Stability studies evaluate how environmental factors affect the quality of the active pharmaceutical ingredient and drug product, enabling the determination of storage conditions and shelf life (SL). According to ICH Q1A(R2), these studies are conducted on the first three commercial batches in marketing containers, focusing on critical attributes. Stability of parenteral dosage forms is influenced by temperature, batch, fill volume, and orientation. A full design tests all factor combinations across time points. To reduce the testing, ICH guideline Q1D allows the use of reduced designs, bracketing and matrixing approaches.
The aim of this doctoral dissertation was to demonstrate that appropriate approaches can be used for reduction of stability study design and still predict the appropriate SL. Based on three hypotheses, we showed that the use of reduced testing concepts represents an effective approach to optimizing stability studies. The first hypothesis employed a matrix design for long-term testing to evaluate whether reducing the number of time points and batches preserves the predictive power of the model compared with a full design. The second hypothesis relied on factorial analysis of accelerated data to identify the combination of parameters that most affect drug stability. A representative sample was selected for long-term testing, allowing rationalized study design. The third hypothesis addressed an approach based on accelerated testing at elevated temperatures, enabling data extrapolation for long-term stability prediction and significantly shortening the study duration.
The proposed methodology reduces the number of samples, analyses, and required capacities, leading to lower costs and shorter drug development timelines. The results contribute to the understanding of parenteral preparations stability and enable application of reduced models to other liquid formulations. Due to their scientific and practical relevance, the presented approaches may significantly influence ICH guideline development and contribute to faster and cost-effective drug registration.
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