Biocontainment laboratories –
Current issues and challenges
Uwe Müller-Doblies
Institute for Animal Health
Pirbright Laboratory
The 2009 Belgian Biosafety Symposium
„Design and Construction of Biocontainment Laboratories‟
3rd Dec 2009
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Biocontainment laboratories –
Current issues and challenges
11. Introduction
2. Implementation of CEN CWA 15793 Biorisk Management Standard
3. Safety Case Approach to high consequence activities
4. “One Biosafety”
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Centre of excellence for
research on infectious diseases of
farm animals
Compton Pirbright
~380 staff + research students + visiting workers
Institute for Animal Health
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IAH: Pirbright Laboratory
1. African Horse Sickness Virus
2. African Swine Fever Virus
3. Bluetongue Virus
4. Classical Swine Fever Virus
5. Foot and Mouth Disease Virus
6. Rinderpest
7. Peste de Petits Ruminants
8. Lumpy Skin Disease Virus
9. Sheep & Goat Pox Virus
10. Swine Vesicular Disease
11. Epizootic Hemorrhagic Disease of
Deer
Vacuum Drains
CL4 Isolation Units
Necropsy facility
• Air supply via socks
creating vertical
laminar flow
• Exhaust at low level
• Prefilters changeable
from below
Current Issues
• Quantifying controls
– air filters, directional
air flow, pipe work,
concrete, seals
• Safety Performance
Indicators
• Green Containment
• Sustainability: flexible
space usage
• standardisation
Systems for biorisk
management
• Forms of Contract for
construction of high
containment facilities
• condition based
maintenance
• ―One Biosafety‖
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International Veterinary Biosafety Workgroup
International Veterinary Biosafety Workgroup
Need to exchange information and share
problems/issues relating to large animal (CL3+)
biocontainment facilities
network of biosafety officers and directors of national
high containment animal facilities
First Meeting USA, 1991
Subsequent meetings in Europe, North America,
Australia, New Zealand, Singapore, Argentina.
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IVBW: Sharing Best Practice
best practice containment solutions
best practice pathogen handling protocols
validation of procedures
facility design
risk assessment and management
Risk Groups and Biosafety Levels
Facility Maintenance
Decontamination
Solutions in Developing Countries
International
Veterinary
Biosafety
Workgroup
IVBW: Outputs
Desirable features of biocontainment facilities for
agricultural and research animals Rev sci Tech Off Int
Epiz (OIE Technical Bulletin) 14 1995
Handbook for Veterinary Containment Facilities 2006
workshops every 18 months on different topics in
changing locations
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Biocontainment laboratories –
Current issues and challenges
21. Introduction
2. Implementation of CEN CWA 15793 Biorisk Management Standard
3. Safety Case Approach to high consequence activities
4. “One Biosafety”
CWA 15793 as seen by some
quality managers
… another hat
CWA 15793 as seen by some
facility directors
… looks good. We are seen to be doing the right
thing.
QuickTime™ and a decompressor
are needed to see this picture.
CWA 15793 as seen by
some biosafety officers
• … an elephant inside a boa ?
CWA 15793 as seen by a
―converted‖ biorisk officer
… a logic extension to ISO 14001 AND OHSAS 18001
QuickTime™ and a decom pr essor
are needed t o see t his pict ur e.
Standards for Veterinary Biosafety ?
• OIE guidelines
• national regulations for veterinary biosafety
• national human biosafety guidelines
• CEN Biorisk Management Standard
• IVBW Handbook for Veterinary Containment
Facilities
• EU Minimum Containment Standards for FMDV
Laboratories
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Minimum Containment Standards for Laboratories
handling FMDV
• 1985, 1993, (2009)
• EU FMD Directive 2003/85/EC
• 1. Minimum Containment Standards for FMD
Laboratories for countries free of FMDV
2. Minimum Standards of Biorisk Management
for Laboratories Undertaking Diagnostic
Investigations of Low-risk Samples During an
Outbreak of FMD
CWA15793 Risk Assessments
• Which risk
assessment
methodology for
which application?
