By Dr. Nima Yazdanpanah
Drug substance isolation by crystallization and filtration and spray drying are last stages of the drug substance manufacturing process, where critical quality attributes (CQAs) and powder properties (such as flowability, stability, particle size distribution, and purity) were defined. These unit operations are scale depended and mixing and heat and mass transfer (scale dependent phenomena) could have significant impact on the CQA of product, performance of equipment, and also impact on downstream (drug product) and bioavailability. The manufacturing scale process development, technology transfer, and scale-up are challenging steps at the interface of R&D and manufacturing. The dynamic correlation of critical process parameters (CPPs) and CQAs should be defined for the design space development, control strategy, and CMC. Some notable examples for spray drying would be atomizer selection, flowrate and drying temperature optimization. However, developing the manufacturing scale process by just utilizing lab scale data could be misleading, or running DoE at that large scale is not efficient, especially when small amount of material available or time to the market is short.
At this presentation, some scale-up issues for spray drying will be discussed. Applications of in-silico tools (mathematical simulation) for rapid scale-up and process development and optimization, and challenges and benefits will be demonstrated with case studies.