Bioequivalence and Bioavailability Forum • Evaluation of Reference variability

Evaluation of Reference variability [Design Issues]

posted by Helmut – Vienna, Austria, 2010-03-16 17:01 (5576 d 03:08 ago) – Posting: # 4921
Views: 3,821

Dear Marcel!

❝ My apologies for dragging this replicate skeleton out of the closet when it seemed like it was comfortably resting.

No problem - if you think we need some more forensics, go for exhumation!

❝ Was there any mention at this meeting as to whether the results of a replicate design study (finding of intra-subject variablility exceeding 30%) with a lower strength can be used to justify widen acceptance limits for a higher strength of the same drug to undergo a standard BE study?

No. Or to be more precise, nobody asked that question, but I would bet the answer would have been a straight "No!" as well.

❝ If this is not allowed, can someone explain why not?

I would say there are two reasons.

The general reason, that no reference to previous studies is allowed when it comes to widening of the acceptance range. CV_intra,ref >30% must be demonstrated within the submitted study.
There is also a pharmacokinetic reason. Drugs with nonlinear PK may show different variability throughout the dose range. Think about e.g., saturation effects. Example: ASS -> salicylic acid.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Complete thread:

Evaluation of Reference variability Nirali 2009-04-13 11:53 [Design Issues]
- Evaluation of Reference variability KR 2009-04-13 14:39
- Evaluation of Reference variability Ravi 2009-04-14 06:25
  - Evaluation of Reference variability Nirali 2009-04-17 07:38
    - Evaluation of Reference variability Ohlbe 2009-04-17 10:04
    - Evaluation of Reference variability Helmut 2009-04-17 13:44
      - Evaluation of Reference variability Nirali 2009-04-18 09:04
        
        Evaluation of Reference variability Helmut 2009-04-18 12:31
        
        Evaluation of Reference variability Nirali 2009-04-18 19:34
      - Evaluation of Reference variability Marcel 2010-03-16 13:10
        
        Evaluation of Reference variabilityHelmut 2010-03-16 16:01
        
        Evaluation of Reference variability ElMaestro 2010-03-16 17:13
        
        Some desultory thoughts Helmut 2010-03-16 18:59
        
        Evaluation of Reference variability Marcel 2010-03-17 12:47