Monoclonal antibodies (mAb) are approved in a wide range of conditions and represent the largest class of biotherapeutic products. mAbs are large molecules with complex structures and functions. Though bestowed with remarkable specificity and flexibility; the unique properties of mAbs remain a challenge to their drug development, with only a few achieving clinical success.
As mAb are proteins, most of the time, there are stability and pharmacokinetics issues, which negatively impair development. Immunogenicity issues and difficulty in translating data points from animals to humans are other challenges.
Unsuitable biophysical properties make large scale manufacture difficult
Protein engineering has rendered mAbs with better functional characteristics; however, given the complexity of these molecules, there are many issues that can create manufacturing problems.
mAbs are large multimeric proteins containing numerous disulfide bonds and post-translational modifications. Hence, the manufacturing of therapeutic antibodies requires large cultures of mammalian cells and extensive purification steps, which leads to high production costs.
Another issue with mAbs is the high concentrations required to achieve clinical efficacy. Many mAb formulations are used at concentrations higher than 100 mg/mL. Highly concentrated formulations can lead to irreversible aggregation, irreversible precipitation, and high viscosity, and these conditions can present unique challenges to product development.
Stability - A matter of huge concern
Maintaining stability within a highly concentrated product is a matter of concern. If proper stability is not achieved, and the product degrades during shipment or storage, patient safety could be at risk.
The efficacy of mAB therapeutics depends on the structural, conformational, and chemical stability; hence preventing physical and chemical degradation is pivotal. A thorough understanding of the mechanisms and the causes of mAB degradation has allowed developers to craft various stabilization strategies, including pH optimization and identifying effective buffer components to stabilize the mAb.
· Addition of stabilizers
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