A Model For Predicting The Shelf Life Of Antivenoms by Using Short Term Storage 

^1,2Velarde, D.T.; ²Clemente, C.A.; ³Barbosa, C.F. and ²Santos, M.A.

1 Fhemig, Belo Horizonte, MG; 2 Divisão de Imunobiológicos, Funed; 3Divisão de Controle de Qualidade, Funed, Belo Horizonte, MG, Brazil

There are several published papers using data obtained from samples stored at elevated temperature to calculate the correct expiry dates of pharmaceutical products. It is generally done by applying the Arrhenius plot through the equation  k= A^(-E/RT). The pourpose of this study was to apply this methodology to Brazilian lyophilised antivenoms, in order to evaluate its advantages over the current liquid preparation. We used bothropic/crotalic antivenom containing 88 mg/ml of protein. Lyomega 20 freeze-dryer equipment from Telstar was used. The product was frozen at –50°C for 6 hours before turning the equipment on; ran for 16 hours until the temperature of the product reached 20°C; then for additional 10 hours until get 38°C to complete the process. The bottles were sealed under vacuum, then stored at 4-8°C for several months. The dryed product was incubated at three diferent constant temperatures: 37, 45 and 53°C. Samples from each temperature were withdrawn in duplicate after 1, 2, 3, 4 and 6 months of incubation and then rehydrated to the original volume. The liquid product was analysed in terms of turbidity (A600nm), SDS-PAGE profile and biological activity (ED-50). The samples analysed showed no turbidity or alteration in SDS-PAGE profile; a small lost of biological activity was observed only for the higher storage temperature. In conclusion, the predicted shelf life of lyophilised antivenom at room temperature showed to be much longer then reported for the liquid preparation.

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