A white paper--consensus and recommendations of a global harmonization team on assessing the impact of immunogenicity on pharmacokinetic measurements.

The Global Bioanalysis Consortium (GBC) set up an international team to explore the impact of immunogenicity on pharmacokinetic (PK) assessments. The intent of this paper is to define the field and propose best practices when developing PK assays for biotherapeutics. We focus on the impact of anti-drug antibodies (ADA) on the performance of PK assay leading to the impact on the reported drug concentration and exposure. The manuscript describes strategies to assess whether the observed change in the drug concentration is due to the ADA impact on drug clearance rates or is a consequence of ADA interference in the bioanalytical method applied to measure drug concentration. This paper provides the bioanalytical scientist guidance for developing ADA-tolerant PK methods. It is essential that the data generated in the PK, ADA, pharmacodynamic and efficacy/toxicity evaluations are viewed together. Therefore, the extent for the investigation of the PK sensitivity to the presence of ADA should be driven by the project needs and risk based.