Scalable Process\nDevelopment of Ceritinib: Application\nof Statistical Design of Experiments

A convenient\nand commercially viable cost-effective, safe manufacturing\nprocess was developed to manufacture ceritinib. This work describes\nthe implementation of the quality by design approach through the identification\nof critical quality attributes (CQAs), critical material attributes\n(CMAs), and critical process parameters (CPPs). Application of the\nstatistical design of experimentation for an experimental plan to\nfind the relationship between CQAs, CMAs, and CPPs. This work also\ndescribes a superior process for large-scale manufacturing of ceritinib\nin terms of process safety, handling, scalability, and enhanced throughput.\nWork captured here addressed the challenges in reported procedures\nsuch as sodium hydride’s explosive hazard, high-temperature\nmicrowave conditions, nitro to amine reduction under high pressure\nusing a palladium catalyst, and column chromatography to purify the\nfinished product.