When is 5-Year NCE Exclusivity Less Than 5 Years?

By Kurt R. Karst –      

Every once in a while we receive a series of similar questions from various quarters such that a critical mass has been reached justifying a blog post on the topic.  This is one of those posts.  And it has to do with the always hot – and particularly hot as of late (see our previous post here) – topic of 5-year New Chemical Entity (“NCE”) exclusivity.  The question is: can 5-year NCE exclusivity be cut short, such that FDA can approve an ANDA or a 505(b)(2) application prior to the expiration of such period?  The answer under one interpretation of the law, surprising to some, appears to be “Yes.”

NCE exclusivity is explained in the FDC Act vis-à-vis the submission and approval of an ANDA (at FDC Act § 505(j)(5)(F)(ii)) or a 505(b)(2) application (at FDC Act § 505(c)(3)(E)(ii)) for a drug product containing an active moiety protected by NCE exclusivity.  For example, FDC Act § 505(j)(5)(F)(ii) states:

If an application submitted under [FDC Act § 505(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 [FDC Act § 505(b)], is approved after September 24, 1984, no [ANDA] may be submitted under [FDC Act § 505(j)] which refers to the drug for which the [FDC Act § 505(b)] application was submitted before the expiration of five years from the date of the approval of the application under [FDC Act § 505(b)], except that [an ANDA] may be submitted under [FDC Act § 505(j)] after the expiration of four years from the date of the approval of the [FDC Act § 505(b)] application if it contains a [Paragraph IV certification].  The approval of such [ANDA] shall be made effective in accordance with [FDC Act § 505(j)(5)(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 [NCE NDA], the thirty-month period referred to in [FDC Act § 505(j)(5)(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 [NCE NDA].

For our purposes here, the important part of the statutory quote above is the reference to FDC Act § 505(j)(5)(B) and the effective date of ANDA approval when there is not a timely filed patent infringement lawsuit made in response to the notice of a Paragraph IV certification contained in an ANDA submitted beginning at year 4 of the 5-year NCE exclusivity period.  Section 505(j)(5)(B) governs the effective date of ANDA approval depending on the type of certification to patent information listed in the Orange Book for the Reference Listed Drug (“RLD”) that forms the basis of submission of an ANDA.  With respect to an ANDA containing a Paragraph IV certification, the statute, at FDC Act § 505(j)(5)(B)(iii), states: 

If the applicant made a [Paragraph IV certification], the approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice described in [FDC Act § 505(j)(2)(B)] is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under [FDC Act §§ 505(b)(1) or (c)(2)] before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted.  If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the [Paragraph IV certification] notice . . . or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, [with certain exceptions . . . . .] [(Emphasis added)]

Bam!  There you have it!  The statute says ANDA approval is made effective “immediately” if there is not a timely filed patent infrongement lawsuit made in response to notice of a Paragraph IV certification.  Thus, in a hypothetical scenario where the 5-year NCE exclusivity period for a drug expires on January 2, 2014, an ANDA containing a Paragraph IV certification to an Orange Book-listed patent can be submitted on January 2, 2013.  Let’s say that our hypothetical ANDA is received after a 60-day review period by FDA’s Office of Generic Drugs.  There is then a 20-day period to send notice of the Paragraph IV certification to the NDA holder and patent owner.  If notice is promptly sent and 45 days pass without the filing of a patent infringement lawsuit, our hypothetical ANDA could be approved with about 8 months of the 5-year NCE exclusivity period remaining on the RLD. 

How often does it happen that the 5-year NCE exclusivity period is cut short?  Not often.  In fact, we cannot immediately think of a case.  And with median ANDA approval times still hovering around 33 to 34 months, it seems more of a theoretical possibility now than a real possibility that FDA could turn around an ANDA within a few months.  Perhaps a 505(b)(2) application containing verly little data and that is granted priority review could be turned around in short order.  With the enactment of the Generic Drug User Fee Amendments and the expectation of significantly reduced ANDA review timelines, however, it might be possible for FDA’s Office of Generic Drugs to promptly act on an ANDA.  Only time will tell.

The possibility that NCE exclusivity might be cut short might be one explanation as to why an NDA sponsor with a single Orange Book patent with a questionable basis for listing might request that FDA delist the patent prior to the expiration of 4 years after the NCE NDA approval.  For example, see our previous post here concerning INVEGA (paliperidone) Extended-release Tablets.  If there is not a resonable basis to assert a patent against the sponsor of an ANDA, then the listing of that patent could actually trigger ANDA approval much earlier than expected.  Alternatively, if there is not a patent, then the ANDA cannot even be submitted until the 5-year NCE exclusivity period expires.