In a May 20, 2014 petition denial to Docket FDA 2013-P-1710 (the second denial on the same subject by the same firm), the FDA made clear that usability studies for transdermal systems are not a requirement for ANDA applicants. FDA noted in its response that “[O]n August 27, 2012, we [FDA] received a petition from Noven requesting that FDA take certain actions, including a request regarding usability studies for ANDAs that reference Daytrana. On January 23, 2013, we issued our response (2013 Daytrana Petition Response) and denied Noven’s request to require usability studies as a condition for approval for ANDAs that reference Daytrana because the current Daytrana labeling already contains considerable information on usability, and we would expect the labeling for the generic products referencing Daytrana to contain the same information regarding usability.”
FDA went on to explain the difference in the approval process for NDA products where usability studies may be requested when indicated; however, for an ANDA product approval, the requirements differ, as the NDA product establishes the safety and efficacy and the ANDA product relies on the previous Agency’s finding of such. The ANDA applicant must demonstrate that its product is bioequivalent and performs in the same manner as the NDA product upon which it relies. FDA went on to explain that ANDA applicants are required to perform adhesion studies and irritation studies and that such studies are conducted using a non-inferiority design.
FDA also pointed out that the need for testing in other than healthy volunteers is not required to demonstrate sameness for this product and FDA especially pointed out that testing in children, as Noven suggested, is not necessary as FDA said in the response:
“We are not aware of a significant difference in the adhesion of Daytrana in adults compared with children or adolescents. Healthy adult volunteers are typically evaluated in the adhesion studies for generic drugs because they have better tolerance for most drugs, and to avoid any unnecessary risk in children. Furthermore, we are not aware of studies relevant to this issue that demonstrate that the adhesion of a transdermal product is significantly different as a function of age. Therefore, considering the risk to children as test subjects, and in the absence of a compelling necessity to test adhesion in children as opposed to adults, adhesion studies in children are not recommended for any ANDA submissions. Thus, we expect that equivalence in adults would imply equivalence in children. As such, there is insufficient evidence to indicate that the current adhesion study design is inadequate or to warrant a requirement for adhesion studies in children. This may be in contrast to the requirements for an NDA, for which it may be appropriate to demonstrate whether relevant real-world differences exist among populations of different ages.”
So it appears that FDA is indeed stuck on this answer, and one that does not seem to be easily peeled-back on repeat application. The FDA has responded to numerous other similar challenges relative to the use of testing in pediatric populations in much the same manner. This response is, however, somewhat unique, as it involves the concept of usability studies in ANDAs when that aspect of safety and efficacy has already been established by the NDA holder.