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ABSTRACT
The culture media optimization is an inevitable part of upstream process development in therapeutic monoclonal antibodies (mAbs) production. The quality by design (QbD) approach defines the assured quality of the final product through the development stage. An important step in QbD is determination of the main quality attributes. During the media optimization, some of the main quality attributes such as glycosylation pattern, charge variants, aggregates, and low-molecular-weight species, could be significantly altered. Here, we provide an overview of how cell culture medium components affects the main quality attributes of the mAbs. Knowing the relationship between the culture media components and the main quality attributes could be successfully utilized for a rational optimization of mammalian cell culture media for industrial mAbs production.
Keywords: Main quality attributes, Monoclonal antibodies, Glycosylation, Fragmentation
INTRODUCTION
Process development is a state-of-the-art method to establish a manufacturing line in biopharmaceuticals. Although a significant shift in productivity is the main goal of process development, achieving appropriate quality attributes is also of great concern. Quality by design (QbD) is a new approach to develop and to manufacture pharmaceutical products. QbD guarantees product quality and ensures that a consistent product with preferred quality attributes is generated[2,3]. Regulatory agencies encourage its application in the manufacture of all new pharmaceuticals containing biological products[2-4].
The cell line and its recombinant DNA construct, culture media, and process conditions are three important parameters that influence recombinant protein quality properties in the manufacture of biopharmaceuticals. The culture media and the control of process conditions are very important in process development^'61. In fact, the cell metabolism directly depends on the culture conditions, including the pH[7], the temperature[8], the oxygen tension[7], the CO2 amount in the culture broth[9], and also the mode of processing, i.e., perfusion or fed-batch mode[10]. Diverse metabolic outcomes states that result from modifications in these culture parameters might produce proteins with altered quality attributes. Many review articles have been published in this field with a focus on the cell line[11-13] and cell culture parameters[14'15]. Moreover, with concentration on the regulation of certain media constituents and by supplementing the medium with specific co-factors, the glycosylation profile[16], the charge variants[17], the aggregation amount[18'19] and the level of lowmolecular-weight (LMW) variants[20] can be controlled.
At this time, monoclonal antibodies (mAbs)...