Relief At Last? DC Circuit Rules on Rx PEG-3350 ANDAs

Only ten years after initiating the withdrawal process, FDA approval for prescription PEG-3350 is officially withdrawn. The D.C. Circuit issued an unpublished opinion this week affirming FDA’s April 2018 Order withdrawing approval for several PEG-3350 ANDAs and denying requests for a hearing by the affected ANDA holders. While FDA initially aimed to withdraw all prescription ANDAs for PEG-3350, which is indicated for use as a laxative, by May 2, 2018, FDA issued a stay extending the withdrawal date to November 2, 2018 to give sponsors time to wind down their sales programs. This D.C. Circuit decision comes just before this deadline – right in time for the withdrawal to take effect as scheduled.

As we explained in a 2014 blog post, FDA initiated these proceedings in 2008 with a Notice for an Opportunity for a Hearing on its proposal to withdraw approval of ANDAs for PEG-3350 due to FDA’s policy prohibiting simultaneous marketing of the same drug as prescription and OTC. FDA approved an OTC version of PEG-3350, MiraLAX, in October 2006, and subsequently sent letters to ANDA sponsors of PEG-3350 stating that section 503(b)(4) of the FDC Act “does not permit both Rx and OTC versions of the same drug product to be marketed at the same time.” As such, the letters state that the prescription PEG-3350 products are misbranded and may not be legally marketed. In 2008, FDA issued its Notice for an Opportunity for a Hearing on the issue, which explained FDA’s position that the same drug product may not be marketed as both a prescription and an OTC drug product unless some meaningful differences between the two products exist. FDA specified that a meaningful difference includes differences in the active ingredient, dosage form, strength, route of administration, indications, or patient population. With no “meaningful difference” between the prescription and OTC version of PEG-3350, FDA determined that the prescription version is now considered misbranded (based on the inclusion of the “Rx Only” statement in its labeling, as is legally required for prescription drug products).

FDA issued its Notice of Opportunity for a Hearing and several sponsors requested a hearing, but FDA did nothing until May 2014. In May 2014, FDA denied the requests for a hearing and issued an order withdrawing approval of the PEG-3350 ANDAs. But FDA didn’t finalize that Order for another 4 years. That’s why this constipation controversy didn’t reach the courts until 12 years after the OTC drug was approved.

In April 2018, FDA issued a final Order denying the requests for a hearing and withdrawing approval for the PEG-3350 ANDAs, and the ANDA holders promptly challenged that Order in the D.C. Circuit.   Hyman, Phelps & McNamara, P.C. represented one of the ANDA holders. The ANDA holders challenged FDA’s determination that “no meaningful difference” exists between the prescription and the OTC versions of the PEG-3350, as well as the procedures FDA used to adopt such an order. The ANDA holders argued that differences in dose duration constitute meaningful differences. The OTC version recommends a one-week period of use while the prescription version recommends a two-week period. The ANDA holders argued that there are safety differences between these two periods of use resulting from misdiagnosis or the masking of more serious conditions, but because patients should be in a doctor’s care by day 8, the Court upheld FDA’s determination that it is not a meaningful difference. The ANDA holders also urged the Court to consider off-label use of the OTC product (i.e. use for more than a week), but the Court held that FDA “properly carried out its analysis within the context of on-label use.”

With respect to the procedural issues raised, the Court held that FDA did not arbitrarily or capriciously decline to give weight to sponsors’ submissions and that they were not entitled to a hearing. Further, the “meaningful difference” standard did not need to be set forth through rulemaking. Indeed, FDA had given petitioners adequate notice of the standard through the initial 2008 Notice.

While the unpublished per curiam decision is not precedential, it does—to our knowledge— represent the first federal appellate court consideration of FDA’s meaningful difference standard. Other issues, such as whether FDA’s interpretation of the prescription and OTC labeling provisions to preclude simultaneous marketing may have First Amendment implications, were not raised in this litigation and may continue to arise and move through the court system. Fortunately, we probably won’t be providing many more laxative puns—at least with respect to this issue—for a while.