Magnus Knutsson

Incurred sample reproducibility: views and recommendations by the European Bioanalysis Forum

Following intensive discussions, review, alignment of procedures and multiple surveys among their member companies, the European Bioanalysis Forum (EBF) is providing a recommendation on how to integrate incurred sample reproducibility (ISR) in the bioanalytical process. The recommendation aims to provide guidance throughout the lifecycle of a validated method, including the application of the method in study support. In its recommendation, the EBF considers both the internal discussions with EBF member companies, as well as the input provided in international meetings where ISR was discussed. The ultimate goal of the EBF recommendation is to ensure that bioanalytical methods can provide accurate and reproducible concentration data for pharmacokinetic and/or toxicokinetic evaluation, without any compromise, while safeguarding the optimal use of laboratory resources.

European Bioanalysis Forum recommendation: scientific validation of quantification by accelerator mass spectrometry

Accelerator mass spectrometry (AMS) is being used more widely to provide PK data for early decision making or to generate absolute bioavailability data in later phases of development. Presently, there is no clear consensus on the level of the scientific validation required for these assays. The European Bioanalysis Forum (EBF) has conducted two surveys with its members and presented the results at its 4th Open Symposium. With AMS being used for discrete scientific assessment, method establishment of AMS assays should focus on science rather than trying to fit the assay parameters into validation criteria used for Regulated Bioanalysis guidance, and an amount of freedom of execution and interpretation is needed. Hence, the EBF focuses their recommendation on introducing terminology around scientific qualification or validation to be used in relation to AMS. Guidance is given on which parameters should be investigated when a qualified method is required. The recommendations of the EBF for scientific validation are described herein. The scientific validation of AMS assays will be different to that applied for LC-MS/MS assays, and an example is that accuracy and precision limits, as used for ligand-binding assays, would be more appropriate.

Tiered approach into practice: scientific validation for chromatography-based assays in early development – a recommendation from the European Bioanalysis Forum

The principles of tiered approach have been part of the bioanalytical toolbox for some years. Nevertheless, an in spite of many valuable discussions in industry, they remain difficult to apply in a harmonized way for a broad array of studies in early drug development where these alternative approaches to regulated validation would make sense. The European Bioanalysis Forum has identified the need to proposes some practical workflows for five categories of studies for chromatography based assays where scientific validation will allow additional freedom while safeguarding scientific rigor and robust documentation: quantification of metabolites in plasma in relation to ICH M3(R2), urine analysis, tissue homogenate analysis, and preclinical and clinical studies in early stages of drug development. The recommendation would introduce a common language and harmonized best practice for these study categories and can help to refocus towards optimized scientific and resource investments for bioanalysis in early drug development.

Anticoagulant counter ion impact on bioanalytical LC-MS/MS assays: results from discussions and experiments within the European Bioanalysis Forum.

BACKGROUND In regulated bioanalysis, the need for partial validation when changing the counter ion of the anticoagulant is currently being debated within the bioanalytical community. To date, industry and the health authorities have not yet reached a consensus on this issue. The aim of the present study was to evaluate the impact of a change in counter ion when using the same anticoagulant on LC-MS/MS assay performance for a broad array of new chemical entities, compiling data generated at companies within the European Bioanalysis Forum (EBF). RESULTS In all, 15 EBF member companies provided experimental data on partial validation. In total, data from 42 LC-MS/MS assays were evaluated. The results show that a change in counter ion when using the same anticoagulant had no impact on assay performance. CONCLUSION Based on these results and on conclusions from previous studies, the EBF recommends that in regulated bioanalysis, plasma samples containing different counter ions, but the same anticoagulant, should be regarded as equal matrices, thus removing any need for partial validation.

Feedback from the European Bioanalysis Forum Workshop: taking tiered approach to the next level.

In this article, we give feedback on the progress in industry on their efforts to provide practical and tangible solutions for a harmonized implementation of the principles of tiered approach. By describing tiered approach as different levels of scientific validation applied as an alternative to apply established regulatory validation principles [1–4] for studies where the guidance was not the intended scope, we hope to provide an acceptable handle for its adoption for an array of study types in industry. The principles of tiered approach became gradually known in regulated bioanalysis about a decade ago [5,6], received positive comments by Health Authority (HA) representatives [7], and were further propagated in regulated bioanalysis with the support of industry consortia [8,9]. Going forward, the bioanalytical community identified more areas in scope of application for tiered approach in a recently published special focus issue of Bioanalysis [10]. The practice of adopting less rigorous (or exhaustive) validation requirements in earlier stages of development, as highlighted in recent (draft) guidance [11] and confirmed during discussions at the recent Crystal City V meeting (Baltimore, MD, USA, 3–5 December 2013) stimulated the European Bioanalysis Forum (EBF) to organize a special workshop on Tiered Approach in June 2014 (Brussels, Belgium) to seek further alignment and provide practical solutions to bring tiered approach to the next level; in other words, in day-today practice. The aim of the workshop, which started from a simple paradigm that a validated assay does not necessarily equate to valid data, was fourfold:

European Bioanalysis Forum: recommendation for dealing with internal standard variability

Adequate monitoring of internal standard (IS) response across an analytical run and identification of anomalies is now a common expectation. However, the means to conduct this assessment in an appropriate manner is unclear and differs widely between laboratories. A European Bioanalysis Forum (EBF) topic team was formed to survey current practices within European Bioanalysis Forum member companies and to recommend a best practice approach for dealing with IS response variability.