Bioequivalence and Bioavailability Forum

Hi wienui,

❝ Could we widen the Cmax rang to 70-143% of HVD (Omeprazole) in a normal (not a replicate) 2x2 crossover BE study.

Regulatory perspective: According to all current guidelines I am aware of, no.
Scientific perspective: Why not? Omeprazole formulations are already OTC in many countries. Hence, the efficacy/safety profile is established. Many other products were approved with an AR of 70–143% in 2×2 studies in the EU (was recommended as the standard [sic] for C_max in the 9^th draft of the NfG¹ following suggestions of Blume et al.²). Following the concept of reference-scaling one has to demonstrate that the reference in the particular study shows a CV of >30%. Given the data in the public domain I would say we can be pretty sure that the reference is a HVDP indeed. Just my two cents.

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References
1. Commission of the European Communities, CPMP Working Party on the Efficacy of Medicinal Products. Investigation of Bioavailability and Bioequivalence. Note for Guidance III/54/89-EN, 9th Draft. Brussels: 1991.
   
2. Blume H, Kübel-Thiel K, Reutter B, Siewert M, Stenzhorn G. [Nifedipin: Monographie zur Prüfung der Bioverfügbarkeit/Bioäquivalenz von schnell-freisetzenden Zubereitungen]. Pharm Ztg. 1988;133:389–93. German.