Who’s on First? FDA Raises the Specter of 180-Day Exclusivity Eligibility/Forfeiture for Generic RESTASIS and Asks If There’s a Phantom “First Applicant”

By Kurt R. Karst –

A “phantom” is defined, in part, to mean “an appearance or illusion without material substance, as a dream image, mirage, or optical illusion.”  That’s probably the best way to sum up what’s at the heart of the issues raised by FDA in the Agency’s latest “Dear Applicant Letter” (Docket No. FDA-2015-N-2713)  requesting comment on a Hatch-Waxman issue.  In this case, the drug is Cyclosporine Ophthalmic Emulsion, 0.05% (the generic name for RESTASIS, which was approved as an “old antibiotic” under NDA 050790 – see here), and the questions on which FDA is seeking comment concern “first applicant” status, 180-day exclusivity eligibilty and forfeiture, and whether an ANDA applicant who certified Paragraph IV to a now-expired patent really qualifies as a first applicant. 

By way of background, FDC Act § 505(j)(5)(B)(iv)(II)(bb) defines a “first applicant” as “an applicant that, on the first day on which a substantially complete application containing a [Paragraph IV certification] is submitted for approval of a drug, submits a substantially complete application that contains and lawfully maintains a [paragraph IV certification] for the drug.”  A first applicant is eligible for 180-day exclusivity vis-à-vis subsequent Paragraph IV ANDA applicants, and, as FDA explained in a prior decision (see our previous post here), can remain a first applicant even if eligibility for 180-day exclusivity is forfeited.  A first applicant can forfeit eligibility for exclusivity under one (or more) of six statutory forfeiture provisions, including if “[a]ll of the patents as to which the applicant submitted a certification qualifying it for the 180-day exclusivity period have expired.”

In the case of Cyclosporine Ophthalmic Emulsion, 0.05%, FDA explains that “[t]he first patents for Restasis were listed in the Orange Book in late 2008: U.S. Patent Nos. 4,839,342 (the ‘342 patent) and 5,474,979 (the ‘979 patent).”  These patent listings were made possible as a result of the October 8, 2008 enactment of the QI Act (see our previous post here).  The ‘342 patent expired on August 2, 2009, and the ‘979 patent expired on May 17, 2014; however, “[o]ne or more ANDAs or patent amendments submitted after the ‘342 patent expired but before January 14, 2014 contained a paragraph IV certification to the ‘979 patent, potentially qualifying the ANDA sponsor(s) as a ‘first applicant’ eligible for 180-day exclusivity,” writes FDA. 

What’s important about January 14, 2014?  That the date on which U.S. Patent No. 8,629,111 (“the ‘111 patent”) was submitted to FDA and listed in the Orange Book for RESTASIS.  Also on that date, “one or more [ANDA] applicants submitted a paragraph IV certification to the ‘111 patent.”

So far, this seems to be a pretty simple forfeiture analysis, right?  After all, as noted above, one 180-day exclusivity forfeiture provision states that a forfeiture event occurs if all exclusivity-bearing patents expired.  But then FDA throws the following facts into the mix:

Until the ‘111 patent was listed on January 14, 2014, the ‘979 patent was the only patent listed in the Orange Book for Restasis since expiry of the ‘342 patent in 2009. 

The one or more paragraph IV certifications to the ‘979 patent submitted to FDA after the ‘342 patent expired but before January 14, 2014, were the first paragraph IV submissions made for Restasis.  But the ‘979 patent expired before FDA issued an Acknowledgement Letter to any applicant with a pending ANDA for this drug product, and before any sponsor had the opportunity to provide notice of the paragraph IV certification to that patent.

Given this complicated scenario, FDA says that there are two issues before the Agency:

(1) the one or more applicants that submitted ANDAs or patent amendments with paragraph IV certifications to the ‘979 patent after the ‘342 patent expired but before January 14, 2014, and that did not receive Acknowledgement Letters until after the ‘979 patent had expired, are “first applicants” under FD&C Act section  505(j)(5)(B)(iv)(II)(bb); and

(2) whether 180-day generic drug exclusivity for this product was forfeited on May 17, 2014, when the ‘979 patent expired, such that no ANDA applicant for Cyclosporine Ophthalmic Emulsion, 0.05%, is eligible for 180-day generic drug exclusivity.

FDA further notes that as part of the Agency’s consideration it “is considering whether the fact that FDA did not issue an Acknowledgement Letter for this drug product until after the patent expired impacts this analysis,” and that the Agency is also seeking comment on “whether there are any other factors that are material to this question.”  Interested parties have until August 28, 2015 to send comments to FDA. 

It’s been a while since we’ve seen a public docket established for a “Dear Applicant Letter” – the last being in early 2014 for PRECEDEX (dexmedetomidine HCl) Injection (see our previous post here).  FDA’s decision in that case led to litigation (see our previous post here), so we’ll be closely watching things in this case to see where the cards fall.  And we’ll also be keeping an eye on any action by FDA (or others) on issues concerning acceptance of ANDAs for generic RESTASIS.  There’s no indication that FDA has responded to a December 2014 Citizen Petition (Docket No. FDA-2015-P-0065) asking the Agency to refuse to receive and approve any ANDA for generic RESTASIS unless certain criteria are met.