Prion Investigational Studies
The objective of prion clearance studies
Prions (PrPres, PrPsc, PrPtse) are non-conventional transmissible agents (NCTAs) that have become of major concern to pharmaceutical companies processing bovine or human material since the emergence of new variant Creutzfeld-Jacob disease (vCJD).
Prion investigation studies may be required by the regulatory agencies in order to:
- demonstrate that a cleaning procedure between each production batch is able to destroy prion proteins in the manufacturing equipment.
- investigate the removal of prions during the purification of biological products (i.e. blood fractionation products, bovine extracts, etc.)
The overall level of prion reduction can be determined by deliberately adding (“spiking”) significant amounts of prion to the crude material (or to a model of the manufacturing vessels) and by demonstrating its removal or inactivation during the subsequent steps. Our highly trained staff perform these spiking experiments on scaled-down processing steps in our biosafety level 3 security laboratory.
Several model strains, spike preparations and titration methods are available. Please ask us to help you choose the most relevant parameters for your prion investigation study. We will advise you on the basis of the latest technical and regulatory constraints.
Choice of the model strain
Model strain of scrapie:
- 263K (adapted to hamsters)
- C506N3 (adapted to mice)
Model strain of BSE (bovine spongiform encephalopathy):
- 6PB1 (adapted to mice)
Choice of the spike preparation
- Crude brain homogenate after Proteinase K treatment
- Clarified brain homogenate after Proteinase K treatment
- Sonicated and clarified brain homogenate after Proteinase K treatment
- Scrapie-associated fibrils (SAF)
- Soluble, non-aggregated PrPres
Choice of the titration method
In vivo titration:
- in hamsters for 10 months
- in mice for 18 months
In vitro titration:
- western blot (a highly specific and sensitive proprietary method)
Further information is willingly disclosed on request.