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Understanding regulatory pathways for medical devices
Medical device regulation ranges from discovery to post-market regulation; however, the regulatory pathways for medical devices depend on classification.
As technology advances and medical devices become an increasingly integral part of healthcare, understanding the regulatory pathways for medical devices is critical for many biotechnology companies and healthcare innovators. Although medical devices are regulated by the FDA, like pharmaceutical products, the paths and nuances of the two differ.
The FDA's definition of a medical device is based on the definition found in Section 201(h) of the Food, Drug, and Cosmetic Act. In short, a medical device is defined as "any instrument, machine, contrivance, implant, in vitro reagent that's intended to treat, cure, prevent, mitigate, diagnose disease in man."
While drugs are regulated through the FDA's Center for Drug Evaluation and Research, medical devices are regulated by the Center for Devices and Radiological Health.
According to the FDA, medical device regulation can be thought of as a five-step process: device discovery and concept, preclinical research and prototypes, pathways to approval, FDA review and FDA post-market safety monitoring.
1. Device discovery and concept
During the device discovery and concept phase, the medical device developer or sponsor must determine the device's classification before proceeding, as different classifications will have varying development processes.
The FDA defines three medical device classifications:
- Class I. Class I medical devices are considered the least risky type of device. These low-risk devices may include bandages, oxygen masks, handheld surgical instruments and nonelectric wheelchairs. The FDA notes that medical devices with class I designation are subject to general controls, which include good manufacturing practices, standards and reporting adverse events to the FDA, registration, and general recordkeeping requirements.
- Class II. Class II medical devices are also called intermediate-risk medical devices, meaning they pose a greater risk to consumers than class I devices. Examples of class II devices include computed tomography scanners and infusion pumps. These medical devices are subject to general controls but also have additional special controls, including labeling requirements, device-specific mandatory performance standards and device-specific testing requirements.
- Class III. Class III medical devices -- high-risk medical devices -- pose the greatest threat to consumers. According to the FDA, these devices typically either support or sustain life, are implanted into the body or pose a higher risk of illness or injury to the consumer. For example, breast implants, pacemakers and deep brain stimulators are considered class III medical devices. These technologies are subject to general controls and premarket approval that require the manufacturer to prove device safety and efficacy.
This phase of the medical device pathway includes determining the device's classification and developing it. Once a researcher or company has identified an unmet need for a medical device and developed a concept or idea for it, it will begin building a proof-of-concept document to determine whether the idea is valid. Development continues for those ideas that show promise.
2. Preclinical research and prototypes
Once the proof-of-concept document has been analyzed and a device shows clinical promise, researchers can move forward to create preclinical research, which involves creating a prototype. It is important to note that prototypes at this stage are not intended for human use and should only be tested in controlled laboratory settings.
Laboratory tests can help researchers adjust and develop a product with human use in mind.
3. Pathways to approval
After the prototype is refined, researchers can decide what device application to submit for their product. The application or pathway is dependent on device classification.
The FDA notes, "As device class increases from Class I, to Class II to Class III, the regulatory controls also increase, with Class I devices subject to the least regulatory control, and Class III devices subject to the most stringent regulatory control."
Most class I devices are exempt from premarket submission. Meanwhile, class II medical devices are generally subject to premarket notification, 510(k) submissions. Class III medical devices require a Premarket Approval (PMA). In addition to those processes, certain medical devices may be eligible for De Novo designation or Humanitarian Device Exemption (HDE).
510(k) submission
A 510(k) submission is typically for class II medical devices. This submission requires the manufacturer or device sponsor to prove that the device is substantially equivalent (SE) to a legally marketed device not subject to PMA.
Substantial equivalence requires proving that a medical device has the same intended use and technological features as a legally marketed medical device. According to the FDA, a legally marketed medical device includes pre-amendment devices that were marketed before May 28, 1976, and do not require a PMA, class III medical devices that were reclassified to class II or I, and devices found SE through the 510(k) submission in the past. These devices include X-ray machines, dialysis machines, fetal monitors and muscle stimulators.
If an applicant can prove their device is SE, it is placed in the same class; however, if it is not, it is placed in class III.
PMA
The PMA is for medical devices classified as class III because of their risk or devices not found SE during the 510(k) submission process.
PMA is the most in-depth regulatory pathway for medical devices, requiring the applicant to prove the device's safety and efficacy using scientific evidence. The evidence must justify the device by showing that the potential benefits outweigh the risks and that it could benefit a large portion of the target population.
Some examples of PMAs include minimally invasive or noninvasive glucose testing devices, implanted defibrillators and implantable middle ear devices.
The FDA adds, "Independence is an important concept for PMAs, meaning that each PMA should establish the safety and effectiveness of the device under review, and that data about one device cannot be used to support another."
De Novo
De Novo device designation is for medical devices not marketed domestically but with a favorable safety profile and well-understood technology.
HDE
HDE pathways are for devices intended for orphan diseases, which impact 4,000 or fewer patients in the U.S. annually.
4. FDA review
The next step to bringing a medical device to market is FDA review. In the previous step, applicants had to choose what kind of application they would file based on their device classification and use. At this point in the process, they submit their application, and the FDA reviews the devices. If necessary, the FDA will consult an advisory committee which can make recommendations for the device's approval.
The FDA will make its final decision and publish it with supporting evidence in the Federal Register.
5. Post-market safety monitoring
Once a device is on the market, it is subject to the FDA's post-market safety monitoring. The FDA conducts post-market surveillance to ensure the continued safety of medical devices.
Part of the post-market monitoring includes inspections of medical device manufacturers, which ensure that the facilities follow good manufacturing practices.
Another component of post-market safety monitoring is reporting problems. Healthcare professionals, manufacturers and consumers can report complications with medical devices to the FDA's MedWatch or Medical Product Safety Network. The FDA then looks into these claims and takes regulatory action accordingly.
Finally, post-market safety monitoring might include active surveillance by the FDA. According to the administration, the FDA is developing systems to spot safety issues faster under the Sentinel Initiative. In the future, this may involve electronic databases to track the safety of approved devices as an additional post-market safety assessment tool.
Veronica Salib has covered news related to the pharmaceutical and life sciences industry since 2022.
