Bioequivalence and Bioavailability Forum

Hi QA,

❝ First of all as per ICH "reanalysis of study samples for a PK reason (e.g., a sample concentration does not fit with the expected profile) is not acceptable, as it may bias the study result."

You are right (ICH M10 of 2022). Heretical question: Will not a wrong (I know, I know…) concentration bias the result?
At a joint EGA/EMA workshop (London, June 2010) Gerald Beurle (TEVA/ratiopharm) presented a hypothetical example, where due to a single sample switch a study would pass BE. However, it would fail if concentrations are swapped or even the entire data of the subject would be excluded from the comparative analysis. Consensus expressed by the panel members of the PK working party (responsible for the GL):

“The value must not be reanalysed. It has to be kept as it is – even if the study would falsely pass BE.”

That was too much for me. I said:

“The EMA is a serious risk to public health!”

IMHO, this is not science anymore but a belief system: What we measure once is the truth.

• The game of science is, in principle, without end. He who decides one day that scientific statements do not call for any further test, and that they can be regarded as finally verified, retires from the game. — Karl R. Popper (1959)
  
• Whenever a theory appears to you as the only possible one, take this as a sign that you have neither understood the theory nor the problem which it was intended to solve. — Karl R. Popper (1972)
  
• Blind commitment to a theory is not an intellectual virtue: it is an intellectual crime. — Lakatos et al. (1978)