One recurrent issue that keeps arising in our consulting practice is the impact of pediatric exclusivity on the ability of the FDA to approve applications during a pediatric exclusivity period associated with a listed patent. For those sponsors that are not careful, a pediatric exclusivity period (or successive periods of pediatric exclusivity that are associated with separate listed patents) can delay approvals of ANDAs or 505(b)(2)s for many months and, in some cases, over a year. Planning must also take into consideration User Fee goal dates for review completion, requests for priority review, and previously submitted patent/legal updates to an application.
The most common misconception that I encounter with clients is the idea that, because an ANDA sponsor has a settlement and license agreement with the NDA holder which will identify a date upon which the ANDA product can be launched, that alone is adequate support for the FDA to issue an approval to an ANDA on or after the date identified in the agreement. During my time at the FDA, the Agency’s position was that the FDA would not interpret the provisions of a license agreement between parties and thus would not base approval decisions on information contained within the license agreement. License agreements can be quite complex, containing accelerator clauses and other clauses that may be triggered based upon certain events that might be identified in the agreement. The FDA doesn’t want to find themselves in a situation where they need to defend an approval action based on their interpretation of a license agreement. The FDA’s goal is for the approval action to be supported by legal documentation that is completely unambiguous.
The FDA ensures that any final approval action taken during a pediatric exclusivity period is supported by unambiguous legal documentation by requiring ANDA sponsors to submit a Pediatric Exclusivity Waiver from the NDA holder. I’m unaware of formal guidance from the FDA stating that a Pediatric Exclusivity Waiver is required and the circumstances in which it is required, but the FDA has conducted presentations over the years which address this as a requirement. The last instance I’m aware of is a presentation from 2019 titled “Exclusivity-Which one is for me?” conducted by Rinku Patel of the Office of Generic Drugs available here. Slide 20 of that presentation states that a Pediatric Exclusivity Waiver is required for approval during a pediatric “window” and the next slide provides an example of how “cascading” pediatric exclusivity period can delay approvals for an extended period of time if the ANDA sponsor has not procured a Pediatric Exclusivity Waiver. For those parties that are unfamiliar with the FDA’s administration of Pediatric Exclusivity, I would advise you to download, review, and save a copy of this presentation.
These issues primarily impact ANDAs that contain Paragraph IV (PIV) certifications to a patent where the patent itself has expired. However, these issues are not just relegated to patents that have been addressed with a PIV certification but also to patents addressed with a Paragraph III (PIII) certification and when ANDA sponsors choose to address a listed patent with a section viii statement resulting in a carve-out of protected language. Based on my experience this has only rarely been an issue for ANDA applicants with section viii statements. No matter the patent certification or statement, the underlying tenet is that once a patent has expired the ANDA sponsor can no longer retain a PIII, PIV, or section viii statement to that patent, it must be converted to a Paragraph II (PII) certification at which point the Pediatric Exclusivity period serves as a barrier to approval per the statutory language found in the Food Drug and Cosmetic Act at 505A(b)(1)(B)(i). To belabor the obvious, this means that a difference of one calendar day is critical because a PIV certification or section viii statement remains valid as long as the patent remains within expiration and the FDA can issue Final Approval prior to patent expiry, but after the patent expires, the FDA is unable to issue final approval unless a Pediatric Exclusivity waiver had been granted and submitted to the application.
Even though language in the statute does not address the impact of the Pediatric Exclusivity period when an ANDA sponsor has submitted a section viii statement to a listed patent, I am aware of several instances from my time at the FDA, where ANDA approvals were delayed because the patent which was the subject of the section viii statement had expired. What makes this more troublesome is that when an ANDA sponsor’s application has a section viii patent statement they are unlikely to have negotiated a license agreement with respect to that particular patent making procurement of a Pediatric Exclusivity Waiver from the NDA holder all the more challenging. Readers would be wise to download FDA’s letter from 2007 available at the link (here) for additional information and to fully understand how FDA administers Pediatric Exclusivity.
ANDA applicants need to carefully evaluate their certifications, the patent expiration dates, and pediatric exclusivity when submitting an amendment to the FDA that requests priority review, conversion from Tentative Approval to Final Approval, or when submitting a response to a CRL where upon completion of the review the FDA may be able to issue Final Approval to the ANDA. Presenting information to the FDA in a clear and accurate manner will help ensure that the FDA is able to issue the Final Approval action either prior to the beginning of any Pediatric Exclusivity period or during a Pediatric Exclusivity period because the ANDA sponsor has submitted the required Pediatric Exclusivity waiver.
