Addressing the challenges of biomarker calibration standards in ligand-binding assays: a European Bioanalysis Forum perspective.

The analysis of biomarkers by ligand-binding assays offers significant challenges compared with the bioanalysis of small and large molecule drugs. The presence of endogenous analyte is a commonly cited issue. Also the sourcing and application of appropriate calibration or reference standards can present many issues. One of the main challenges is ensuring the continuity and validity of biomarker data when the source or lot number of calibration standard changes within or between studies. Several strategies exist in attempting to deal with this and standardize the biomarker data through the assay life or looking for ways to compare and normalize biomarker data. In this manuscript, the European Bioanalysis Forum view on dealing with calibration standards in biomarker assays is described.

Conference report: AAPS and US FDA Crystal City V meeting on Quantitative Bioanalytical Method Validation and Implementation: feedback from the EBF.

Crystal City V meeting on Quantitative Bioanalytical Method Validation and Implementation: 2013 Revised US FDA Guidance 3-5 December 2013, Hilton Baltimore, MD, USA The meeting provided an opportunity for Industry and regulators from the US FDA to discuss the recently published revised draft FDA Guidance for Industry on Bioanalytical Methods Validation during the 90 day review period. Key perspective and philosophical positions were shared leading to a healthy exchange of views and ideas on topics in the revised document. Discussions covered all aspects of bioanalytical method validation and method utilization. However, the main dialogue was focused on chromatographic methods, ligand-binding assay methods and biomarker analysis. The resulting open debate led to greater understanding of the document, but also provided clear feedback, including the request on harmonization with approved Bioanalytical Methods Validation guidance's release from other health authorities, as well as the consensus view between industry and the FDA. Members of the European Bioanalysis Forum summarized prospective discussions during the meeting in Baltimore; however, this Report is not intended to constitute the official proceedings from the meeting, which are expected to be published later this year.

European Bioanalysis Forum recommendation on method establishment and bioanalysis of biomarkers in support of drug development.

Biomarkers have become increasingly important in drug development and many bioanalysts are getting involved. Consequently, different views on how to approach the bioanalysis of biomarkers have been published or are being developed. The European Bioanalysis Forum has intensively discussed this topic since 2010 and is ready with their recommendation on method establishment and bioanalysis of biomarkers. Acknowledging that the challenges step outside the bioanalytical laboratory is a cornerstone of our recommendation. The importance of integrating all scientific aspects, from purely analytical aspects, all the way to understanding the biology and effects of the biomarker, prior to embarking on method establishment or sample analysis, cannot be underestimated. Close and iterative interactions with the teams requesting the data is imperative to develop a bioanalytical strategy that combines science, analytical performance and regulations. The European Bioanalysis Forum developed a straightforward decision tree to help the scientific community in developing a bioanalytical strategy for any biomarker in drug development.