Systematic assessment of process analytical technologies for biologics

作者：Christopher Gillespie, Dhanuka P. Wasalathanthri, Diana Ritz, George Zhou, Keith A. Davis, Thomas Wucherpfennig, Nadine Hazelwood · 发表于：Biotechnology and Bioengineering · 年份：2021 · DOI：10.1002/bit.27990 · 被引用次数：40 · 研究领域：Viral Infectious Diseases and Gene Expression in Insects、Protein purification and stability、Biosimilars and Bioanalytical Methods

The application of process analytical technology (PAT) for biotherapeutic development and manufacturing has been employed owing to technological, economic, and regulatory advantages across the industry. Typically, chromatographic, spectroscopic, and/or mass spectrometric sensors are integrated into upstream and downstream unit operations in in-line, on-line, or at-line fashion to enable real-time monitoring and control of the process. Despite the widespread utility of PAT technologies at various unit operations of the bioprocess, a holistic business value assessment of PAT has not been well addressed in biologics. Thus, in this study, we evaluated PAT technologies based on predefined criteria for their technological attributes such as enablement of better process understanding, control, and high-throughput capabilities; as well as for business attributes such as simplicity of implementation, lead time, and cost reduction. The study involved an industry-wide survey, where input from subject matter industry experts on various PAT tools were collected, assessed, and ranked. The survey results demonstrated on-line liquid Chromatography (LC), in-line Raman, and gas analysis techniques are of high business value especially at the production bioreactor unit operation of upstream processing. In-line variable path-length UV/VIS measurements (VPE), on-line LC, multiangle light scattering (MALS), and automated sampling are of high business value in Protein A purification and polishing s...