Bioequivalence and Bioavailability Forum

Dear forum members

The recent EMA guideline on bioanalytical method validation clearly states that full validation should be performed using matrix which has the same anticoagulant as the study samples. The general approach employed is that blood is collected into vacutainers which contain EDTA as an anticoagulant agent. However the plasma collection bags contain citrate-phosphate buffer. Is it possible (does the guideline allow it?) for a lab to conduct full validation with spiked plasma samples, with citrate-phosphate buffer as anticoagulant, and then run the main study samples, with EDTA as anticoagulant and not face major invalidation issues during an audit? Would a series of QC samples, covering the whole quantification range, prepared by spiking EDTA-plasma be enough to prove that there is no interference? The same guideline later on states that only a partial validation is required when there is a change in the anticoagulant.

In the case that the guideline is binding regarding the above matter could someone propose a solution, as we have not been able to find large volumes of blank plasma (to be used for pre-study validation) which has been treated with EDTA.

Thank you in advance

Constantinos