Strategy to Evaluate Performance of Lyophilization Stoppers

Lyophilization, the process of dehydrating a material at low temperature and reduced pressure, is used to extend the shelf life of biologic drug products. Because the object is extended shelf life, long-term performance testing of any lyophilization containment system is essential. That testing must include not only measurement of container closure integrity (CCI), but measurement of system ability to maintain drug product water content. Both parameters depend upon stopper composition. This presentation discusses a strategy for two-year evaluation of four types of lyophilization stoppers (two bromobutyl elastomers, two chlorobutyl elastomers) in both 13 mm and 20 mm sizes, paired with borosilicate glass vials and aluminum seals. Lyophilization was performed in a commercial chamber using a solution blend of 20 mg/ml mannitol and 40 mg/ml sucrose - nitrogen backfill was to 11.6 psi. Evaluation comprised: - CCI (unsealed) - ability to maintain vacuum (24 hrs) - CCI (sealed) - ability to maintain vacuum - water vapor pressure in headspace - water content of cake - water content of stopper. The strategy proved effective in demonstrating that while all systems maintained acceptable CCI and water levels, composition of stopper does influence water level of drug product.