Bioequivalence and Bioavailability Forum • Health Canada: 2012 guidance

Health Canada: 2012 guidance [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2018-01-16 14:07 (2290 d 05:14 ago) – Posting: # 18181
Views: 2,777

Hi ElMaestro and all,

can we ignore at least part of the 2004 guidance? In Appendix 1 (Tables A1-B&C) to the 2012 BE-guidance BQLs are given as such with an exploratory footnote:

Lower limit of quantitation is 5 ng/mL. Any concentration below this limit is reported as Below Limit of Quantitation (BLQ) except at time 0. Zero is used in the calculation of area under the curve (AUC) for times preceding the first observed concentration and in the calculation of summary statistics.

What do we have?

2004 guidance
0.00 0.00 52.01 95.03 122.20 77.88 65.15 46.24 19.20 14.99 0.00 0.00
2012 guidance
0.00 BLQ 52.01 95.03 122.20 77.88 65.15 46.24 19.20 14.99 BLQ BLQ
Output of Phoenix/WinNonlin
0.00 0.00 52.01 95.03 122.20 77.88 65.15 46.24 19.20 14.99 BQL BQL
That’s PHX/WNL’s most commonly applied BQL Rule Set.
With unconditional substitution (BQL → 0) one could comply with the 2004 guidance.
To comply with the 2012 guidance one could keep the data as reported (BQLs) and set up a replacement in a Data Wizard (if t=0: BQL → 0).
Output of bear
0.00 NA 52.01 95.03 122.20 77.88 65.15 46.24 19.20 14.99 NA NA
Complies with the 2012 guidance.
To comply with the 2004 guidance the data have to be modified outside of bear (in R, a spreadsheet, …) before import.

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Helmut Schütz

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Science Quotes

Health Canada: Data format Helmut 2018-01-15 12:32
- Health Canada: Data format ElMaestro 2018-01-15 16:53
  - Data integrity? Helmut 2018-01-16 00:16
  - Health Canada: 2012 guidanceHelmut 2018-01-16 13:07