Understanding Biopharmaceuticals: The Future of Medicine

Abstract

Biopharmaceuticals are novel therapeutic products developed from living systems that are manufactured using biotechnology and complex biologics. They include widely used monoclonal antibodies and hormones, as well as emerging novel treatments, oftentimes composed of complex biomolecules engineered from living organisms. These products offer a system-based and disease-targeting solutions to chronic, prevalent, debilitating diseases. Biopharmaceutical drugs make up a substantial part of the global drug market and a majority of the new drug approvals. Most developers of mammalian cell-grown biopharmaceuticals manufacture drugs via pools of static clear plastic vessels stirred to keep cells in suspension. Although extensively used, this traditional batch fed production system suffers several drawbacks and is an obstacle to meeting the ever-increasing global demand for biopharmaceutical drugs. Replacing traditional batch fed with continuous perfusion bioreactors has been demonstrated to be highly beneficial yet remains a nascent state in the industry. In order to develop a rapid and high performing continuous perfusion upstream process, there is a need to better understand the biopharmaceutical production systems and identify and characterize engineering, cellular, and perfusion design factors that could potentially influence perfusion system performance. Dissecting and modeling performance in batch fed systems is an essential first step. In this biopharmaceutical systems case study, the state of the industry regarding processes and technologies for biopharmaceutical production is described, with an emphasis on upstream processes. New bioprocess analytical technologies on both the molecular and process scale develop and adopt suitable modeling and control technologies to replace the traditional batch approach to product realization with a continuous, more efficient approach.

In the present review, advances made in plant-based bio-pharming as drug production systems are presented. The paradigm shift in the drug discovery pipeline away from the synthetic drug mentality from screening small molecules towards the bio-pharming pathways is discussed; influences that have resulted in more consideration of drug discovery and production in plants are presented. The emergence of plants as monoclonal antibody systems and drug production bioreactors are illustrated by several case studies based on collaborative efforts based on established and emerging transgenic technologies. Potential major advantages of the biopharming paradigm in terms of the production of complex glycoproteins in a more affordable, readily available technology relative to mammalian cell and other systems are highlighted. However, the uncertainties and challenges facing such technology from competing platforms, unresolved technical problems, patent politics, regulatory issues, potential risks to human health, issues of gene escape, and animal welfare concerns are also discussed. The paper concludes with the view that the infidelity of rigging plant-based systems cannot be allowed to diminish this major opportunity for bioproduction mastery of the post-genomic era.