Complexities of Protein Therapeutics and Immunogenicity

Abstract

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.

Issues in Regulatory Progress of Biosimilars-An Update

“…The critics of this program claim that it does not highlight sufficiently the inherent difference between biosimilars and their reference products. Since they are biological, as discussed earlier [3,4] they cannot be identical with their originals. Instead, a biosimilar has to demonstrate similarity to the reference product in terms of quality characteristics, biological activity, safety, and efficacy based on the comprehensive comparability exercise [8,9].…”

“…As the use of biotherapeutics continues to expand within pharmaceutical marketplace, the development of biosimilars represents great potential or vast expansion within the industry. Unfortunately, biosimilar manufacturing is often different from the brand name drug due to variances in preparation starting from raw materials to finalized products [3,4]. As a result, such variations may trigger unwanted adverse events.…”

“…In the meantime FDA issued two important long waited guidance [1-3]: one on labeling and the other one in inter changeability of drug product. Several organizations from both countries commented on the labelling and inter changeability [3][4][5]. According to these comments it is important to provide complete, accurate, transparent prescribing and dispensing information of bio similar and interchangeable biological products [5][6][7][8][9].…”

Drug safety and immunogenicity of tumour necrosis factor inhibitors: the story so far

“…However, often the study design and data source make conclusions about causal associations between ADAbs and AEs challenging. Repeated drug exposure can result in a break in immune tolerance to self-antigens, leading to allergic reactions, immune complex disease and subsequent AEs [ 6 ]. In drug safety assessment, immunogenicity testing is now mandatory prior to approval of new biopharmaceuticals by both the US Food and Drug Administration (FDA) [ 7 ] and the European Medicines Agency (EMA) [ 8 ].…”