Bioequivalence and Bioavailability Forum • Steady state (no accumulation)

Steady state (no accumulation) [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2011-06-06 15:05 (5081 d 00:56 ago) – Posting: # 7073
Views: 10,398

Dear Ohlbe and Jagankm!

❝ […] but it will take another couple of years before the draft is published for 6-month consultation, comments are received, a final version gets adopted and it comes into force. Until then the current guidance remains applicable...

The draft is expected to be published early 2012. Agree with your remaining points.

❝ I would say the attitude depends on how critical this project is for your company, how much time you are ready to spend in discussions with various Agencies, in which EU Member State you plan to submit your dossier and when.

True.

❝ If you want to be on the safe side, running the steady state study is expensive and may not sound scientifically necessary, but it may in the end be faster and with a more certain result.

Agree with the former, but not the latter. From my little story: CVs of AUC_t ≈7 %, C_max ≈15 %, C_min^* ≈75 %. According to the current NfG C_min is required – no scaling (EMA is considering scaling for HVDs/HVDPs if accumulation occurs as an alternative to multiple dose studies). For the usual stuff (AR 80–125%, α≤0.05, power 80%, PE 0.95) that would require increasing the sample size from 12 to 194 (!) in a 2×2 cross-over. IMHO it is not ethical to perform such a study just to show BE for a PK metric which is not relevant from a clinical point of view.
BTW, we performed the multiple dose study following my little story – but will report C_min only. Both the EC and BfArM followed our arguments and approved the protocol.

Following EMA's definition: Concentration at the end of the dosing interval (see Edit 2 in this post and the two references given above).

—
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Helmut Schütz

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Science Quotes

Complete thread:

metformin steady state study jagankm 2011-06-01 11:19 [Regulatives / Guidelines]
- metformin steady state study Ohlbe 2011-06-01 11:31
- metformin steady state study drgunasakaran1 2011-06-02 04:24
  - metformin steady state study Ohlbe 2011-06-02 08:56
  - metformin steady state study jagankm 2011-06-02 10:35
    - Steady state (no accumulation) Helmut 2011-06-03 14:58
      - Steady state (no accumulation) Ohlbe 2011-06-06 10:46
        
        Steady state (no accumulation)Helmut 2011-06-06 13:05
        
        Steady state (no accumulation) Ohlbe 2011-06-06 13:54
        
        Science ↔ Guidelines Helmut 2011-06-06 14:06
        
        Science ↔ Guidelines ElMaestro 2011-06-06 22:35
        
        Science ↔ Guidelines Helmut 2011-06-06 23:25
    - metformin steady state study kvgreddy06 2014-07-23 18:32