Bioequivalence and Bioavailability Forum

Dear all,

EMEA's Draft Guideline on Validation of Bioanalytical Methods (19 November 2009) was just published. Comments as usual using this template to [email protected] until 31 May 2010.
I've heard that last week's meeting in Barcelona was a lively one with more than 400 participants...

The Draft follows closely FDA's Guidance (2001) and the Arlington III WP (2007). Some interesting points:

• Recovery not mentioned (great; superfluous)
  
• Selectivity: Absence of interfering components is accepted where the response is less than 20% of the lower limit of quantitation for the analyte. (The neverending story. How to calculate any percentage of a response below the LLOQ?)
  
• Chromatogram integration should be described in a SOP. Any deviation from this SOP should be discussed in the analytical report. (Nice. No blabla about manual reintegration like in the BE draft.)
  
• Normally reanalysis of study samples because of a pharmacokinetic reason is not acceptable. This is especially important for bioequivalence studies, as this may affect and bias the outcome of such a study. (Oops. In contradiction to Canada, the FDA and the Arlington III WP. Needs discussion. Reanalysis for identification of sample analyte in pre-dose samples or placebo sample is acceptable - what's the difference?)
  
• For BE studies analysis of incurred samples should always be carried out. Incurred sample analysis should be evaluated as early as possible. It is recommended that study samples are obtained from several subjects close to the expected maximal concentration and in the elimination phase. […] The difference between the two values obtained should be ≤20% of the mean (30% for LBAs) for at least 67% of the repeats.
  (I don't get it: x₁=110, x₂=90, mean=100, difference x₁-x₂=20% of the mean? That's a CV of 14% - sounds somewhat tough.)