MANAGING BIOLOGICAL RISK
CONCERNS IN THE VETERINARY
LABORATORY AND ANIMAL FACILITIES
18th WAVLD, 9th June 2017, Sorrento, Italy OIE Seminar: Implementing new biorisk standards
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Biosafe
Uwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSE [email protected] +44 7920 284 023
Thanks
Slide 2
EBSA20 – 26-28 Apr 2017
IVBW18 12-15 June 2017
2030 Biosafety Themes
People
• Competencies
• Accountability
• Biorisk Management Culture
• Roles and Responsibilities
• Occupational Health
• High Reliability Organisations
Processes
• Risk Management
• Learning /Knowledge sharing
• Setting acceptable residual risk levels
• Measure Safety Performance
• Taking biological risk management from thelab to the field
Facilities
• Fit for purpose
• Attractive to work in
• Low carbon foot print
• Affordable
• Simplicity
• Reliability
• Certification to relevant performance criteria
Science
• Why
• Data
• Capability
• Capacity
• Accountability
4
Structure
Dr. Uwe Mueller-DobliesUwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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• One Health Goals of for biological risk management
• Defining the target agents and activities
• Assessing the risk paths
• Defining the Controls
• Defining the management aspects of maintaining the controls
Moving towards risk based performance standards
Uwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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Defining the Biohazard
Dr. Uwe Mueller-DobliesUwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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• Agents
• Activities
• Scale
1
Host
Protocols
Scale
Pathogen
Large Animals
Horses, Cattle
Pigs, Sheep
Camels
Wild ungulates
Ostriches
In vitro - In vivo
Diagnostics – Research
Molecular
Cellular
Analytical - preparative
Immunology
Pathogenesis
Epidemiology
Vaccine/drug testing
GLP/GMP compliance
VirusesFoot and Mouth Disease
Avian Influenza
Blue Tongue Disease
Rinderpest
Hog Cholera
African Horse Sickness
African Swine Fever
Rift Valley Fever
BacteriaSalmonella
Bacillus anthracis
Coxiella burnetti
ParasitesTheileria parva
Cryptosporidium spp.
Eimeria spp.
Echinococcus multilocularis
Fungi Dermatophilus congolensis
Encephalitozoon.
Unconventional AgentsCJD, TSE
Small Animals
Rabbits
Poultry
Rodents
Ticks
Mosquitoes
Frogs
Bats
constant - sporadic
small vs large
short term vs long term
Biohazard Definition
Understanding risks from virus / a situation – what to consider
Pathogen inherent hazards
• Viral v’s Bacterial v’s parasitic
• Zoonotic or non-zoonotic (control risk to humans and / or animals)
• host range (people, animals (which?))
• Infectious dose (1 - 100,000 particles)
• Infection routes (oral, respiratory, contact, vector)
• Vector control (spread by vector)
• Latent infection (animal infected, not symptomatic)
• Shedding (whilst / after animal has ‘recovered’)
• Pathogen inactivation profiles (chemical, physical)
• Pathogen tenacity (survival outside of host)
• Exotic (not in UK, eg FMD) or Endemic (in UK, E. coli)
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Prevalence and Economics
is driving Risk Groups
RG-2
CL-2/BSL-
2
RG-3
CL-3/BSL-3
RG-4
CL-4/BSL-
3Ag/4
EBOLA exotic x
EBOLA epizootic x
Rinderpest
endemic
x
Rinderpest exotic vitro Vivo
FMDV endemic (x)
FMDV epizootic X
FMDV exotic X
Understanding risks from virus / a situation
Protocol inherent risks
• Aerosolisation (easier for pathogen to escape / contaminate larger area)
• Primary containment constraints (can’t put a cow in a safety cabinet)
• Fomites (an item which can be contaminated with virus)
• Volume & Concentration (what is the potential challenge from a loss of primary containment)
• Pathogen inactivation steps (ensure they work)
• Changing normal safe operating conditions (pressures, humidity etc. Pre-assessed and agreed)
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Advancing Risk Assessment
Approaches
Encourages solutions tailored to local settings
A framework for conducting targeted risk assessments,
setting out why and where controls are needed.
