OS18 - Open Session 2018 Borgo Egnazia (Puglia), Italy 29 - 31 /10/2018 EuFMD Sessions\Open Session\Archive-2018\Open 2018 - Italy\6. Online & Streaming\PPTs

1. OS18
Biosafety barriers
Kirsten Tjørnehøj, biosafety officer
National Veterinary Institute,
Technical University of Denmark,
Lindholm

2. OS18
Eufmd SCBRM:
Eufmd Special Committee for Biorisk Management
Biorisk officers (BRO/biorisk professionals/duty
holders) from FMD containment facilities in the
European area
Countries: UK, The Netherlands, Switzerland, Spain,
Sweden, Italy, Israel, Germany, Denmark
Background: Agronomists, Microbiologists,
Engineers, Veterinarians
Most have a general BRO role for their institutes, also
covering other agents – involvement in research
varies

3. OS18
Background for the FMD facility
biosafety level:
• FMDV one of the most contagious animal pathogens
• Countries can be free, free with vaccination, free with
infected zones, endemic
• Free countries:
• Outbreaks have high consequences
• Work with FMDV is highly regulated and controlled
• Containment for FMDV:
• Environment highest protection: level 4
• Workers much lower: most countries level 2

4. OS18
FMD biorisk management – legal basis:
FAO Eufmd:
Minimum Biorisk Management Standards For
Laboratories Working With Foot-and-mouth Disease
Virus (Eufmd MS)
• Version GS40/4.2bis as adopted by the 40TH GENERAL SESSION OF THE
EUFMDCOMMISSION, 22-24 APRIL 2013, ROME, ITALY
• EU: implemented through ANNEX XII to COUNCIL
DIRECTIVE 2003/85/EC:
• ”….. must operate at least in accordance with Section I
of the ‘Minimum biorisk management standards for
laboratories working with foot-and- mouth disease virus
in vitro and in vivo’…. 2013….”

5. OS18
Eufmd MS – quick summary:
• Defines the roles, duties and responsibilities of the
management and the biorisk officers
• Institutes biorisk, risk assessment (RA) and hazard
identification
• Has 70 specific points covering management,
personnel, training, biosecurity, design, handling of
live FMDV, air, waste, effluent and materials,
biological materials across barriers and shipment,
commissioning and decommissioning,
• The Eufmd MS are regularly reviewed by the Eufmd
SCBRM

6. OS18
How a FMD facility may look to the
people working in it:

7. OS18
Fence
FMD
facility
Rodent and insect
protection
Reservoirs for treated
waste water
Zone free from
susceptible species
Fumigation
chamber
Dunktank
Public sewer
HEPA-filters and
exhaust air
Movement
sensors
and alarms
Liquid waste kill
plant
24/7 reception/guard,
storage
Parking lot
Solid waste incinerator, digester,
renderer
Autoclave
Changing rooms
with showers
In the Biorisk professionals’ eyes:

8. OS18
A lot of steel and electronics:

9. OS18
New developments – new biorisk
questions:
• Genetically engineered viruses are being developed
for use as vaccines for FMDV
• Purpose:
• Reduce risk during the production
• Increase vaccine availability by cost reduction
• Making better vaccines with the ultimate purpose to
eliminate FMDV (DIVA, thermostable, etc.)
• Question: if, how and when can we loosen the
production facility containment requirements ?

10. OS18
If FMD containment level at production
site is lowered:
• Higher risk for live virus to escape the facility with
air, water, waste, materials, people –
• More exposure to environment, microbes, animals,
viruses –
• What could/would happen ?

11. OS18
SCBRM initial points for Risk Assessment
(RA):
• RA is a tool to be used in the decision process to possibly
change the Eufmd MS
• Actual decision to lower containment measures would be
taken by the involved country and EU (for EU countries)
• And should be based on the actual vaccine candidate
• GMP rules and laws/directives for GMO may also provide
some containment
• SCBRM should be part of RA – others need to be equally/more
involved: scientific SC, regulators, independent pharmaceutical
experts, EU

12. OS18
SCBRM input to Risk Assessment (RA):
• RA is based on:
• Current knowledge
• Imagination, “what if” scenarios
• Experimental data (possibly limited scope/number of animals)
• Modelling ?
• RA will be different for individual vaccines/vaccine
platforms – initial key questions:
• Is it an FMD virus at all?
• Is it viable during production ?
• More ?

13. OS18
SCBRM thoughts for biorisk assessment
points:
• Factors that ease the risk assessment:
• Modified FMDV used as an inactivated vaccine – risk is restricted to the
production phase
• Expression of FMDV proteins by non-FMD viruses (e.g. recombinant
adenovirus)
• Risks during production of inactivated FMD virus vaccines:
• Recombine with closely related viruses in the culture system ? – e.g. bovine
rhinoviruses ?
→ risk is mitigated by strict exclusion of contaminating viruses (GMP) and
closed systems
• Mutate to more aggressive form during culturing ?
→ limit the number of virus passages during production, use well-defined
master seeds
• Escape to environment due to lowered biosafety measures

14. OS18
SCBRM thoughts for biorisk assessment
points:
• Production of inactivated FMD virus vaccines:
• If infectious modified FMD virus escapes the production containment:
• Could it establish itself as a subclinical, low transfer FMD virus in the
susceptible populations ?
• Would that be a problem ? Is it an FMD outbreak ?
• Modified-live (attenuated) FMD virus vaccines:
• Overlap with GMO laws/directives – release of GMO into environment
• Stability depends on mechanism of attenuation (deletions, codon usage, …)
• Risk of recombination and/or reversion – likelihood ? consequences ?

15. OS18
Conclusion:
• The Eufmd Minimum Standards are risk-based
• Thus, IF the risk has truly changed, there is
potential to change the containment rules
• We need a framework and a process to consider
both risk and appropriate containment
- RA should include stakeholders from science,
biorisk managers, pharmaceutical industry,
regulators, EU, more stakeholders ?