A critical review of recent trends, and a future perspective of optical spectroscopy as PAT in biopharmaceutical downstream processing.

As competition in the biopharmaceutical market gets keener due to the market entry of biosimilars, process analytical technologies (PATs) play an important role for process automation and cost reduction. This article will give a general overview and address the recent innovations and applications of spectroscopic methods as PAT tools in the downstream processing of biologics. As data analysis strategies are a crucial part of PAT, the review discusses frequently used data analysis techniques and addresses data fusion methodologies as the combination of several sensors is moving forward in the field. The last chapter will give an outlook on the application of spectroscopic methods in combination with chemometrics and model predictive control (MPC) for downstream processes. Graphical abstract.