The European Medicines Agency (EMA) assessed the risk trypsin extracted from pigs poses to human health when used as a culture reagent in vaccine production or as a processing aid in biomanufacturing. And the conclusion is a concern.
The agency said: “Despite the application of control measures intended for food safety, there is a risk that an animal-derived starting material may be contaminated with transmissible agents.”
It cited a 2010 study which revealed that porcine cicovirus DNA sequences found in a rotavirus vaccine came from contaminated trypsin that had been used during manufacture.
In light of the conclusion the EMA made a number of recommendations drug firms can use to minimize the danger including: only using trypsin extracted from the glands of pigs that have appropriate official health certificates; and testing for specific viruses using both porcine and primate cell lines.
It also advised that: “Given the limitations on the control of raw materials and limitations on testing for viruses, it is advisable to incorporate two complementary virus reduction steps,” specifically, low pH and irradiation treatments.
The ultimate responsibility for ensuring the safety steps are carried out rests with the drug firm although – according to the EMA – virus testing may be carried out by the trypsin supplier.
“The Marketing Authorisation Holder of the medicinal product should have sufficient information on the trypsin to allow a comprehensive risk assessment and provide a sufficient data package to the competent authority for assessment.
“This should include a description of testing methods and the stage at which virus testing is performed, as well as the volumes and sensitivity of the virus tests. Study reports validating virus reduction steps should be provided according to Guideline CHMP/BWP/268/95.”
The EMA also discussed potential alternatives citing recombinant bacterial or plant-derived trypsin or enzymes from invertebrae as examples.
“The use of bacterial or plant derived recombinant trypsin minimises in principle the risk for animal virus contamination and the application of such alternatives is therefore encouraged.
“However, no general recommendation to replace porcine trypsin can currently be given considering that these alternatives need a careful assessment of suitability, quality, sterility and performance characteristics.”
The EMA also acknowledged the possibility of replacing porcine derived trypsin with an equivalent obtain from cows, again with the caveat the testing is carried out.
Whether, given the current questions over the European food chain, the EMA will include a recommendation for equine virus testing of such products in the future is unclear.