An alternative design for long-term stability testing of large molecules: a scientific discussion paper from an EBF Topic Team

Abstract

Aim: Long-term stability testing of drug candidates in biological matrix is a key parameter in bioanalytical method validation. The European Bioanalysis Forum formed a Topic Team to evaluate the use of isochronic design for long-term stability testing of large molecules. Method: Isochronic design is based on storage of samples at a reference temperature (below -130°C) where the samples are considered stable. The stability samples are stored at the intended storage temperature and then transferred to the reference temperature, while a set of reference samples is stored the entire storage period at the reference temperature. Stability and reference samples will then be analyzed in one run at the end of the storage period. The mean concentrations of the stability samples are compared either to their nominal concentrations or to the mean concentrations of the reference samples. Conclusion: The design minimizes day-to-day variation, reduces workload and adds to the flexibility in the laboratory.