Reanalysis for PK Reason: Gone with the Wind [Bioanalytics]

posted by Ohlbe – France, 2020-07-16 17:16 (457 d 16:23 ago) – Posting: # 21718
Views: 3,611

Dear Scopy and Helmut,

» » I am trying to get my head around why reanalyzing a blank sample because it had values above LLOQ in the initial analysis is not considered reanalysis for pharmacokinetic reason.
»
» Congratulations for discovering this inconsistency.

Not necessarily an inconsistency: in the EMA guideline, PK re-analysis is not acceptable only for BE trials, but the guideline is applicable to all bioanalytical work. Confirming the presence of the analyte in a pre-dose sample could be relevant for other types of studies (and even worse, finding analyte in a placebo-treated subject, or animal in a TK study).

» » My thinking is...if a pre-dose sample gives a detectable peak area on analysis and on evaluation, there seem to be no explanation for this, why is it okay to reanalyze it again?
»
» That’s against scientific thinking.

I do see a scientific value: trying to understand whether this could be due to a contamination or analytical carry-over. But I agree this could be done under the reanalysis for "laboratory investigations" allowed by the guideline.

Other potential argument: the potential influence on AUC is very limited and there is no influence on Cmax, so there is no risk that such re-analysis may be done in order to make a failing study pass (which I did see once in the past).

» According to the current guidelines (EMA 2011, FDA 2018, ICH draft 2019) it is no more acceptable. IMHO, bad science.

Agreed.

» In the past it was acceptable to perform a blinded review of data and have rules for reanalysis / exclusion in the protocol. Regrettably, those days are gone and – understandable – paranoia (driven by the many cases of fraud) prevails.

Strangely enough, according to discussions I had with people involved in drafting the EMA guideline, it seems that it was the assessors who did not want to hear about PK repeats, not the inspectors – though the latter are well known for their paranoia, and for good reasons.

» * Funny term. What is ‘rich chromatography’?

:-D

Regards
Ohlbe

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