Non-constant mean relative potency for antibody-dependent cellular cytotoxicity assays

Area of Science:

• Biopharmaceutical analysis
• Quantitative pharmacology
• Analytical chemistry

Background:

• Bioassays are critical for ensuring biological product potency and stability.
• Traditional relative potency calculations assume similar concentration-response curve shapes, which is not always biologically feasible.
• Non-similar curve shapes limit the applicability of standard bioassay methods, particularly in antibody-mediated cytotoxicity assays, toxicology, and pharmacology.

Purpose of the Study:

• To introduce a novel non-constant mean relative potency approach for bioassays.
• To provide a method for calculating a summary statistic that reflects changing relative potency.
• To enable reliable batch calibration and quality control when curve similarity is not met.

Main Methods:

• Development of a non-constant mean relative potency method averaging potency across a common concentration range.
• Establishment of inferential statistical methods for the proposed summary statistic.
• Simulation studies to evaluate the performance of the new method under various non-constant relative potency scenarios and assay conditions.

Main Results:

• The proposed non-constant mean relative potency approach effectively captures changing potency characteristics.
• The method provides a robust summary statistic suitable for quality control applications.
• Simulation results demonstrate the method's utility across diverse non-constant relative potency situations.

Conclusions:

• The non-constant mean relative potency approach offers a viable solution for bioassays where traditional assumptions fail.
• This method enhances the accuracy and reliability of potency determination for biological products.
• The developed inferential methods and simulations support the practical application of this approach in biopharmaceutical quality control.