How Diabetes Devices Win FDA Approval
From the lowly bedpan to the artificial heart, the Food and Drug Administration (FDA) must regulate any apparatus involved in diagnosing or treating disease. Most people with diabetes use medical devices regularly, including lancets, lancing devices, blood glucose meters, insulin pumps, and continuous glucose monitors (CGMs). Though they are all used to manage the same disease, diabetes medical devices are subject to different types of FDA regulation, depending on how much oversight is needed to ensure that a device works as intended and is safe.
Risk and Reward
"It doesn't make sense to treat a tongue depressor the same way you would treat an insulin pump," says Stayce Beck, PhD, the acting leader of the artificial pancreas team at the FDA. The FDA classifies devices as belonging to one of three categories ("Device Classification," below). "The FDA has done a great job assessing the risk associated with devices," says Henry Anhalt, MD, chief medical officer and medical director of the artificial pancreas program at Animas, which makes diabetes devices. How the FDA classifies a device determines its approval pathway. Devices can change categories as their record of safety becomes established. "Suffice it to say, the process by which insulin pumps today are approved is not the same as when it was approved years ago," says Anhalt.
To seek FDA approval of a device, manufacturers conduct studies that aim to demonstrate the device's safety and efficacy. Before a device can be studied in people, its developer must submit an "investigational device exemption" to
the FDA laying out how the trial will be done and how the safety of participants will be ensured. A big part of a device maker's application for approval to the FDA is to explain how the device will be labeled. "Labeling is extremely important for devices," says Courtney Lias, PhD, director of the FDA's Division of Chemistry and Toxicology Devices. "The package label has to say what the patient is getting, including the limitations."
This category includes the least dangerous medical devices. Examples: lancets and lancing devices.
Device makers don't generally need to notify the Food and Drug Administration prior to marketing these devices, though they must be listed in the FDA's medical device registry.
These devices have an established safety record and don't do anything radically new. Examples: test strips, blood glucose meters, syringes, insulin pens, pumps.
Class II device makers must make a submission known as a 510(k) to the FDA prior to marketing. It compares the new device to an already-approved device, establishing their rough equivalence. In addition, a 510(k) details how the device would be used, how accurate it is, and anything else the FDA decides should be on the device's label.
These devices are the most likely to pose a danger to users and/or use novel technology. Examples: continuous glucose monitors, artificial pancreas.
PMA (Premarket Approval)
The PMA includes the results of studies that have assessed the performance of the device in people. The FDA and manufacturers of a new Class III device often will work together to determine how many patients should be studied and for how long, as well as where the study should be done—such as in homes or at a hospital.
Once the submission is made, the FDA begins considering the device ("Device Approval"). A recent report by the Government Accountability Office found that the average time between submission of a 510(k)—which covers moderate-risk devices—and the FDA's final decision was 161 days in fiscal year 2010. A Premarket Approval (PMA)—the submission for higher-risk devices—took an average of 627 days for a decision to be made in fiscal year 2008.
By now, manufacturers are pretty clear on what they need to do to get approval for new blood glucose meters, insulin pumps, and CGMs, but the pathway for approval of the artificial pancreas is still evolving. The artificial pancreas, which is still experimental, is a combination CGM and insulin pump that automatically doses insulin based on sensor-transmitted glucose levels and complex software programs designed to keep glucose levels in a safe range.
In December 2011, the FDA issued a "draft guidance" to help inform developers what steps would be required for the approval of an artificial pancreas. The agency posted the draft for public comment; various groups, including the American Diabetes Association, weighed in to help shape the final version. "It's fairly uncommon for us to put out guidances," says Beck, but she says the agency is dedicated to doing what it can to bring this technology to market. "The regulatory process needs to be not too burdensome," Beck adds. "We want to work very interactively and prioritize the review of these [devices], so they are getting out the door."
The final FDA guidance is yet to come. The draft lays out three basic stages of development for the artificial pancreas: feasibility studies, transitional studies, and pivotal studies. Feasibility studies are clinical trials done under the tightest control, usually in a hospital setting and with round-the-clock supervision. Transitional studies involve patients using an artificial pancreas in an environment like a hotel or camp, so users can have some freedom, but help is on hand at all times. Even without the final guidance, manufacturers are already testing prototypes of the artificial pancreas to help speed the devices to market. Various experimental versions of the artificial pancreas are undergoing feasibility studies, and a few of the most advanced are entering transitional studies. The pivotal studies will be done in "real world" settings. They will include enough participants and last long enough to establish the limitations and benefits of the artificial pancreas.
"We'll do whatever appropriate studies need to be done to make sure the final design is safe and effective," says Anhalt of Animas. "We are always seeking FDA input to ensure we have their support and their guidance."
The FDA's Beck says she talks every day with people in the industry about the artificial pancreas. "We really do believe," she says, "that these devices could have a positive impact on people's lives."
For Class II and III devices, the Food and Drug Administration (FDA) requires a manufacturer to do consumer studies to establish that a device is safe and accurate, and works as indicated on the proposed label.
The manufacturer submits an application for approval, including the results of studies and other information about the device, to the FDA.
The FDA assigns a lead reviewer to the application, who can choose to consult with experts, including patient representatives, before making a decision on approval. Meetings are open to the public.
A. Approved: The manufacturer may begin marketing the device to consumers and health care providers.
B. More Data Required: The FDA puts the application on hold and asks the device maker for more data.
C. Rejected: The device may not be put on the market.
5. Post-Market Actions
The FDA generally requires that manufacturers track devices, register where they are made or distributed, and report malfunctions and serious injuries or deaths. Devices approved through a PMA may require post-market studies.