Bioequivalence and Bioavailability Forum 10:58 CEST

Replicate vs. 2×2×2 [Regulatives / Guidelines]

posted by M.tareq - 2017-05-14 23:04  - Posting: # 17353
Views: 11,640

Hi Helmut,

Thanks for your comprehensive reply and explanation,

» while ago I reviewed a manuscript exploring the pros and cons of TSDs vs. ABEL. Was very interesting and I hope that the authors submit a revised MS soon.

Can i get the link or the name of the paper when the authors submit it ?

In General, if a drug isn't known to be HVDP and by definition of HVDP that, they have wide therapeutic index yet the CRO/Sponsor went with replicate design.

How the assessor would consider that? mean if the published literature or pilot study suggest low CV of the reference /test product yet the cro/sponsor went with replicate design?

Like abusing the use of scABE ?

» Nobody knows how to deal with this story. Regulations ≠ science. Not required by the FDA…

Agree, yet i read an ANDA submission -can't find the link now- where the sponsor detected outliers based on T/R ratio of each subject and redosing of such subjects along with other subjects who exhibited normal pkp profile; though it was after reviewing with FDA regulator.

Another published paper about ibandronic acid https://www.ncbi.nlm.nih.gov/pubmed/24756462 the sponsor/CRO stated the definition of outliers using studentized residuals and boxplot to eliminate subjects with values away from the boxplot by more than 3 IQR.

My point is, as your kindly said, it's best to state in the protocol how to deal with outliers especially regarding variability estimation and proving/showing to the assessor the reasons for excluding such outlier(s) from study or reviewing it with the regulator before submission of the data?

Thanks and Best Regards.

P.S:
Apologies for being information/knowledge leecher atm, will try to get my seed/leech ratio up ^^

Complete thread:

• Highly Variable Drug BE Justification - jag009, 2017-03-20 04:42 [Regulatives / Guidelines] 
  • Highly Variable Drug BE Justification - ElMaestro, 2017-03-20 06:55
    • Study costs: Replicate vs. 2×2×2 - Helmut, 2017-03-20 13:12
      • Study costs: Replicate seems to be cheaper - VStus, 2017-03-21 12:49
        • Study costs: Replicate seems to be cheaper - Dr_Dan, 2017-03-21 13:06
          • Study costs: Replicate seems to be cheaper - Helmut, 2017-03-21 14:50
            • expected power - d_labes, 2017-03-21 15:16
            • Doesn't hurt! - VStus, 2017-03-23 14:24
      • Study costs: Replicate vs. 2×2×2 - mahmoud-teaima, 2017-03-23 08:17
      • Study costs: Replicate vs. 2×2×2 - M.tareq, 2017-05-07 21:21
        • Replicate vs. 2×2×2 (ethics?) - Helmut, 2017-05-08 14:21
          • Replicate vs. 2×2×2 (ethics?) - nobody, 2017-05-08 14:52
            • Applicability of reference-scaling - Helmut, 2017-05-10 14:10
          • Replicate vs. 2×2×2 - M.tareq, 2017-05-14 23:04
            • Replicate vs. 2×2×2 - Helmut, 2017-05-15 19:07
              • Replicate vs. 2×2×2 - M.tareq, 2017-05-15 21:02
              • Regulators view of HVD drugs - DavidManteigas, 2017-05-16 12:41
                • Regulators view of HVD drugs - Helmut, 2017-05-16 15:01
                • What's the problem? - ElMaestro, 2017-05-17 03:30
                  • What's the problem? - nobody, 2017-05-17 07:48
                    • What's the problem? - nobody, 2017-05-17 09:31
                      • What's the problem? - DavidManteigas, 2017-05-17 11:25
                        • What's the problem? - ElMaestro, 2017-05-17 12:07
                          • What's the problem? - kumarnaidu, 2017-07-11 14:43
                            • What's the problem? - ElMaestro, 2017-07-11 14:56