FDA, EMA Confidentiality Agreement Expanding Into "Clusters"

The "chatter" between reviewers and scientists at FDA and the European Medicines Agency appears to be increasing as the two bodies move toward renewing their confidential information sharing agreement.

An extension is expected to be signed in late September, FDA said. The latest version will include all products the agency regulates. That includes tobacco, over which FDA just recently gained jurisdiction. This new agreement will remain in effect until terminated by either side, the agency said.

The first confidential agreement between the FDA and EMA was signed in 2003. The two agencies are now talking with increasing frequency about new and pending applications.

The ongoing dialogue is expanding with each year, EMA Executive Director Thomas Lönngren said June 14 during the Drug Information Association annual meeting. He said the agencies' "clusters" - topic-specific groups where both sides collaborate - are becoming increasingly popular.

"People are starting to develop a chatter on both sides," Lönngren said. "It's very easy to communicate in the clusters of course when product-related issues are discussed, ongoing applications ... issues of scientific advice, of common interest in this area."

The agency already has clusters related to oncology, vaccines, orphan drugs, pediatrics, pharmacogenomics, veterinary products and adenosine triphosphate (ATP).

A new cluster focused on blood products was created in April and groups targeting cardiovascular and gastrointestinal issues are under discussion, Lönngren said.

Murray Lumpkin, FDA deputy commissioner for international programs, said the new groups could be in place next year. Agency representatives also participate in the other's advisory committee meetings, he said.

"If you are filing an oncology product in the U.S. and Europe at the same time, be sure that it's the same filing because we both talk to each other," Lönngren said, which solicited some chuckles from the audience.

Lönngren said interactions between FDA and EMA increased last year compared to 2008, but collaboration is not required.

"The confidentiality agreement gave us the possibility if we want to exchange information," he said. "It's not pushing us to constantly exchange information."

The Flu Shall Bring Them Together

The global response to the influenza pandemic may have been a driver to better familiarize FDA with its EMA colleagues.

The two sides, along with the Japanese Pharmaceuticals and Medical Devices Agency, were talking regularly as they moved vaccine applications through the regulatory pipeline.

Lönngren said the collaboration was particularly helpful with vaccine safety concerns, as well as with the use of adjuvants. European regulators have worked with the compounds added to vaccines to boost the immune system's response, while U.S. regulators had not. In the end, though, FDA opted against using adjuvants for the pandemic vaccine, prompting industry criticism after traditional manufacturing methods failed to produce an adequate supply rapidly enough (¹ (Also see "Adjuvant Vaccines Could Have Helped To Prevent H1N1 Shortfall, Industry Tells Congress" - Pink Sheet, 18 Nov, 2009.)).

"It was very, very intense collaboration between us," Lönngren said. "And of course there was a need for it because no one else did really know in the beginning how to solve this, how to get the new vaccines on the market."

He added, "I think if we emphasize the strong international need for the collaboration in a situation like this, then it's good for the future because ... this is not the last one I think."

Agencies Not Looking For Total Reliance

While FDA and EMA increasingly get closer in terms of information sharing, it is unlikely the two will share regulatory decisions.

Lumpkin said FDA wants to move from simply receiving information from other regulatory agencies to actually relying on it to make decisions.

"I'm not talking about relying on the decisions of other regulatory authorities, but relying on their information to inform our decisions as a way to reduce duplication and to leverage resources of others," he said.

EMA wants more collaboration between world regulatory agencies, but it has remained largely theoretical because of countries' different health system and politics.

While FDA and EMA have had bilateral agreements for many years, they still have disagreed on approval decisions (² (Also see "EU Regulator Wants Closer Ties With Health Technology Assessors" - Pink Sheet, 19 Feb, 2010.)).

As recently as last year, FDA officials defended themselves against a claim they were more conservative in approval decisions than the EMA by studying new molecular entity approvals between 2006 and 2008. The results indicated FDA approved slightly fewer applications than its European counterpart (³ (Also see "FDA Not More Conservative Than EU, Jenkins Says; Investors Not Convinced" - Pink Sheet, 5 Jan, 2009.)).

In one high-profile case, FDA kept a product on the market that EMA suspended. In considering Abbott's application for the antiobesity drug sibutramine, marketed in Europe as Reductil , Reduxade Zelium and other names, EMA recommended suspension after a study found people on the drug had an increased risk of cardiovascular events.

FDA, on the same day as the EMA announcement, decided the drug, marketed as Meridia in the U.S., should have its label adjusted to disallow use in people with a history of cardiovascular disease.

EMA said the risks outweighed the benefits, while FDA decided the risks were only in patients with a cardiovascular disease history (⁴ (Also see "Weighing Obesity Risk: FDA, EMEA Use Different Scales For Abbott's Meridia" - Pink Sheet, 21 Jan, 2010.)).

While the sides may disagree, Lumpkin said inter-agency talks are becoming a requirement, not a luxury.

"Regulatory cooperation is no longer discretionary as one might have argued 10, 15 years ago," he said. "It is a standard operating procedure of any 21 century medicinal product regulatory authority."

- Derrick Gingery ( ⁵ [email protected] )