Risk Assessment

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Risk Assessment Risk Management

• EMD 545b Lecture 2

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Risk Assessment
US Airways Magazine, October 1991
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Risk Management
US Airways Magazine, October 1991
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Risk Assessment/Risk Management

• Risk Identification
• Adverse events?
• Risk Estimation
• Probability of adverse event?
• Risk Management
• Control measures?

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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

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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

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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

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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)

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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)

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Hierarchy of Controls

• Anticipation
• Recognition
• Evaluation
• Control
• substitution
• administrative
• engineering
• work practices
• personal protective clothing
• facility features

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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

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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

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Biohazard Risk Assessment Pathway

• Principal Investigator (initiates risk review)
• Biosafety Officer (assists PI)
• Institutional Biosafety Committee (must review
  and approve PIs 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.)

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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

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Routes of Exposure to Infectious Agents

• 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)

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Infectious Agents are Classified by Level of
Hazard

• 4 Agent Risk Group Classifications
• RG1 RG2 RG3 RG4

Moderate individual risk
Low individual risk
High individual risk
High risk to community
No risk to community
Low risk to community
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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

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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

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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

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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

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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
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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

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Unknown Specimens

• Facility Evaluation (highest level of protection
  available)
• B.A.R.E
• Block All Routes
  of Exposure

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Containment achieved with

• Good microbiological practices
• Safety Equipment
• Facility Design

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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

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Find Assigned Risk Group for

• 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

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Risk Assessment Risk Management

• Prior Planning Prevents Poor Performance

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Risk Assessment Risk Management

• Pathogen (Agent)
• Procedures (Protocol)
• Personnel
• Protective Equipment
• Place (Proposed lab facility)

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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.

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PATHOGEN

• Agent Classification (Prior LAIs)
• Source of agent
• Routes of Exposure
• Infectious Dose (LD50s for toxins)
• Pathogenicity
• Virulence
• Antibiotic resistance

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Infectious Dose

• Agent
• Ebola virus
• TB
• Tularemia
• Anthrax
• Cholera
• Salmonella typhi
• E. coli
• Shigella

• Dose
• 1
• 1 - 10
• 10
• gt1300?????
• 108
• 105
• 108
• 109

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PATHOGEN

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

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Immunizations

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

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rDNA Molecules

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

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P-2 Personnel

• Are the proposed researchers capable of safely
  conducting these experiments?

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PERSONNEL

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

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PERSONNEL

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

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PERSONNEL

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

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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)

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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)

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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?

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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.

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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

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PERSONAL PROTECTIVE EQUIPMENT

• Disposable
• Decontamination
• Dedicated to area
• Donning/Doffing
• Compromised (wet/contaminated/torn)
• Respiratory Protection Program

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P-4 Place (Facility Design)

• Does this research group have (or have access to)
  a laboratory with the requisite containment
  features this work?

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PLACE FACILITY DESIGN

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

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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

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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?

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PROCEDURES

• Develop standard written practices (SOPs) 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

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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.

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Viable Particles Recovered from Air (Chatigny,
1974)

• Procedure
• sonic oscillator
• mixing w/ pipette
• overflow from mixer
• opening lyophilized vial
• top removed after blending
• dropping flask of culture
• dropping lyophilized culture

• Particles/ft3 of air
• 6
• 7
• 9
• 135
• 1500
• 1551
• 4839

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Procedures - Sharps Hazards

• Syringe/Needle
• adjusting volume
• withdrawal from stopper
• separation from syringe
• leaking syringe
• leakage from injection site
• inappropriate disposal
• poor work practices

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Procedures - Sharps Precautions

• Syringe/Needle
• use needle-locking syringes
• cover with disinfectant soaked gauze
• animal restraints
• cleanse inoculation site
• safe needle practices
• immediate collection/disposal

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Procedures - Sharps Precautions

• 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

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Procedures presenting risk

• Microbiological loop
• streaking plates
• spreading material on slides
• cooling loop in media
• heating loop in an open flame

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Precautions in bacteriology

• Microbiological loop
• smooth plates
• disposable plastic loops
• well formed loops with short staff
• glass spreaders
• electric (walled) micro-incinerators
• work within a biosafety cabinet

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Procedures with general risk

• Pipetting
• mouth pipetting
• glass Pasteur pipettes
• blow-out pipettes
• mixing suspensions
• spill of droplets onto hard surfaces
• Eating, drinking, smoking, applying cosmetics

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PROCEDURES

• Pipetting
• no mouth pipetting
• disposable plastic pipettes
• mark to mark pipettes
• collect within biosafety cabinet
• work over disinfectant-wet pad
• Restrict consumption of food or beverage to well
  defined break areas

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PROCEDURES

• Centrifugation
• broken/leaking tubes
• microfuge tubes (snap caps)
• (flawed/overfilled)
• Protective Measures
• check O-rings on rotors (use O-ring tubes)
• safety cups/sealed rotors
• load/unload in a biosafety cabinet

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Risk Assessment Example

• Hantavirus Protocol
• Application of 5 Ps
• Hierarchy of controls
• Pathogen
• Personnel
• Place
• Procedures
• Protective Equipment