The most rewarding part of the job for medical device manufacturers is seeing the result of their hard work making a real difference in patients’ lives. But getting an effective, innovative, and safe product to market in the U.S. and the European Union (EU) means navigating a series of regulatory hurdles. One blog post in a two-part series, we will look at the best way to achieve that goal in the U.S.
The regulatory difficulties of bringing a medical device to market are almost as complex as the process itself. The U.S. Food and Drug Administration (FDA) regulates the manufacturing and use of medical devices and has done so since the passing of the 1938 U.S. Food, Drug & Cosmetics Act. Over the decades, the U.S. FDA’s approach to this regulation has changed, and today the agency adopts a risk-based approach to medical devices.
Specificity matters in the regulatory process
The U.S. FDA has classified around 1,700 medical devices to date, sorting them into 16 specialty areas—also called panels—and then organizing them into the Code of Federal Regulations (CFR). The classification considers the intended use of the device and its indications for use. That’s not quite as simple as it sounds.
For example, a scalpel is used to cut tissue, so its intended use is reasonably clear-cut. But its indication for use (most often found in the device’s label) can be much more specialized. A scalpel that cuts delicate corneal tissue will include a different indication than one designed to slice through thicker dermal tissue. The different indications can impact the device’s classification.
Classification of risk
Risk is an essential part of the classification process. Devices are sorted into groups based on their perceived risk to a patient. Class I devices pose the lowest risk, while Class III devices pose the highest potential risks. This classification determines the device’s route to regulatory clearance.
Most Class II medical devices obtain regulatory clearance through a premarket notification (i.e., a 510(k) submission). This submission must show that the device is substantially equivalent (SE) to a device with an identical intended use already cleared for sale in the United States. Due to their perceived low level of risk, most Class I devices are exempt from premarket notification 510(k).
For Class III devices, a 501(k) isn’t enough—they often require premarket approval (PMA). A PMA is an application that documents the device’s safety and effectiveness. The application consists of three sections—technical, non-clinical lab studies and clinical investigations—designed to demonstrate sound scientific analysis and reasoning around the device. The PMA process is intricate, and around 20% of manufacturers are required to include clinical data in their PMA submissions. If a Class III device doesn’t meet PMA requirements, it cannot be marketed.
Moreover, PMAs that are incomplete, inaccurate or omit critical information may be delayed or rejected outright. Manufacturers are encouraged to audit any PMA applications for consistency, accuracy and scientific soundness before submitting it to the U.S FDA.
Finding an equivalent medical device
Whenever possible, manufacturers should choose one of their own medical devices as the predicate.
They can provide details of manufacturing sites, processes, processing aids, and quality controls that aid in establishing equivalence. This level of detail would not otherwise be available if they were to select a competitor’s product as the predicate device. If a competitor’s product is selected, manufacturers would do well to choose one that has recently been cleared under 510(k) guidelines.
But what makes a device substantially equivalent? The U.S. FDA wants something that has:
- An identical intended use to the predicate; and
- Identical technological characteristics to the predicate; or
- An identical intended use to the predicate; and
- Different technological characteristics but has the same safety and effectiveness assurances; and
- Information submitted to FDA demonstrates the device is as safe and effective as a legally marketed device.
Manufacturers cannot distribute devices requiring a 510(k) submission until they receive a letter of SE from the FDA, which acknowledges that the device is as safe and effective as the predicate.
The process gets a little trickier if the device is novel and has no predicate. If the device has a Class I or Class II risk level, manufacturers can apply for a “De Novo” request. The U.S. FDA advises submitting a De Novo application and a pre-submission evaluation so the regulators can provide feedback or guidance before the next stage: official premarket submission.
Alternative paths to regulatory approval
The U.S. FDA has demonstrated a willingness to grant emergency use authorization (EUA) to new medical devices designed to help the fight against SARS-CoV-2 (i.e., COVID-19). EUAs extend beyond that one disease and can allow the U.S. FDA to authorize unapproved devices or unapproved uses of devices in other emergencies.
Class III medical devices that treat rare diseases or conditions can also take a less stringent path to market. Manufacturers can apply for humanitarian use designation (HUD) through the FDA’s Office of Orphan Products Development (OPD). The definition of rare in this case refers to diseases or conditions that affect no more than 8,000 individuals in the U.S.
Combination products, which contain a mix of drugs, devices and biologics, require an alternative path through the regulatory system. One of three different regulatory centers may oversee combination products’ pathways, but that determination comes down to the device’s primary mode of action. The complexity of these devices requires additional guidance from the U.S. FDA’s Office of Combination Products.
Final advice for navigating the regulatory system
The above guidance simplifies what can be a very complex process. To streamline the submission process for devices bound for the U.S. market, U.S. FDA regulators encourage manufacturers to take a more active and collaborative approach to their submissions. Part of this effort includes scheduling a pre-submission meeting with regulators to discuss the device, review testing strategies and connect with the experts on your team. Doing so can help save time and money long-term by garnering nonbinding regulatory insight on the road to a successful submission in the U.S. But the whole process can be daunting and time-consuming, especially for device manufacturers new to the U.S. market or those looking to gain regulatory clearance or approval for novel or humanitarian devices. Missing one small step in the process can cause a giant setback, so using an experienced laboratory testing partner can improve manufacturers’ chances of a smooth journey through the regulatory process.
