Best Practices in mAb and Soluble Target Assay Selection for Quantitative Modelling and Qualitative Interpretation

Area of Science:

• Pharmaceutical Science
• Biotechnology
• Drug Discovery

Background:

• Biologics, particularly monoclonal antibodies (mAbs), are crucial in pharmaceutical R&D.
• Accurate measurement of mAb-target interactions is vital for drug development, especially for soluble targets.
• Current assay development for mAb-target interactions can be resource-intensive and yield contradictory data.

Purpose of the Study:

• To recommend a more robust and efficient strategy for developing assays to measure mAb-target interactions.
• To address the limitations of traditional 'free target' assays in drug development.
• To guide the development and interpretation of data from specialized assays for biologics.

Main Methods:

• Comparative analysis of 'total' vs. 'free' target assay methodologies.
• Evaluation of assay sensitivity to sample preparation and experimental conditions.
• Discussion of model-based estimation for free target concentrations.

Main Results:

• Total assays are less susceptible to re-equilibration and sample handling artifacts compared to free assays.
• Direct measurement of free target can be inaccurate due to pre-analytical variables.
• Model-based estimation using total assay data offers a more reliable approach to determine free target concentrations.

Conclusions:

• Early investment in developing total assays for both mAbs and targets is recommended for efficient drug development.
• Utilizing total assay data with model-based estimation provides a more robust assessment of free target dynamics.
• Prospective consideration of biases is crucial when using free target assay data for quantitative analysis.