From cell line engineering to the formulated drug product: The art of
manufacturing therapeutic monoclonal antibodies
Abstract
Therapeutic monoclonal antibodies and related products have steadily
grown to become the dominant product class within the biopharmaceutical
market. Production of antibodies requires special precautions to ensure
safety and efficacy of the product. In particular, minimizing antibody
product heterogeneity is crucial as drug substance variants may impair
the activity, efficacy, safety and pharmacokinetic properties of an
antibody, consequently resulting in the failure of a product in
pre-clinical and clinical development. This review will cover the
manufacturing and formulation challenges and advances of therapeutic
monoclonal antibodies, with a focus on improved processes to minimize
variants and ensure batch-to-batch consistency. Processes put in place
by regulatory agencies such as Quality-by-Design (QbD) and current Good
Manufacturing Practices (cGMP) will be reviewed, and how their
implementation has aided drug development in pharmaceutical companies.
Advances in formulation and considerations on the intended use of a
therapeutic antibody, including route of administration and patient
compliance, will be discussed.