Integration of Near-Infrared Spectroscopy-Based Process Analytical Technology with a Bench-Scale Continuous Manufacturing Process for an Omega-3 Phospholipid Pharmaceutical Product

目前制药公司用于液体药品质量保证和工艺优化的QC方法需要使用湿化学法和基于层析的方法，这些方法费时且可能导致生产效率降低。在某些情况下，样品被送到配备了先进仪器的外部实验室，这会导致产品发布的进一步延迟(长达8-21天)。因此，制药公司有必要实施在线过程分析技术来解决上述缺点。根据NSERC-Engage赠款(2018年)，一家总部位于魁北克的制药公司与麦吉尔大学的Ashraf Ismail教授开展了一项合作研究，以调查实施近红外光谱分析来监控从磷虾油中提取的活性药物成分的制造过程的可行性。可行性研究的结果是开发了基于近红外光谱的初步校准模型，用于确定生产过程中原料和中间体中的关键成分。基于这项研究的积极成果，该公司计划在NSERC-CRD赠款的支持下，扩大与麦吉尔大学的合作，通过光谱和质谱学技术对最终产品(原料药)生产过程中提取的磷虾油馏分进行全面表征。NSERC-CRD建议还需要开发和验证强大的近红外校准模型，用于在线监测活性药物成分连续生产过程中的四个关键点。这项合作研发计划汇集了来自McGill和魁北克一家制药创新者的团队成员，他们拥有进行基于近红外光谱分析技术的创新实施所需的互补专业知识。

Current QC methods employed by pharmaceutical companies for quality assurance and process optimization of liquid-based pharmaceutical products entail the use of wet-chemical and chromatographic-based methods which are time consuming and can lead to reduced production efficiency. In some cases, the samples are sent to external labs that are equipped with advanced instrumentation which causes further delays in product release (up to 8-21 days). Accordingly, there is a need for pharmaceutical companies to implement online process analytical technologies to address the above drawbacks. Under an NSERC-Engage grant (2018), a Quebec-based pharmaceutical company initiated a collaborative study with Professor Ashraf Ismail (McGill University) to investigate the feasibility of implementing near-infrared spectroscopy to monitor the manufacturing process for an active pharmaceutical ingredient derived from krill oil. The outcome of the feasibility study was the development of preliminary near-infrared (NIR) spectroscopy-based calibration models for the determination of key components in the starting material and intermediates in the production process. Based on the positive outcome of the study, the company plans to expand its collaborative efforts with McGill University under the auspices of an NSERC-CRD grant to fully characterize the krill oil fractions, extracted during the manufacture of the final product (API), by both spectroscopic and mass-spectrometric techniques. The NSERC-CRD proposal also entails the development and validation of robust NIR calibration models for on-line monitoring at four key points in the continuous manufacturing process of the active pharmaceutical ingredient. This collaborative R&D initiative bring together team members from McGill and from a Québec-based pharmaceutical innovator who have the complementary expertise required to undertake this innovative implementation of NIR spectroscopy-based process analytical technology.