FDA Facing Daunting Task of Vetting More Complex Carve-Out of “Protected” Labeling – Is this the New Evergreening?

Remember the problem associated with the evergreening of patents, which was the practice of obtaining and listing newly issued patents sequentially, and the resultant multiple 30-month stays that essentially kept generics off the market for prolonged periods of time?  This caused so much of a stir that ultimately, statutory relief was required to resolve the problem.  Now, if an ANDA has been submitted with an appropriate patent certification at the time of a later listing patent, while the ANDA applicant must still certify to the patent, will (in most all cases) not be subject to a second 30-month stay.

Now the focus may be changing relative to the Hatch-Waxman label carve-out provisions and, with the recent rash of petitions and court challenges relating to carve-outs, the FDA may be somewhat worried.  We know that an applicant that cites a reference listed drug (RLD) subject to a period of patent or market exclusivity may carve out language in its label related to an indication or other protected information if the resultant carve-out does not result in a product that is less safe than that of the RLD.

If historical performance is an indication, one might think that FDA’s record of permitting carve outs and its use of tools, such as the Best Pharmaceuticals for Children Act (BPCA) and the Hatch-Waxman carve-out provisions have worked well for FDA,  as only a handful of carve-out requests have been denied (e.g., Rapamnune and its titration dosing with cyclosporine) over the course of Hatch-Waxman.  However, the complexity and sophistication of some of the recent protected label additions post-NDA approval and prior to generic entry has the FDA shaking in its boots, worried that the RLD holders have perhaps found a new strategy for the delay of generic entry.  FDA has been pretty good at assuring that, in all but the clear cases of potential safety relative to a label carve out have resulted in delay of approval, but now the sophistication of some of these protected labels have gotten to such a level that the once seemingly rare decision to delay a generic because the carve-out would create a product that is less safe, appears to perhaps become the next potential patent “evergreening” play and is giving the FDA fits.

FDA recently responded to a claim that there is no statutory provision to permit the carve out of Orphan Drug Exclusivity information, something it has permitted since the passage of Hatch-Waxman in a response it posted on its web site (here) as it relates to its recent approval of aripiprazole.   But this (according to an FDA official) is just “one in a series of similar issues” it has in its queue for evaluation.  I think we all can agree that the current statutory provisions protect the public and assure that when a generic is approved with a carve out that it is no less safe than the RLD, but now, as the Agency faces more complex challenges relative to assuring such, we may see more denials of carve outs.  This is certainly an issue that the entire pharmaceutical industry should show a great interest in.  But, remember, there is a balance to be struck in each decision the FDA makes and it cannot make a decision that does not assure the safety of the patient.