CQA based Impact Assessment

Since the introduction of the ICH Q9 guideline the pharmaceutical industry has been running around in a frenzy conducting risk assessments on practically all aspects related to drug manufacturing. However, for all the workshops and risk assessment matrixes prepared one thing remains fundamentally the same: Your risk assessment is never stronger than the data you have at hand and the knowledge of the people involved in conducting the risk assessment.

During clinical development of a new drug product focus must be on process design and control. The commercial process has not been established at this point so it makes little sense to discuss and evaluate risks. Instead we need a systematic approach to evaluate the impact of the process on the CQAs taking into account our level of knowledge or even more important our lack of knowledge. Ultimately, It is our understanding of the correlations between process input and output which facilitates design of a proper process control strategy. From a conceptual point of view, this is also in line with the approach suggested by the ICH Q8 guideline. Sponsors should determine:

the functional relationships that link material attributes and process parameters to product CQAs

Once process understanding is at an appropiate level a robust control strategy can be be implemented followed by formal process validation to demonstrate reproducibility. Until then, rigorous testing and experimentation is required to generate sufficient knowledge to ensure adequate product quality and safety.

For inspiration, a CQA based impact assessment tool is available for free download. The tool which is in Excel format fulfils the regulatory expectations and can be used throughout clinical process development. The tool is tailored to technical development teams working with drug substance and/or drug product development.