The research and development of therapeutic antibodies in the world is rapidly rising in recent years. It is a huge challenge to obtain a robust process and achieve the consistency of consistent product quality, because most of the antibody drugs are produced from mammalian cells of which the production processes are long and complex. To develop a robust and high yield production process for a biotherapeutic, one needs to have a general consideration of entire R&D project working flow. First of all, it is necessary to start with a good drug candidate, which not only meets the requirement for both the effectiveness and drug safety, but also suits for manufacture. Then, the expression system and host cell line used for the product expression need to be determined based on availability and regulatory requirements. Cell line development needs to combine with early upstream and downstream process developments as well as product quality assessment. Once a suitable stable cell line is selected, the Master Cell Bank (MCB) and the Working Cell Bank (WCB) are established according to the regulatory requirements, and tested for growth, production stability and cellular safety. Finally, process optimization and scale-up production are carried out to obtain a consistent production. Upstream process development is mainly to optimize a variety of process parameters, including physical parameters, chemical parameters, metabolite levels, and feed strategy and foam control; downstream process development focuses on product quality, recovery rate, and cost efficiency. For scale-up production, enterprises need to make decisions whether to use traditional stainless steel system or the single-use disposable system based on demands on product market potential and available technical supports. In this review, combined with the development of new technologies in recent years and the authors’ personal working experience, the factors that need to be considered in process development are discussed.
Impact Factors in the Process Development for Therapeutic Antibodies, International Journal of Pharmacy and Chemistry.
Vol. 4, No. 2,
2018, pp. 16-22.
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