A Continuous Process for Manufacturing Apremilast. Part II: Process Characterization to Establish a Parametric Control Strategy,Organic Process Research & Development

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A Continuous Process for Manufacturing Apremilast. Part II: Process Characterization to Establish a Parametric Control Strategy
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2024-02-13 , DOI: 10.1021/acs.oprd.3c00403
Daniel J. Griffin ₁ , Hsiao-Wu Hsieh ₁ , Nadide Hazal Avci ₁ , Nandini Sarkar ₂ , James D. Fostinis ₁ , Nicholas Klitzing ₃ , James I. Murray ₃ , Rasangi Wimalasinghe ₂ , Simone Spada ₁ , Alicia Zeng ₂ , Matthew G. Beaver ₁

Affiliation

This is Part II of a series on the development and characterization of an integrated continuous manufacturing (CM) process developed for the penultimate step in the synthesis of the drug substance Apremilast (Otezla). Part I gives the development history and highlights the achieved process intensification. Here, we describe the process characterization (PC) undertaken. In doing so, we point out aspects of characterization that are unique to an integrated CM process and give our strategy for navigating PC in this scenario. Moreover, we provide data that support a robust control strategy which relies on parametric control only (i.e., no in-process controls) followed by batch release of the produced Apremilast drug substance intermediate. Such a control strategy is advantageous as it minimizes divert-to-waste loss and operational costs.

中文翻译：

Apremilast 的连续生产工艺。第二部分：建立参数控制策略的过程表征

这是关于集成连续制造 (CM) 工艺的开发和表征系列的第二部分，该工艺是为合成原料药 Apremilast (Otezla) 的倒数第二步而开发的。第一部分介绍了发展历史并重点介绍了所实现的流程强化。在这里，我们描述了所进行的过程表征（PC）。在此过程中，我们指出了集成 CM 流程特有的特征方面，并给出了在此场景中导航 PC 的策略。此外，我们提供支持稳健控制策略的数据，该策略仅依赖于参数控制（即无过程控制），然后批量释放所生产的阿普斯特原料药中间体。这种控制策略是有利的，因为它可以最大限度地减少转为废物的损失和运营成本。

更新日期：2024-02-13

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