When it comes to recombinant protein drugs, the selection of the correct expression technology is of paramount importance. This is true from the first steps of development through clinical production to commercial manufacturing thereafter.
This is so important because, the correct balance between time and cost against yield and quality is essential to maximize return on investment. Although the creation of a regulatory-compliant cell line is a basic step in the production of clinical material, the starting choice of expression technology is sometimes a quick and not well-considered activity that is sometimes sacrificed in importance over financial expediency..
Recently, there has been increasing pressure within the biopharmaceutical community to produce high-quality batches in shorter production times, which is only possible through flexible and robust, low-cost processes.
An increasingly important number of recombinant proteins in development are monoclonal antibodies, which usually require multiple clinical doses at 10–100 times greater dosage concentrations than some other successful recombinant protein drugs, such as erythropoietin and human growth hormone. As a result there is a concerns in the industry about the sufficiency of manufacturing capacity for Cell Culture products.
To make up for these potential short falls in available capacity, there is intense focus on increasing expression levels to 1 g/L, with some now reporting 5 g/L. Demand for greater productivity has caused cell line development and optimization to become an increasingly critical step in the development process and one to be considered very early so as to guarantee effectiveness.
Some key factors in the cell line optimization process include deciding on the appropriate expression vector, cell line stability, media choice, media development, clone analysis, and process optimization Strategy.
Like in every biopharmaceutical process, the possible benefits of using proprietary expression technologies need to be carefully considered against the costs; in particular intellectual property rights costs, which may trigger eventual royalty accumulation. In the production of a clonal cell line, the expected development of molecular biology, transfection/selection and the minimum two rounds of cloning along with some scaled evaluation of each clone is often limited by deadlines, cost and the utility of the cell line. Identifying the critical decision points and key steps of cell line development is essential when putting together the strategies and methodologies for successful recombinant products manufacture.