Bioequivalence and Bioavailability Forum

Dear Shabana,

following our conversation earlier this year I want to quote a guideline issued by the FDA (Erlotinib HCl; recommended Jan 2006, updated Aug 2007) which may help sorting things out.

❝ no regulatory body recommends a washout less than at least 7-10 half-lives in steady state studies.

Quoting the guideline (my emphases):

Dosing on each treatment should continue for a sufficient time to allow equilibration on the test and reference treatments, hence for four to five half-lives prior to bioequivalence study plasma sampling.

❝ of course, if the drug has accumulated and not completely removed from body in the washout period, it will show up as significant pre-dose concentration in the next period,and there you are caught!!! then the second period will never be considered for PK and statistical analysis at all.

Again the Guideline:

Similarly, sufficient time for re-equilibration should be allowed for the crossover treatment. Washout between treatment periods is not recommended.