High Concentration Monoclonal Antibody Drugs Manufacturing Challenges

The specificity, and at the same time, versatility, of monoclonal antibody (mAb) therapies continues to make them a strong candidate for the treatment of a wide variety of diseases, including autoimmune and cancer therapies. As the list of diseases that can be targeted by mAb and recombinant proteins (rPro) grows, their relative maturity permits opportunities to address challenges with the method of administration, thereby improving the experience of the patient and easing the burden of the healthcare provider.

The last decade has seen the most rapid advances in the enablement of subcutaneous delivery methods as opposed to the routine intravenous (IV) infusion. Subcutaneous delivery provides the option of self-administration of the therapeutic by the patient, reducing frequency and duration of any visit to the clinic, improving both the patient experience, and reducing healthcare costs associated with the longer, more complex IV infusion. Producing a drug product that can be administered in this way requires careful formulation to deliver the desired dose in a volume that can be tolerated and absorbed.

This paper reviews manufacturing challenges including viscosity, aggregation, and instability, and the effect of excipients on formulation, filtration, and fill and finish and bioavailability when formulating high concentration monoclonal antibody drugs.