FDA is Asked for a Third Time About Orange Book Patent Listings for Drug Delivery Systems

July 12, 2007

For the third time in as many years, FDA has been requested to provide an advisory opinion on the Agency’s policy for the submission of patents for Orange Book listing that cover drug delivery systems (e.g., metered-dose and dry powder inhalers, and transdermal patches) that do not recite the approved active ingredient or formulation.  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). 

On June 21, 2007, AstraZeneca submitted a request for an advisory opinion (Docket No. 2007A-0261) requesting that FDA comment on two issues:

(1) what constitutes an approved pre-filled drug delivery system for the purposes of determining whether patents relating to that system should be listed [in the Orange Book]; and

(2)  whether patents relating to an approved pre-filled drug delivery system should be listed if they (a) disclose but do not claim the active ingredient or formulation of the approved drug product or (b) neither disclose nor claim the active ingredient or formulation of the approved drug product.

Similar requests were submitted to FDA in 2006 by AstraZeneca (Docket No. 2006A-0318), and in 2005 by GlaxoSmithKline (Docket No. 2005A-0015), but the Agency has failed to substantively respond to either request thus far.  In those requests, FDA was asked whether “patents directed to drug delivery systems . . . that do not recite the approved active ingredient or formulation should be listed in the [Orange Book],” and whether “a patent [that] claims a drug delivery device or elements of a drug delivery device as part of [an NDA], but the patent does not specifically claim the active ingredient or mention the active ingredient or ingredients contained in the approved drug product, or if a patent claims the protective overwrapping of a drug delivery system,” should be submitted to FDA for Orange Book listing, respectively. AstraZeneca’s latest advisory opinion request differs from the previous requests in that it specifically asks FDA about “what types of products fall within the meaning of the term ‘pre-filled drug delivery systems.’” 

In response to comments seeking clarification as to whether patents claiming delivery devices or containers “integral” to a drug product should be submitted for Orange Book listing, FDA stated in the preamble to the Agency’s June 2003 regulations implementing the FDC Act’s patent listing provisions 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.”  In this respect, FDA also noted in the preamble that Appendix C of the Orange Book includes a current list of approved drug product dosage forms. 

Although FDA’s distinction between patents covering packaging and drug delivery systems is helpful in a very general sense, the Agency’s failure (or unwillingness) to provide more specific comment at that time (and in subsequent years) “leaves certain questions unanswered and in need of further clarification,” as AstraZeneca correctly points out in the advisory opinion request.  Specifically, AstraZeneca’s advisory opinion request states:

First, it remains unclear as to what types of products fall within the meaning of the term “pre-filled drug delivery systems,” particularly when such products are not expressly identified in the definition of dosage forms or listed in Appendix C of the Orange Book.  This is also especially true when the agency has not in other contexts, such as guidance documents, expressed any opinion on such questions. . . .  Second, FDA has not directly addressed the question whether the listing requirement applies to patents for approved drug delivery systems where the patents disclose but do not claim, or neither disclose nor disclaim, the active ingredient or formulation of the approved drug product.

In addition, AstraZeneca stakes out what could be a reasonable policy position on the issue:

[L]isting in the Orange Book of patents claiming an approved pre-filled drug delivery system and/or one identified in the labeling of the product would further the goals of the Hatch-Waxman Amendments, even if the approved formulation or active ingredient is not claimed but is disclosed in the patent or the active ingredient is neither claimed nor disclosed in the patent.  Listing such patents would provide generic manufacturers with notice of their potential infringement and an opportunity to challenge the patents early on before introducing the generic product into the marketplace.  In fact, because such patents may not claim or disclose the formulation or active ingredient specifically, a generic manufacturer searching for patents that refer to the product might not uncover them if they are not listed in the Orange Book. . . .  Accordingly, AstraZeneca will continue to list these patents unless and until it otherwise receives guidance or an advisory opinion from FDA that such listings are improper.

Categories: Hatch-Waxman