Pacira Settles and Heralds Changes to How FDA Will Regulate Off-Label Promotion in the New Year

By David C. Gibbons & Jeffrey N. Wasserstein – 

Pacira Pharmaceuticals, Inc. (“Pacira” or the “Company”) announced today that it had reached agreement with FDA to settle its First Amendment challenge regarding the promotion of its drug, EXPAREL. As we discussed in a previous post, Pacira filed a Complaint in the U.S. District Court for the Southern District of New York on September 8, 2015, seeking to prevent FDA from bringing an enforcement action against the Company for its truthful and nonmisleading speech concerning EXPAREL, and then filed a Motion for Preliminary Injunction. The central issue was whether FDA could limit the scope of a generally approved product to only those specific uses in which the drug has been studied and approved. As the litigation progressed, the court issued a revised Scheduling Order on October 22, indicating that the parties were in settlement negotiations. The instant lawsuit has now been resolved in a joint Stipulation and Order (“Settlement Agreement”) that was filed yesterday, December 14.

The Settlement Agreement contains a number of important provisions. These include: 

• The Warning Letter issued to Pacira on September 22, 2014, was formally withdrawn and FDA issued a letter clarifying the reasons for its withdrawal (“Rescission Letter”). Stipulation and Order at 2, Pacira Pharms., Inc. v. FDA, No. 15-7055 (S.D.N.Y. Dec. 14, 2015), ECF No. 45.
• In conjunction with the Settlement Agreement, FDA approved a labeling supplement, including revisions to EXPAREL’s U.S. Prescribing Information intended to “describe accurately the scope of the indication initially approved by FDA, which will avoid confusion by the FDA or any other entity about the scope of EXPAREL’s approval by FDA . . . .” Id. at 3 (emphasis added). 
• Confirms the broad scope of EXPAREL’s indication “for use in a variety of surgeries not limited to those studied in [EXPAREL’s] pivotal trials.” Id.

We consider these provisions now, in turn. In the Rescission Letter, FDA stated that it determined there was “ambiguity” in EXPAREL’s approved labeling regarding the scope of the product’s indication. FDA ultimately determined that the use described in the label “broadly referred to ‘surgical sites’” and was not limited to the two types of surgeries studied in the pivotal trials supporting EXPAREL’s NDA approval. FDA stated that, in light of its determination, it rescinded the Warning Letter on October 13, 2015, and removed the Warning Letter from FDA’s website on the same day. See our previous post (here) when FDA “unpublished” the Warning Letter to Pacira.

Consistent with FDA’s determination in the Rescission Letter, FDA approved changes to EXPAREL’s label. Notably, the revised label does not contain the statement: “EXPAREL has not been demonstrated to be safe and effective in other procedures.” See EXPAREL (bupivacaine liposome injectable suspension) Label, NDA 022496, 16 (Nov. 2014); Stipulation and Proposed Order, Exhibit 1.

Both the Rescission Letter and the revised label confirm that EXPAREL’s use encompasses a broad range of surgeries, not limited to the clinical studies included in the label. Also, importantly, FDA stipulated 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, back in 2011, thus exculpating Pacira from 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.

There are several key takeaways from this settlement. First, clearly this represents a victory for Pacira and paves the way for the Company to continue its promotional efforts directed towards the use of EXPAREL in specific surgeries, as it had done prior to receiving the Warning Letter in September 2014.

Second, we believe there may be broader implications to this settlement for products bearing general indications in their label. As we noted in our previous post concerning this litigation, medical device companies frequently face this “general versus specific use” issue because it is not uncommon for a medical device to receive clearance for a general use. Therefore, device companies may have found a victory here as well, particularly if the approval or clearance was predicated on clinical studies.

Finally, at the end of a tumultuous year that saw FDA face multiple First Amendment challenges (see our Amarin posts here and here), the ability of FDA to effectively ban off-label promotion has been seriously called into question. Following unfavorable decisions in Caronia and Amarin, FDA took a new tack by settling the Pacira matter, making concessions favorable to the Company. We note that FDA’s Center for Drug Evaluation and Research has identified, as one of its “front burner” priorities for 2016, the need to “[r]e-evaluate our regulation of drug advertising and promotion in light of current jurisprudence around the 1st Amendment: ongoing, progress made, but more work needed.” Janet Woodcock, CDER 2016 Priorities, at 10. Indeed more work is needed and we are encouraged that FDA is working with industry stakeholders to arrive at solutions that ultimately benefit patients by giving healthcare providers greater access to more information, as it did here in Pacira. Hopefully, in 2016 and beyond, we will see less litigation and more openness that will forestall the need for legal action. But, if not, the U.S. District Court for the Southern District of New York has proven a helpful forum for First Amendment challenges by pharmaceutical manufacturers.