Dr Lourens Heres

1. Framework for a microbiologicalriskassessmenttoassessvirussafetyofbloodproductsforfeed DrLourensHeres

2. Question • How can virus safety of blood plasma be quantified? • What are the critical processes to assure virus safety and which steps are insufficiently quantified?

3. Manyexamples of risk assessments • Milkpowderand Foot-and-Mouth-Disease • No reports of diseaseoutbreaks • pasteurisations • BSE: MBM, Fat, gelatine, waste water, etc… • Different steps – exclusion SRM critical • Severe heat inactivation • Risk of introductionanimaldiseases

4. Risk assessment elements • Identification and characterization of the hazard • Virus: PEDV / all porcine viruses • Describing the pathways • Exposure assessment • Processes (dilution, inactivation, etc.) • consumption • Dose-respons assessment

5. Pig viruses posing a risk for porcine products in feed • Endemicvirusses • PRRSV • PCV2 • PPV • Influenza • Hepatitis E • PEDV • Parvo-virus • … • Epidemic Virusses – OIE listed • Classical Swine Fever (CSF) • Foot and Mouth Disease (FMD) • African Swine Fever • Swine Vesicular Disease (SVD) • Aujesky‘s disease

6. PEDV • Coronavirusses • Non-stable virus • Easily inactivated • Virus in blood through leakage through enterocites in intestine, or faecal contamination during blood collection • Infectivity in blood not (yet) shown • Infectivity of spay dried plasma not shown, and due to spray drying and storage unlikely.

7. Collection of blood Blood from clinically healthy animals (virus dilution) Anti-coagulants centrifugation Possibilities for chemical / physical treatment filtration Spray - drying Heated to 80°C (thermal inactivation) standardisation Possibilities for chemical / physical treatment storage Inactivation during storage

8. Risk assessment: critical • Virus control along the chain • killed animal: no more multiplication • Log-reduction steps • One or some infected animals in batch with multiple animals (pooling effect) • Heat and chemical treatments • Drying (heat treatment) • Storage • Other reduction with: splitting plasma and cells,…. • Exposure • Several grams of the product are consumed during different days

9. Single hit

10. Infectivity – Infectious Dose Max infectivity level infectedanimals InfectiousDose in susceptibleanimals (allanimalsinfectedwith:) PCV2 ~104-5TCID50 ~103,5 TCID50 FMDV (intranasal, depending on strain) ID50 PRRSV ~105,5 TCID50 Virus load/ml blood: • PCV2 106 DNA • FMDV 105,5 TCID50 • PRRSV 103-4TCID50

11. Where could a quantitative risk assessment help advantages challenges Unknown parameters Uncertainty Variability Overestimation of risk • Generic approach • Understanding the principles • Structured approach

12. Limitations for virus QMRA • The outcome will never be a zero risk. • Data from publications • PCR positive or culture infectious dose or animal infectious dose • Power of the experiment: • numbers tested: plates, wells, or animals inoculated • Amount of virus added in inactivation tests • Detection limit of diagnostic tests  uncertainty • Lab-condition versus Field-conditions • Spray driers • Number of animals

13. Safe: to overcome the non-zero risk outcomes • Risk assessment on animal diseases shows that under the current control measures • The probility of introduction • of CSF in The Netherlands 1 per 16 years • of FMDV in the US 1 per 240 years • Of FMDV in Spain 1 per 40 years

14. Risk assessments • University of Minnesota • Funded by National Pork Board • Risk assessment ingredients of porcine origin • Started in April • APC • Many studies, see summary next presentation J. Polo • Sonac • With NIZO and Wageningen-UR • Validation of virus safety • Different processes • Different model viruses

15. Thankyouforyour attention