Inactivation of the bovine-spongiform-encephalopathy (BSE) agent by the acid and alkaline processes used in the manufacture of bone gelatine

A validation study was carried out to determine the capacity of the traditional acid and alkaline processes used in the manufacture of bovine bone gelatine to remove and/or inactivate the transmissible agent that causes BSE (bovine spongiform encephalopathy). Using an accurately scaled down laboratory process that precisely mimicked the minimum conditions of the industrial processes, gelatine (gelatin) was manufactured from industrial starting material that had been spiked with mouse brain infected with the 301V strain of mouse-passaged BSE agent. Clearance factors were determined by titrating the infectivity levels of the infected mouse brain tissue, the gelatine extracts, and the final sterilized gelatine solution. The infectivity level of the spiked starting material was 10^8.4 mouse intracerebral ID50/kg (ID50 is the dose at which half of the challenged animals were infected). Clearance factors of 10^2.6 and 10^3.7 ID50 were demonstrated for the first stages of the acid and alkaline processes respectively during which the bones are converted to crude gelatine. It was further demonstrated that the complete acid and alkaline processes both reduced infectivity to undetectable levels, giving clearance factors of >=10^4.8 ID50 for the acid process, and >=10^4.9 ID50 for the alkaline process.