Like a Bad Penny, Pre-MMA 180-Day Exclusivity Keeps Turning Up!

By Kurt R. Karst – 

Although it’s been more than 10 years since the December 8, 2003 enactment of the Medicare Modernization Act (“MMA”) – or, more accurately, The Medicare Prescription Drug, Improvement, and Modernization Act, Pub. L. No. 108-173 – which created a new regime for 180-day generic drug marketing exclusivity, the pre-MMA version of the statute governing 180-day exclusivity is still alive and kicking.  In fact, because of how the pre-MMA-to-post-MMA changeover operates, pre-MMA 180-day exclusivity may be around for quite some time, frustrating some generic drug applicants along the way, but rewarding others.

Under the pre-MMA version of FDC Act § 505(j), 180-day exclusivity is patent-based, such that an ANDA applicant is (or different applicants are) eligible for 180-day exclusivity with respect to different Orange Book-listed patents covering the Reference Listed Drug if such applicant submitted the first ANDA to FDA containing a Paragraph IV certification to a particular patent.  Pre-MMA 180-day exclusivity is triggered by the earlier of either the first commercial marketing (for all patents certified to as Paragraph IV by a first-filer), or by a court decision favorable to an ANDA applicant (with respect to a particular patent).  Of course, where there is no court decision (because, for example, an ANDA applicant was not sued for patent infrongement, or there was a settlement of litigation without a holding on the merits), the possibility of “parked” exclusivity arises . . . at least until there is commercial marketing of the drug or the patent(s) on which 180-day exclusivity is based expires. 

The MMA amended the FDC Act such that the first company to submit an ANDA to FDA containing a Paragraph IV certification to any Orange Book-listed patent covering the RLD – i.e., a “first applicant” – is eligible for 180-day exclusivity.  Post-MMA, 180-day exclusivity is considered drug product-based and is triggered by first commercial marketing of the drug product by any first applicant.  A first applicant can forfeit 180-day exclusivity eligibility under one or more forfeiture provisions created by the MMA. 

The MMA includes – at § 1102(b)(1) – an effective date provision for purposes of deciphering when the pre- or post-MMA 180-day exclusivity regime will apply.  That provision states: “the amendment made by subsection (a) shall be effective only with respect to an [ANDA] filed . . . after [December 8, 2003] for a listed drug for which no [Paragraph IV certification] was made before [December 8, 2003].”

As a result of the MMA’s effective date provision, a drug product subject to the pre-MMA rules on 180-day exclusivity is forever evaluated under the old version of the statute.  This includes, as FDA previously determined, so-called “MMA Straddles.”  An MMA-Straddle situation arises  when one or more ANDAs were submitted to FDA on or before December 8, 2003, but the first Paragraph IV certification was submitted to FDA after December 8, 2003.  A few known MMA Staddle drug products include Topiramate Sprinkle Capsules, 15 mg and 25 mg (TOPAMAX) and Methylphenidate HCl Extended-Release Tablets, 18 mg, 27 mg, 36 mg, and 54 mg (CONCERTA). 

Also included the pre-MMA category of drugs are brand-name products for which an ANDA was submitted to FDA on or before December 8, 2003 containing a Paragraph IV certification that may have already resulted in a period of 180-day exclusivity associated with that patent, and for which a new patent is issued post-MMA and information for which is listed in the Orange Book.  The new patent listing gives rise to the possibility of another period of 180-day exclusivity – either by operation of an amendment to a pending ANDA or through the submission of a new original ANDA – for a brand-name drug that went generic long ago.  It also means, however, that subsequent ANDA sponsors certifying to a newly listed patent cannot be approved until the first-filer’s exclusivity is over (or is otherwise lost).   Thus, for example, U.S. Patent No. 7,022,340 applicable to NDA No. 019955 for DDAVP Tablets (desmopressin acetate), 0.1 mg and 0.2 mg, has given rise to a new period of 180-day exclusivity eligibility and has blocked subsequent applicants from opbtaining final approval.  Similarly, U.S. Patent No. 8,476,010 applicable to NDA No. 019627 for DIPRIVAN (propofol) Injection, 10 mg/mL, has given rise to a new period of 180-day exclusivity eligibility for generic versions of that drug product.  (Another interesting case is the listing of U.S. Patent No. 7,091,236 for various Glycopyrrolate Tablet drug products approved in August 1961 under NDA No. 012827, and marketed under the ROBINUL trade name.  The patent is apparently the first patent listed in the Orange Book for those brand-name drug products.)  

Because of the pre-MMA patent-by-patent approach to 180-day exclusivity, FDA’s interpretation of when the pre-MMA statute applies in a post-MMA world, and the issuance of new patents for drugs approved long ago, any list of pre-MMA drug products is naturally fluid.  Drug products can move on or off of that list.  Although ANDAs with a number less than or equal to 076933 are applications submitted to FDA on or before December 8, 2003 (pre-MMA), and ANDAs with a number equal to or greater than 076934 are post-MMA applications, a post-076934 ANDA could be subject to (or be eligible for) pre-MMA exclusivity because of an older ANDA submission.  In some cases, that means a revision to a pre-MMA list of drugs to add a new drug.  In another situation, a brand-name drug for which an ANDA was submitted to FDA pre-MMA may be withdrawn for reasons of safety or effectiveness (e.g., TEQUIN, SELDANE, and “old” OXYCONTIN), or converted in a prescription-to OTC switch under a new NDA (e.g., MIRALAX).  Those products have to be removed from any pre-MMA list of drugs.

So what’s this all leading up to you ask?  You guessed it, as part of our celebration of the 30th anniversary of the Hatch-Waxman Amendments we put together a current list of all the drug products we think are subject to the pre-MMA 180-day exclusivity statute.  The list may not be perfect (after all, not all of the MMA Straddles are known), but it’s as complete a list as we have ever seen.  Here you go . . . and enjoy!