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Recommendations for singlet-based approach in ligand binding assays: an IQ Consortium perspective
Renuka Pillutla1, Boris Gorovits2, Carol Gleason1
1Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
Bioanalysis
|June 20, 2020
Summary
This study found that singlet-based testing is acceptable for ligand-binding assays with low variability (CV ≤15%). This approach can be the default, improving efficiency in pharmacokinetic sample analysis.
Area of Science:
- Pharmacokinetics
- Bioanalytical Sciences
- Pharmaceutical Development
Background:
- Ligand-binding assays (LBAs) traditionally use duplicate sample analysis for pharmacokinetic (PK) studies.
- The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) aimed to evaluate the necessity of duplicate testing versus singlet-based analysis.
Purpose of the Study:
- To determine the scientific and operational value of duplicate versus singlet-based testing in LBAs for PK samples.
- To establish criteria for adopting singlet-based analysis to potentially increase efficiency.
Main Methods:
- Analysis of validation and in-study quality control data from eight organizations across 20 drug candidates.
- Utilized four analytical platforms and seven molecular types.
- Employed statistical comparisons and simulation models to assess bioequivalence outcomes.
Main Results:
- Good agreement was observed between duplicate sets for validation and quality control samples.
- Singlet-based testing is statistically acceptable for LBAs demonstrating %CV ≤15% between duplicates.
- Simulation models indicated that singlet testing does not negatively impact bioequivalence outcomes under specific precision criteria.
Conclusions:
- Singlet-based analysis is proposed as the default approach for LBAs when assay precision and accuracy are adequate (%CV ≤15%).
- Duplicate-based analysis remains necessary for assays with significant imprecision or inaccuracy that hinder validation.