ABSTRACT
Background Biosimilar products are almost universally manufactured using recombinant technology that comprises distinct upstream and downstream stages. The upstream phase consists of expressing a recombinant protein or antibody in a culture medium and harvesting it; the downstream phase consists of separating and purifying the target product. It is noteworthy that the scale of production bears a signicant consideration on the upstream system optimization process since the dosing of biosimilar products may vary from a few micrograms to a few grams, making the choice of the upstream process critical to the success of biosimilar products. Hence, these products must be manufactured at a reasonable cost considering their market price will inevitably be lower, reducing prot margins signicantly. This is particularly true for monoclonal antibodies (mAbs); mAbs doses are high, and the process methods are generally more intricate and complex. Developers of biosimilar products are faced with the challenge of the large investment requirement when embarking on the development of monoclonal antibodies, which is why biosimilar products developers’ focus is rather on using innovative systems with lower capital requirements, high titer cell lines, and simplied purication processes, etc. The manufacturing of recombinant DNA products, for example, is a process that involves the two stages discussed earlier:
1. Upstream processing consists of a pure culture of the chosen organism, in sufcient quantity and in the correct physiological state; sterilized, properly formulated media, a seed bioreactor to develop inoculum to initiate the process in the main bioreactor; the production scale bioreactor.
