After Years of Waiting, FDA Finally Lets Rip With Prescription PEG 3350 ANDA Withdrawal Proposal

May 26, 2014

By Kurt R. Karst –      

We’re not sure if it was merely the passage of time or something else that relieved the constipation, but FDA has finally acted on an October 24, 2008 Notice for an Opportunity for Hearing (Docket No. FDA-2008-N-0549) proposing to withdraw approval of ANDAs for the prescription laxative Polyethylene Glycol 3350 (“PEG 3350”) on the basis that the Durham-Humphrey Amendments prohibit the simultaneous marketing of the same drug as prescription and Over-the-Counter (“OTC”).  In letters dated May 22, 2014, and sent to Paddock Laboratories, Inc. (ANDA No. 077893), Nexgen Pharma Inc. (ANDA No. 077706), Breckenridge Pharmaceutical, Inc. (ANDA No. 077736), and Kremers Urban Pharmaceuticals Inc. (ANDA No. 076652), FDA proposes to deny pending hearing requests and to order ANDA withdrawal.  According to FDA:

After reviewing the request and the supporting data, information, and analysis submitted, we have concluded that there is no genuine and substantial issue of fact that precludes the withdrawal of [your ANDA] or justifies a hearing.  Accordingly, pursuant to Title 21 of the Code of Federal Regulations Part 314, please find enclosed a proposed Order denying your request for a hearing and withdrawing approval of [your ANDA].  Under 21 CFR 314.200(g)(3), you have 60 days after the receipt of this proposed order to respond with sufficient data, information, and analyses to demonstrate that there is a genuine and substantial issue of fact which justifies a hearing.

FDA issued the November 2008 notice after approving, on October 6, 2006, NDA No. 022015 for the OTC use of MiraLAX (polyethylene glycol 3350) powder for solution with a period of 3-year new clinical investigation exclusivity.  MiraLAX was previously approved for presciption use only under NDA No. 020698, and the above-referenced ANDAs were approved as generic versions of prescription MiraLAX.  Following the Rx-to-OTC switch of MiraLAX under a new NDA (and that ANDA sponsors were prohibited from citing in a supplement to their applications), FDA removed all Orange Book references to NDA No. 020698 and objected to the continued marketing of approved generic prescription versions of prescription MiraLAX.  Specifically, in April 2007, FDA’s Office of Generic Drugs sent letters to ANDA sponsors of prescription PEG 3350 stating that the FDC Act “does not permit both Rx and OTC versions of the same drug product to be marketed at the same time.”  The letters rely on FDC Act § 503(b)(4) to contend that prescription PEG 3350 products are “misbranded and may not be legally marketed.”  The letters also cite FDC Act § 503(b), generally, for the assertion that the statute does not permit the simultaneous Rx and OTC marketing of the same drug.

The response from some ANDA sponsors to FDA’s November 2008 notice was, shall we say, “explosive.”  Volumes of comments were initially submitted to FDA – see, e.g., here and here – laying out the reasons as to why the Agency should hold a hearing.  Some comments argued that there is a “meaningful difference” between the Rx and OTC versions of PEG 3350, or that even in the absence of a “meaningful difference” FDA’s interpretation of the law prohibiting simultaneous Rx and OTC marketing of the same drug is off the mark.  The docket went dark for a few years, and then in January 2013, Merck & Co, Inc. submitted a comment urging FDA to deny the pending hearing requests and conclude withdrawal proceedings, because, among other things, “[t]he simultaneous marketing of PEG 3350 as an Rx only and OTC laxative continues to create substantial confusion in the marketplace.” 

FDA’s 54-page Proposed Order deals (in one way or another) with each issue raised in comments, and concludes:

[T]the Commissioner finds that the PEG 3350 ANDA holders have failed to raise a genuine and substantial issue of fact requiring a hearing in their responses to the NOOH.  A hearing, therefore, is not required under 21 CFR 12.24(b).  The PEG 3350 ANDA holders submitted anecdotal evidence to support their factual assertions and did not submit any specifically identified reliable evidence demonstrating that a hearing is necessary.  Even if the Commissioner were to accept these factual assertions as having some weight, such evidence does not present a sufficient area of disagreement to require an evidentiary hearing.  Rather, the evidence is “so one-sided that [FDA] must prevail as a matter of law.”  (See Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 252 (1986)).

In addition to finding that the ANDA holders have failed to raise a genuine and substantial issue of fact that requires a hearing, the Commissioner does not find the arguments advanced by the PEG 3350 ANDA holders persuasive and is entering summary judgment against them. Therefore, under section 505(e) of the FD&C Act and under authority delegated to the Commissioner under 21 CFR § 5.10, the PEG 3350 ANDA holders’ requests for a hearing are denied, and approval of the ANDAs for prescription PEG 3350 listed in this notice, and all amendments and supplements to them, is hereby withdrawn, effective [INSERT DATE 30 DAYS AFTER DATE OF PUBLICATION IN THE FEDERAL REGISTER]. Introduction or delivery for introduction into interstate commerce of products without approved new drug applications violates sections 301(a) and (d) of the FD&C Act. 

We won’t know for a few months whether ANDA sponsors will, after FDA issues a final Order withdrawing approval, challenge FDA in court or just (uh-hem) “let it go.”