Your 510(k) Hasn't Sailed Through. Now What?

By Jim Kasic, Boulder iQ

Medical device companies can live and die by the 510(k) process. It lets the market know that the device is safe and effective, and it protects users from liability if the device doesn't perform as claimed. Most importantly, 510(k) clearance allows a company to market its device in the United States. Without it, there’s no opportunity for sales, business growth, and market expansion with the device. For a company that has put substantial resources into developing an essential medical device, 510(k) clearance really can mean life or death.

Understanding The Process

Under the 510(k) pathway, a medical device manufacturer submits a premarket notification to the FDA. That notification includes information about the device's intended use, design, and performance characteristics compared to a predicate device – a device that already has 510(k) clearance and is being legally marketed. The new device must be shown to be at least as safe and effective as the predicate, or reference, device. 

When the FDA determines that the new device is “substantially equivalent” to a predicate device, it will issue a clearance letter allowing the developer to market the device in the United States. The result of the 510(k) process is indeed “clearance,” not “approval,” from the FDA. It simply indicates that the FDA has determined the device is equivalent to a similar device already on the market.

While each device and each 510(k) submission are unique, it’s important to note that preparing a 510(k) submission is a major undertaking for any company. The time, detail, and allocation of resources to the regulatory process can be all-consuming. Just getting the submission into the FDA review process is a major accomplishment. Whatever the outcome, device developers should take a moment to appreciate how far they have come in the development process.

Questions, Clearance, Questions

Developers sometimes talk about a 510(k) getting “rejected.” While full rejection of a submission does occasionally happen, it is far more common that the FDA will not grant clearance immediately but, rather, will come back and request additional information. In fact, it’s extremely rare to receive 510(k) clearance without additional questions.

The process is an iterative one between the FDA and the device manufacturer. When the FDA receives a 510(k) submission, the “review clock” starts ticking. That means the FDA has 90 days to respond to the device manufacturer – and it’s not atypical for the response to arrive around Day 80. During its review process, the FDA breaks the submission up into sections and assigns reviewers to each section.

Each reviewer may have questions or request “additional information” on their section. Some questions may be simple to answer. Some may require more involved responses. In some situations, the device developer may need to provide a rationale to clarify the information in the submission or provide additional data.

To illustrate, the FDA may come back with 10 questions. Five might be relatively easy to answer. Perhaps a reviewer did not see some key data in a particular section or is asking for another piece of information that is relatively easy to obtain. In many cases, the request will involve labeling. Manufacturers do often need to revise labeling – a critical, but often-overlooked step in the product development process.

The other five questions in this hypothetical example may be a little tougher. Maybe the FDA will ask for justification for specific results. Or they will ask for more testing, which, depending on the request and the device, can take weeks, months, or even longer. Developers may need to design and conduct different types of tests and/or build more devices to conduct the required tests.

As you work through this iterative process, sometimes the FDA will just wholly disagree with a subset of the data provided and fully reject the 510(k) submission. In this situation, you usually will have a fairly good idea of the reason through the correspondence you have had in responding to previous questions.

What To Do When The FDA Disagrees And Rejects Your Submission

If this occurs, and you want to resubmit your 510(k), the next step is to determine the FDA’s specific reasoning for not accepting the data. This is an excellent opportunity to put the FDA’s Q-Submission Program into play.

Dubbed “Q-Sub” for short, the program allows manufacturers of medical devices to obtain feedback on the regulatory process and requirements via an actual conversation with FDA experts. One-hour meetings can take place on the phone, in written form or in person at the FDA’s Silver Spring, MD, campus.

The FDA supports and encourages Q-Subs, as they afford the chance for its staff to learn more about developments in the field. Since the FDA does not charge a fee for Q-Subs, developers may at times be almost too eager to take advantage of the program. It’s common for a startup to submit a multitude of questions to the FDA, and then end up with little information six weeks later — the typical time frame to obtain a Q-Sub written response or meeting.

However, when done in response to an FDA rejection, the Q-Sub can be very effective. With the information from the submission fresh in the reviewer’s mind, the meeting offers the chance to clear up miscommunications and refine ideas. A developer can ask specific, to-the-point questions to elicit the type of information they need to obtain acceptance of additional information they will prepare and submit.

