Prometheus shared REMS petition denied for now but FDA leaves door open

On October 7, 2013, in the midst of the government shutdown, FDA responded to a Citizen Petition filed by Prometheus Laboratories, Inc. ("Prometheus") concerning shared risk evaluation and mitigation strategies ("REMS"), FDA Docket No. FDA-2013-P-0572. In its Petition, Prometheus requested "complete notice and comment rulemaking establishing the standards and processes for a single, shared REMS [Risk Evaluation and Mitigation Strategies]" and waivers for the requirement for a single, shared REMS. Prometheus also requested that it be given notice and the opportunity to engage in any process used by FDA to determine whether to grant a waiver from the requirement for a single, shared REMS for Lotronex® (alosetron hydrochloride). Additional details concerning their Petition may be found in a previous blog here.

As with many citizen petition responses these days, FDA granted the Petition in part and denied it in part, but for now the requests were essentially denied. First, FDA said that it was still deciding whether to initiate notice-and-comment rulemaking or issue guidance for single, shared REMS system development and denied this request at this time. Instead, FDA described how it has handled other single, shared REMS with elements to assure safe use ("ETASU") where the statute mandates innovator and generic companies to work together to implement a single, shared REMS rather than having multiple programs that create an additional healthcare burden. First, FDA said that it notifies both the innovator and generic companies of the single, shared REMS requirement. The Petition states that then:

FDA has expected that negotiation of the single, shared REMS would begin promptly thereafter, and would proceed concurrently with the review of the ANDA [abbreviated new drug application] application. . . .

In addition to monitoring the IWG's [industry working group's"] progress on developing a REMS, FDA has acted to help ensure that sponsors were cooperating and that there were no obstacles to developing a single, shared system. When a company indicated to the Agency that another company (brand or generic) was not receptive or responsive to such efforts, the Agency has held teleconferences, individually or jointly, with firms involved, and/or has asked them to come to FDA for face-to-face discussions to help facilitate resolution of any issues that were preventing moving forward on a single, shared
system. . . .

Unlike the elements of the REMS, which are reviewed and approved by FDA, cost-sharing, governance, and other business issues relating to the implementation of single, shared REMS are left to the discretion of the sponsors.

FDA's response did not appear to specifically address, however, a number of Promotheus's concerns about a single, shared REMS to the extent that some shared REMS negotiations are undergone concurrently with patent litigation. In particular, Prometheus requested guidance for criteria when an innovator's failure to agree to a single, shared system constitutes blocking or delaying of generic competition under the prohibition of the Federal Food, Drug and Cosmetic Act ("FD&C Act"). In a recent GPhA/FDA/USP ANDA Labeling Conference, however, FDA did provide some guidance regarding the criteria FDA considers when granting a waiver to the ANDA applicants for the single, shared REMS requirement. (See related blog here.) Prometheus also asserted that without FDA rulemaking or guidance on this issue, innovator companies would face significant resource commitments and uncertain risks arising from antitrust law and product liability. To the latter, FDA said in its response: "To the extent that Prometheus believes that there may be antitrust issues associated with establishing single, shared systems, we suggest it consult with the FTC [Federal Trade Commission]." FDA did not appear to address the related issues of resource commitments or product liability other than to acknowledge that other single, shared REMS had been successfully agreed to and implemented.

Finally, FDA denied providing Prometheus with an opportunity to participate in the process whether FDA would waive the requirement for ANDA applicants to agree to a single, shared REMS with the innovator for a product with a REMS with ETASU. FDA said that it would invite comments from both innovator and generic companies on the process to develop a single, shared REMS, but reserved the right to determine by specific request or on its own whether a waiver should be granted based on its evaluation of the burdens and benefits to create a single, shared REMS.

We will continue to monitor this issue and follow up with additional related developments, including FDA's expected REMS implementation report expected in the early part of 2014.