Will the Fourth Time be the Charm? FDA is Once Again Asked for Guidance on Drug Delivery Device Patent Orange Book Listing

By Kurt R. Karst –      

FDA has been asked for a fourth time to provide an advisory opinion on compliance with the Hatch-Waxman Orange Book patent listing requirements for a patent that claims a drug delivery device integral to the administration of the active ingredient, but where the patent does not recite the active ingredient.  The latest Advisory Opinion Request (Docket No. FDA-2011-A-0363), submitted on behalf of Forest Laboratories, Inc. (“Forest”) (and with respect to a drug product under an NDA – NDA No. 202-450 – that apparently has not yet been approved), follows almost identical Advisory Opinion Requests filed in January 2005 by GlaxoSmithKline (Docket No. 2005A-0015), in August  2006 by AstraZeneca (Docket No. 2006A-0318), and in June 2007 by AstraZeneca (Docket No. 2007A-0261).  Forest’s Advisory Opinion Request raises the issue of whether a patent with certain characteristics should be submitted to FDA for Orange Book listing; specifically, where:

a)  the patent claims a drug delivery device: (i) whose use is integral to the administration of the active ingredient subject of the NDA, (ii) whose approval, therefore, is part of the approval of the active ingredient subject of the NDA, and (iii) that is recited in the “Indications and Usage” section of the Prescribing Information for the active ingredient subject of the NDA (“label”); and

b)  the claims in the patent do not recite the active ingredient subject of the NDA.

As we previously reported, the advisory opinion requests previously submitted to FDA were apparently prompted by FDA’s response to comments stated in the preamble to the Agency’s June 2003 final rule implementing the FDC Act’s patent listing provisions.  Those comments sought clarification as to whether patents claiming delivery devices or containers “integral” to a drug product should be submitted to FDA for Orange Book listing.  FDA did not directly address the issue, but rather stated that the key factor in determining whether a drug product patent must be submitted for Orange Book listing is “whether the patent being submitted claims the finished dosage form of the approved drug product.” 

FDA’s failure to provide clear statements on the issue has led some companies to interpret the law and FDA’s patent listing regulations at 21 C.F.R. § 314.53 to require patent submission and Orange Book listing if such patents claim an integral part of an approved drug product rather than merely packaging (patents claiming packaging may not be submitted for Orange Book listing).  Indeed, GlaxoSmithKline, apparently tired of waiting for a response from FDA to its Advisory Opinion request, informed FDA in February 2009 that “in the absence of further guidance from the FDA, [the company] has modified its Orange Book listing practice to list those patents whose claims read on the drug product subject to FDA approval, including those patents that claim all or a portion of integrated drug-device products, regardless of whether the approved drug substance is specifically mentioned in the claims of such patents.” (See our previous post here.)  Other companies have apparently followed suit, as there are now several patents listed in the Orange Book that could be characterized as drug delivery device patents. 

Forest says in its Advisory Opinion Request that the FDC Act “imposes a duty on an NDA applicant to submit a patent for listing when the patent claims a drug product that can be asserted against a generic manufacturer in an infringement action,” and that:

In Forest’s view, that duty exists when the patent claims a drug delivery device that is an integral part of the administration of the active ingredient to a patient, especially when the approval of the drug product NDA is conditioned on the concurrent approval of the drug delivery device.  This duty should exists irrespective of whether the patent recites the active ingredient in the claims.  This is because the patent would be, in either case, a patent with respect to which a claim of patent infringement could reasonably be asserted under the conditions recited in the statute.

Moreover, says Forest, there are two reasons that “strongly suggest that the FDA accepts the practice of submitting drug delivery device patents that do not recite the drug substance in the claims for listing in the Orange Book.”  First, “the FDA has not condemned the practice publicly, even after given the explicit opportunity to do so via the three requests for an advisory opinion cited above.”  Second, “the FDA accepts the submissions of such patents and later lists them in the Orange Book.”

The Orange Book listing of one patent alleged to be a drug delivery device patent has already led one company to assert in court the patent delisting counterclaim provisions at FDC Act §505(c)(3)(D)(ii)(I) added to the statute by the Medicare Modernization Act (“MMA”) available to 505(b)(2) NDA sponsors.  (The MMA also added a parallel counterclaim provisions at FDC Act §505(j)(5)(C)(ii)(I) applicable to ANDA sponsors.)  As we previously reported, Intelliject, Inc. alleges in a court filing from earlier this year that U.S. Patent No. 7,794,432 (‘the ‘432 Patent”), which is listed in the Orange Book for EpiPen and EpiPen Jr Auto-Injectors (epinephrine injection) solution, 0.3mg/ml and 0.415/0.3 ml (NDA No. 19-430), must be delisted from the Orange Book, because “the ‘432 patent does not claim either the drug for which Meridian’s NDA was approved or an approved method of using the drug.”