– sensitivity
– specificity
– time & cost
– reproducibility
• HAZOP
• CHAZOP
• FMEA
• SWIFT
• Bow Tie
• LOPA
• Human Factor Analysis
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Factors determining the fumigation strategy
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Toxicity
Penetration into porous materials(e.g. paper/cloth)
Work Place Exposure Limits
4log or 6 log
with or without soiling
BIs or target organisms
validation requirements
fumigant dispersion properties
Material Compatibility
Fumigant Specific Issues
Pressure differentials
fumigant concentrations
ventilation in adjacent spaces
means of testing sealability beforefumigation
Overpressure protection
Sealability
no hot and cold spots
stable relative humidity
Temperature >20 degree C
air mixing in the space
Environmental Conditioning
Frequency
emergency or planned
Operational Requirements
Fumigation Requirements
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Biocontainment laboratories –
Current issues and challenges
31. Introduction
2. Implementation of CEN CWA 15793 Biorisk Management Standard
3. Safety Case Approach to high consequence activities
4. “One Biosafety”
Piper Alpha
• An explosion and resulting fire destroyed it
on July 6, 1988, killing 167 men.
• “Piper Alpha must never happen again”
• ... Safety Case Approach23
The Cullen Report—Offshore Safety
Case
• New improved Safety Regime
• Safety Case Process 1993
• Goal Setting Approach
• 75% reduction in incidents off-
shore
24http://www.hse.gov.uk/offshore/safetycases.htm
Piper Alpha and FMDV
• 167 deaths in 22 minutes
• >3.4 billion GBP
• Safety Case regime in
1993
• 2007 outbreak – 200 m GBP
• 2001 outbreak – 8 billion GBP
• No proven transmission chain
• HSE: FMDV facilities –high
hazard industries
• Single Regulatory Framework
• IEC61508 philosophy
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Safety and Risk Data
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Setting a safety target for a facility handling
high consequence animal pathogens
• Balance between cost of the facility and cost of a
consequential release
• Cost benefit of the facility:
• FMD outbreaks through accidental introduction occur at
a rate of 30-50 years without an FMD facility,
• Benefit from operating FMD facilities: reduce the impact
through rapid diagnostics, disease intelligence and pre-
import testing.
• target of 1 consequential release in 500 years puts the
laboratory release into the noise of the ―natural‖ signal
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Integrated Protection Layers
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Layer of Protection Analysis
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Target Risk Concept
Lab SOPs
disinfection
lab SOP
SOP
MBSC
Barrier Process
PPE
1°HEPA
off-site Process
Barrier Shower
2° HEPAInward airflow
heat inactivation
off-site quarantine
0 200 400 600 800
aerosol
effluent
fomites
people
10-Dec-09IAH Target Risk Level fora consequential release
years -1
IEC 61508 Functional safety of
electrical/electronic/programmable electronic safety-
related systems
• performance target setting
• layer of protection analysis
• assessment of safety instrumentation
systems
• ―safety case‖ approach
• safety life cycle management
• Safety Integrity Levels
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Bowtie Risk Management Diagram
Thesis Enterprise Risk Management Tool
courtesy ABS Consulting
Environmental Protection
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Operator Protection
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Formalised Bowtie
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Use of Thesis SoftwareCourtesy of ABS Consultingfile
Setting a safety target for a facility
handling high risk animal pathogens
• Balance between cost of the facility and cost of a
consequential release
• Cost benefit of the facility:
• FMD outbreaks through accidental introduction
occur at a rate of 30-50 years, operating facilities
limit the damage through early response and
preimport testing
• target of 1 in 500 years puts the laboratory
release into the noise of the ―natural‖ signal
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Controls
Passive Controls Active Controls Management Controls
air tight barrier
construction
directional inward air
flow
latched alarms on loss of
pressure differential
Double Exhaust HEPA
filtration, supply HEPA
protection
Air changes HEPA filter validation
Supply Open door velocity air
flow
Control system separate
from alarm system
Multiple compartment
access lobbies
Barrier shower & change
protocols
Process validation
Box in a box principle Fully encapsulated suits
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SEWAGE COLLECTION
SEWAGE TREATMENT
HEPAFILTERAIRSUPPLY
HEPAFILTERAIREXHAUST
-200Pa
-100Pa
SHWR-250Pa
-300Pa
-300Pa
-250Pa
Level 5
Level 4
Level 3
Level 2
Level 1
Plant room(clean)
Airdistributionand treatment
Work floor
BIOCONTAINMENT AT AAHL
What is achievable and what is
sustainable?
