Critical Paths: The Stability Game

Stability studies are performed at various stages in the development of a pharmaceutical product – from development through to manufacture – to ensure that the dosage form has a consistent potency and has not acquired any undesirable changes in performance or appearance during storage. The testing is designed to provide evidence on how the quality of the drug product will vary when it is exposed to a variety of environmental factors such as temperature, humidity and light. Data generated from the studies helps to establish either a re-test period for a drug substance or a shelf-life and recommended storage conditions for a manufactured product.

DEVELOPMENT STAGES

Informal stability studies are performed at early stage development to assess different formulations before selecting the final candidates to undergo formal testing. Studies undertaken during the development phase will include testing the stability of the drug substance alone and with key intermediates, and packaging studies to show that adequate protection from the external environment is provided. Depending on the nature of the final product, there may also be requirements for in-use testing – for instance, to evaluate the effect of air and moisture entrance into multi-dose formulations after opening.

In the past, stability study protocols used to vary according to the development experience of the pharmaceutical company. However, following the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) these studies are becoming more consistent. ICH guidelines have been issued and are regularly updated.