With an increase in biopharmaceutical products in development, including antibodies and therapeutic proteins, the need for a robust immunogenicity assay is critical to assess the safety and efficacy of these therapeutics. The dosing of biotherapeutics can often illicit an immune response, in the form of anti-drug antibodies. The potential for these therapeutics to develop an immune response is dependent on several factors: the nature of the drug (degree of foreignness, aggregation, purity, formulation), nature of the dose (route of administration, chronic vs. acute dosing, PK), and nature of the patient (immunosuppression, autoimmune diseases).
The development and validation of methods for detection of host anti-drug antibodies are required by the US FDA and other regulatory authorities. At AIT Bioscience we have developed our processes for immunogenicity evaluation based upon the FDA Draft Guidance for Assay Development for Immunogenicity Testing of Therapeutic Proteins (2009) and several other industry standard reviews. The detection of anti-drug antibodies is dependent on key elements including sensitivity, interference, functional/physiological consequences, and a risk-based application. There are multiple analytical approaches which may be appropriate for immunogenicity testing during pre-clinical and clinical trials. We use a three-tiered approach, where sample analysis begins with an anti-drug antibody screening step that will identify potentially positive samples. Potentially positive samples are tested further by using a confirmatory procedure (e.g. competition-based method) in which samples are pre-incubated in the presence and absence of excess drug to demonstrate specificity of the assay response. If sufficient inhibition is found to confirm a true positive, the positive samples will undergo a titration procedure to assign a quasi-quantitative value as the titer.
For more information about AITB immunogenicity evaluation processes, contact us by email or phone at 317-715-8800.