A Citizen Petition submitted recently by McDermott Will & Emory (here) on behalf of Vanda Pharmaceuticals requests that the FDA “revoke approval of Abbreviated New Drug Application (ANDA) No. 211654, submitted by MSN Pharmaceuticals Inc. (MSN), for 20 mg tasimelteon capsules, and order a recall of any product that has been distributed under ANDA No. 211654 (if any) because it fails to satisfy the bioequivalence requirement.”  While other reasons are cited in the petition, the focus of this blog post centers on the issue that the bioequivalence (BE) study submitted in the now‑approved ANDA used only male subject versus the FDA’s “suggested” use of equal numbers of male and female subjects in BE studies.

While the FDA guidance does suggest use of equal numbers of male and female subjects in most BE studies, there is no current regulatory requirement for such inclusion.  Meanwhile, the petition is correct that the FDA has recently reinforced its desire to have firms follow its recommendation, and the Agency has begun to question firms that do not include an explanation and justification if they do not follow this recommendation.  A number of firms have recently received letters requesting justification when a study with all‑male subjects is used in support of BE testing.  If you are one of the firms that have received such an FDA letter, the outcome provided in the petition response may be something you want to review closely.

Of course, Vanda has also included other issues it believes are out of line with the FDA’s BE approval requirements (which the FDA will have to sort out and explain in its petition response), but the male/female issue is something that, for years, the FDA has been attempting focus on, but still a number of studies are being submitted to the FDA with only one sex represented.  In some countries, it is difficult to recruit female subjects for several reasons, and different countries’ regulatory authorities have different views on the subject.  The FDA’s response may well be a bellwether on the issue.  We will keep an eye out for the Agency’s response and update you on the issue at that time.