FDA pathways for medical devices
The 1976 Amendment Act allows the US FDA (Federal Food, Drug, and Cosmetic Act) to oversee and regulate medical devices in addition to its drug role. Through the amendment, the FDA strives to make sure that novel medical treatments get to the public as fast as possible and at the same time, ensuring patients’ protection and a positive balance between benefit and potential risks. Nonetheless, the FDA approaches this objective in dissimilar ways.
Medical devices are utilized for diagnosis, prevention or treatment of medical conditions or illnesses without chemically reacting with any part of the human body.
Medical devices are preconceived by either a physician or bioengineer as a solution to a medical issue. These devices are classified on the basis of their risk level
- Class I as low risk (e.g. bandages and nonelectric wheelchairs)
- Class II as moderate risk (e.g. syringes and contact lenses)
- Class III as high risk (e.g. high-frequency ventilators and pacemakers).
Before introducing a medical device into the US market, various types of premarket submissions to the FDA are compulsory.
Clinical trial submissions to the FDA are the primary way which medical device manufacturers follow when introducing new devices to the US market. These submissions include the premarket approval PMA, premarket notification 510(k), grants (de novo), the humanitarian device exemption (HDE) and Humanitarian Use Device (HUD). This article compares these different clinical trial submissions.
What is a 510k Submission?
A 510 (K) submission is required for most Class I and is compulsory for Class II devices meant for human use in which application for premarket approval (PMA) is not needed. However, a device may be exempted from the requirements of 510 (K) by the FDA and does not exceed the limitations of exemptions in .9 of the device classification regulation chapters (e.g., 21 CFR 862.9, 21 CFR 864.9). The premarket notification 510(k) is submitted to the FDA to show that the device is safe and effective.
Manufacturers making 510(k) submissions must compare their device to similar devices that have legal market rights, make and support their claim of substantial equivalence.
What are the requirements for a 510K?
510(k) is required to show substantial equivalence of predicate devices that are already in the US market. Substantial equivalence indicates that the new medical device is equally safe and effective as the predicate. Substantially equivalent devices when compared to a predicate should have similar intended use and technological features or similar intended use but different technological features without compromising safety and effectiveness and submit information showing that the device is safe and effective as the predicate to the FDA.
How to submit a 510K?
510(K) submission to the FDA follows four categories of parties. The first is manufacturers of finished devices who manufacture their devices based on their own specifications and intend to market it in the US. However, device component and contract manufacturers are not required to make submissions to the FDA. Secondly, specification developers that develops the specifications for a finished device introducing a device to the US market. Thirdly, Repackers or relabelers who make labeling changes or whose operations significantly affect the device. Lastly, Foreign manufacturers/exporters or U.S. representatives of foreign manufacturers or exporters introducing a device to the U.S. market.
Unlike 510(K), PMA submission to the FDA includes clinical experiments and non-clinical laboratory investigations.
What is a Pre Market Approval (PMA)?
Premarket approval (PMA) is a requirement by the FDA for Class III medical devices to assess their safety and effectiveness through scientific and regulatory review processes. A Class III medical device is one that supports or sustains human life, substantially vital to prevent impairment of human health or which has the potential of unreasonable risk of illness or injury. Clinical trial submissions through the PMA application regulation and justification is found under section 515 of the FD&C Act.
The premarket approval is the most restrictive form of device marketing application required by FDA and all applicants must get the approval of FDA before they can market their devices.
What are the requirements for a PMA?
PMA is required for Class III devices, the most restrictive regulatory category for medical devices. These devices are available in the database of the Code for Federal Regulations (CFR) for Class III devices.
If a device poses high risk such that it supports or sustains human life, is of substantial importance in preventing impairment of human health, or presents a potential, unreasonable risk of illness or injury) and has been found to be not substantially equivalent (NSE) to a Class I, II, or III [Class III requiring 510(k)] device, then the device must have an approved PMA before marketing in the U.S.
PMA Submission
For PMA to be approved, onsite facility inspection is required to confirm compliance to 21 CFR 820 before approval. On the other hand, when a De Novo submission is successfully reviewed, the FDA classifies the device, regulates it if need be and identifies any special controls required for future premarket submissions of substantially equivalent devices.
What is a De Novo pathway?
The De Novo process is a pathway that helps to classify new medical devices for which only general control or both general and special controls provide reasonable assurance of safety and effectiveness for the initially proposed use, for which no legally marketed predicate device exists. The De Novo classification is not a risk-free classification process. De Novo requests for class I or II devices may enter the market and serve as predicate devices for future 510(K) submissions.
Requirements for a De Novo
The requirement for the preparation of a De Novo Request is based on two options where the requester can submit a De Novo request for the FDA to make a risk-based assessment for classification of the device into class I or II. Firstly, when no predicate that questions the safety or effectiveness of the De Novo request exists. Secondly, when there is no legally marketed device which can serve as a substantial equivalent for 510(K) submissions.
De Novo Submission
Other: HUD and HDE
Devices that are classified through the De Novo process may be marketed and used as predicates for future 510(k) submissions.
Humanitarian Use Device (HUD) is a medical device that is meant for the treatment or diagnosis of a disease or condition that manifests in less than 8,000 individuals in the United States per year. The HUD regulations can be found in section 3052 of the 21st Century Cures Act (Pub. L. No. 114-255). Humanitarian Device Exemption (HDE) is an application to market an HUD (Section 520(m) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)). HDE applications are exempted from the effectiveness requirements of sections 514 and 515 of the FD&C Act and are subject to certain profit and use restrictions.
Review System
Clinical trial submissions on medical devices may undergo a review process by the FDA or exempted from review depending on the class of the device and the type of already marketed similar devices. Most 510(K) submissions that are in class I and very few in class II are exempted from review if the pose extremely low risk or are very similar to already existing marketed devices.
Other class II medical devices in 510(K) submission, undergo 510(K) review. The 510(K) review is necessary to determine if the new device is substantially equivalent to a predicate. FDA review for PMA submissions (class III) devices include clinical studies result. However, for PMA submission concerning minor changes on an existing class III device, PMA supplements are submitted rather than a full PMA. On the other hand, De Novo undergoes acceptance and substantive review by the FDA.
The acceptance review also known as administrative review is done to evaluate the completeness of the application as well as whether it meets the minimum threshold of acceptability. The substantive review is also known as the classification review, which indicates whether another legally marketed device of the same type exists. HDE submissions are only reviewed when the medical devices are intended to solve very rare illnesses or conditions.
Conclusion
On a final note, Clinical trial submissions under the 510(K) are not required when an unfinished device is being sold to another company, when the medical device is not being marketed or commercially distributed, when you distribute another firm’s domestically manufactured device, for repackagers or relabelers who do not significantly change the labelling or condition of the device, for importers of foreign-made medical devices and for devices exempted from 510(K) by the 21 CFR 862-892 regulation. Unlike the PMA and De Novo submissions, 510(K) is supported by a third-party review program.
Third-party program allows manufacturers of certain devices of submitting their 510(k) to private parties (Recognized Third Parties) identified by FDA for review instead of submitting directly to The Center for Devices and Radiological Health (CDRH)
