Bioequivalence and Bioavailability Forum • T/R 110%

T/R 110% [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2013-11-30 15:02 (4234 d 20:53 ago) – Posting: # 11992
Views: 8,354

Hi Kumar,

❝ If in my earlier studies I am getting T/R ratio= 110% means >5% difference then for planning another study for another market should I go with the T/R=110% or 95% for sample size estimation.

The former. Although with another reference product the ratio might be better, without a pilot study I would suggest a conservative approach.

❝ As per EMA guideline (2010) "batches should not differ more than 5%" so taking 10% difference in T/R ratio is considerable.

Yes, why not? The ≤5% refer to measured contents, not the assumed in vivo ratio.

❝ Also if I am taking the T/R ratio=110% I am getting sample size around 50 (without dropout) …

Correct (given the CV of 24.3%).

❝ … but many studies I found for this drug is around 40 even …

Some drug, but different formulations.

❝ … our earlier study had 42.

❝ LnCmax ratio=110.3 (90%CI- 101.06-120.54) CV=24.3.

Passed by luck. “Power” was 76%.

❝ then in that case if am exceeding sample size will it considered as a forced bioequivalence?

Don’t think so – unless you go to Denmark* (100% not included in CI).

In the opinion of the Danish Medicines Agency, the 90 % confidence intervals for the ratio of the test and reference products should include 100 %.
Reference

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Complete thread:

Difference between test and reference nlpati 2013-10-10 13:40 [Regulatives / Guidelines]
- Assayed content Helmut 2013-10-10 14:46
- Difference between test and reference jag009 2013-10-10 15:19
  - ∆ <5% ⇒ T/R 95% Helmut 2013-10-10 16:08
    - ∆ <5% ⇒ T/R 95% nlpati 2013-10-11 04:37
    - ∆ <5% ⇒ T/R 95% jag009 2013-10-13 21:02
      - Optimism Helmut 2013-10-14 17:50
        
        T/R 90% to 110% for sample size estimation kumarnaidu 2013-11-26 05:36
        
        T/R 110%Helmut 2013-11-30 14:02
        
        T/R 110% kumarnaidu 2013-12-02 05:35
        the basis of T/R in the Protocol mittyri 2014-03-14 08:10
        
        the basis of T/R in the Protocol Helmut 2014-03-14 13:53
        
        the basis of T/R in the Protocol mittyri 2014-03-14 14:31
        
        the basis of T/R in the Protocol Helmut 2014-03-14 15:01
        
        the basis of T/R in the Protocol mittyri 2014-03-14 21:08
        
        the basis of T/R in the Protocol Helmut 2014-03-14 23:02