Applying Pediatric Exclusivity After Product Approval; FDA Interpretations About Which You Might Not be Aware

By Kurt R. Karst –      

FDA’s September 1999 guidance document, “Qualifying for Pediatric Exclusivity Under Section 505A of the Federal Food, Drug, and Cosmetic Act,” includes a section addressing the following question: “If my study qualifies for pediatric exclusivity, to what will the period of pediatric exclusivity attach?”  FDA’s response (in relevant part):

Pediatric exclusivity will attach to exclusivity and patent protection listed in the Orange Book for any drug product containing the same active moiety as the drug studied and for which the party submitting the studies holds the approved new drug application (505A(a) and (c)).  For studies conducted on an unapproved drug, pediatric exclusivity will also attach to any exclusivity or patent protection that will be listed in the Orange Book upon approval of that unapproved drug.  FDA will attach pediatric exclusivity to protections listed at any time for a drug product as approved at the time pediatric exclusivity is obtained, as described further in section X.C.

Section X.C. of the guidance document, titled “Later-filed Applications Containing the Same Active Moiety,” states (again, in relevant part):

Previously earned pediatric exclusivity will not apply to new patents or exclusivity covering later-filed applications or supplements containing the same active moiety for which a sponsor previously earned pediatric exclusivity, unless the data that earned the prior pediatric exclusivity is essential to approval of the new application or supplement.

These statements reflect interpretations that appear simple enough to apply, but that in reality are a bit more complex. 

Consider, for example, FDA’s January 30, 2009 approval of NDA #22-287 for KAPIDEX (dexlansoprazole) Delayed Release Capsules.  Dexlansoprazole is the R-enantiomer of lansoprazole (a racemic mixture of the R- and S-enantiomers), which is approved and marketed under the proprietary name PREVACID.  FDA issued a Pediatric Written Request (“PWR”) for PREVACID in August 1999 (last amended in September 2005) and granted pediatric exclusivity on July 15, 2008, while the KAPIDEX NDA was under review at FDA.  Although FDA’s PWR does not mention dexlansoprazole, FDA nevertheless granted pediatric exclusivity with respect to all of the KAPIDEX Orange Book listings when the NDA was aproved in January 2009. 

FDA’s decision to grant pediatric exclusivity with respect to KAPIDEX clarifies two Agency interpretations: (1) when FDA issues a PWR for a drug product that is a racemic mixture, any pediatric exclusivity granted as a result of that PWR applies not only to the racemic mixture, but also to the sponsor’s other products containing either enantiomer, whether or not FDA’s PWR specifically identifies each enantiomer in the racemic mixture; and (2) FDA will apply previously earned exclusivity to later-approved applications that are under review at the time FDA grants pediatric exclusivity.

Another FDA interpretation stemming from FDA’s September 1999 guidance document that is not widely known is that previously earned pediatric exclusivity can apply to certain new Orange Book-listed patents if those patents relate back to the drug product when pediatric exclusivity was granted.  For example, if FDA granted pediatric exclusivity in 2000 for a drug product that was approved for indication A, and in 2007 two new patents are listed in the Orange Book covering the drug substance and newly approved indication B, then FDA could apply pediatric exclusivity to the newly listed drug substance patent, but not to the patent covering newly approved indication B, because the drug substance patent relates back to the drug product when pediatric exclusivity was granted, but the method-of-use patent does not.  FDA could take the same position on drug product patents and would grant pediatric exclusivity, provided the patent-protected formulation relates back to the drug product when pediatric exclusivity was granted.  FDA has applied this policy on a few occasions, including, for example, with respect to COMBIVIR (lamivudine; zidovudine).