Perspectives on the manufacture of combination vaccines.

Evolving regulatory requirements in the United States and Europe create major challenges for manufacturers tasked with production of vaccines that contain ≥9 separate antigens capable of protecting against infectious diseases, such as diphtheria, tetanus, pertussis, polio, hepatitis B, and Haemophilus influenza b, in a single shot. This article describes 10 steps that can facilitate the process of licensing these complex vaccines. It also points out problems associated with the use of animal tests for the crucial step of potency testing for batch release caused by the inherent variability of such tests and the difficulties of interpreting their results.