Long term better risk management and lower total cost of
ownership
High requirements for risk assessment resource to enable
and justify different approaches for local controls
Risk Group (A)BSL
Agent & Activity Based
RA
Target Risk Level
Matching Containment
Controls
Hazard Group ActivityContainment
Level
A
Compliance
C
High Hazard Industries
B
EU GM Assessments
con
pro
1. Human Safety
Protect staff and the general public from infectious
biological agents
2. Environment, Animals & Plants
Protect the Environment from the release of biological
agents
3. Security of Valuable Biological Materials
Protect the biological materials from misappropriation
4. Quality of Science
Protect the integrity of scientific work from cross contamination
5. Stakeholder Confidence in the Organisation/professional
performance
Being perceived as meeting best practice
One Health Biorisk Management Goals
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2
Think in processes!
Depending on the
facility size the multiple
processes can be
bundled for the purpose
of documentation. It is
important to keep these
relevant to the people
with roles and
responsibilities.
These interfaces
between teams can
make useful interfaces
between management
elements.
Scope
Definition
Training and
Competency
DOC
Operational
Arrangements
(SOP, Manual)
Risk & Impact
Assessment
Roles &
Responsibilities
Process
Maintenance &
Monitoring
3
Sample Flow from Receipt to
Disposal
Sample Receipt and Storage
Sample Classification and Inventory
Sample flow in the laboratory
handling of infectious samples (general)
Centrifugation
Homogenisation
Disposal
SaR
SaC
I
SaF
SaH
SaC
e
Sa
M
SaD
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Risk Path Focussed Elements
Fomite-borne release/exposure
Water-borne release/exposure
Air-borne release/exposure
Solid Waste-borne release/exposure
Theft Misappropriation of biological materials
Release on People
Release in biological materials e.g. as cross contamination
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Biorisk Control Elements
Waste Management
Cleaning and Disinfection
Primary Containment Devices
Facility Design and Physical Requirements
Personal Protective Equipment
Gaseous decontamination
Security
WM
C&D
PC
FD
PPE
GD
Se
Process Mapping Biorisk Element
Examples
BiolMaterials
Receipt
Classification
Storage
Activities
Solid Waste Mgmt
Laboratory Procedures
Waste Categories
Barrier Inactivation
off site disposal
Fomite Mgmt
Laboratory Procedures
Equipment specification
Equipment Decon
Material Flows
People
Training and Competency
Primary Containment
Spills
PPE
Security
Physical Security of sensitive
installations
Physical Site Security
Security Procedures & Management
Staff Security incl vetting
Primary Containment
Equipment
PPE
Procedures
Contingency Measures
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Structured Risk Assessment and Risk Management –
The Biorisk Bowtie
Dr. Uwe Mueller-DobliesUwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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4
Assess the Risks
Environmental Release
Cross Contaminati
on
Operator Exposure
Theft
Likelihood
Severity
Detectability
Acceptability of the Residual Risk
Define the Loss of Control
Events, e.g.
Loss of primary containment
Release into the environment
Cross contamination of samples
Exposure of operators
Breach in Chain of Custody
Develop the enabling Risk
Paths
Air
Water
People
Waste
Fomites
Animals
Security –personnel, data, facilities
1
•Biological Hazard
•F(agent, activity, scale, frequency)
2
•Consequence
•Impact (health, economic, societal…)
3
•Critical Event = Loss of control
•environmental release)
Risk Assessment Process
• Biological Hazard
• F(agent, activity, scale, frequency)
RC• Risk Controls (Protection Layers)
• Critical Event = Loss of control
• environmental release)
Mi• Mitigations/Recovery Measures
• Consequence
• Impact (health, economic, societal…)
Risk Assessment Process
1• Vaccine Storage
2
• Wild type material Storage and One Step inactivation
3• In vitro handling, small scale culture
4
• In vivo experiments and large scale culture)
Activity Types
Risk Management
Can everybody in your facility explain why (s)he has to
apply which control and where?
