On December 14, 2015 a settlement was reached between Pacira Pharmaceuticals, Inc. (“Pacira”) and the Food and Drug Administration (FDA) regarding Pacira’s First Amendment challenge to FDA’s ability to take enforcement action against the company’s truthful and non-misleading communications about an FDA-approved drug. As we noted in previous Client Alerts on September 21, 2015 and October 28, 2015, Pacira filed a Complaint in the U.S. District Court for the Southern District of New York on September 8, 2015, challenging FDA’s authority to limit the scope of promotion of Pacira’s approved drug, Exparel® for treatment of pain in only the specific surgical procedures that were studied in clinical trials (bunion and hemorrhoid surgeries). While the drug’s FDA-approved label noted that the drug had not been studied for use with other surgeries, the label did not explicitly state that the medication could only be used for surgeries that had been studied. This lawsuit was filed one month after the same court held that FDA cannot prosecute companies under the Federal Food, Drug, and Cosmetic Act for truthful, non-misleading communications about an approved drug, even if they involve off-label uses. Amarin Pharma, Inc. v. United States Food and Drug Administration, No. 15 Civ. 3588 (PAE)(S.D.N.Y. August 5, 2015).
The Pacira settlement followed lengthy negotiations with FDA and includes these principal features:
- The Warning Letter issued to Pacira on September 22, 2014, was formally withdrawn and FDA issued a letter, dated December 14, 2015 (Recission Letter) clarifying the reasons for its withdrawal. FDA acknowledged there was ambiguity in the approved label for EXPAREL and that the use described in the label was broad enough to not be limited to the two types of surgeries studied in the pivotal trials supporting the drug’s NDA approval. The Recission Letter can be accessed here.
- As part of the settlement, FDA approved a labeling supplement, which Pacira submitted to FDA on November 17, 2015, including revisions to EXPAREL’s U.S. Prescribing Information to remove the statement “EXPAREL has not been demonstrated to be safe and effective in other procedures.”
- FDA determined that this broad use of EXPAREL does not represent the approval of a new indication, but rather clarifies EXPAREL’s use, “as initially approved” at the time EXPAREL’s NDA was approved in 2011. This acknowledgment is significant because it works to exculpate Pacira from exposure to prosecution or potential False Claims Act liability related to its past, current, and future promotion of EXPAREL for specific surgery types that are encompassed by its general indication.
- The resolution of the litigation confirms that FDA, in a post-Amarin and Coronia world, remains concerned about its ability to completely silence off-label promotion campaigns, especially those that involve truthful and non-misleading information about an approved drug. In short, as we’ve noted previously, FDA continues to struggle to maintain its jurisdictional authority to take enforcement action against what it perceives as unlawful, off-label promotion, while at the same time facing the reality that recent court decisions call into question the agency’s legal ability to ban all off-label promotion by pharmaceutical manufacturers.
- It’s important to understand that the Pacira settlement, as well as the recent decisions upholding First Amendment challenges to FDA enforcement actions involving off-label promotion, are very fact-specific and are focused in one judicial circuit. As a result, caution in this area remains a solid strategy. Companies should continue to evaluate carefully (through promotional review committees and legal counsel) all off-label promotions and not succumb to wishful thinking that no legal constraints or regulatory concerns remain in this area. But as a general rule, these recent events suggest that companies should have a reasonable prospect of avoiding a legal challenge by FDA over off-label promotion so long as there is valid scientific evidence to support the off-label use and the off-label use presents no safety or effectiveness issues. If despite a manufacturer’s ability to satisfy these factors, FDA decides to take enforcement action, the matter will be well-positioned for legal challenge on First Amendment grounds.
- At the same time, expect FDA to be more willing to enter into discussions with industry regarding the intended use and promotion of approved medical products. Indeed, the Pacira settlement may be a prelude to similar negotiations in the future that will forestall litigation and instead provide medical product manufacturers greater predictability about their ability to supply healthcare providers greater access to relevant information about approved drugs. In a press release, Pacira’s CEO stated “[w]e are pleased to announce a successful collaboration with the FDA to resolve this matter in an expeditious and meaningful way that allows us to get back to the important matter at hand—reducing postsurgical opioid exposure by providing a non-opioid option like EXPAREL to as many patients as appropriate.”
- The settlement may also pave the way for manufacturers of products that bear general indications in their approved labels, especially those predicated on clinical studies, to argue they are entitled to greater leeway in off-label promotion.
- Finally, the evaluation of what constitutes the permissible limits of off-label promotion remains an “open” discussion both within industry and at FDA. In that regard, it’s worth noting that FDA’s Center for Drug Evaluation and Research has identified as a “Front Burner Priority” for 2016, the need to “[r]e-evaluate our regulation of drug advertising and promotion in light of current jurisprudence around the 1st Amendment…”
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