Bioequivalence and Bioavailability Forum

Dear shankar!

❝ This study for EU Submission.

See this post on *prazoles and my experiences in the EU.

Where did you get your CV% from? Even for lansoprazole >50% is rather high!
There are studies published with a CV% of 30–40 for C_max.

According to the 'Q&A Document to the NfG' and the 'Concept Paper on HVDs/HVDPs', I would guess that:

• you will have to demonstrate high variability in a replicate design study (this is not the pivotal BE).
  
• if you were able to do so, you may widen the acceptance range (for C_max only), if clinically justifiable.
  
• you may perform the pivotal BE either as a conventional 2×2 (sample size N), a replicate design (3×2 of sample size 2N/3), or a replicate design (4×2 of sample size N/2). If your 2×2 sample size is 48, you essentially get the same power in a 3×2 replicate in 36 subjects and in a 4×2 replicate in 24 subjects.
  
• since in the Recommendation for an Update of the NfG Reference Scaled Average Bioequivalence (RSABE) is not mentioned (some European members states raised major objects to the Concept Paper on HVDs), I would not dare suggesting this approach any more (at least not before a positive opinion in a scientific advisory meeting).
  
• Although some members states may accept RSABE, in my opinion a centralized application or a MRP procedure would be almost futile...

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Edit: The Concept Paper on HVDs/HVDPs was deleted from the EMEA's website in October 2007; you may download a copy here.