Development of a Scalable Process for an IL-17A Inhibitor LY3509754: Part III. Assembly of Drug Substance, Salt Formation, and Impurity Control

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-04-02 DOI:10.1021/acs.oprd.5c0000510.1021/acs.oprd.5c00005

Qiang Yang*, Ryan J. Linder, Yu Lu, Thomas J. Beauchamp, Timothy A. Woods, David A. Coates, Brandon J. Reizman, Jonas Y. Buser, Michael E. Laurila, Nicholas A. Magnus, Yongjie Yu, Lili Han and Ping Huang,

引用次数: 0

Abstract

A 5-step cGMP sequence for the preparation of an IL-17A inhibitor 1 was optimized and scaled up to deliver a total of 66 kg of the final drug substance 1 to support clinical and product development studies. Salt formation and polymorph screening identified a suitable polymorph of the hemiedisylate salt that provided desirable physical properties. Key impurities in the final drug substance were identified, and control strategies were developed and executed to control them to acceptable levels in the production batches.

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IL-17A抑制剂LY3509754可扩展工艺的开发：第三部分。原料药的组装、盐的形成和杂质控制

制备IL-17A抑制剂1的5步cGMP序列进行了优化和放大，以提供总共66公斤的最终药物1，以支持临床和产品开发研究。盐的形成和多晶型筛选确定了半二酸盐的合适多晶型，提供了理想的物理性能。确定最终原料药中的关键杂质，制定并执行控制策略，将其控制在生产批次中可接受的水平。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

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.