Bioequivalence and Bioavailability Forum

BE for HVD (EMA): no 2x2 crossover [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2014-02-14 10:27 (4517 d 02:33 ago) – Posting: # 12425
Views: 6,596

Dear nasir,

❝ My question is if drug was shown as HVD in a pilot RR study. Then can we go for 2 way design, with Cmax limits widened?

No chance . The EMA guidance clearly states:
"For the acceptance interval to be widened the bioequivalence study must be of a replicate design where it has been demonstrated that the within-subject variability for Cmax of the reference compound in the study is >30%."
(Emphasis by me).

Don't forget the sentence just before the above citation: "Those HVDP for which a wider difference in Cmax is considered clinically irrelevant based on a sound clinical justification can be assessed with a widened acceptance range."

Complete thread:

• BE for HVD (EMA) nasir 2014-02-14 06:38 
  • BE for HVD (EMA): no 2x2 crossoverd_labes 2014-02-14 09:27
    • CV >30% in the study Helmut 2014-02-14 14:35
  • BE for HVD (EMA) kvgreddy06 2014-02-14 16:18
    • BE for HVD (EMA) PK_Lover 2014-02-14 18:37
      • EMA: No widening of acceptance limits for AUC d_labes 2014-02-14 20:03
      • BE for HVD (EMA) Helmut 2014-02-15 15:10
        • BE for HVD (EMA) nasir 2014-02-18 07:24
          • Single point metric… Helmut 2014-02-18 13:03
            • Single point metric… nasir 2014-02-18 19:57
              • Single point metric… Helmut 2014-02-18 20:38
                • Single point metric… nasir 2014-02-19 07:09
                  • MR GL – when? Helmut 2014-02-19 13:10