Veliparib: Analytical Tools and Process Design Strategies for the Control of Mutagenic Impurities and Other Drug Substance Critical Quality Attributes

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-11-08 DOI:10.1021/acs.oprd.4c0032810.1021/acs.oprd.4c00328

Rajarathnam E. Reddy*, David M. Barnes*, Adam P. Schellinger, Travis B. Dunn, Lawrence Kolaczkowski, Wayne A. Pritts, Yao-En David Li, Samrat Mukherjee and Andrew Staley,

{"title":"Veliparib: Analytical Tools and Process Design Strategies for the Control of Mutagenic Impurities and Other Drug Substance Critical Quality Attributes","authors":"Rajarathnam E. Reddy*, David M. Barnes*, Adam P. Schellinger, Travis B. Dunn, Lawrence Kolaczkowski, Wayne A. Pritts, Yao-En David Li, Samrat Mukherjee and Andrew Staley, ","doi":"10.1021/acs.oprd.4c0032810.1021/acs.oprd.4c00328","DOIUrl":null,"url":null,"abstract":"(R)-Veliparib (ABT-888) is a poly(ADP-ribose)polymerase (PARP) inhibitor that is being investigated for the treatment of a broad spectrum of oncology indications, including BRCA1/2-mutated breast cancer and other solid tumors. The (R)-veliparib process consists of three stages utilizing two proposed regulatory starting materials, (R)-Boc-2-methylproline and 2,3-diaminobenzamide dihydrochloride, with two isolated intermediates. The drug substance control strategy, which was established based on a combination of analytical tools and uniquely designed manufacturing process and unit operations, provides robust controls for mutagenic and other impurities and ensures that (R)-veliparib drug substance consistently meets all critical quality attributes (CQAs) and acceptance criteria. The purpose of this article is to provide details of how the (R)-veliparib control strategy for the selected CQAs was cross-functionally developed using analytical measurement tools and specially designed unit operations.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"28 12","pages":"4303–4316 4303–4316"},"PeriodicalIF":3.1000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00328","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}

引用次数: 0

Abstract

(R)-Veliparib (ABT-888) is a poly(ADP-ribose)polymerase (PARP) inhibitor that is being investigated for the treatment of a broad spectrum of oncology indications, including BRCA1/2-mutated breast cancer and other solid tumors. The (R)-veliparib process consists of three stages utilizing two proposed regulatory starting materials, (R)-Boc-2-methylproline and 2,3-diaminobenzamide dihydrochloride, with two isolated intermediates. The drug substance control strategy, which was established based on a combination of analytical tools and uniquely designed manufacturing process and unit operations, provides robust controls for mutagenic and other impurities and ensures that (R)-veliparib drug substance consistently meets all critical quality attributes (CQAs) and acceptance criteria. The purpose of this article is to provide details of how the (R)-veliparib control strategy for the selected CQAs was cross-functionally developed using analytical measurement tools and specially designed unit operations.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Veliparib：致突变杂质和其他原料药关键质量属性控制的分析工具和工艺设计策略

(R)-Veliparib （ABT-888）是一种聚（adp -核糖）聚合酶（PARP）抑制剂，正在研究用于治疗广泛的肿瘤适应症，包括brca1 /2突变乳腺癌和其他实体肿瘤。(R)-veliparib工艺包括三个阶段，使用两种拟议的监管起始材料，(R)- boc -2-甲基脯氨酸和2,3-二氨基苯甲酰胺二盐酸，以及两种分离的中间体。原料药控制策略建立在分析工具和独特设计的制造工艺和单元操作的基础上，提供了对致突变性和其他杂质的强有力控制，并确保(R)-veliparib原料药始终符合所有关键质量属性（cqa）和验收标准。本文的目的是详细介绍如何使用分析测量工具和专门设计的单元操作跨功能开发所选cqa的(R)-veliparib控制策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

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.