Monoclonal antibodies – definition, benefits & application

How are monoclonal antibodies produced?

The production processes for biopharmaceuticals have evolved over time. Earlier methods focused on extracting and purifying natural sources. Contemporary methods are more precise, beginning with identifying, isolating, and expressing of the gene of interest.⁽³⁾ The production process can be broken down into two stages: upstream and downstream, but before these steps and commercial manufacture, significant time is spent evaluating the developability, characterization and process development.

The upstream process spans approximately 2-3 weeks for a batch or fed-batch bioreactor, starting with a working cell bank, progressing to a seed train, then the inoculation phase, and finally production in a bioreactor. A typical bioreactor campaign will last ~2 weeks for a fed-batch or batch process or longer if continuous processing is deployed. Process engineers closely monitor the bioreactor to maintain cell viability of 70% or higher to maintain yield and minimize impurities released by deteriorated cells. During upstream production, some key product attributes are monitored, including viable cell count, relevant cell culture media components, titer, and critical process parameters like pH, evolved gases and temperature are closely monitored.

The downstream process focuses on the preparation of the final product. It starts with clarification, followed by virus activation, purification and polishing, viral clearance, concentrating the product, final formulation, sterile filtration, fill-finish, and finally, lot release. In between these steps, the samples are gathered and assessed in an analytical laboratory for titer, aggregation, purity, the presence of proteases, and identity verification. Verification of post-translation modifications (PTMs) like charge variants and glycosylation are of specific interest as they can significantly alter the efficacy and safety of the final product. Each facility differs what is monitored between each step with many if not all the attributes listed, executed in the QC labs, that focus on safety, efficacy, integrity, and purity.