Systematic Assessment of Process Analytical Technologies for Biologics.

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 a pre-defined 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 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 VPE (In-line variable path-length UV/VIS measurements), on-line LC, MALS (Multi-angle light scattering), and automated sampling are of high business value in Protein A purification and polishing steps of the downstream process. We also provide insights, based on our experience in clinical and commercial manufacturing of biologics, into the development and implementation of some of the PAT tools. The results presented in this study are intended to be helpful for the current practitioners of PAT as well as those new to the field to gauge, prioritize and steer their projects for success. This article is protected by copyright. All rights reserved.