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2013-08-05 FDA Law Blog

New Legislation Seeks to Provide 5-Year NCE Exclusivity For Certain Combination Drugs
By Kt R. Karst

Last Friday, Representative Jason Chaffetz (R-UT) introduced H.R. 2985, the Combination Drug Development Incentive Act of 2013. The bill would amend the 5-year New Chemical Entity (“NCE”) exclusivity provisions of the FDC Act that affect the submission and approval of ANDAs and 505(b)(2) applications that cite as a listed drug in their applications certain combination drug products. According to a statement provided to FDA Law Blog from the office of Rep. Chaffetz, “[t]he lack of adequate incentives under current law makes it extremely difficult, if not impossible, for companies to raise the capital necessary to pursue the development of new combination drugs. This proposed legislation to create additional incentives is good public policy both economically and scientifically.”

FDA’s long-standing position has been that in order for a fixed-dose combination drug to be eligible for 5-year NCE exclusivity, each of the active moieties in the drug product must be new (i.e., not previously approved). This interpretation is based on FDA's reading of the statutory language at FDC Act §§ 505(j)(5)(F)(ii) (concerning ANDAs) and 505(c)(3)(E)(ii) (concerning 505(b)(2) applications) and the Agency’s implementing regulation at 21 C.F.R. § 314.108(b)(2), which precludes FDA from accepting ANDAs and 505(b)(2) applications for drugs that contain the same active moiety as in a previously approved NCE for five years (absent a Paragraph IVcertification).

As we previously reported (here and here), there are three Citizen Petitions pending at FDA requesting that the Agency interpret the statute to grant 5-year exclusivity for a fixed-dose combination drug product containing both a never-before-approved active moiety and a previously approved active moiety. The first petition concerns STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058), which FDA approved on August 27, 2012 under NDA No. 203100 and for which the Agency has not yet made an exclusivity decision. The second petition concerns PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution (Docket No. FDA-2013-P-0119), which FDA approved on July 16, 2012 under NDA No. 202535 and awarded a period of 3-year exclusivity that expires in July 2015. The third petition concerns NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471), which FDA approved on May 6, 2010 under NDA No. 022252 and awarded a period of 3-year exclusivity that expired in May 2013.

The Combination Drug Development Incentive Act of 2013 would, in one sense, go further than the three pending petitions. It would amend the statute to allow for a grant of NCE exclusivity for a new combination of drugs even if both were previously approved separately. Specifically, the bill would amend FDC Act §§ 505(j)(5)(F)(ii) and 505(c)(3)(E)(ii) in a parallel fashion (and make a conforming amendment to subsection (iii) in each case) as shown below. We use FDC Act § 505(j)(5)(F)(ii) as the model for both statutory changes and show in bold italic typeface the proposed additions to the statute, and show in strikethrough typeface the language that would be removed from the statute.

(ii)(I) If an application submitted under subsection (b) for a drug, and described in subclause (II) or (III), If an application submitted under subsection (b) of this section for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b) of this section, is approved after the date of enactment of this subsection is approved after January 1, 2014, in the case of an application described in subclause (II) or subclause (III), no application may be submitted under this subsection which refers to the drug for which the subsection (b) application was submitted before the expiration of five years from the date of the approval of the application under subsection (b) of this section, except that such an application may be submitted under this subsection after the expiration of four years from the date of the approval of the subsection (b) application if it contains a certification of patent invalidity or noninfringement described in subclause (IV) of paragraph (2)(A)(vii). The approval of such an application shall be made effective in accordance with subparagraph (B) except that, if an action for patent infringement is commenced during the one-year period beginning forty-eight months after the date of the approval of the subsection (b) application, the thirty-month period referred to in subparagraph (B)(iii) shall be extended by such amount of time (if any) which is required for seven and one-half years to have elapsed from the date of approval of the subsection (b) application.

(II) An application is described in this subclause if no active ingredient (including any ester or salt of the active ingredient) of the drug for which the application has been submitted has been approved in any other application under subsection (b).

(III) An application is described in this subclause if—

(aa) the application contains reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application and conducted or sponsored by the applicant;

(bb) the application is for a drug which contains a combination of active ingredients; and

(cc) no such combination of active ingredients has been approved in any other application under subsection (b).

In other words, under H.R. 2985 the current statute would be captured in new subclause (II) and the new exclusivity provision would be captured in new subclause (III). As Rep. Chaffetz's office conveyed to us:
[T]he legislation would give a new drug product – which contains a combination of active ingredients that have not previously been approved for use together – the same period of market exclusivity – five years – as a drug product containing a new active ingredient. The current period of exclusivity for these combination products is three years. Such exclusivity for a combination new drug product would, however, only be allowed if the application contains new clinical studies essential for approval, including multi-faceted efficacy studies... It's important to note that: the bill is designed to make virtually no substantive changes to the overall Hatch-Waxman scheme. It merely takes new combination drugs out of the three years of market exclusivity basket and places them in the five year category without making any other substantive changes to the law.” (Emphasis in original)

We also note that under the Generating Antibiotic Incentives Now Act (FDC Act § 505E), as added by the 2012 FDA Safety and Innovation Act (see here, pages 47-50), certain drug products designated as Qualified Infectious Disease Products are eligible for an additional 5 years of exclusivity that is added on to existing 3-year new clinical investigation exclusivity and/or 5-year NCE exclusivity. Thus, the enactment of H.R. 2985 would presumably mean that a combination drug that today might be eligible for only 3-years of exclusivity would be eligible for 10 years of exclusivity.

As currently drafted, H.R. 2985 would not apply to the three drug products referenced above that are the subject of pending petitions, because of their current approval status (i.e., approved before January 1, 2014). Nevertheless, it seems possible that the bill could be amended to account for them as the legislation moves through Congress.