FDA Denies Petition on Guidance for Single Shared REMS, but Agency May Issue in Future

| 22 October 2013 |  By 

In May 2013, Prometheus Laboratories submitted to the US Food and Drug Administration (FDA) a citizen petition calling for the establishment of "standards and processes" for single shared Risk Evaluation and Mitigation Strategies (REMS). But in an interesting turn of events, FDA has declined Prometheus' request, saying that while it may issue guidance in the future, it will not be forthcoming at this time.


In 2007, Prometheus Laboratories purchased Lotronex (alosetron hydrochloride), a treatment for irritable bowel syndrome, from GlaxoSmithKline. The drug was first approved in February 2000, but was later temporarily withdrawn after FDA began to receive reports of obstructed or ruptured bowels.

To reintroduce the drug back into the marketplace, GSK developed a risk management plan, then known as a RiskMAP, which succeeded in allaying FDA's concerns about the drug and allowed it to return to the market in June 2002. The entire process, Prometheus explains, was both lengthy and costly to GSK.

Then, with the 2007 passage of the FDA Amendments Act (FDAAA), that RiskMAP started the process of becoming a REMS, a set of safety plans meant to ensure that a risky product is used appropriately. In the case of Lotronex, its REMS includes prescriber controls, patient education and acknowledgement requirements, pharmacy distribution of educational materials and program monitoring. FDA signed off on the company's REMS in 2010.

Then, in January 2011, Roxane Laboratories submitted an abbreviated new drug application (ANDA) to FDA and filed Paragraph IV certification claiming that Prometheus' patent protection on the drug was no longer valid. Prometheus counter-sued, alleging infringement. The lawsuit would later include Cipla, which also filed an ANDA with FDA for the same claim.

Single Shared REMS

Under FDAAA, Prometheus is required to negotiate with its generic competitors to develop what is known as a single shared REMS. They process is intended to ensure that a product is used consistently throughout the healthcare system no matter who the manufacturer is.

However, Prometheus has maintained that it has been unable to resolve a lengthy set of issues with its would-be generic competitors, leaving it nervous about potential anti-trust issues. It would help, it argued, if FDA issued guidance on the subject-something it has not done at this time.

For example, Prometheus said it has no clarity regarding the timeline for entering into negotiations with the ANDA applicant (parallel to the review process, or subsequent to approval?), whether the costs of the process should fall entirely on the generic manufacturer or be shared, the collection of adverse events under a shared system, how a shared system should be modified in the future as additional generic companies seek approval, and what factors constitute a "block or delay" of an ANDA under FDAAA (behavior which would violate statute).

"FDA's failure to provide meaningful direction to industry … has likely contributed to the scarcity of single shared REMS approved" under the law, Prometheus charged.  Because of this, Prometheus complained that it is unable to even look to existing precedent to inform its decision-making process since only six drugs operate under a single shared REMS, and none of those have been negotiated between companies.

FDA's Actions

As Focus wrote at the time, it appeared that FDA was amicable to addressing Prometheus' concerns. It had recently called for a meeting to discuss ways of standardizing REMS to make them "more predictable and simpler to understand, implement and measure." In addition, it said a reform of REMS could standardize REMS elements and "associated tools and assessment methodologies in the future."

But if those questions bore similarities to those asked by Prometheus, it doesn't mean that FDA is looking to take action on the timeframe called for in the company's Citizen Petition.

In a response sent to Prometheus on 7 October 2013, FDA said it is still "considering whether regulations or guidance in this area would assist industry with the development and implementation of these systems," but that it is not currently in the works.

In its stead, FDA has advised Prometheus to work with the ANDA holders in an industry working group to develop a proposal for a single shared REMS. FDA added that it could help facilitate those meetings should a company not be "receptive or responsive to such efforts."

However, "To the extent that Prometheus' Petition requests that the Agency engage in rulemaking on this matter at this time," FDA wrote, "your request is denied."

Such rulemaking, however, was left very much open for future and further activity.

FDA Response to Prometheus

Focus' Prior Coverage


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