FDA: The 510(k) clearance (Premarket Notification)

510(k) clearance is the primary procedure for obtaining marketing clearance in the United States. It is also referred to as Premarket Notification (PMN).

This article provides a quick overview of the procedure and the documents that must be submitted.

1. General information on the 510(k) clearance by the FDA

In contrast to the European jurisdiction with the conformity assessment procedures, the FDA requires an explicit approval or clearance of medical devices. The most prominent procedure is named after an article of the Food, Drug, and Cosmetic Act (FD&C):510(k).

Manufacturers can generally use this procedure when their devices fall into Class II, and there is a comparable device that has already been cleared. This device, known as the predicate device, must also actually be comparable. This is referred to as substantially equivalent.

Learn more about "predicate devices" below.

The 510(k) procedure is also applicable to certain class I devices that are not "510(k)-exempt," as well as a small number of class III devices.

The 510(k) variants

The FDA distinguishes between three variants of premarket notifications:

1. Traditional 510(k)

The traditional procedure is used for "me too" devices and serves as a fallback if the FDA does not recognize Special 510(k) and Abbreviated 510(k).

2. Special 510(k)

Special 510(k) is an expedited procedure that can be used when changes are made to a user's own device.

3. Abbreviated 510(k)

Abbreviated 510(k) is a procedure that relies on compliance and adherence to standards, "Special Controls," and "Guidance Documents." A special form of this procedure is the novel Safety and Performance Based Pathway.

2. Content and format of the submission documents

a) Content

There is no official format, but manufacturers must follow the requirements of 21 CFR part 807 Subpart E. In addition, the FDA has published guidance on the structure and content of 510(k) submissions.

Accordingly, documentation should follow this chapter structure:

1. Medical Device User Fee Cover Sheet (Form FDA 3601)
2. Center for Devices and Radiological Health (CDRH) Premarket Review Submission Cover Sheet (Form FDA 3514)
3. 510(k) Cover Letter
4. Indications for Use Statement (Form FDA 3881)
5. 510(k) Summary or 510(k) Statement
6. Truthful and Accuracy Statement
7. Class III Summary and Certification
8. Financial Certification or Disclosure Statement
9. Declarations of Conformity and Summary Reports
10. Device Description
11. Executive Summary/Predicate Comparison
12. Substantial Equivalence Discussion
13. Proposed Labeling
14. Sterilization and Shelf Life
15. Biocompatibility
16. Software
17. Electromagnetic Compatibility and Electrical Safety
18. Performance Testing – Bench
19. Performance Testing – Animal
20. Performance Testing – Clinical
21. Other

Nearly identical requirements can be found on the FDA's "Content of a 510(k)" page. In the future, the submission will be purely electronic via eSTAR format. This follows the internationally recognized ToC format of the IMDRF.

b) Formatting

Regarding formatting, the FDA actually specifies the paper size, hole punching, or margin width. Among other things, it has published these 510(k) Format Tips. However, the FDA now waives paper submissions, so some of the tips are no longer relevant.

3. Predicate Device

A predicate device is a medical device already (legally) marketed in the U.S. that medical device manufacturers can refer to for clearance. Such a predicate device is a prerequisite for the 510(k) clearance preferred by manufacturers, which is less complex than a PMA (premarket approval).

Proof of equivalence

In order for the manufacturer to be allowed to cite this predicate device, he must prove that it is substantially equivalent.

In most cases, however, manufacturers do not want to market an identical device (e.g., the umpteenth syringe) but one that has the same intended purpose but differs in technical implementation.

The revised guidance Evaluating Substantial Equivalence in Premarket Notifications gives you very specific guidance on when you may cite a device as "substantially equivalent" and thus reference it as a predicate device for a Premarket Notification. In doing so, the FDA looks at the following:

• Do the devices have the same intended purpose?
• Do no new safety or effectiveness issues arise?
• Are the devices equivalent (technically, biologically, etc.)?

4. Criticism

The approval procedure is based on the existence of a predicate device. The risk-benefit ratio has already been evaluated for this device. A re-evaluation, therefore, usually no longer takes place.

However, this predicate device can itself have a predicate device. In this way, entire chains of references are created, which ultimately end with medical devices that first came onto the US market decades ago. This means that the current state of the art is no longer guaranteed.

This was already criticized by John Oliver many years ago (see video).

The FDA is aware of this problem and is working on new approval procedures.

5. Summary and conclusion

The 510(k) is still the most popular approval process in the USA. It is clearly described and predictable, and when all documents are available, the FDA is obliged to make a decision within 90 days.

However, this leads to manufacturers approving "me too" devices rather than innovative products. Therefore, the approval process will become less important in the future.