FDA: Generic transdermal patches should be tested in divergent climates
A patch that delivers medicine transdermally may act very differently on a resident of Fargo, N.D., than on someone in South Florida. Thus, the amount of medicine that enters their bloodstreams may be different. That’s the assertion of the FDA’s Office of Generic Drugs, and that’s why the regulatory body now asks that drug developers working on transdermal patches—at least in the generics realm—test their patches in multiple divergent climates.
It’s also why early-stage CRO Cetero Research recently expanded its transdermal delivery systems and other dermatology services to all four of its sites. Luckily for Cetero, it already has operations in some pretty divergent climates: Miami, Fla.; St. Louis, Mo.; Toronto, Ontario; and Fargo, N.D.
Cetero can offer sponsors the divergent climates required for testing their transdermal delivery systems, so they don’t have to find separate CROs or unrelated sites around the country, said Paul Lehman, Cetero’s director of clinical and pre-clinical dermatology.
But what’s behind the FDA’s suggestion? “Each of several draft guidances indicates that the FDA suspects the patch adhesion as well as the potential for skin irritation and sensitivity may be related to climate,” Lehman explained.
The Office of Generic Drugs started suggesting different climates for testing patches in 2006, when it began releasing draft guidances specific to each product being tested. Since then, there have been several such draft guidances, with the most recent one released in June.
Lehman said the FDA hasn’t been specific on exactly how different the climates should be. Nor has the agency said exactly how it suspects climate may affect the patch and, by extension, absorption of the drug. But, he said, “One could infer that if you live in a very warm, humid environment that may negatively affect how well the patch stays attached to the skin, and, if it becomes detached in any way, less surface area is covered, there’s less delivery of the drug and less absorption.”
The key to successfully conducting these trials in multiple locations, Lehman said, lies in standardizing operations so employees at each site are analyzing the data the same way.
Chris Hendy agrees. “Cross validation of all operations across all clinical sites is critical,” explained Hendy, president and CEO of Novum Pharmaceutical Research Services, which has been conducting adhesion and irritation testing of transdermal patches for generics since 2003. “You have to put together standardized training and validation testing for each study to make sure clinical staff at all locations are doing readings in the same way, so you don’t get a huge difference in the way the person in Houston is doing it versus the person in Las Vegas.”
Novum has three offices—in Houston, Las Vegas and Pittsburgh—and has been testing patches in various climates for over seven years, Hendy said.
The multiple climates suggestion has become “stock language” in draft guidances regarding transdermal delivery systems from the Office of Generic Drugs, but will that soon expand to new drugs? Lehman says he’s not sure. But Hendy said it makes sense: “It would seem prudent for new and generic manufacturers to test for this prior to putting these types of products on the market and then finding out later that there may be a problem based on consumer complaints.”