While the U.S. regulatory system can be credited with ensuring high standards of patient safety and device effectiveness, the process of submitting a 510(k) can pose many challenges for medical device manufacturers both inside and outside of the United States.
Each 510(k) submission is nuanced and dynamic, with any number of variations, depending on the type of device, the risk level, its history, etc. Therefore, it is essential to have a strong understanding of the most up-to-date 510(k) submission requirements and how they relate to your device.
To help medical device manufacturers—especially smaller start-ups and medical device companies outside of the United States (OUS)—to increase the likelihood that their 510(k) submissions will be reviewed and cleared with minimal delays, the following Top 10 Pitfalls should be understood and successfully navigated.
1. Misconceptions about 510(k)’s goals. In the 510(k) review process, devices that meet eligibility requirements are “cleared” as opposed to being “approved” by FDA. But completing a compliant 510(k) can be confusing, time-consuming, expensive, and frustrating. No longer is the 510(k) process about filling out numerous forms and sending them to the FDA along with a user fee payment. The requirements and expectations for a properly completed 510(k) have evolved along with medical technology.
For a device to receive 510(k) clearance, the documentation must show that the device is “substantially equivalent” to a previously cleared (predicate) device. The device needs to have the same intended use and technical characteristics. If there are technical differences, the 510(k) must show that those differences don’t affect safety or efficacy (when compared to the predicate). The reviewers will also want to see data substantiating that the device’s performance, safety, and effectiveness are equivalent to the predicate.
2. Not knowing the regulatory history of your product in the United States. 510(k)s are based on devices that were previously cleared in the United States. Therefore, it is imperative for a medical device company to know, and to be able to explain, the regulatory history of its device in the United States. For instance, the last metal-on-metal hip implant was cleared in October of 2012. On January 13, 2013, the FDA issued an order proposing that future metal-on-metal hips be required to meet certain elements of the PMA program.
3. Choosing the wrong comparison (predicate) device. The entire 510(k) philosophy is based on previously cleared devices, so it’s necessary to find one that closely matches your device parameters. Predicates should be carefully selected based on design, materials, sizes, sterility, indications for use, and packaging, among other considerations. For example, a company may consider its suture anchor to be just like every other one on the market. But if the device is sterilized by the user before use, and the predicate they’ve picked is supplied already sterile, (or vice versa), it is likely that FDA will ask for additional data or clarification, which slows the review process.
4. Choosing a predicate that is not available to test. Since the basis of a 510(k) is the comparison of a device to a previously cleared device, testing data is often a crucial part of a complete 510(k) submission. Note that for some testing data, there are cases in which the comparison may be based on published literature on the predicate and performance standards recognized by FDA.
To adequately test the two devices side-by-side, samples of the predicate device must be acquired. This process can be challenging. There are devices with 510(k) clearance that have never been brought to market, have limited production, have controlled distribution, or are considered antiquated. And more often than not, a predicate is a competitor’s product, which can make obtaining samples a difficult and often expensive proposition.
5. Choosing a predicate that is not available in the U.S. Just because a predicate is available in another jurisdiction does not mean it’s available in the United States. Many devices have line extensions of sizes, product features, or materials that may not be covered by a 510(k) clearance. For example, a device may have seven sizes available OUS, but only four of them have been cleared in the United States. To complicate matters, it is not always possible to determine this from the available marketing materials or 510(k) information. Therefore, it is crucial for medical device companies to have in-depth knowledge of the history and regulatory status of their predicate in the United States.
6. Not understanding (or being able to find) appropriate guidance. FDA publishes guidance documents on various topics from general procedural recommendations to specific device testing. While using the FDA’s Guidance is not required, it is highly recommended by the agency, and it is expected that any deviation from a guidance document be justified. The way FDA handles guidance has been a point of contention for many in the industry for some time. Guidance documents can be difficult to find, and may even be obsolete, outdated, or withdrawn. Without experience with FDA and its operations, locating the appropriate guidance documents can be complicated, time-consuming and frustrating.
7. Not starting validation testing. In some cases, it may be appropriate to submit a 510(k) while validation testing is still in process. What’s important is to make absolutely sure that the testing is actually in process. If the 510(k) states that a 60-day sterility validation is “in process” on the day it’s submitted, and the reviewer asks for them on day 84, that information must be readily available.
8. Errors and inconsistencies in the 510(k). When you have been working on a 510(k) submission for weeks, it is easy to develop blind spots to mistakes and discrepancies (after all, you probably made them!). Because of this, it is valuable to have a knowledgeable individual proofread the entire document before submitting. Enlisting a second (or third) set of eyes helps prevent minor errors or typos that could hold up the review of your submission.
9. Inattention to FDA’s instructions. FDA has very clear instructions for how a 510(k) should be formatted and submitted. For example, the entire document must be paginated, and page numbers must match the Table of Contents, etc. Last year FDA published two very useful guidance documents. The first is the “Refuse to Accept Policy for 510(k)s,” which, despite its rather daunting title, is a very clear and comprehensive checklist for a properly formatted submission.
The second is the “eCopy Program for Medical Device Submissions.” Both documents provide detailed and thorough descriptions of the Agency’s requirements and expectations with regard to 510(k) submission structure and format.
10. Missing and incomplete forms. With 510(k) submissions, every form is influential. With comprehensive instructions provided on each form, there is little excuse for omitting information. Read each and every form carefully and fill them out completely. Every item is there for a reason and should be considered equally significant.
For many small medical device companies, and in particular those outside of the United States, the process of compiling and submitting a 510(k) can be confusing and frustrating. It also requires substantial investments in patience, time, and resources. Toiling through the process can often feel like an overwhelming administrative hurdle or an exercise in bureaucratic control. However, it’s important to remember that the purpose of a 510(k) is to improve public health and well being. As a result, it deserves the same level of attention, expertise, and commitment that was applied to the design and development of the device.
510(k)s that meet the requirements and expectations set by FDA have a much greater chance of gaining clearance because they sufficiently demonstrated that the device is safe and effective. As a result, the medical device company is able to fulfill the true design intent of their technology, which is to improve the quality of life, and in some cases, to save lives.
Tim M. Lohnes is the senior regulatory consultant at Orchid Design. He is an experienced medical device regulatory professional, with over 25 years in quality and regulatory affairs. His contributions to the development of laparoscopic devices, as well as suture, mesh, orthopedic, and other advanced surgical device designs and applications is complimented by his extensive background in quality systems management, design control, and regulatory affairs. He has a proven track record of obtaining FDA and CE Mark clearance, as well as developing and maintaining strategies and procedures to ensure and maintain compliance with regulatory and corporate standards.