Bioequivalence and Bioavailability Forum

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

posted by Ohlbe – France, 2020-07-16 19:16 (1552 d 10:17 ago) – Posting: # 21718
Views: 6,199

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’?

Complete thread:

• Reanalysis for Pharmacokinetic Reason Obinoscopy 2020-07-16 14:30 [Bioanalytics] 
  • Reanalysis for PK Reason: Gone with the Wind Helmut 2020-07-16 15:10
    • Reanalysis for PK Reason: Gone with the WindOhlbe 2020-07-16 17:16
      • Reanalysis for PK Reason: Gone with the Wind Helmut 2020-07-16 18:39
        • Reanalysis for PK Reason: Gone with the Wind Ohlbe 2020-07-16 19:15
      • Reanalysis for PK Reason: Gone with the Wind Obinoscopy 2020-07-16 21:48
        • PK assessors variability Ohlbe 2020-07-16 23:07
          • Sometimes PK assessors ≈ scientists Helmut 2020-07-17 16:11
          • PK assessors variability Obinoscopy 2020-07-17 23:48
        • Reanalysis for PK Reason: Gone with the Wind ElMaestro 2020-07-16 23:19
          • Reanalysis for PK Reason: Gone with the Wind dshah 2020-07-17 06:40
            • Reanalysis for PK Reason: Gone with the Wind Obinoscopy 2020-07-18 00:27
              • Reanalysis for PK Reason: Gone with the Wind dshah 2020-07-20 07:22
                • Reanalysis for PK Reason: Gone with the Wind Obinoscopy 2020-07-20 14:12
                • Positive pre-dose Ohlbe 2020-07-20 14:43
          • Reanalysis for PK Reason: Gone with the Wind Obinoscopy 2020-07-18 00:00
            • Reanalysis for PK Reason: Gone with the Wind ElMaestro 2020-07-20 07:49
              • Reanalysis for PK Reason: Gone with the Wind Helmut 2020-07-20 10:52
                • Sightly OT (for once) ElMaestro 2020-07-20 12:12
  • Reanalysis for Pharmacokinetic Reason Achievwin 2020-07-27 23:47