Work with Biohazardous Agents:
Risk Assessment
Betty Kupskay, MSc, RBP
Biosafety Officer
University of Minnesota
[email protected]
Nov. 21, 2013
What is a Hazardous Substance?
Any biological agent and other disease-causing agent
which after release into the environment and upon
exposure, ingestion, inhalation, or assimilation into any
person...will or may reasonably be anticipated to cause
death, disease, behavioral abnormalities, cancer, genetic
mutation, physiological malfunctions...or physiological
deformations in such persons or their offspring.
HAZWOPER standard, April 13, 1990
2
Basic Groups of Microorganisms






Viruses
Bacteria
Fungi
Protozoa
Algae
(Prions)
3
Viruses

Size - 20 to 300 nanometers (nm)
You can fit 83,333 of that virus in an inch!

Require another living cell to reproduce
The ultimate parasite
NOT killed by antibiotics
Require an electron microscope to see them



4
Types of Microorganisms
Bacteria


10 X larger than viruses
Only need a light microscope to view them
Rods (E. coli)
Spheres (Staph. aureus)
Spirals (T. pallidum)
6
Fungi

Molds & yeast

Yeast are 5-10 X larger than bacteria (still require a
microscope to see)

Fuzzy stuff on moldy bread is a fungus
(microscope is required to see details)
7
Protozoa

Grow in moist environments (fresh & marine water)

Also found in decaying organic matter, soil, beach
sand

Make up a large part of plankton
Giardia lamblia (beaver fever)
8
Algae

Found in water (fresh, marine or brackish)

Some grow on surface of moist soil, on moist rocks,
wood & trees

Lichens formed by association of algae & fungi
9
Prions


Only causes disease when mutated or over-produced
Causes brain damage that leads to death in man &
animals (e.g.,Creutzfeld-Jacob Disease, Mad Cow
Disease)
10
Types of Microorganisms
Benefits of Microorganisms
12
13
The ‘Down-Side’ of Microorganisms
14
Infectious dose
The number of microorganisms required to initiate
infection
Q fever
10 organisms by inhalation
E. coli
108 organisms by ingestion
Malaria
10 organisms by IV injection
Poliovirus 1
2 pfu by ingestion
Reference: Wedum, A.G., Barkley, W.E., and Hellman, A. 1972. J Am Vet. Med Assoc. 161:11, 1557-1567.
 Estimated that there have been 1000’s of LAI’s
 Many people have died
 Shigellosis and brucellosis – two most commonly
reported bacterial diseases
 Hepatitis B – Most commonly reported lab infection in
lab workers
Efforts made to determine how an infection has
come about to enhance development of better
preventative measures.
Routes of Exposure
Routes of Exposure
Routes of Exposure
Routes of Exposure
What is Risk?
Risk is the probability of an adverse effect as a
result of exposure to a hazardous substance.
22
Interaction of Factors
Agent?
Agent?
Risk
Group?
Risk Group?
Biological
Agent
Host
Risk
Mode of
Transmission
Medical Status
PPE
Quantity
of Agent
Environment
Quantity of Agent
Equipment
23
Procedures
Procedures
Facility
Facility
Risk Assessment
 The first step toward ensuring that all workers
have a safe and healthy working environment

A documented process to recognize or identify hazards
and assess the risk or probability that something will
happen because of that hazard

Severity of the consequences must be considered
Risk Assessment
For work with biohazardous agents or materials, a risk
assessment must:
 Reduce the risk of handling & provide protection

Be based on valid information re:







Pathogenicity
Route of transmission
Host range
Concentration
Infectious dose
Stability in the environment
Availability of treatment or prophylaxis
25
Chain of Infection
Pathogenic Agent
Susceptible Host
Route of Entry\
Infectious Dose
Reservoir
Portal of escape
Route of Transmission
Breaking the Chain to Manage the Risk
Eliminate:
Pathogen
Reservoir of pathogen
Portal of escape
Breaking the Chain to Manage the Risk
Eliminate:
Transmission
Route of entry/infectious dose
Susceptible host
Worker-Related Factors

