Bioequivalence and Bioavailability Forum

Dear Ramesh,

❝ I performed PQ of winnonlin by using Canada Part-B guidelines,but i am getting lot of variations in the result compare to guidelines. Is there any criteria to compare result. please let me know.

What do you mean by 'lot of variations'? We have discussed already in the past, that Canada's guideline contains a lot of typing errors. If you want to compare PHX/WNL to these results, you have to be cautious. If you estimate lambda_z, be sure not to use the automatic method based on the maximum R²_adj, but set datapoints individually (Tables 11-E/F: TLIN is the starting point and LQCT the end point). All (!!) starting points of the reference (Table 11-F) are wrong - they should be set to 22 instead of 12! Most subjects' profiles show double peaks; 12 hours is ridiculous. IMHO you cannot PQ WNL based on such an erroneous data set - unless you start clicking around to get a match by trial-and-error.

Next problem: NCA results (Tables 11-E/F) are given with limited precision. If you continue with WinNonlin's results you will get differences in the BE calculation. You have to round WNL's values to Canada's precison in order to match results... You can see this as an opportunity to learn WinNonlin's data transformation functions like ROUND(). BTW, you have to calculate the wrong CV_intra as the square-root of the residual MSE manually, because only the correct value is given in the output.

@Nirali: How did you...?

❝ documented PQ of WinNonlin and few programs of SAS as per above example and it is accepted by regulatory auditors.