Advances in the Development of Therapeutic Monoclonal Antibodies
Since the commercialization of the first therapeutic monoclonal antibody products in the early 1990’s, these products have become a dominant component of the biopharmaceutical market with combined revenues of several billion dollars. The early monoclonal antibody products were generally chimeric antibodies containing murine variable regions and human constant regions. As a result, these products posed a moderate risk of immunogenicity to patients from the residual murine components. With the development of new technologies for humanization and for generation of fully human antibody products, the industry standard has changed and most future antibody products will be humanized or fully human antibodies. One challenging feature of most therapeutic antibody products is that the doses required these products are much higher than other biologic products resulting in significant annual production requirements. To meet these needs, companies have made substantial progress in developing more efficient and cost effective methods for manufacturing antibody products, especially in the critical areas of cell line generation and antibody productivity from a production cell line. Advances in cell culture technology over the past decade include new expression vectors and transfection technology, novel parental cell lines that have been selected or designed to grow to maximum density and productivity under bioreactor conditions, and high throughput, robust screening technologies that in combination can enable rapid generation of production cell lines expressing multi-gram quantities of antibody per liter of culture media. In the future, the competing demands of growing production requirements and reduced cost to the patient will present challenges to the industry to make manufacturing processes even more efficient, including making downstream processing more robust and capable of processing the increased product quantities produced with increased bioreactor titers, advances in product formulations for greater stability of high concentration antibody products and alternative delivery systems, and the implementation of Quality by Design to reduce the cost and development timelines for monoclonal antibody products without adversely impacting the quality of these products.