Diary of a Hatch-Waxman Addict – Day 4,079: They’re Here! FDA Finally Proposes Regulations to Implement Some of the Provisions of the 2003 MMA!

By Kurt R. Karst –      

There was some big news out of FDA today.  Yes, there was the news that FDA Commissioner, Dr. Margaret Hamburg, one of the longest-serving FDA commissioners in the modern era (see here), has decided to resign her post effective next month.  But even bigger than that (at least for this blogger) was some other news.  For quite some time now this blogger has opened the pre-publication website of the Federal Register hoping to see posted a notice of FDA’s long-awaited proposed regulations to implement the December 8, 2003 Medicare Modernization Act (“MMA”).  We were disappointed when the proposed regulations – which have been in the works for many years – did not get published by the MMA’s 10th anniversary.  That was day 3,655 in our Hatch-Waxman diary (see our previous post here).  Fast-forward to day 4,079, February 6, 2015, and the proposed regulations will make their official debut in the Federal Register. 

The pre-publication version of the proposal is a massive 341 pages (and includes a slew of tables), while the official version printed in the Federal Register comes in at a cool 96 pages.  And this is only part one of what will likely be a two-part series.  Part two, which we don’t think will come out any time soon, will deal with forfeiture of 180-day exclusivity eligibility.  Part one largely deals with the MMA’s provisions concerning Paragraph IV notice, 30-month litigation stays, amendments to ANDAs and 505(b)(2) applications, the types of bioavailability and bioequivalence data that can be used to support ANDAs and 505(b)(2) applications, as well other changes “to facilitate compliance with and efficient enforcement of the FD&C Act.”  What does that last passage mean?  FDA provides an example: “we are proposing to clarify requirements for the NDA holder’s description of the patented method of use (the “use code”) required for publication in [the Orange Book] to avoid overbroad use codes that may delay approval of generic drugs.” 

We’re still poring over the behemoth of a proposal.  And because this is Hatch-Waxman we’re talking about, there’s a lot of nitty-gritty to consider.  Nevertheless, below are a few goodies to whet you Hatch-Waxman appetite (taken from FDA’s highlight summary).  We’re sure to have more to say on the proposal in the coming weeks.

Submission of Patent Information – In addition to revising and streamlining the requirements related to submission of information for certain patent types, FDA’s proposed rule tackles reissued patents and describes the Agency’s approach to treating original and reissued patents as a bundle of patent rights.  As FDA later explains in the proposal:

Proposed § 314.53(c)(2)(i)(J) and (c)(2)(ii)(K) would provide that an NDA applicant or holder is required to include information on whether a patent submitted for listing is a reissuance of a patent previously submitted for listing for the NDA or supplement. . . .  [T]he timely filing of patent information for a reissued patent (including a reissued patent with a broadened scope of claims) does not alter the patent certification obligations of a 505(b)(2) or ANDA applicant whose application was pending when the original patent was filed by the holder of an approved application for listing more than 30 days after patent issuance (“late listed”).  In other words, if a 505(b)(2) or ANDA applicant is not required to provide a patent certification or statement to the original patent pursuant to § 314.50(i)(4) or § 314.94(a)(12)(vi) because the patent was late listed, the 505(b)(2) or ANDA applicant would not be required to provide a patent certification or statement to the reissued patent even if timely filed following reissuance.

In addition, to “restrain overbroad use codes,” FDA’s proposal “would expressly require that if the scope of the method-of-use claim(s) of the patent does not cover every approved use of the drug, the NDA holder’s use code must describe only the specific portion(s) of the indication or other method of use claimed by the patent.” 

Timing of Submission of Patent Information – FDA expressly describes the Agency’s current practice with respect to the late listing of patent information, and proposes “to expand the category of untimely filed patent information to include certain amendments to the NDA holder’s description of the approved method(s) of use claimed by the patent, if such changes do not relate to a corresponding change in approved labeling or are submitted more than 30 days after such labeling change.”  According to FDA, this revision “is intended to reduce delays in approval related to manipulation of patent use codes. . . .”

Correction or Change of Patent Information – Among other things, FDA wants to enhance its response to challenges to the accuracy or relevance of Orange Book patent information.  FDA’s current regulation at 21 C.F.R. § 314.53(f) to challenge Orange Book patent information is rather toothless.  “If, in response to such a challenge, the NDA holder confirms the accuracy of the information, fails to timely respond, or submits a revision to the use code that does not provide adequate clarity for FDA to determine whether the scope of a proposed labeling carve-out would be appropriate based on the NDA holder’s use code and approved labeling,” says FDA, then “we are proposing to review proposed labeling carve-out(s) for the 505(b)(2) application or ANDA with deference to the 505(b)(2) or ANDA applicant’s interpretation of the scope of the patent.”

Notice of Paragraph IV Certification (Timing) – FDA proposes to delineate the two limitations on the timeframe within which Paragraph IV certification notice can be provided to the NDA holder and patent owner: “(1) [t]he date before which notice may not be given (reflecting FDA’s long-standing practice) and (2) the date, established by MMA, by which notice must be given.”  In addition, FDA reiterates that pramature notice is inavalid “and will not be considered to comply with the FD&C Act’s notice requirement.”  The Agency is also proposing “administrative consequences” for ANDA applicants who fail to send Paragraph IV notice within the statutory timeframe.  Specifically, “[t]he date the ANDA was submitted would be deemed to be delayed by the number of days by which the time frame was exceeded, which may result in the applicant losing eligibility for 180-day exclusivity.”  This is a topic on which we previously posted.

