Low moisture content is seen as crucial to achieving long term stability of freeze dried biologics and reference materials. Highly hygroscopic freeze-dried material are susceptible to moisture ingress over time which can lead to degradation and loss of biological potency. This study compared vials with unprocessed stoppers, vials with vacuum-oven dried stoppers and glass ampoules in order to determine the superior long term storage format in terms of moisture ingress and potency. B/Phuket influenza antigen was chosen as the model biological standard and the lyophilized antigen was stored at -20, 25 and 45 °C over a 1 year period. Ampoules had no significant moisture change across all storage temperatures as would be anticipated. Moisture content results at -20 °C showed no significant differences between ampoules, vials with vacuum-oven dried stoppers and vials with unprocessed stoppers over 12 months. Vials with vacuum-oven dried stoppers performed similarly to ampoules at -20 °C and 20 °C, but had a small increase in moisture content after 6 months at 45 °C. Vials with unprocessed stoppers preformed the worst and exhibited the largest moisture ingress after just 3 months at both 20 °C and 45 °C. Single radial immunodiffusion (SRD) potency assays showed at -20 °C and 20 °C there was no significant difference between all closure formats. At 45 °C there was a drop in potency for all closure formats, but ampoules and vials with vacuum-oven dried stoppers retained higher potency than vials with unprocessed stoppers. Thus, while ampoules are still considered to be the gold standard format for long term storage stability, using vials with vacuum-oven dried stoppers provides comparable stability and moisture integrity at -20 °C and 20 °C storage.
Keywords: Ampoules; Freeze-drying; Moisture; Potency; Stability; Stopper; Vacuum oven; Vials.
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