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Lyophilized Influenza antigen reference reagents are a critical resource in the quality control of influenza vaccines. A standard formulation has been used successfully at NIBSC for many years however, following the unexpected occurrence of a collapsed appearance in a particular batch a study was carried out to establish the impact of the sugar concentration in the formulation using modulated differential scanning calorimetry (mDSC) and nuclear magnetic resonance spectroscopy (NMR). There was a correlation between the presence and size of the mDSC eutectic temperature events and the freeze dried appearance of the cakes, which became progressively worse with increasing amounts of sugar. NMR spectroscopy could be used to positively identify and quantify the sugars in the formulations. MDSC can rapidly predict if the freeze dried appearance will be acceptable so as to assure the successful lyophilization of influenza reference preparations., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Stability studies represent a significant workload for both manufacturers and regulatory reviewers and therefore a careful selection of the study design and of the stability indicator test is required to make sure that the study will provide the relevant information. Moreover, alternatives to the existing regulatory approaches should be favoured in order to better or quicker analyze the impact of a specific change. In this article, examples of alternative approaches are given. For the stability monitoring study, emphasis is put on the bulk stability program. Concerning comparability stability study, two case studies illustrating how accelerated stability studies could be used to support manufacturing changes are presented.