Bioequivalence and Bioavailability Forum

Dear all,

on Feb 26, the FDA published a new draft Guidance

Bioavailability Studies Submitted in NDAs or INDs — General Considerations.

As usual the previous draft (of Feb 2014) was removed from the FDA’s site (still at www.regulations.gov*) but can be comfortably obtained from the  Internet Archive.

Interesting that between the paragraphs

Subjects with pre-dose plasma concentrations

and

Data deletion because of vomiting

there is a new one (p 27, lines 952–961):

Handling Outliers
If any data are identified as statistical outliers, sponsors should not remove the data from the statistical analysis of BA studies solely based on this fact. The only instance where outlier data can be removed from the statistical analysis of a BA study is when there is coinciding documentation demonstrating a protocol violation (e.g., real-time documentation of a sample processing error as opposed to a retrospective investigation based on the analytical results). Data from re-dosing studies are not considered as evidence to support the removal of outlier data from the statistical analysis. Data from all subjects should be submitted, and potential outliers should be flagged with appropriate documentation as part of the submission.

This is like what we have in the EU but contradicts what we discussed at the 2^nd GBHI-conference in Rockville…

I expect a similar move in the ANDA-guidance.

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• According to the docket folder 20 comments were received. Then we read:
  This count refers to the total comment/submissions received on this docket, as of 11:59 PM yesterday. Note: Agencies review all submissions, however some agencies may choose to redact, or withhold, certain submissions (or portions thereof) such as those containing private or proprietary information, inappropriate language, or duplicate/near duplicate examples of a mass-mail campaign.
  Oops. Only one is public.