Bioequivalence and Bioavailability Forum

Confidence intervals vs. point estimates [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2010-08-06 15:20 (4802 d 02:54 ago) – Posting: # 5729
Views: 14,870

Dear ElMastro, Dan & all!

❝ […] the guideline specifically reads: "The test product should usually originate from a batch of at least 1/10 of production scale or 100,000 units, whichever is greater, unless otherwiseustified."

❝ This is because everybody knows that there is variability between batches and that performance of a pilot batch is not necessarily equal to a full scale batch. So, you will just with kind words remind the assessor that a bunch of his/her colleagues acknowledge that fact that pilot performance is not pivotal performance and cannot be expected to be. Yes, there is variability between batches. No, it is not a problem, you are handling it well by separating pivotal data from pilot data.

I would say, this argument holds exactly for Study 1 (lab batch). Study 2 (pilot) was performed with a full size batch (I assume), but due to power considerations (sample size!) and the property of HVDs (variable PE across studies) a direct comparison with pivotal studies is futile.

Agree with the mixed model – would be fun setting up (other factors: study and center).
But I would not dive too deep into the murky waters of statistics, but rather go with common sense. According to guidelines (not only BE) nobody expects that all studies in the file were performed with the same batches. Imagine a hypothetical situation: Two studies fasting/fed. The same batch of test, but two batches of the reference. There is a true food effect of -20% and a true ‘batch effect’ of +25%. What would we get? BE fasting and BE fed. As ElMaestro suggested I would remind the assessor in nice words, that following his/her arguments would call for a requirement which is not covered in GL(s).

❝ S.

  ^

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


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Science Quotes

Complete thread:

• inter-batch variability? Dr_Dan 2010-08-04 10:29 [Regulatives / Guidelines] 
  • inter-batch variability? Pavidus 2010-08-04 11:57
  • inter-batch variability? d_labes 2010-08-04 13:58
  • inter-batch variability? ElMaestro 2010-08-04 17:09
    • Between study variability common for HVDs Helmut 2010-08-04 19:45
      • Between study variability common for HVDs ElMaestro 2010-08-04 21:01
        • Representative batches? Helmut 2010-08-04 23:42
          • Representative batches? ElMaestro 2010-08-05 08:40
            • Representative batches? Helmut 2010-08-05 12:30
          • Representative batches? Dr_Dan 2010-08-05 08:58
            • Representative batches? Helmut 2010-08-05 12:45
              • Confidence intervals vs. point estimators Dr_Dan 2010-08-06 09:55
                • Confidence intervals vs. point estimators ElMaestro 2010-08-06 12:34
                  • Confidence intervals vs. point estimatesHelmut 2010-08-06 13:20
                  • Confidence intervals vs. point estimators Dr_Dan 2010-08-06 14:44
                    • Confidence intervals vs. point estimators ElMaestro 2010-08-06 15:01
                      • meta analysis? martin 2010-08-06 17:25
                        • meta analysis? ElMaestro 2010-08-06 17:57
                          • meta analysis? Helmut 2010-08-06 18:31
                        • meta analysis? Ohlbe 2010-08-06 23:21
                          • No chance against RMS? Dr_Dan 2010-08-10 12:27
                            • No chance against RMS? ElMaestro 2010-08-10 16:26
    • Batch-to-Batch Pharmacokinetic Variability kumarnaidu 2016-07-20 07:16
      • tlast (Common) Helmut 2016-07-20 10:48
        • tlast (Common) nobody 2019-02-21 15:20
          • tlast (Common) ElMaestro 2019-02-21 16:32
            • tlast (Common) nobody 2019-02-21 17:02
              • tlast (Common) ElMaestro 2019-02-21 18:02
                • tlast (Common) nobody 2019-02-21 18:17