Abstract

Based on the control scheme of nutrients and metabolites, there are many modes of cell culture processes, including batch, repeated-batch, fed-batch, chemostat, and perfusion, among which batch, fed-batch, and perfusion modes are used for industrial-scale biologics production. Batch is the simplest with little operation control of nutrients and metabolites, whereas perfusion is the most complex with intensive control. Generally, high-level control leads to high productivity, but with a tradeoff of high complexity, increasing risk of failure, and developmental time and cost. The choice of the culture mode is largely dependent on process capacity and quality requirements. Different culture modes are well distinguishable in cell growth, nutrient consumption, and product formation kinetics. Understanding the kinetics is the starting point for process development and improvement. The development of more sophisticated fed-batch and perfusion cultures is rooted in the understanding of the process established in batch culture. Batch culture is the indispensable first step for establishing a proper cell maintenance schedule and for further developing other culture modes with more complexity and higher performance. This article provides detailed discussions on different culture modes and associated culture kinetics and process design and operation considerations in the biotechnology industry.

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