Bioequivalence and Bioavailability Forum • No RSABE

No RSABE [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2014-12-09 15:50 (4209 d 11:25 ago) – Posting: # 14035
Views: 15,153

Hi Kumar,

❝ Actually one of my friend recently did this study and according to him he is getting ISCV around 32% for one of the partial AUCs and the upper limit of T/R ratio for that parameter is 127%.

Tell your friend that he should evaluate the study according to the protocol. Since the study is already completed it was performed according to the ”old” guidance, right? Not a word about RSABE. Upper CL 127% = study failed to show BE. Interesting that he performed a replicate design.

❝ And he planning to use scaled approach.

In an attempt to “safe” a study which failed according to the protocol? Maybe. See the RTR guidance, Section “Failed In Vivo BE Studies”:

FDA will refuse-to-receive an ANDA if only a failed in vivo BE study is submitted. FDA regulations require applicants to submit information on failed BE studies. Typically, a failed study is one that does not satisfy the 90% confidence interval (CI) criterion (i.e., falls outside of the 0.8–1.25 acceptance criterion limits) for either area under curve (AUC) or the peak plasma concentration (Cmax) parameter. If this occurs for highly variable drug products, the applicant should submit a study using a replicate study design and analyze data using a reference-scaled average (RSA) approach for the failed parameter. Alternatively, applicants should consult the BE recommendations webpage for product-specific study information or contact OGD’s Division of Bioequivalence via a BE Guidance Request for further guidance if needed.

Some thoughts:

The study failed according to the “old” product-specific guidance.
The study was already performed in a replicate design which would allow RSABE.
From the wording I get the impression that the FDA wants to see another study. Duno whether FDA would allow a post hoc switch from ABE to RSABE in the same study.
But: The current guidance does not mention RSABE as well.
I would contact the OGD via controlled correspondence.

❝ One more thing for one of the parameter he is getting σ²D >0.03 and the T/R ratio within 80 to 125 (borderline pass). How to justify here ? :-|

What do you mean by “justify”? That’s really bad luck.

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Helmut Schütz

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Complete thread:

Draft FDA guidance on Methylphenidate Hydrochloride kumarnaidu 2014-11-10 08:16 [Regulatives / Guidelines]
- Five PK metrics + S×F interaction Helmut 2014-11-10 13:57
  - Five PK metrics + S×F interaction AngusMcLean 2014-11-11 19:26
    - Phoenix Helmut 2014-11-11 21:05
      - Phoenix AngusMcLean 2014-11-12 19:25
      - Phoenix AngusMcLean 2014-11-21 00:28
  - Five PK metrics + S×F interaction jag009 2014-11-16 03:39
    - Acceptance limit for the upper 95% confidence bound? Helmut 2014-11-17 12:49
      - Acceptance limit for the upper 95% confidence bound? jag009 2014-11-17 17:29
        
        Quoting László Helmut 2014-11-18 03:56
      - Acceptance limit for the upper 95% confidence bound? AngusMcLean 2014-11-19 13:28
  - Five PK metrics + S×F interaction kumarnaidu 2014-12-09 08:36
    - No RSABE Helmut 2014-12-09 13:18
      - No RSABE kumarnaidu 2014-12-09 14:19
        
        No RSABEHelmut 2014-12-09 14:50
- Five PK metrics + S×F interaction drgunasakaran1 2014-11-10 18:29
  - Five PK metrics + S×F interaction jag009 2014-11-11 18:04
  - Five PK metrics + S×F interaction AngusMcLean 2014-11-11 19:22
    - Five PK metrics + S×F interaction jag009 2014-11-11 20:08
      - Tada! jag009 2014-11-13 20:17
        
        Tada! AngusMcLean 2014-11-13 23:06
        
        Tada! nobody 2014-11-19 09:30
        
        Tada! AngusMcLean 2014-11-19 13:42
        
        Tada! nobody 2014-11-19 13:55
        
        ABEL Helmut 2014-11-19 15:44
        
        ABEL nobody 2014-11-19 16:05
        
        ABEL Helmut 2014-11-19 16:59
        
        ABEL nobody 2014-11-19 17:10
        
        ABEL Helmut 2014-11-19 17:16
        
        ABEL AngusMcLean 2014-11-19 17:45
        
        Difficult formulations Helmut 2014-11-19 20:15
        
        Difficult formulations nobody 2014-11-19 21:04
        
        Difficult formulations Helmut 2014-11-19 21:49