Critical Future Challenges for Ligand-Binding Assays

4 CRITICAL FUTURE CHALLENGES FOR LIGAND-BINDING ASSAYS 

Given the foregoing discussion of some of the unique characteristics of macromolecules that lead to clear differences in their pharmacokinetics compared to those typical of small-molecule drugs, there is a subset of the entire group of bioanalytical assay validation parameters that are of key importance in support of pharmacokinetics of candidate macromolecular therapeutics. Assuming demonstration of accuracy and precision of sufficient quality for the intended application of the assay (e.g., non-GLP discovery support or GLP toxicokinetic support, as discussed above), the most important characteristics of a given assay in support of pharmacokinetic studies are likely to be selectivity, specificity, and reproducibility for analysis of incurred samples. These are all related to the ability of the LBA to detect and quantitate solely, or as closely as possible to solely, the analyte of interest. 

The true specificity of LBAs for macromolecules is rarely addressed in depth, primarily for the reason that breakdown products of the macromolecule (metabolites and catabolites) are rarely available as reference standards for inclusion in crossreactivity studies. Where possible, attempts are made to derive some data to support 

DeSilva, B., Smith, W., Wiener, R., Kelley, M., Smolec, J., Lee, B., Khan, M., Tacey, R., Hill, H., and Celniker, A. (2003) Recommendations for the bioanalytical method validation of ligand binding assays to support pharmacokinetic assessments of macromolecules. Pharmaceutical Research, 20, 1885 1900. 

2008 PhRMA Report, Medicines in Development Biotechnology. Available athttp //www. phrma.org/files/Biotech%202008.pdf. Accessed December 24, 2008. 

---