Bioequivalence and Bioavailability Forum

"ISR" – resolved [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2013-09-20 23:50 (4272 d 09:23 ago) – Posting: # 11537
Views: 13,725

Hi all,

17 pages of justification – essentially following the Q&A (simulations, later studies with ISR, literature data, back-conversion neither under physiological nor sample treatment conditions chemically possible, ).

Day 145 (NL)
Clinical aspects
Potential Serious Risks to Public Health
Pharmacokinetics

Study #1: The conclusion of the preliminary assessment report stands true as both prerequisites are met for waiving ISR: At the time point of the studies the Guideline on analytical validation was not in operation and back conversion is not an issue (re-esterfication is not an issue under physiological or sample preparation conditions; interconversion can be excluded, plasma concen­tra­tions are consistent with literature data). Moreover the applicant provided sup­portive data e.g. ISR results of studies #2 and #3 using the same ana­lyti­cal method and results of remeasurements confirming the robustness and re­li­ability of the analytical method.

Study #2: ISR has been performed and the results comply with the actual re­com­mendations, however formal requirements for the sample size were not met. This is considered acceptable as the same considerations as for study #1 are applicable. Moreover the results demonstrated very high reproducibility as 100% of ISR in study #3 were within the acceptance criteria for deviation.

Overall Summary and Conclusion
Issues resolved.

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Edit: PAR from HMA as of 2014-01-27. DE (RMS), AT, DK, ES, FI, LU, NL, NO, PL, SE, UK (CMS). Both studies were performed in a Two-Stage Design (Potvin’s “Method C”) – already passing in the first stage (no α-ad­justment = 90% CIs). The estimated Ĉ_min was assessed in the MD study.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


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Complete thread:

• Incurred sample reanalysis sarada06884 2013-04-09 12:22 [Regulatives / Guidelines] 
  • Incurred sample reanalysis Ohlbe 2013-04-09 14:09
    • Incurred sample reanalysis The Outlaw Torn 2013-04-10 08:40
      • Clopidogrel Ohlbe 2013-04-10 10:34
        • Clopidogrel The Outlaw Torn 2013-04-10 11:31
          • Lack of ISR / only 5% ISR in study with 656 samples Helmut 2013-04-22 17:01
            • Lack of ISR / only 5% ISR in study with 656 samples ElMaestro 2013-04-22 18:56
              • Lack of ISR / only 5% ISR in study with 656 samples Helmut 2013-04-22 19:35
                • "Meth" - apologies ElMaestro 2013-04-22 20:03
                  • "Meth" - apologies The Outlaw Torn 2013-04-23 08:27
                    • "Meth" - apologies ElMaestro 2013-04-23 14:29
                      • "ISR" - apologies The Outlaw Torn 2013-04-24 07:44
                        • Repeat use ElMaestro 2013-04-24 11:08
                          • Repeat use Ohlbe 2013-04-24 11:41
                            • Repeat use ElMaestro 2013-04-24 13:45
                        • "ISR" – resolvedHelmut 2013-09-20 21:50
                          • "ISR" – resolved Dr_Dan 2013-09-22 16:56
            • Lack of ISR / only 5% ISR in study with 656 samples ElMaestro 2013-04-23 23:31
              • Some more stuff Helmut 2013-04-24 02:08
              • Lack of ISR / only 5% ISR in study with 656 samples nobody 2014-10-23 10:06