Impact of the new European Guideline for the bioanalytical method validation

Dr Patrick Duchêne, Eurofins ADME Bioanalyses, France

For over a decade, the main regulatory reference for the bioanalytical method validation has been the US Food and Drug Administration’s (FDA) Guidance on that topic.

Last July, the European Medicines Agency (EMA) proposed its own Guideline, effective 1st February 2012.

With regards to the US FDA guidance and subsequent white papers, the EU guidance adds new requirements mainly for matrix effect, selectivity and stability.

In addition to the normal matrix, EU guidance recommends to investigate the matrix effect on other samples e.g. haemolysed and hyperlipidaemic plasma and also in samples from specific populations. The impact of the co-medications, metabolites (including back-conversion) and excipients on the selectivity has also to be studied.

Stability should be ensured for every step in the analytical method e.g. same anticoagulant, in the presence of metabolites and co-medication. Recommendations differ according to the reference concentration to be used for the calculation of longterm stability, i.e. the nominal concentration (EMA), or the mean of back calculated values on the first day of long term stability testing (FDA).

In conclusion, both guidances are compatible, even if the FDA does not require today these complimentary tests, the US and the other medical agencies agree on the importance of these criteria to increase and assure the robustness of the bioanalytical method. Concerning long term stability both criteria should be satisfied to avoid any discussion. Bioanalytical (BA) procedures within BA Eurofins labs have been reviewed to comply with these new requirements.

Contact: bioanalysis@eurofins.com