Assume the worker (host) is an immunocompetent
adult

Evaluate worker training, expertise, and attitude in the
risk assessment
Risk Assessment

Process is not as straightforward for biohazardous
agents as for inanimate hazardous materials

Livings agents do not lend themselves to a rigid
classification

Determination of relative risks is possible through
classification into Risk Groups

Risk Groups reflect the assessment of increasing risk to
the user and/or environment (RG 1-4)
30
Risk Assessment
RG can be predicted from guidelines or reg.’s available from:

government agencies

professional organizations

academic institutions
31
Risk Assessment

4 Risk Groups are defined

Differ from intent of the BMBL &
other countries – do not mention
aerosol transmission & are
‘human-centric’
32
Risk Group 1
(low individual and community risk)

Agents not associated with disease in healthy
adult humans
e.g.
E. coli K12
Bacillus subtilis
Adeno-associated virus (AAV)
Risk Group 2
(moderate individual risk, limited community risk)
 Agents that are associated with human disease which is
rarely serious and for which preventative or therapeutic
interventions are often available
e.g.
Salmonella food poisoning
E.coli 0157
Risk Group 3
(high individual risk, low community risk)

Agents that are associated with serious or lethal human
disease for which preventative or therapeutic
interventions may be available.
e.g. Mycobacterium tuberculosis
Risk Group 4
(high individual risk, high community risk)

Agents that are likely to cause serious or lethal
human disease for which preventative or therapeutic
interventions are not usually available
e.g. Ebola virus
Risk Groups vs. Biological Safety Levels
Risk groups do not consider specific procedures Biosafety Levels are more appropriate.

Includes engineering, operational, technical &
physical requirements
No such thing as a “BSL-X” agent or organism!
Risk Groups vs. Biological Safety Levels
For example:

HIV is classified as RG3 in many guidelines

The containment recommendations range from BSL-2 to
BSL-3
38
Risk Groups vs. Biological Safety Levels

This lack of uniformity poses a challenge to those used
to rigid classifications of chemical & physical hazards

Must be accepted & appropriately applied by those
professionals who assess risk of work with biohzardous
agents
39
Risk Assessment

Leaves the responsibility of risk
evaluation to the PI

Refers to the biological safety levels
(BSL’s) at which the agents may be
handled
40
Biosafety Level 1 (BSL-1)

Requires no special design features beyond those
suitable for a well-designed lab

BSC’s not required

Work may be done on the bench top
e.g. High school lab
BSL-1
Laboratory Facilities
BSL-1
Laboratory Facilities
Easily cleaned &
decontaminated.
Biosafety Level 2 (BSL-2)

Primary containment, such as BSC’s
& PPE must be used

Hand & eye washing facilities
 Autoclaves or off-site waste treatment
BSL-2
Laboratory Facilities
Biosafety Level 3 (BSL-3)

Emphasizes additional 1° & 2°
barriers to minimize release of
organisms into lab & environment

Appropriate respiratory protection

HEPA filtration of lab exhaust air & strictly
controlled lab access
BSL-3
Laboratory Facilities
BSL-3
BSL-3 lab
interior
Facility Design (BSL-3)
Hallway
Clean Change
Shower
Dirty Change
Facility Design (BSL-3)
Personal
Shower
Facility Design (BSL-3)
Dunk tank
Facility Design (BSL-3)
Directional
Airflow (BSL-3)
Facility Design (BSL-3)

Solid floors and ceilings

Sealed penetrations

Air supply/exhaust system with bioseal
dampers
BSL-3
Access Control
PIN access
Card & biometric access
Security camera
Biosafety Level 4 (BSL-4)
BSL-4
BSL-4
BSL-4
Agent-based, Qualitative Risk Assessment
Higher or lower levels of containment may be required
because of:



Developed drug resistance
Avirulent strains of a wild-type pathogen
Attenuated vaccine strains
59
When risk of exposure to infectious aerosols is
present, higher levels of 1° containment with multiple
2° barriers may be needed.
Agent-based, Qualitative Risk Assessment

