FDA’s PLAIR Program Collides With Hatch-Waxman

By Kurt R. Karst –   

FDA’s recent approval of ANDAs for generic versions of sanofi-aventis’ (“sanofi’s”) blockbuster blood thinner drug PLAVIX (clopidogrel bisulfate) Tablets (approved under NDA No. 020839) upon the May 17, 2012 expiration of a period of pediatric exclusivity associated with Orange Book-listed U.S. Patent No. 4,847,265 (“the ‘265 patent”) was preceded by a sideshow that brings to light an interesting tension between the Hatch-Waxman Amendments and FDA’s Pre-Launch Activities Importation Request (“PLAIR”) program.  As we previously discussed, FDA’s PLAIR program allows, on a case-by-case basis, the importation and warehousing of finished drugs where an application for drug approval (i.e., an NDA or ANDA) is pending approval and where the import and warehousing will expedite the commercial launch of the drug once FDA approves an application.

Apotex, Inc. (“Apotex”) is one of several companies that years ago submitted an ANDA to FDA seeking approval of generic PLAVIX and whose applications each contained a Paragraph IV certification to the ‘265 patent.  Apotex submitted is application – ANDA No. 076274 – to  FDA in 2001, prior to the enactment of the Medicare Modernization Act (“MMA”), and was the first filer with respect to the ‘265 patent, thereby making Apotex eligible for 180-day exclusivity.  In March 2002, Sanofi sued Apotex for infringement of the ‘265 patent in the U.S. District Court for the Southern District of New York, thereby triggering a 30-month stay of approval of Apotex’s ANDA.  FDA first approved ANDA No. 076274 on January 20, 2006, after the 30-month stay expired in May 2005 without a relevant court decision.  Almost six months later, on August 8, 2006, Apotex began commercially marketing its generic clopidogrel drug product at risk of an adverse court decision, thereby triggering the company’s 180-day exclusivity under the pre-MMA statute.  Sanofi quickly sought a permanent injunction barring Apotex from further marketing the drug product, and on August 31, 2006, the district court granted the injunction pending the outcome of the case.  (Apotex subsequently petitioned and sued FDA – see here and here – to recover 180-day exclusivity.  The lawsuit was voluntarily dismissed in April 2009, and FDA denied Apotex’s petition as moot on May 17, 2012.) 

In June 2007, the New York District Court ruled that Apotex failed to prove that the ‘265 patent is invalid and entered a permanent injunction.  Apotex appealed the decision, but in December 2008, the U.S. Court of Appeals for the Federal Circuit affirmed the district court’s decision.  On June 22, 2009, FDA converted the final approval of ANDA No. 076274 to a tentative approval to conform the status of the ANDA to the district court’s June 2007 Order issued pursuant to 35 U.S.C. 271(e)(4).  That Order (as amended) states in relevant part:

5. Plaintiffs are entitled to permanent injunctive relief.  [Apotex is] hereby permanently enjoined from engaging in the commercial manufacture, use, offer to sell or sale within the United States, or importation into the United States of drug products as claimed in [the ‘265 patent], until the expiration of [the ‘265 patent] and any period of pediatric exclusivity that may be granted.

6. Pursuant to 35 U.S.C. § 271(e)(4) and 21 U.S.C. § 355a [(FDC Act § 505A)], the effective date of [Apotex’s ANDA No. 076274] shall be reset until the later of expiration of (i) [the ‘265 patent] and (ii) any period of pediatric exclusivity that may be granted. [(Emphasis added)]

Fast forward to 2012 . . . .

In April, Apotex submitted a PLAIR to FDA seeking the Agency’s permission to import a substantial amount of generic PLAVIX into the United States in anticipation of FDA approving ANDA No. 076274 on May 17, 2012.  (FDA granted Apotex a PLAIR on May 7th.)  After making the PLAIR request, Apotex filed a motion under Fed. R. Civ. P. 60(b)(6) to modify the New Your District Court’s June 2007 amended judgment by adding the bolded clause below:   

[Apotex is] hereby permanently enjoined from engaging in the commercial manufacture, use, offer to sell or sale within the United States, or importation into the United States of drug products as claimed in [the ‘265 patent], until the expiration of [the ‘265 patent] and any period of pediatric exclusivity that may be granted, except for importation by Apotex to its own warehouse facilities prior to the expiration of the pediatric exclusivity period to the extent such importation is permitted by [FDA] pursuant to a [PLAIR] made by Apotex and granted by the FDA.

In support of its motion, Apotex argued that if the company “is unable to ship goods to customers on May 17, 2012 (because Apotex cannot even begin to import goods to its warehouses until May 17th) Apotex will be at an extreme and undue commercial and competitive disadvantage” vis-à-vis other ANDA applicants who might be in a position to launch their drug products immediately upon FDA approval.  Sanofi opposed the motion saying, among other things, that Apotex’s motion was not made within a reasonable time and that a modification would harm sanofi.  The district court denied the motion on May 10th.  Apotex promptly appealed the decision to the Federal Circuit, which, on May 15th, also denied Apotex’s requested relief, saying that summary reversal of the New York District Court’s decision is not appropriate. 

Although a sideshow in the decade-old clopidogrel patent infringement litigation, the dispute over Apotex’s PLAIR could very well signal the beginning of something much larger.  To our knowledge, it is the first Hatch-Waxman case in which FDA’s PLAIR program has been raised as an issue.  And it probably won’t be the last, as the PLAIR program gains increasing attention and as companies increasingly seek to import finished drug product into the United States in anticipation of FDA approval.  Companies – both brand and generic – may seek to have PLAIR-related language incorporated into agreements and court orders. 

REMINDER:  HP&M is hosting a webinar, Garbage Runs, Fake Identities, and Surprise Home Visits; Strategies to Deal With FDA's Nontraditional Investigative Tools, on Wednesday, June 20, 2012 from 12:30 – 2:00 p.m. ET.  Click here to register.