Application of a Statistical Approach to Process Development of Futibatinib by Employing Quality-by-Design Principles. Part 1: Identification of Critical Process Parameters for Impurities
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引用次数: 2
Abstract
We focus on a novel experimental design and statistical analysis to identify the critical process parameters (CPPs) of impurities in futibatinib, which is a fibroblast growth factor receptor inhibitor. First, using failure mode and effects analysis, we identify 11 potential CPPs as the process parameters to be investigated. Next, an L12 orthogonal experiment of the Plackett–Burman type is designed for risk analysis to check whether the 11 potential CPPs are in fact CPPs. Finally, for each impurity, analysis of variance, regression analysis, and regression diagnosis are carried out, enabling the CPPs to be analyzed correctly. Based on the quality-by-design concept, we identify three impurities that impact the impurity profile of the active pharmaceutical ingredient and five CPPs of the impurities, focusing on design of experiment and statistical analysis. We also clarify the process parameters to be examined in more detail for commercial production.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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