Pacira Pharmaceuticals announced a settlement with the United States Food and Drug Administration (FDA) in connection with their First Amendment challenge regarding the promotion of its drug, Exparel. Pacira had previously sought to prevent the FDA from bringing an enforcement action against Pacira for its truthful and nonmisleading speech about Exparel.
The settlement not only required FDA to remove the Warning Letter previously posted on its website and provide an explanation for the removal, but it also required a revision of the Prescribing Information (PI) to be submitted with the Exparel Labeling Supplement. The revision is "intended to describe accurately the scope of the indication initially approved by FDA," which is expected to avoid any future confusion by any entity or agency about the scope of Exparel's FDA approval.
The settlement also included a promising agreement between both parties that Pacira and the FDA would agree to "deal with each other in an open, forthright, and fair manner," which could eventually lead to more cooperation, understanding, and openness on behalf of the FDA when it comes to interacting with life science companies.
Dave Stack, Chief Executive Officer and Chairman of Pacira, stated,
We 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 task at hand – reducing postsurgical opioid exposure by providing a non-opioid option like Exparel to as many patients as appropriate. This is especially important given the burgeoning U.S. opioid epidemic, underscored by the reality that one in 15 patients will go on to long-term use after receiving an opioid in the hospital setting.
Removal of the Warning Letter
The settlement follows the much-discussed removal of Pacira's warning letter from the FDA website, which helps to confirm that Exparel is broadly indicated for "administration into the surgical site to produce postsurgical analgesia," and has been indicated as such since its approval in 2011.
Janet Woodcock, M.D., the Director of the Center for Drug Evaluation and Research at the Food and Drug Administration, issued a letter to David Stack, explicating the reasons for the rescission of the 2014 Warning Letter. Dr. Woodcock believes that the withdrawal of the Warning Letter, taken together with the FDA's recent approval of Exparel's labeling supplement, clarifies the FDA's positions and conclusions "regarding the scope of Exparel's indication."
After a review of the Warning Letter, the FDA determined that "different statements in various parts of the approved labeling created ambiguity with respect to the scope of the approved indication." Based on plain language found in Exparel's Indications and Usage section of the full prescribing information, as well as clinical trials, the FDA determined that the indication was not limited to bunionectomy and hemorrhoidectomy procedures, and therefore rescinded the Warning Letter issued to Pacira.
What Does This Mean?
This settlement marks a clear victory for Pacira in that it allows Pacira to continue promoting the use of Exparel in specific surgeries. This settlement also likely provides a larger benefit to the life sciences industry: a generous clarification of "general versus specific use" indications. Medical device companies often face a similar "general versus specific use" question as many medical devices receive clearance for general use. This settlement may have given medical device companies a victory, particularly if the approval or clearance of the medical device was based on clinical studies.
It is also important to note that the FDA has not been successful in many of their First Amendment cases over the past several years, see Caronia and Amarin. As such, the ability of the FDA to ban off-label promotion has been called into question and the pace and style of the agency is likely to change in the coming months. In fact, one of the priorities in 2016 for Center for Drug Evaluation and Research is to "[r]e-evaluate our regulation of drug advertising and promotion in light of current jurisprudence around the 1st Amendment."
These cases, taken together, could signal upcoming FDA changes on how carefully they approve indication statements – especially broadly worded ones – which might, in turn, affect FDA class labeling policies. This settlement likely provides an opportunity for pharmaceutical and medical device companies to successfully put forth medical arguments that support broader extrapolation, especially if they have a favorable regulatory history.
This settlement should be considered encouraging to the life science industry, as it shows that the FDA is starting to learn from past mistakes, permit companies to take advantage of their First Amendment rights, and work with industry to create solutions that benefit patients.