Bioequivalence and Bioavailability Forum

Dear All!
I'd like to refresh this topic:

❝ Nothing? OK, to be more precise, if:

❝ • the study was performed in healthy subjects,

❝ • the drug is not an endogenous entity, and

❝ • an adequate washout (no predose concentrations in period II) were maintained.

Is meeting these criteria enough to ignore sequence effect?
From reference given previously I can see that also equivalence must be present.
And in study that I'm currently participating in, it turned out that test drug did not meet BQ criteria for Cmax when compared to reference drug and significant sequence effect for Cmax was detected.
Now this publication http://cat.inist.fr/?aModele=afficheN&cpsidt=984872 claims that:

"The sequence effect is confounding with the unequal residual effect and with the formulation by period interaction. Since the existence of the sequence effect questions the quality of the trial, the applicant should provide possible explanations and information on the subjects, the trial conditions, the clinical settings and the assay methodology. An additional statistical analysis on the data from the first period of the trial may support the bioequivalence. If it is proven that the sequence effect is a true effect then the generic may be approved for marketing authorization."

So should we go deeper and try to find explanation for sequence effect? Is it possible at all to find anything if we pass criteria mentioned by HS (cited above)?
Thanks in advance for your opinions.
Łukasz