Bioequivalence and Bioavailability Forum • RSABE (EU)

RSABE (EU) [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2010-01-06 18:01 (6012 d 14:55 ago) – Posting: # 4565
Views: 5,922

Dear Raveendranath!

❝ We want to conduct a study with partial replicated design (Reference twice)

❝ for Europe regulatory. My doubt is

❝

❝ 1. Does the Europe Regulatory accepts the Scaled Average Bioequivalence

❝ method for highly variable drugs?

Right now: No, though there are rumours, that RSABE will 'make it' to the final BE-Guideline (for C_max only) - but we have to wait until publication (March 2010?).

❝ 2. If we can show that the Intra cv for reference product is > 30% then

❝ can we use wider limits (75-133)?

Yes. According to 2006's Q&A-document (Sections 2 and 8), if clinical justifiable (high variability of the reference alone is not enough).
It's important that you power your study to show BE for the case that CV<30%.
Example: expected CV 40%, expected T/R 95%, power 80%, n for a partial replicate design with 75%-133% = 36; if CV in the study = 29 (no widening; AR 80%-125% applicable), T/R 95.5%.

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Helmut Schütz

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Complete thread:

Scaled Average Bioequivalence graveendranath 2010-01-06 07:36 [Regulatives / Guidelines]
- RSABE (EU)Helmut 2010-01-06 17:01
  - RSABE (EU) d_labes 2010-01-07 09:14
    - RSABE (EU) Helmut 2010-01-07 13:21
      - Sample size partial replicate design d_labes 2010-01-07 13:56
        
        Sample size partial replicate design Helmut 2010-01-07 14:23
        
        Sample size partial replicate design: df d_labes 2010-01-07 16:21
        Sample size partial replicate design: variance d_labes 2010-01-08 10:37