Bioequivalence and Bioavailability Forum • Scaling of Cmin

Scaling of Cmin [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2014-11-27 14:47 (3766 d 11:27 ago) – Posting: # 13932
Views: 15,446

Hi Kumar,

❝ But I think for applying widening criteria we need to show CV>30% for reference product and the study should be reference replicate (3way or 4way).

Correct. I wouldn’t be too optimistic with the CV_intra of 23.1% you reported.

❝ Can we use Pre-dose concentration and Ctau of steady state to show variability? :confused:

This idea was discussed in Bonn last year. Members of EMA’s PKWP seemed to be happy with it. I guess the MR-GL was adopted at EMA’s CHMP-meeting last week. Let’s wait for it (and the comments). The analysis is a little bit tricky* because the replicates originate from the same period.

Liu J-P. Use of the Repeated Crossover Design in Assessing Bioequivalence. Stat Med. 1995;14(9–10):1067–78. doi:10.1002/sim.4780140926

Edit: The MR-GL was adopted indeed. See here.

Edit: GL, Section 6.8.2.2:

Any widening of the acceptance criteria for C_max should follow the recommendations on highly variable drug products in the Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98).
A similar approach can be used for widening the acceptance criteria for C_max,ss, C_τ,ss, and _partialAUC. Calculation of the intra-subject variability in multiple dose studies can be based on two consecutive administrations of the same product after reaching steady state.

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Complete thread:

Type of study in modified release formulation EMEA Compliance 2014-03-13 09:43 [Regulatives / Guidelines]
- Type of study in modified release formulation EMEA nobody 2014-03-13 09:52
- Type of study in modified release formulation EMEA fno 2014-03-13 11:16
  - Type of study in modified release formulation EMEA kumarnaidu 2014-11-27 11:02
    - Type of study in modified release formulation EMEA nobody 2014-11-27 11:37
      - Type of study in modified release formulation EMEA kumarnaidu 2014-11-27 12:53
        
        Scaling of CminHelmut 2014-11-27 13:47
        
        Scaling of Cmin kumarnaidu 2014-11-27 15:12
        Scaling of Cmin kumarnaidu 2014-12-05 06:03
        
        Steady state kumarnaidu 2014-12-10 11:15
        
        Steady state nobody 2014-12-10 17:04
        
        Scaling of Cmin Dr_Dan 2014-12-10 17:21
        
        Scaling of Cmin Helmut 2014-12-10 18:40
        
        Scaling of Cmin d_labes 2014-12-11 13:09
        
        Scaling of Cmin Helmut 2014-12-11 14:53
        
        Scaling of Cmin VStus 2017-02-03 13:04
        
        Scaling of Cmin zizou 2017-02-03 13:49
        
        Scaling of Cmin VStus 2017-02-03 15:37
        Scaling of Cmin VStus 2017-02-06 08:55