Bioequivalence and Bioavailability Forum

Hi Krish85,

❝ In one of the webinar hosted by FDA where speaker said that FDA is aware that these are crossover studies and overall it may not have significant impact but FDA still wants similar proportions of males and females.

That is correct. New winds are blowing.

❝ If PK of a drug in male and female are similar then a scientific justification can be drafted.

Technically, this is not about PK being similar or dissimilar among the genders. It is about the ratio of AUC or Cmax being similar or dissimilar and that is a completely different ballgame.

The originator industry has tried for years to convince FDA that a conclusion of BE changes depending on the population (patients vs healthy volunteers, Caucasians vs Indians, smokers vs nonsmokers, females vs males etc). yet it was never clearly shown that this might be the case. And that's why it has so far always been appropriate to test medicines in one population and extrapolate to others. Meaning if BE is shown in healthy adult nonsmoking Indians then it is credible that the product is also BE in female argentinians who own a rusty bicycle. And so on.

Yet, in spite of the above, FDA have begun asking for or expecting approximate gender balance, like you noticed. You can plan for it in the future. CROs in India and Jordan -where populations tended to be exclusively male in the the past- are really going full throttle in that direction.

❝ But how can CRO respond to the query where CRO has not included similar proportion of male and female (obivious reason is unavailability of female volunteers) and PK in male and female are different.

Depending on your specific situation you may find inspiration in Deniz ôzdin's recent publication. Other than that state the argument above and hope for the best. Or make a promise to redo your study in a more balanced population - I am sure FDA would appreciate it.