Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-01-22 DOI:10.1021/acs.oprd.4c00399

Nicole M. Ralbovsky, Gunjan Dixit, Justin P. Lomont, Jay Desai, Cristina Butu, Anumita Saha-Shah, Emily Costello, Janelle Lukens, Michael Mazur, Patrick M. McHugh, Rodell C. Barrientos, Andrew Semple, Gregory J. Hughes, Rebecca Chmielowski, Sheng-Ching Wang, Bhumit A. Patel, Joseph P. Smith

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Abstract

Process analytical technology (PAT) is increasingly being explored within pharmaceutical production and process development, with a particular emphasis in the vaccine and biologics space. PAT aims to provide increased process understanding and control through real-time monitoring of critical quality attributes and key process parameters as well as detection of process deviations. Downstream purification in pharmaceutical manufacturing processes can be complex and requires copious analytical characterization. Herein, we showcase the successful implementation of PAT for monitoring bioconjugation reactions related to both vaccine and biologic pharmaceutical manufacturing processes. Specifically, we explore a variety of PAT-based techniques and their utility for monitoring polysaccharide–protein and protein–small molecule bioconjugation reactions. PAT applications using at-line multiangle light scattering, in situ fluorescence spectroscopy, in situ viscosity, and at-line hydrophobic interaction chromatography are shown to each provide distinct, real-time analytical information to enhance the understanding and characterization of bioconjugation reactions.

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药物生物偶联反应实时监测的过程分析技术

在制药生产和工艺开发中，越来越多地探索过程分析技术（PAT），特别强调在疫苗和生物制剂领域。PAT旨在通过实时监控关键质量属性和关键工艺参数以及检测工艺偏差，提供更多的工艺理解和控制。制药生产过程中的下游纯化可能是复杂的，需要大量的分析表征。在此，我们展示了PAT的成功实施，用于监测与疫苗和生物制药制造过程相关的生物偶联反应。具体来说，我们探索了各种基于pat的技术及其在监测多糖-蛋白质和蛋白质-小分子生物偶联反应中的应用。PAT应用包括近线多角度光散射、原位荧光光谱、原位粘度和近线疏水相互作用色谱，每一种都提供了独特的实时分析信息，以增强对生物偶联反应的理解和表征。

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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.