Purpose: The purpose of this study is to establish a material library and discuss potential applications of the material library to continuous manufacturing. Particularly, this study addresses the importance of selecting process-relevant testing conditions for material characterization, and proposes a methodology to capture process-relevant information with a reduced set of measurements.
Methods: This study included 20 pharmaceutical materials and each material was characterized for 44 properties. The stress conditions of commonly used feeder hoppers were estimated. Multivariate analysis, such as principal component analysis and clustering analysis, was used to explore the knowledge space of the material library. Material properties were correlated with process performance using a loss-in-weight feeder.
Results: Consolidation stress during testing significantly impact material properties. Twenty inactive pharmaceutical ingredients and model drugs included in this study show a wide range of material properties. These materials were then grouped into six clusters based on the similarity of material properties as shown in Figure 1. Based on correlations with various material properties and quantification of material similarity, potential reduced set of characterization tests that captures > 95% of relevant information was identified. Material properties have predictive correlation with the design space of feeding process.
Conclusion: Additional material understanding regarding flow properties may be needed to implement a continuous manufacturing process. Characterization using multiple tests under process-relevant conditions can be helpful to establish the correlation between material properties and process and product performance.
Thomas O’Connor– US Food and Drug Administration
Tianyi Li– US Food and Drug Administration
Muhammad Ashraf– Supervisory Chemist, US Food and Drug Administration, Silver Spring, Maryland
Celia N. Cruz– Director, DPQR, FDA/CDER/OTR/DPQR, Silver Spring, Maryland