In addition, FDA's proposal would, if implemented, get rid of those pesky “serial certifications” – a practice many ANDA applicants have used throughout the years in an attempt to secure first-filer status and eligibility for 180-day exclusivity by preemptively sububmitting a Paragraph IV certification each day (sometimes for several months) until (or in case) a patent is listed in the Orange Book.  According to FDA's proposal: 

We are proposing to establish a date (the first working day after the day the patent is published in the Orange Book) before which an ANDA applicant cannot send valid notice of a paragraph IV certification to a newly listed patent.  This approach is intended to promote equity among ANDA applicants seeking eligibility for 180-day exclusivity and to reduce the burden on industry and FDA associated with serial submissions and multiple notices of paragraph IV certifications related to a newly issued patent.

Notice of Paragraph IV Certification (Content and Methods) – FDA is proposing to expand the acceptable methods of sending Paragraph IV notice beyond the now archaic registered or certified mail routes to include “designated delivery services.”

Amended Patent Certifications – In an effort to codify FDA’s current practice of not removing a withdrawn patent from the Orange Book until the resolution of 180-day exclusivity issues, the Agency proposes to “clarify the requirements for a 505(b)(2) or ANDA applicant to amend a paragraph IV certification after a judicial finding of patent infringement to reflect statutory changes made by the MMA,” and to “clarify the circumstances and time frame in which a 505(b)(2) or ANDA applicant must submit an amended patent certification after an NDA holder has withdrawn a patent and requested removal of the patent from the Orange Book.”

Amendments or Supplements (Patent Certification Requirements) – FDA’s proposal would augment the current regulations on patent certification requirements for amendments and supplements (for both ANDA and 505(b)(2) applicants) by “requiring a new patent certification with an amendment to make other-than-minor changes in product formulation or to change the physical form or crystalline structure of the active ingredient.”  That is, FDA finally addresses the issue of when an applicant must recertification and renotification. 

Limitation on Submission of Certain Amendments and Supplements to a 505(b)(2) Application or ANDA – FDA’s proposal codifies the Agency’s current interpretation of the statutory prohibition on amending or supplementing an application to refer to a different listed drug (see our previous posts here, here, and here).  “We are implementing these parallel restrictions on submission of certain types of changes in an amendment or a supplement to a 505(b)(2) application or ANDA in a manner that is consistent with the statutory text and preserves a meaningful opportunity for a single 30-month stay,” says FDA. 

505(b)(2) Applications – Turning to an issue that is part of ongoing litigation (see our previous post here), FDA proposes “to require a 505(b)(2) applicant to identify a pharmaceutically equivalent product, if already approved, as a listed drug relied upon, and comply with applicable regulatory requirements.”  FDA later explains that:

If a pharmaceutically equivalent drug product has been approved before a 505(b)(2) application is submitted, then we consider the 505(b)(2) applicant to be implicitly relying on the approval of such drug product.  We are proposing to revise § 314.54(a)(1)(iii) to require that the listed drug or drugs identified as relied upon by a 505(b)(2) applicant must include any approved drug product that: (1) Is pharmaceutically equivalent to the drug product for which the 505(b)(2) application is submitted and (2) was approved before the 505(b)(2) application was submitted.

Date of Approval of a 505(b)(2) Application or ANDA – With respect to application approval and 30-month patent litigation stays, FDA, among other things in the proposal, codifies the MMA’s provisions on the type of court decisions that will terminate a 30-month stay.  FDA also brings up other scenarios in which a 30-month stay may be terminated (e.g., written consent to approval by the patent owner or exclusive patent licensee, a court order terminating the stay, or a court order of dismissal without a finding of infringement). 

Notification of Commercial Marketing – Under FDA’s proposal, an ANDA applicant’s failure to timely notify the Agency about the date of commercial marketing (and thus the trigger for the start of 180-day exclusivity) can have significant consequences:

A first applicant would be required to submit correspondence to its ANDA notifying FDA within 30 days of the date of first commercial marketing of the drug product.  If the first applicant does not notify FDA within this time frame, we are proposing to deem the date of first commercial marketing to be the date of the drug product’s approval.  This may have the effect of shortening the 180-day exclusivity period in a similar manner to the current regulatory consequence for failure to provide “prompt” notice of first commercial marketing.

Notification of Court Actions or Documented Agreements – In what appears to be an effort by FDA to be better informed of the patent infringement litigation landscape, the Agency proposes to “expand the scope of documentation that an applicant must submit to FDA regarding patent-related court actions and documented agreements to ensure that FDA is promptly advised of information that may affect the timing of approval of a 505(b)(2) application or ANDA.”  This includes a copy of any judgment (or settlement order or consent decree signed and entered) by a court (district court or mandate of the court of appeals) finding a patent invalid, unenforceable, or not infringed (or finding the patent valid and infringed).