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Production Flow Chart
Inactivation of FMD by BEI
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Inactivation is one of the most critical steps in the production of FMD
vaccine; many of the FMD outbreaks in Europe during the 1980s were traced
to the production or improper inactivation of FMD vaccines (Beck
and Strohmaier, 1987). In early vaccines, formaldehyde was used to
inactivate alum-adsorbed virus. In-process evaluation of this system proved
to be difficult and it has mostly been superseded by the use of first
order kinetics inactivants of the aziridine group of chemicals, most recently
binary ethylenimine (BEI) (Bahnemann,
1974). Inactivation should ideally be done with clarified virus harvest
before any concentration step because of the recognised problem of inactivating
virus within virus/cell debris aggregates. Two full inactivating doses
of BEI are used in a 'two-tank' system over two inactivation periods.
The inactivation kinetics during the process and final inocuity are measured
carefully (tissue culture titration in sensitive cells, spectrophotometric
analysis or serological assays) to ensure complete inactivation and compliance
with the requirements of the European Pharmacopoeia.
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