Complexities of Protein Therapeutics and Immunogenicity

Overview & Synopsis

Biopharmaceuticals like monoclonal antibodies are widely used in clinical medicine for various therapies e.g. cancer, inflammatory and autoimmune diseases. Immunogenicity is one of the issues for safety. Such undesired immunogenicity can also limit the use of biopharmaceuticals, particularly for the treatment of chronic diseases that necessitate repeated treatments over long period. Assessment of immunogenicity is an important component of drug safety evaluation, which is presently performed by estimating risk factors. Risk based approach considers both probability of induction of immune response and expected clinical consequences. A combination of the two may result in high, medium or low risk levels and will depend on the product, patient and treatment related characteristics. Well engineered cells, well designed formulation coupled with good manufacturing scheme may sometimes reduce some of the extrinsic and intrinsic factors and increase the stability of drug product. One of the proposal for remedies is to purify the drug product to homogeneity or near homogeneity retaining its stability and functional activity. On the other hand, quite a few biosimilar drugs, which are supposed to be economical version of branded biotherapeutics, is expected to be in the market in next several years. Unfortunately, biosimilar manufacturing is often different from the brand name drug due to variation in manufacturing processes. As a result, such variations may trigger unwanted immunogenicity. Risk based approach, like branded drug, is more likely be required for drug development of therapeutic proteins for evaluation of immunogenicity followed by a development plan for risk mitigation.