After submitting five Citizen Petitions to FDA since 2016 (see Docket Nos. FDA-2018-P-2851; FDA-2017-P-4352; FDA-2017-P-3064; FDA-2017-P-1359; FDA-2016-P-0645) alleging that evidence does not support approval of opioids, Pharmaceutical Manufacturing Research Services (“PMRS”) is trying a new tactic to challenge FDA’s regulatory scheme for abuse-deterrent opioids: court. PMRS is a contract manufacturer who appears to have been petitioning FDA to stop the approval of pending and future opioids indicated for chronic use. Garnering little support from FDA, PMRS appears to have submitted its own 505(b)(2) NDA for an opioid with abuse-deterrent labeling: NDA 209155 for Oxycodone HCl Immediate-release Oral Capsules, 5 mg, 15 mg, and 30 mg. But is it, as Admiral Ackbar uttered in Return of the Jedi, a trap? (“It’s A Trap!”)
In February 2018, FDA published in the Federal Register a proposal to refuse to approve NDA 209155, and a Notice of Opportunity for a Hearing (Docket No. FDA-2018-N-0188). FDA apparently refused to approve NDA 209155 based on a litany of deficiencies, including chemistry, manufacturing, and controls, GMP issues, failure to comply with patent certification requirements, impurity problems, and others. FDA also noted that the product could not be approved with abuse-deterrent labeling because the application did not demonstrate the necessary abuse-deterrent properties. PMRS responded with a timely Request for a Hearing, which FDA denied. (As a side note – it is certainly not unusual for FDA to deny such a hearing, as FDA denies these hearings fairly often.) PMRS responded to the denial with allegations of genuine and substantial issues of fact requiring a hearing, but FDA has not yet responded.
Rather than wait for another denial, PMRS decided to sue FDA. In the Complaint, filed in the U.S. District Court for the Eastern District of Pennsylvania, PMRS alleges that FDA’s failure to have a hearing within the statutory period violates the Administrative Procedure Act and the Mandamus Act. “Requiring PMRS to wait any longer for the hearing on its NDA to commence would be unjust, wasteful, and significantly harmful to the public health, because absent PMRS is being precluded from bringing its product to market with correct labeling, while other, mislabeled and dangerous opioids are permitted to proceed to market,” alleges PMRS in the Complaint.
But it seems from the Complaint that PMRS may be using this litigation as a bully pulpit to protest FDA’s framework for evaluating purported abuse-deterrent opioids. Indeed, the 22-page Complaint dedicates 15 pages to discussion of the opioid epidemic, FDA’s reliance on Abuse-Deterrent Opioid guidance, “chronic use” labeling with abuse-deterrent claims, and the scientific evidence supporting the effectiveness of long-term opioid therapy for chronic pain. The Complaint also alleges that FDA improperly approved several opioids based on previous findings of effectiveness for referenced listed drugs, including Roxybond, Roxicodone, and Percodan.
Reviewing the Request for a Hearing raises the question of whether the entire NDA was submitted simply to contest FDA’s approach to abuse-deterrent and chronic use opioid approval. The Request for a Hearing challenges FDA’s regulatory approach rather than any specific deficiency in its application. Given that PMRS does not appear to hold any approved drug applications, it is possible that this NDA was submitted to make a point – and to provide PMRS with standing to sue FDA for its review practices with respect to opioids. If so, it is a creative – albeit expensive – strategy. It’s difficult to say how far a court will let this go given that the FDC Act only requires FDA to give the applicant notice of an opportunity of hearing, but we don’t expect PMRS to give up quietly. Once final action is taken with respect to this hearing request, this NDA may serve as the basis for a lawsuit challenging FDA’s entire regulatory scheme for abuse-deterrent and chronic use opioids.