The effects of stopper drying on moisture levels of Haemophilus influenzae conjugate vaccine.

The discovery and development of increasingly potent biological and pharmaceutical products have resulted in very small amounts of the active ingredient in final product formulations. Pediatric vaccines with sub-milliliter dose sizes pose unique problems for final formulation and lyophilization, especially when stabilizers used are present in small amounts or are hygroscopic. Lyophilized Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PedvaxHIB) has a plug weight of about 3 mg in its final formulation. Microgram amounts of water absorbed by the lyophilized plug can cause drastic changes in the moisture content of the product. In a small percentage of the final containers absorption of moisture by the vaccine may cause aesthetic defects (plug collapse) over time, or at elevated temperatures. This paper describes drying methods developed to control residual moisture levels in stoppers used as final container closures. Results on the moisture stability of the product capped with dried and non-dried stoppers are presented.