• Are our engineering controls sustainable in a marginally
funded lab with poor access to electricity, fresh water,
service engineers?
• What biosafety measures are sustainable and
acceptable under local conditions?
• How can we move biological agents both ways without
common principles of containment barriers?
• Can we deny access to reference agents on the basis of
insufficient evidence of ―suitable‖ biocontainment at the
receiving laboratory?
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Safety Integrity Levels
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PFD (Probability of Failure on Demand) and RRF (Risk Reduction Factor)
probability of dangerous failures per hour (PFHd)
SIL PFD RRF PFHd
1 0.1-0.01 10-100 ≥10-6 to < 10-5
2 0.01-0.001 100-1000 ≥10-7 to < 10-6
3 0.001-0.0001 1000-10,000 ≥10-8 to < 10-7
4 0.0001-0.00001 10,000-100,000
Animal versus human biosafety in CL3/4
human biosafety
• operator is at risk
• most in vivo work is done
in animal models that fit
into isolators
– with exceptions
animal biosafety
• operator is not at risk
• cattle and other livestock
species do not fit into
isolators
-isolation rooms
• most in vivo work is done
in the target species
• quarantine is used as a
tertiary control
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Cost Benefit
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• Consider a chemical plant with a process that if it were to explode could lead to:
• * 20 fatalities• * 40 permanently injured• * 100 seriously injured• * 200 slightly injured
• The rate of this explosion happening has been analysed to be about 1 x 10-5 per year, which is 1 in 100,000 per year. The plant has an estimated lifetime of 25 years.
• How much could the company reasonably spend to eliminate (reduce to zero) the risk from the explosion?
• If the risk of explosion were to be eliminated the benefits can be assessed to be:• Fatalities: 20 x 1,336,800 x 1 x 10-5 x 25 yrs =6684• Permanent injuries: 40 x 207,200 x 1 x 10-5 x 25 yrs = 2072• Serious injuries: 100 x 20,500 x 1 x 10-5 x 25 yrs = 512• Slight Injuries: 200 x 300 x 1 x 10-5 x 25 yrs = 15• Total benefits = £9,283
Layers of Protection Vacuum vs
Gravity
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Showers in a risk model
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Biocontainment laboratories –
Current issues and challenges
41. Introduction
2. Implementation of CEN CWA 15793 Biorisk Management Standard
3. Safety Case Approach to high consequence activities
4. “One Biosafety”
―One Biosafety‖
• More emphasis on zoonotic diseases
• sustainable biocontainment solutions for
countries and facilities without
infrastructure to sustain hi-tech/hi-
maintenance facilities and equipment.
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Top Events
Operator exposure
• tight primary containment
• isolator
• overpressure suit
Environmental Release
• primary containment
• secondary containment
• isolation room within
secondary containment
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One Biosafety
• activity based containment solutions
• reduce the risk at source - diagnostics on
inactivated samples
• an un-maintainable or unmaintained
engineering control can be worse than a
well managed procedure
• Which standards should developing
countries follow?
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Hazard Groups for Viruses
vhg 4FMDV
Rinderpest
ASFV
ENDV, SVDV HPAI, RabiesNipah, Ebola,
Marburg
vhg 3BTV,
(BVDV)VSV, NSDV
RVFV,
Akabane, EEE,
WEE, VEE, JE,
WNV
Hendra
vhg 2RHDV, BVDV AI, NDV BSE, Q Fever OHFV, (TBE),
vhg 1
HIV, HepEVCCHFV, Lassa,
Junin,
Machupo,KFDV
hhg 1 hhg 2 hhg 3 hhg 4
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En
vir
on
men
tal/
vete
rin
ary
h
azard
gro
up
(En
vir
on
me
nta
l P
rote
cti
on
)
Human hazard group (operator protection)
Environmental and Human Health Hazard Groups
Thank you!
• Questions ?
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