If agent not well characterized, may not be enough data
for RA

Must use information available to develop a rational
default process for handling unknown agents

OSHA mandates this for work with blood-borne
pathogens

Supervisor is responsible to assess the risks, or obtain a
risk assessment in consultation with a biosafety
professional
61
Agent-based, Qualitative Risk Assessment

Classifying the agent into a RG does not itself allow for
the selection of appropriate admin controls, work
practices, & engineering controls

A more quantitative risk evaluation of agent-host-activity
required to develop appropriate containment
62
Risk Assessment Factors
Anthology of Biosafety IV, Issues in Public Health, Chapter 10. J.Y. Richmond, Ed. ABSA, 2001 page 152
Quantitative Risk Assessment
A quantitative RA can be done with:



Information on biohzardous material
Knowledge or assumption of health status of worker
Thorough understanding of practices, procedures, &
volumes used
Severity rating is reflected in containment level for the work.
64
Host Factors – Health Status

Published guidelines assume immunocompetancy

Identification of impaired host defense factors is
employee’s responsibility

Must be evaluated on a case-by-case basis

Workers have the ‘right to know’ about the specific
hazard & the protection provided
65
Agent-Activity Interaction: Job Safety
Analysis






Thorough evaluation of hazard potential of work practices,
procedures, & equipment used
Completed in advance of work
Inform workers
Responsibility of the supervisor
OSHA requirement for blood-borne pathogen work
Should be applied for all work with biohazardous agents
66
Risk Management

Focus on high priority risks first
 Develop safety protocols, procedures, SOPs based on
your assessment
 Maintain records of your assessments and use them for
in-lab training and orientation (new staff, students etc.)
Risk Management
Protection for:
Conclusions…

Advisable to use results-oriented general guidelines, e.g.,
the success of the blood-borne pathogen standard

Measuring risk is objective, but judging the acceptability of
that risk involves value judgments & knowledge of subject

More likely to misjudge as unsafe if not understood

Cannot actually measure if something is unsafe, but can
measure risk in terms of probability
70
Conclusions…

A safe activity is one with acceptable risks

Acceptability of risk is constantly changing due to changes
in social values, even though level of risk may be constant

“Safety is not an intrinsic, absolute, & measurable property
of things” (Fleming, 2000)

Biosafety is an inexact science – interactions of agents,
activities & persons performing them are constantly
changing
71
Conclusions…

New technologies pose a challenge – unanticipated
problems that lead to unanticipated new risks

Risk Groups can be used a default method to estimate
containment required when nothing specific known

IBC must approve for work with recombinant or synthetic
nucleic acid experiments
72
Conclusions…

Codification of risks along with prescribed requirements
tends to stifle search for better work procedures

List of biohazardous agents based on risk is flexible if
containment is varied according to specific factors of the
agent

As risk is assessed & translated into work practices, we
must continue to search for better control methods

Must continue to assess risk based on current info &
recommend appropriate, realistic methods of containment
73
Risk Management
What’s Happening at the U of Minnesota?








Regents Policy – IBC reviews ALL work with infectious
agents
IACUC review prior to ordering animals
Select Agent Program
BSL-3 Advisory Committee
Certification/annual recertification of BSL-3’s
On-line biosafety training
Research Safety Officers
Risk recalibration
75
Risk Recalibration
From:
To:
•
•
•
•
•
•
•
•
•
•
•
•
Tactical
Transaction-oriented
Rule-based
Hierarchical
Reactive
Silos
Strategic
Service-oriented
Problem-solving
Team-based
Anticipatory
Enterprise
Risk Recalibration
Action steps:






Identify Risk
Explore Change
Plan Change
Approve Change
Implement Change
Evaluate Change
77
Risk Recalibration
Examples:

Research Safety Self-Inspection/Audits
78
Risk Recalibration
Examples:

Smart Labs initiative
79
Risk Recalibration
80
Thank you!!
Images c/o: UMN, CSCHAH, Google Images
©2006 Regents of the University of Minnesota. All rights reserved.