Bioequivalence and Bioavailability Forum

Dear all,

does anyone have experience with the 2004 „Draft Guidance for Industry. Preparation of Comparative Bioavailability Information for Drug Submissions in the CTD Format”?

Appendix B: Computer Format for the Submission of Data for Comparative Bioavailability Studies
2. Detailed Specifications

states

• Concentrations below the limit of quantitation (LOQ) should be entered as 0.0.

What? Also strange:

The following provides an example of a hard copy of the data set and should be included with the submission:

01 AB 1 A 000.00 000.00² 052.012³ 095.03 122.20 .⁴ 065.15 046.24 019.20 014.99 000.00 000.00
─────────
² Concentrations below the limit of quantitation (LOQ) should be entered as 0.0.
³ The entered drug concentrations must be the measured (uncorrected) concentration and should not be below the lowest or above the highest nominal concentrations of the standard curve.
⁴ Missing data must be entered as a period (.).

What I don’t get:

• The format of the second file does not allow for giving the actual sampling times (only the scheduled ones in the first file).
  
• BQLs as zero? Whilst it makes sense to set BQLs before the first measured concentration to zero I’m not so sure about later ones.

Which software is HC using? I expect that the results of NCA will not match the standard output of commercial software (e.g., Phoenix WinNonlin) and R-package bear.