Weidong Tong, Victor L. Schultz, Yingying Yang, Junyong Jo, Yu He, Marco E. Armenante, Sandra A. Robaire, Samantha A. Burgess, Yun Chen, Erica L. Schwalm, Matthew Gunsch, Xiao Wang, Qi Gao, Cyndi Q. He, Mikhail Reibarkh, Jeffrey T. Kuethe, Gregory J. Hughes
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引用次数: 0
Abstract
The identification, quantification, understanding, and control of impurities in starting materials, intermediates, and substances are crucial during the evaluation of new molecular entities in the clinical development of the pharmaceutical industry. Through process characterization development in islatravir (MK-8591), two impurities from the regulatory starting material, TMS-Triol, were discovered in a late stage that persisted in the product. However, they were not detectable by the gas chromatography (GC) method that the process used. This paper describes the use of orthogonal analytical approaches for impurity investigations, which aim to provide a comprehensive understanding of the impurity profile of a drug substance with a particular emphasis on comprehending the origin and fate of impurities from upstream steps. The understanding serves as a guide for making decisions on process controls and optimizations of the islatravir drug substance. This paper also outlines quality control strategies for the starting material of the islatravir drug substance commercial process. The knowledge gained from these investigations forms a solid foundation for establishing specifications for impurities in regulatory starting materials.
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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