FDA Claims No Change in Off-Label Guidance Policy

Published August 12, 2011

Medical device manufacturers say they’re worried new Food and Drug Administration regulations would extend the legal doctrine known as “intended use,” making the manufacturers legally liable even without any actual promotion of off-label uses of their products by doctors or clinical laboratories.

At issue is the FDA’s choice to revisit its guidance document for the regulation of Analyte Specific Reagents (ASRs). These regulations cover off-label use for a category of medical devices known as IVDs, or In vitro Diagnostic tests, which consist of reagents (a reaction-causing substance used in analysis and synthesis), instruments, and systems intended for use in diagnosis of disease or other conditions.

These products, which must be labeled RUO (for research use only) or IUO (investigative use only) by manufacturers, are intended for use in the collection, preparation, and examination of specimens taken from the human body. 

FDA Claims No Expansion

Paul Citron, a founding member of the American Institute for Medical and Biological Engineering, says he believes the FDA’s decision could have profoundly negative consequences for the medical device industry. Yet Dr. Alberto Gutierrez, the head of the Office of In Vitro Diagnostics at the FDA, claims it is not the agency’s intention to expand the definition of “intended use” as a backdoor means of regulating doctors.

“The compliance guidelines were originally written in the early 1990s. Since then, we’ve been seeing many device manufacturers providing research laboratories with reagents and devices that were improperly marked to get around the regulations. The FDA is revisiting the guidance document now to remind the IVD industry about the regulations, which are unique among medical devices,” he explains.

Gutierrez says after the publication of the ASR rule in the ’90s, many manufacturers started producing devices and bundling them together as a whole kit.

“The rule was rewritten in 2007, so some manufacturers went back in and got their devices relisted. They changed the label to research use only (RUO), or they dismantled them and sold the parts as individual components. This is all legal and as it should be. And for that reason, we put our guidance statement out there again to remind the device manufacturers what their obligations are,” says Gutierrez.

Expanded Definition or Not?

Gutierrez says the guidance document speaks to ‘intent’ only because some manufacturers are gaming the system to get around the FDA’s regulations.

“The right thing to do would be for them to not label the devices as RUO. They can go about their business without mislabeling the device,” said Gutierrez. “This is not a change of policy. It’s just a reminder to the manufacturers of their responsibilities.”

Manufacturers, however, are still asking whether the rule constrains the clinical use of unapproved, uncleared diagnostic tests by seeking to hold them liable for the manner in which their customers use these products.

“This guidance doesn’t go any further. There is fear among manufacturers that this is some sort of backdoor attempt at regulation, but this is not the case,” Guttierez explains. “There are ways for labs and manufacturers to use reagents legally. We don’t think this harms manufacturers or labs, because there are ways for them to legally come into compliance. The FDA, however, still exercises enforcement discretion.”

Gutierrez says penalizing device manufacturers from promoting off-label use will not harm innovation in the medical device industry.

“There are ways for the manufactures to provide instruments and reagents to labs for testing and off-label use. And there are means for investigative use. We are not worried about loss of innovation. In fact, this is one area where innovation has occurred quite rapidly in America, especially when you compare it to the European Union.  We expect it to remain that way,” says Gutierrez.

Critics Remain Unconvinced

Gutierrez’s promises do not pass muster with Dr. Gualberto Ruano, president and CEO of Genomas Inc. and director of genetics research at Hartford Hospital in Connecticut. He directs a laboratory that provides clinical guidance to psychiatrists and psychologists, and he says he’s concerned the FDA’s decision could disrupt the supply chain.

“Treatments require lots of trial and error to find the best and even the worst medications to treat each patient’s disorder. We are dependent upon suppliers to provide us with DNA, reagents, etc. We keep records on every test, and I sign them. We have stringent requirements. We’re part of an ecosystem,” Ruano says. “What the FDA has done in their guidance document is disrupting the ecosystem.”

He says the FDA’s guidance principal is a knee-jerk reaction to a problem that doesn’t exist.

“What is going to happen is that the FDA is going to spook investors and disrupt the process patients need to get better. Once the well is dry, there will be no more innovations in health care. I got into medicine so that I could not only provide good health care to patients but also improve health care for patients,” says Ruano.

Devon Herrick, a senior fellow with the National Center for Policy Analysis, says the FDA is uncomfortable with the idea that once medicines and devices are approved, doctors are free to use them as they see fit.  

“The FDA would prefer drug companies and medical device companies seek FDA approval for all uses. Most of the actions taken to date are restrictions preventing drug makers from communicating off-label uses to doctors. The FDA appears to be further extending this,” Herrick says.