Are our risk assessments fit for purpose?
Are they available to everybody?
Are they kept upto date?
Do they help us to optimize risk?
Bowtie Risk Assessment
Methodology
Source………………………………critical event……………………….receiver
Environmental
Risk Model
Critical Event: Loss of
environmental
containment
Risk Path Category
Risk Path defined by
biohazard, activity
and escalation path
Definition of
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Risk Control Systems Air
1. Primary containment devices
2. HEPA filtration on extract
3. 2nd HEPA on extract and HEPA on supply
4. Deep seal traps
5. Soil vent filters
6. Airlocks
7. Inward directional airflow (pressure cascades)
8. Room Sealability for gaseous decontamination
9. Ability to isolate each space on supply and exhaust
10. Air pre-filtration in primary containment spaces
11. Air changes in laboratories
12. Laminar airflow
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Risk Control Systems Air
1. Primary containment devices
2. HEPA filtration on extract
3. 2nd HEPA on extract and HEPA on supply
4. Deep seal traps
5. Soil vent filters
6. Airlocks
7. Inward directional airflow (pressure cascades)
8. Room Sealability for gaseous decontamination
9. Ability to isolate each space on supply and exhaust
10. Air pre-filtration in primary containment spaces
11. Air changes in laboratories
12. Laminar airflow
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Risk Control Systems – Fomites &
Solid Waste
1. Cleaning
2. Disinfection
3. Gaseous
decontaminati
on
4. Steam
Autoclave
5. Dunk Tank
6. On/off- site
incineration
7. (natural
inactivation)During operation fomites can be any inanimate object that is removed from the containment, including waste. During shut-down and with respect to operator exposure the ability to decontaminate fabric, fixtures and fittings is equally important
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Passive Controls Dynamic Controls Management Controls
air tight barrier
construction
directional inward air
flow
Alarm Response
Protocol
Double Exhaust HEPA
filtration, supply HEPA
protection
Air changes
Open door velocity air
flow
HEPA filter validation
Compression seal door Inflatable seal door Protective Clothing
Multiple compartment
access lobbies
Barrier shower &
change protocols
Process validation
Box in a box principle Fully encapsulated
suits ?
Procedures
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•risk path consequence
•risk path likelihood
•detectability of failure
Controls – Protection Layers
Conclusions
Application of the new process must focus on meeting the needs of all stakeholder, including those who receive downstream materials from a facility
To enable trust between countries, it is necessary to better characterise the performance of alternative and conventional controls
For suitable biorisk management setups in any resource settings good training in risk assessment is essential
33
Relative Residual Target Risk
Different residual target risks apply in different geographic settings
Uwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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Relative Risk Concept
disease prevalence / frequency of disease incursion
imp
ac
t /
be
ne
fit
/ c
ost
Societal
risk tolerance to disease/
acceptable residual risk
Local benefit from
laboratory
capacityLikelihood of
disease originating
from laboratory
Required biorisk mitigation level
for the same pathogen/activity
2
•Volume off set -unmonitored
3
•Volume off-set with flow indicator
•Pressure control with Manometer
•Supply/exhaust interlock
4
•Pressure control with central alarm
•Wrap around systems to ensure fail safe
•Multiple exhaust air handlers for redundancy
Directional Airflow
Effect is dependent on closed doors
Protective open door velocities
Cost and Complexity
Au
dit t
rail
& h
igh
er
resi
lien
ce
Reduce
Isolate Engineering
controls
Administrative Controls
Personal Protective Equipment
Discipline
Hierarchy of Controls in the
local context…
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• Cost of control
• Safety benefit• Operating requirements –
Electricity, water, ….
