Monoclonal Anitbody (mAb)

Monoclonal antibodies (mAbs) are the most successful class of biologics today, and this class of therapies has grown rapidly over the past 20 years, with hundreds of mAbs in clinical development and numerous mAb products already approved for a variety of indications, including oncology, autoimmune diseases, and rare disease indications. While the ability to target cell surface targets with high specificity has been the reason behind the rise of mAbs, another key enabler has been the ability to rapidly develop robust manufacturing processes to advance mAb candidates into clinical trials and commercialization, namely, the ease and speed of producing mAbs enables rapid entry of these product candidates into clinical trials, and the scalability and robustness of these processes greatly facilitates large-scale commercial supply.

The development of protein production processes requires consideration of many different factors, including removal of impurities, robustness, scalability, and ready availability of raw materials for large-scale production. Consider not only the scale required for early clinical supply, but also the ability of the process to support long-term supply needs and scale. Therefore, utilizing well-established unit operations is a critical aspect in developing a production process. Aspects such as robustness, scalability, and reproducibility mean that production processes often look quite different from methods used in the laboratory to purify small amounts of protein. Process development can be a time-consuming activity requiring extensive experimentation. Therefore, where possible, the industry favors a platform approach.

From a business perspective, the platform approach has clear advantages. Clinical speed is often a key determinant of a company's success. mAb platforms can progress from gene to IND in less than a year, a significant improvement over molecules that require up to 2 years of development work. This reduced experimentation also means lower development costs. The predictability of the platform process enables departments such as production and quality control to adopt a templated set of documents, which also reduces the time and resources spent on production and release testing. The mAb process platform enables a high-yield, robust manufacturing process from the start of clinical development through product commercialization. The consistency and predictability of the platform approach greatly facilitates the development of such therapies.

mAb therapeutics are particularly well-suited for the application of a platform approach. Stable cell lines for mAbs can be developed in a very rapid and templated manner using well-established mammalian cell culture expression systems. Several expression vectors have been optimized specifically for mAb production, and industry has developed robust fed-batch cell culture processes for mAbs, some of which have been scaled up to large-scale production and extensively characterized, allowing better understanding of the operating parameters that affect these processes. Cell line development and upstream cell culture processes are well suited for templated approaches. For most proteins, the biggest difference is in the form of the downstream purification process, which must be tailored for each protein based on its properties as well as those of key impurities. The Fc region of the mAb binds very specifically to immobilized Protein A, component derived from Staphylococcus aureus. Protein A affinity chromatography has been shown to be broadly applicable to mAbs and can achieve >95% purity. The main challenge after Protein A chromatography is the removal of residual host cell protein impurities, high molecular

Many factors are driving changes in traditional biopharmaceutical production, including the rise of biosimilars, the establishment of a global manufacturing network, and the development of next-generation antibody structures (such as bispecific antibodies, Fc fusion proteins, and antibody drug conjugates (ADCs)) , the continuous improvement of upstream titers achieved by technologies such as perfusion, the development of new downstream process technologies, and the wider adoption of single-use technologies, meanwhile, the production cost has increasingly become the focus of attention. Companies with production capacity are looking to use existing plants more efficiently, and incorporate concept of cost savings and efficiency while building new facilities.