The Scope of New Chemical Entity Exclusivity and FDA’s “Umbrella” Exclusivity Policy

By Kurt R. Karst –      

Suppose FDA approves a New Drug Application (“NDA”) – NDA No. 1 – and grants a period of 5-year New Chemical Entity (“NCE”) exclusivity, but there are no patents listed in FDA’s Orange Book for the NDA, and therefore, there is no opportunity for a generic drug sponsor to submit to FDA an ANDA containing a Paragraph IV certification on the so-called “NCE-1 date.”  Suppose further that a couple of years after the approval the NDA No. 1, FDA approves a second NDA from the same sponsor – NDA No. 2 – for a drug product containing the same active moiety as in NDA No. 1, but perhaps in a different dosage form, but the NDA sponsor does submit to FDA for listing in the Orange Book a patent for NDA No. 2.  While the remainder of the period of NCE exclusivity granted for the approval of NDA No. 1 would apply under FDA’s “umbrella policy” to NDA No. 2, does the fact that NDA No. 1 is not listed in the Orange Book with a patent preclude an NCE-1 Paragraph IV ANDA submission for the drug product covered under NDA No. 2?  It’s an interesting scenario – and probably quite rare – but one we thought should be tackled. 

The statutory 5-year NCE exclusivity provision at FDC Act § 505(j)(5)(F)(ii) applicable to ANDAs (there is a slightly different parallel provision at FDC Act § 505(c)(3)(E)(ii) applicable to 505(b)(2) applications) governing the scope of NCE exclusivity states in relevant part:

If an application submitted under subsection (b) 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), is approved after the date of the enactment of this subsection, 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), 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 [Paragraph IV certification]. [(Emphasis added)]

Is the emphasis in this statutory provision on the phrase “the drug” (subsequently clarified by FDA to mean “active moiety”), which would argue in favor of an NCE-1 Paragraph IV ANDA submission for NDA No. 2, or on “the subsection (b) application,” which would seem to argue otherwise?

FDA’s regulation at 21 C.F.R. § 314.108(b)(2) implementing FDC Act § 505(j)(5)(F)(ii) sheds some light on this statutory provision and states, in relevant part, that:

If a drug product that contains a [NCE] was approved after September 24, 1984, in an application submitted under section 505(b) of the act, no person may submit a 505(b)(2) application or [ANDA] under section 505(j) of the act for a drug product that contains the same active moiety as in the [NCE] for a period of 5 years from the date of approval of the first approved [NDA], except that the 505(b)(2) application or abbreviated application may be submitted after 4 years if it contains a [Paragraph IV] certification . . . .[(Emphasis added)]

This regulations seems to say that the decisive factor in determining the scope of NCE exclusivity is the active moiety.  Indeed, if FDA intended the reference to “the subsection (b) application” in FDC Act § 505(j)(5)(F)(ii) to be the decisive factor in determining the scope of NCE exclusivity, then 21 C.F.R. § 314.108(b)(2) presumably would not emphasize the active moiety as it does.  Thus, if FDA were presented with the scenario above, it seems that the Agency would determine that NCE exclusivity prevents the submission of an ANDA for a proposed drug product containing the protected active moiety for 5 years – whether that protected active moiety is in a drug product approved under NDA No. 1 or under NDA No. 2 – unless an ANDA for a generic version of the drug product covered under NDA No. 2 protected by the umbrella NCE exclusivity stemming from the approval of NDA No. 1 contains a Paragraph IV certification to an Orange Book-listed patent.  In other words, an ANDA for a generic version of the drug product covered by NDA No. 2 could be submitted on the NCE-1 date if it contains a Paragraph IV certification.

Such an interpretation of FDC Act § 505(j)(5)(F)(ii) seems to be consistent with FDA’s NCE exclusivity “umbrella policy.”  Under that policy:

[W]hen exclusivity attaches to an active moiety or to an innovative change in an already approved drug, the submission or effective date of approval of ANDA’s and 505(b)(2) applications for a drug with that active moiety or innovative change will be delayed until the innovator’s exclusivity has expired, whether or not FDA has approved subsequent versions of the drugs entitled to exclusivity, and regardless of the specific listed drug product to which the ANDA or 505(b)(2) application refers.

FDA, Proposed Rule, ANDA Regulations, 54 Fed. Reg. 28,872, 28,897 (July 10, 1989) (emphasis added). 

Thus, NCE exclusivity protects the active moiety in subsequent NDA approvals made within the 5-year NCE exclusivity period; however, that exclusivity would seem to apply separately with respect to each approved drug product, particularly when there is a patent listed in the Orange Book covering NDA No. 2 in our scenario but not for the original NDA No. 1 approval from which the NCE exclusivity flows.