• Service requirements
• Parts and maintenance
• Good procedures
• locally maintainable
• Lower level controls
• Training investment into Good
microbiol. practice
Eliminate
Conclusion:
Different local settings
will have different
solutions.
It is important that the
Safety systems
implemented locally
have full ownership by
operators
They have to be able
to maintain the
systems and ensure
the safety they require
or perceive to require
is achieved
Concept
Biosafety requirements determined
by lab function-
Where is the right cost – benefit
balance for biological risk
management
Uwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
Epi
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39
Biosafety and laboratory biosecurity
has made great advancements but
is entirely focussed on laboratories
>99% transmission events occur outside microbiology laboratories without active biological risk management programs
Are we getting the balance right between biosafety, infection control, industrial hygiene?
How can we better measure
Good biological risk management across society is the least expensive option for preventing disease, food security and increasing population densities
Biological risk management needs to be applied across
Animal feed
Animal breeding
animal transport
Health Care
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Setting in which biological
samples are handled Primary care medical/veterinary field staff
Primary care surgery
Routine laboratory handling “non-infectious” samples
Laboratory handling samples suspected to contain specific infectious diseases for direct detection ( no culture)
Post Mortems on routine carcasses
______________________________
Laboratory handling specific infectious disease agents including culture and other processes involving high concentrations
41
Setting A priori likelihood
Multiple animals with clinical signs high
Suspected disease based on one
single animal with clinical signs in an
endemic setting
Surveillance samples from healthy
animals in a zone with disease
prevalence
Exclusion of the disease suspicion in a
free zone
Surveillance samples in a free zone low
Probability of pathogen in the
sample material42
Activity
Relative
hazard
(indicative)
Nucleic acid extraction from filter paper
samples: no aerosol, agent inactivated in
membrane
low
Handling of liquid samples, e.g. serological
assays
In vitro culture of the organism
Production of inactivated vaccines from
field strains in closed systems
Post mortems, on infected animals/people
In vivo work with infected animals high
Activity inherent exposure risk of
laboratory and personnel43
Risk Based Minimum Standards
Tier Activities Goal Activities
Tier A
(endemic)
Primary care
front line
“laboratory” in
endemic setting
basic precautions, to
reduce the likelihood of
primary care
contributing to enzootic
burden and spread
Sample Collection &
Clinical Care of herds
Tier B
(endemic)
Specific
diagnosis (
laboratory
serving region)
Perform primary
diagnosis on FMDV in
endemic setting; ability
to ship materials
internationally
Laboratory diagnosis
using non replicating
assays and or
inactivated materials
Tier C
(epidemic)
Tier C for
endemic strains
no infected
animals (
Perform primary
diagnosis in acute
epizootic setting, only
current strains)
Tier C Outbreak
Contingency
Laboratories; no virus
propagation; no
infected animals
Tier D
(Exotic)
R&D exotic
strains
Safe handling of exitic Tier D Reference
Laboratories and
Research Facilities on
exotic strains
44
Conclusion
Moving organisations to excellence in biological risk
management is a journey.
Compliance without risk ownership and risk
management provides a false sense of security
Managing high consequence pathogens requires
complex facilities, which require a mature risk
management culture
High Reliability Organisations thrive on excellence in
risk management to stay compliant, safe, and
sustainable
Thank You
Thank You to the
organisers and to OIE for
Sponsoring this seminar and
my attendance.
Thanks to MSD for releasing
me to come to Italy
Note: This presentation is not
uwe.ulex.mueller-
Thank You to my colleagues for
sharing their insights
46
Disclaimer
No information in this
presentation is representing
Merck MSD. All s
Thank You to my colleagues for
sharing their insights
47
Contact
OIE
International Biosafety Standard for Veterinary Facilities
Dr. Uwe Mueller-DobliesUwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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OIE
“A world that is safe and secure from the accidental or deliberate release of animal pathogens, including zoonoses.”
