Best Practice Recommendations for The Transfer of Cell-Based Assays for The Measurement of Neutralizing Anti-Drug Antibodies

Abstract

We recommend the application of a strategically designed step-wise approach to transfer cell-based assays that includes assessing analytical performance (through a fit for purpose validation and/or design of experiment robustness characterization), clinical performance (i.e., concordance) and performance or proficiency testing for long-term method monitoring. Here we focus on the application of this strategy to cell-based assays for the measurement of neutralizing anti-drug antibodies. This application is unique in that it requires a custom cell-based assay to be used over a long period of time (potentially phase 1a through the life of a marketed product) with the confidence of consistent method performance and result reporting. But, the process is adaptable to a variety of assay types and applications. We present lessons learned from two cell-based assay transfers that met relevant challenges while implementing alternative permutations of the recommended method transfer process.

Systems pharmacology and enhanced pharmacodynamic models for understanding antibody-based drug action and toxicity

“…Regulatory documents and literature reports have provided guidance to meet the regulatory requirements of characterizing and quantifying immune responses to mAb therapeutics. 52,53 Circulating ADA can exhibit different specificities and binding affinities and have different effects on the PK/PD of mAbs: 1) a neutralizing effect on drug activity by interfering with mAb binding to its pharmacological target, 2) a non-neutralizing effect on drug activity and a sustaining effect on the PK, and 3) non-neutralizing effect on drug activity, but an enhanced elimination of the mAb. The mechanisms by which ADA alter the PK of mAbs are not completely known.…”