In particular, the Q-Sub affords the opportunity to specifically ask the FDA if you can refer back to your rejected 510(k) when you resubmit. Reference to your previous submission means that you will then only need to resubmit information for the outstanding issues and obtains the agency’s buy-in to get to the next set of testing and data to support your submission. The time savings in having the FDA refer to previous work, versus having to resubmit all material, can be substantial when trying to get a device to market.

Examples of the types of questions to ask in the Q-Sub include:

• What specific information is necessary to adequately address the question?
• What specifically would the FDA like to see in a protocol to provide additional data?
• If (particular) section/area/data is the only area you are rejecting, can we come back with the additional information requested, and then have you refer to our previous work in the initial submission?

Q-Subs are not binding conversations, but the transcript of what takes place in each meeting goes into the developer’s record with the FDA. Since everything will be in the Q-Sub meeting notes, making sure to ask exacting questions, and obtaining exacting answers, will improve the probability of success with the submission of additional information.

Iterative Process Example

The ongoing experience of a developer of a minimally invasive device for the interventional radiology market offers a good look at this iterative process.

The industry, in which issues of biocompatibility with extractables and leachables are of paramount importance, uses a complex set of calculations and assumptions to determine a margin of safety and toxicological risk assessment. When the FDA did not accept the developer’s assessment in its initial submission, the company went through the Q-Sub process to clarify the protocol it needed to run to resubmit the risk assessment. When the company completes the additional testing it clarified in the Q-Sub meeting, it can submit that data. At that point, the FDA may come back (again, within 90 days) and have one or two questions left. When the FDA stops asking follow-up questions on a given section, it has accepted that section.

Given the iterative nature of the 510(k) process, with the need for time to supply results from additional testing or to clarify information, the typical time from submission to clearance is around six months. The fastest the process could take would be 90 days, but the timeline will vary dramatically by device. For these reasons, when the FDA wholly disagrees with a subset of data, it is critically important to determine if it will accept submission information with which it has no issues. Then the manufacturer can focus fully on the outstanding questions and submit only the relevant data when ready.

Work With Experts

Given the vital importance of obtaining 510(k) clearance — as quickly and efficiently as possible — device developers routinely work with knowledgeable, experienced regulatory experts. Experience in communicating with the FDA, making calls on critical testing, and keeping up to date with the latest regulatory developments pay off in getting a device through the regulatory pathway and into the market.

For many developers, especially startups, outsourcing the regulatory affairs function is usually the most effective route. While contract consulting firms may work with their own expert regulatory contractors, it can be helpful to work with a firm with in-house expertise. Dealing directly with people who have worked in med device firms themselves may be the best way to navigate the complex regulatory pathway and avoid costly missteps.

In addition, experienced experts know how to integrate regulatory affairs throughout the product development process to achieve success. For instance, they might be able to tell that a series of smaller steps will work better than what appears to be a straightforward regulatory path. Or they could identify ways to slightly modify a device’s intended use and/or indications for use that could significantly ease the 510(k) process. Again, solid experience in walking the 510(k) road, maintaining focus on getting products to market, will pay off for the developer.

Conclusion

While full-out rejection of a 510(k) submission may be uncommon, obtaining acceptance and the all-important clearance letter can be a complex, time-consuming, iterative process. Understanding the FDA’s requirements, processes, and practices is essential, and working with a regulatory expert – especially one who has walked in your shoes – will maximize chances of success.

About The Author:

Jim Kasic is the founder and chairman of Boulder iQ. With more than 30 years of experience in the Class I, II, and III medical device industry, he holds more than 40 U.S. and international patents. His career includes experience with companies ranging from large multinational corporations to startups with a national and international scope. Kasic has served as president and CEO of Sophono, Inc., a multinational manufacturer and distributor of implantable hearing devices, which was acquired by Medtronic. He also was the president of OrthoWin, acquired by Zimmer-BioMed. He received a B.S. in physics and an M.S. in chemical/biological engineering from the University of Colorado, and an MBA from the University of Phoenix. He can be reached at jim.kasic@boulderiq.com or on LinkedIn.