Technology outlook for real‐time quality attribute and process parameter monitoring in biopharmaceutical development—A review

• Published in: Biotechnology and bioengineering Vol. 117; no. 10; pp. 3182 - 3198
• Main Authors: Wasalathanthri, Dhanuka P., Rehmann, Matthew S., Song, Yuanli, Gu, Yan, Mi, Luo, Shao, Chun, Chemmalil, Letha, Lee, Jongchan, Ghose, Sanchayita, Borys, Michael C., Ding, Julia, Li, Zheng Jian
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc 01.10.2020
• Subjects: Automation; Biopharmaceuticals; Data analysis; Integration; Learning algorithms; Machine learning; Mass spectrometry; Mass spectroscopy; Mathematical analysis; Monitoring; Multivariate analysis; process analytical technology; Process parameters; quality by design; Quality management; real‐time monitoring; Scientific visualization; Technology assessment; Visualization
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.27461

Real‐time monitoring of bioprocesses by the integration of analytics at critical unit operations is one of the paramount necessities for quality by design manufacturing and real‐time release (RTR) of biopharmaceuticals. A well‐defined process analytical technology (PAT) roadmap enables the monitoring of critical process parameters and quality attributes at appropriate unit operations to develop an analytical paradigm that is capable of providing real‐time data. We believe a comprehensive PAT roadmap should entail not only integration of analytical tools into the bioprocess but also should address automated‐data piping, analysis, aggregation, visualization, and smart utility of data for advanced‐data analytics such as machine and deep learning for holistic process understanding. In this review, we discuss a broad spectrum of PAT technologies spanning from vibrational spectroscopy, multivariate data analysis, multiattribute chromatography, mass spectrometry, sensors, and automated‐sampling technologies. We also provide insights, based on our experience in clinical and commercial manufacturing, into data automation, data visualization, and smart utility of data for advanced‐analytics in PAT. This review is catered for a broad audience, including those new to the field to those well versed in applying these technologies. The article is also intended to give some insight into the strategies we have undertaken to implement PAT tools in biologics process development with the vision of realizing RTR testing in biomanufacturing and to meet regulatory expectations. Process analytical technology (PAT) landscape featuring sensors, automation, data management and data interrogation techniques for real time quality attribute monitoring in biopharmaceutical process development is reviewed. Here, Wasalathanthri and coworkers describe a systematic roadmap for developing PAT tools in bioprocess and the progression of techniques to manufacturing suites based on clinical and biomanufacturing expertise to meet regulatory expectations.