With drug-eluting stents as just the first of countless high-profile combination products that are skidding onto the medical marketplace, the Food and Drug Administration has proposed a regulation designed to simplify their review.
But as the lines between drugs, devices and biological products have blurred, the FDA seems to have simply chosen to codify a process for combination products that has been in place for more than a decade. Though the regulation's intent is to clarify and shed some transparency on the process, the rule as proposed it doesn't seem to change much.
"I don't think they really achieve that purpose" of greater transparency, said Mark Heller, senior partner at the Boston law firm Hale and Dorr. As an FDA lawyer in 1990, Heller was sent to Congress to work on the Safe Medical Device Act of 1990, which provided the framework for evaluating combination products. "Many of the issues relating to combination product regulation would remain, and transparency in the decision-making is not achieved through the promulgation of the proposed regulation."
Combination products represent a nascent category that is employing cutting-edge technologies "that hold great promise for advancing patient care," the FDA noted. The most celebrated of these products are drug-eluting stents, which have been on the market for a little more than a year. Other combination products include orthopedic implants with genetically engineered human protein and antibiotic bone cement. They don't fit neatly into the FDA's traditional categories for regulatory review: drugs, devices and biological products.
The proposed regulation intends to codify the definition of "primary mode of action," the criteria the FDA has used since 1990 when assigning combination products to one of its three centers. The FDA said the second purpose of the regulation is to simplify the assignment process for regulatory review. The proposal was published in the Federal Register on May 7 and is subject to a 60-day comment period before being made final 30 days after that.
Typically, the FDA has asked manufacturers to identify for themselves the "primary mode of action" of the product and recommend the center that should lead the review. Under the proposal, the "primary mode of action" would be defined as "the single mode of action (drug, device or biological product) of a combination product that provides the most important therapeutic action." It added, "This would be the mode of action that is expected to make the greatest contribution to the overall therapeutic effects." When the most important therapeutic action cannot be easily determined, the FDA would assign the product to the center evaluating similar products.
So far manufacturers haven't had a lot to say about the proposed regulation. "We're still soliciting comment from our members," said Mark Brager, a spokesman for AdvaMed, a trade group for device manufacturers. The proposal seems to be "basically a codification of their current policy," he said. "We like the way that the process has been in the past."