disposal of intact needle/syringe – location of needlebox (vicinity, height) – replacement of needleboxes – eliminate/minimize use/safe sharp devices – avoid glass Pasteur pipettes
Procedures presenting risk n Microbiological loop – streaking plates – spreading material on slides – cooling loop in media – heating loop in an open flame
Precautions in bacteriology n Microbiological loop – smooth plates – disposable plastic loops – well formed loops with short staff – glass spreaders – electric (walled) micro-incinerators – work within a biosafety cabinet
Procedures with general risk n Pipetting – mouth pipetting – glass Pasteur pipettes – blow-out pipettes – mixing suspensions – spill of droplets onto hard surfaces n Eating, drinking, smoking, applying cosmetics
PROCEDURES n Pipetting – no mouth pipetting – disposable plastic pipettes – mark to mark pipettes – collect within biosafety cabinet – work over disinfectant-wet pad n Restrict consumption of food or beverage to well defined break areas
PROCEDURES n Centrifugation – broken/leaking tubes – microfuge tubes (snap caps) – (flawed/overfilled) n Protective Measures – check O-rings on rotors (use O-ring tubes) – safety cups/sealed rotors – load/unload in a biosafety cabinet
Risk Assessment Example n Hantavirus Protocol – Application of 5 P’s – Hierarchy of controls • • • Pathogen Personnel Place Procedures Protective Equipment
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