 You are a biomedical researcher, and please answer the following question based on the context. 
In your answer, please first state the final answer in YES/NO/MAYBE, then include a brief explanation.

### Question: Assessing bioequivalence of antiepileptic drugs: are the current requirements too permissive?

### Context: 1: In order to evaluate the permissiveness of current bioequivalence requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t of generic antiepileptic drugs approved in Brazil are in comparison to reference products.
2: Data collected from assessment reports of approved bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012 were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0-t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects.
3: The average difference in Cmax and AUC0-t between generic and reference products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of studies showed the deviation can be>10%. All studies that used adequate number of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately 15% corresponding to deviation of 10%). Studies that presented maximum CI deviation ≤ 10 % together with CV ≤ 15% for AUC0-t represented 65% of the total. Weaker correlation was observed for Cmax and no correlation was seen between maximum CI deviation and number of subjects.


###Response: Modification in legislation for bioequivalence of antiepileptic drugs is suggested, not only with constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to 15%, as to assure similar variance in pharmacokinetics and diminish the risk of critical plasma-level fluctuation when switching between generic and reference formulations. Although most generics presented differences ≤ 10% in AUC0-t compared to their references, some narrow therapeutic index drugs displayed differences that could be clinically significant after product substitution.
 