Office International des Epizooties
World Organisation for Animal Health • OIE sets international standards for animal health – adopted by
the World Assembly of Delegates and applicable in all 180
Member Countries
• capacity building allowing compliance with OIE standards and
strengthening national veterinary services
• FAO/OIE/WHO work together (one health approach) for a
comprehensive Biological Risk Management framework on
human and animal health
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Chapter 1.1.3.:
Biosafety and Biosecurity: Standard for
Managing Biological Risk in the Veterinary
Laboratory and Animal Facilities.
A new chapter in the Terrestrial Manual was adopted as the current standard
for member countries during the May 2015 General Session of the OIE:
http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/1.01.3_BIOSAFETY_BIOSECURI
TY.pdf
Replacing Chapter 1.1.3., “Biosafety and biosecurity in the
veterinary diagnostic microbiology laboratory and animal
facilities”.
OIE Biosafety and Biosecurity Resources
- OIE Standards -51
CEN
12128:1998
F D UK RU USA AU
PCL1 L1 S1 CL-1 4 BSL1 ABSL1 PC1
PCL2 P2 L2 S2 CL-2 3 BSL2 ABSL2 PC2
PCL3 P3 L3 S3 CL-3 2 BSL3 ABSL3 PC3
SAPO-4 BSL3Ag
ABSL3Ag
PCL4 P4 L4 S4 CL-4 1 BSL4 ABSL4, PC4
Departure from “traditional
laboratory safety categories
5
2
“Retired Chapter”
“a one fit all” approach of prescriptive requirements
“western” perspective assuming an abundance of energy, water, consumables, service and maintenance support
Containment requirements that are unrealistic in many parts of the world
No alternatives for low resource settings that are endorsed at international level
Without the required resources safety systems can increase rather than reduce the risk.
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What is the hazard of
the materials and
activities?
Laboratory Biorisk Analysis
Biorisk Analysis is the process comprised of biohazard identification, biorisk assessment, biorisk management and biorisk communication.
Biohazard Identification
Biorisk Assessment
Biorisk Management
Biorisk Communication
How likely and how severe
would be the consequence?
How can these risks be
reduced to an
acceptable level?
Is the harm benefit analysis and residual risk acceptable to
workers, society and international stakeholders?
Verification/continual improvement
54
“Challenges and opportunities for implementing the
new OIE biosafety standard in low resource
settings” A much stronger emphasis on risk
assessment will require the technical resource to complete and to define controls for local or regional implementation
Defining the local biosafety priorities
Defining alternative controls in theabsence of data
Setting acceptable targets for the residual risk from work with biological agents
Developing “template biorisk management systems” for typicalfunctional laboratory groups to providethe technical guidance that is neededfor alternative safety systems
55
Why more regional and
specialist guidance/standards?
Dr. Uwe Mueller-DobliesUwe Mueller-DobliesDr med vet Diplomate ECVPH MRCVSVeterinary Public Health ConsultantE [email protected] M +44 7920 284 023Skype oxpecker
www.epibiosafe.com
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USDA ARS 4th International Biosafety & Biocontainment
Symposium, Baltimore, 6-9 Feb 2017
What is the difference between
Defined Benefit and Defined
Contribution pension schemes?
• The pension fund carries the risk
• Output performanceDB
• The member carries the risk
• Input SpecificationDC
Who needs it
Clarity for duty holders – what do they
have to achieve
Regulators – enable the best balance of
laboratory safety and societal benefit
from laboratories
Building and maintaining trust between
laboratories exchanging high
consequence pathogens and staff
A risk based approach driven by
relative risk
Sustainable
Affordable
Functional
Effective
Realistic
More emphasis has to
be placed on making
best use of locally
available solutions that
are focussed on the
critical safety
requirements, are
compatible with local
culture and society.
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Locally Sustainable
Management of Biological Risks
Framework for managing
biological risk at national and
Institutional Level
Agent and
Activity
Controls to match the
Risk
Local Needs and Constraints
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