Washington Editor

PHILADELPHIA - The regulatory process can be cumbersome in any country, according to speakers at a third-day session of the BIO 2005 conference, and those hurdles increase measurably when planning for multinational product registration.

"Every country has some regulatory oversight for drug registration," said Robert Simon, the senior vice president of regulatory affairs at OSI Pharmaceuticals Inc. "But few countries have detailed guidelines."

The Melville, N.Y.-based company has had recent regulatory success in the U.S., when the FDA late last year approved Tarceva (erlotinib) for non-small-cell lung cancer. OSI's rights to the daily-use oral tablet are partnered with Genentech Inc. in the U.S. and F. Hoffmann-La Roche Ltd. outside the U.S.

Tarceva remains under regulatory review in Europe, where regulatory requirements and procedures are similar but not identical to the FDA process, a fact certainly not lost on conference attendees but an issue on which they nonetheless must remain cognizant. As Simon added, registration procedures "aren't always clear, and always are subject to change."

Still, he noted that ongoing synchronization efforts between regulatory bodies in the U.S. and Europe, as well as in Japan, have led to a bit of commonality for registering products in the world's biggest markets. Known as International Conference of Harmonization (ICH) guidelines, drug developers can look to 13 safety-related guidances, 15 for efficacy and 18 on quality, as well as common technical documents for some applications, for mutual multinational registration procedures. Regulatory bodies in Canada and Australia also have been subscribing to the ICH guidelines.

Nevertheless, such a push toward harmony doesn't fully lead to the sweet music of simplified worldwide approvals. While the ICH guidelines "should make it possible to file simultaneously a document in all three of those regions," Simon said, the process is not that easy in the end.

In the U.S., drug approval routes are relatively clear, as the process goes through the FDA's Center for Drug Research and Evaluation or Center for Biologics Research and Evaluation. But in Europe, where there are several routes to ultimate approval, the process can be more difficult to navigate. According to Stuart Woods, of the Brussels, Belgium, law firm Allen & Overy LLP, "a plethora of different committees and groups" lead to such complexities, as do "several hundred guidance documents" and ongoing revisions of the European Union's regulatory laws for pharmaceuticals.

Drug developers must be ready for "change, change and more change," he said.

To illustrate some of the differences between U.S. and European regulatory differences, Simon talked about advancing a cancer drug through the processes. Notably, he pointed out that pivotal trials in the U.S. compare investigational drugs to placebo, while in Europe those trials are designed to compare investigational drugs to already-approved products. "One study for efficacy," Simon said, "is not possible."

And in Japan, regulatory authorities require that clinical studies also be carried out specifically in Japanese patients, to supplement other data used for regulatory reviews elsewhere in the world.

Other issues that lead to multinational product registration difficulties include varying requirements to get study drugs into humans, export and product transportation matters, the frequency of regulatory changes and translational difficulties.

"There is no easy, simple or rapid way," Simon said, "to develop or register drugs around the world."

No Comments