Paul Marshall, Director of Global Regulatory Affairs at Jazz Pharmaceuticals, talked the audience through stability guidance. Stability testing is a legal requirement in both the EU and the US, as outlined in various directives and regulations.
Stability testing is necessary because it provides evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light. Essentially, stability testing makes sure that drug substances or drug products are fit for purpose concerning quality, safety, and efficacy throughout their usage.
The ICH guidelines for stability testing are being consolidated into a comprehensive guidance with product-specific appendices, and new techniques are being introduced to generate stability data quickly during development. The guidelines cover the importance of selection batches, storage conditions, shelf-life specification, and photo stability testing.
Marshall added that one can decide to be a full member or an observer of the ICH. He also urged the audience to read and take the opportunity to make comments on the guidelines, since it is an important opportunity for the scientific community to influence change.
In his opinion, as an ex-assessor at the MHRA, bracketing and matrixing are overlooked aspects of the guidance. Bracketing refers to testing the extremes of certain design factors. Matrixing involves selecting a subset of samples for all factor combinations that would be tested at a given time point.
Alongside ICH guidance, there is region-specific guidance. US and European guidance is similar to the ICH, but there may be slight differences that scientists and regulators must be aware of. During his time as a regulatory assessor, Marshall came up with tweaks and improvements for stability dossiers to ensure that they were comprehensive and included the relevant information.
Unfortunately, a significant number of applications have deficiencies in their stability packages. Common deficiencies include insufficient stability data, missing photo stability data, and inappropriate shelf-life acceptance limits. Marshall listed some practical tips to assist the audience; he suggested that stating retest periods, tabulating details of primary batches, and confirming that stability batches are representative of commercial products are essential.
