Perfusion Cell Cultures: Is the Technology Worthwhile for Biopharmaceutical Production?

An increasing demand for biopharmaceuticals, the growing pressure from the market, and the necessity to compress process development times represent current challenges in biopharma manufacturing. Traditional discontinuous bioreactors start to appear as obsolescent and unsuitable to address these challenges. On the other hand, perfusion cultures have been reported as promising alternatives, allowing to alleviate the batch‐to‐batch variability and to improve the volumetric yield. However, industrial inertia, requirement of higher investment costs, and increased complexity represent challenges limiting the scale up of the operation to manufacturing platforms. The aim of this review is to deconstruct the intricate perfusion problem and examine the potential advantages this technology could bring. Starting from basic operational fundamentals and an overview of the most recent applications, this review will span from an economic assessment of perfusion cultures to the analysis of their environmental sustainability and integration with advanced monitoring techniques. Finally, a discussion of existing hurdles and of the way to tackle the current inertia in industrial adoption is proposed.