Dialogue with the FDA is helpful during development of a medical device. After all, we will ultimately need the FDA to clear or approve any class II or class III device prior to commercialization. One of the mechanisms for applicants to request feedback from the FDA is the pre-submission (pre-sub) process. In this process, a person or organization anticipating the need to make a future submission to the FDA (e.g., Investigational Device Exemption, 510k Premarket Notification, Premarket Approval) can make a written request to obtain feedback prior to, or during, preparation of the submission. In recent negotiations between industry and the FDA related to Medical Device User Fee Amendments (MDUFA) IV, coming in 2018, FDA expects the volume of pre-subs each year to continue to increase, while industry would like to receive pre-sub feedback sooner.
Popular reasons to do so include: obtaining feedback on your assumed device classification and associated regulatory requirements, obtaining feedback on your clinical plan or on the decision clinical data will not be necessary, and obtaining feedback on the claims you plan to make for the device, as well as the data provided to support them. Pre-subs have seen steady growth in popularity due to their utility, and quite possibly the fact they’re still FREE! The FDA currently handles about 1,500 pre-subs per year and, according to projections in the MDUFA IV reauthorization summary, this volume is expected to increase to about 2,350 pre-subs by 2022.
The process itself is rather straightforward: a pre-sub package is prepared following the FDA guidance document Requests for Feedback on Medical Device Submissions, including appropriate supporting descriptions and data. You also need to decide whether written feedback from the FDA will be enough, or if it’s necessary to schedule a telephone conference or an in-person meeting. If you choose a teleconference or meeting, you also need to specify three dates, 75-90 days in the future, when you and your team will be available. Simple, right? What could possibly go wrong? Well, let’s talk about that a bit. I share the following three bad ideas with you in hope you never have to live through a bad pre-sub.
1. Allowing The Inventor To Talk Too Much
Inventors of new technology pour themselves into their work and it becomes very, very personal. They also rarely finish innovating. Whatever their invention can do today, the next generation will do even more. For these reasons, extreme caution is necessary in planning for your pre-sub meeting.
I was helping a client prepare for a pre-sub meeting. The device was new and the inventor talked about the far-reaching future plans for the technology, but we agreed to present a limited intended use and claims consistent with the predicate device to avoid a massive clinical trial. We planned for a nice, clean 510(k) submission to get the company moving toward revenue generation. As we prepared for the pre-sub teleconference with the FDA, I coached the inventor on what not to say or do during the call, and I explained that we would only need him to speak if the FDA requested detailed technical information.
Well, as my luck often goes, the FDA did have technical questions for the inventor to answer, but he couldn’t stop himself. The inventor began to explain how this device was “far superior” to the predicate device and how this first clearance would take little advantage of the true power of the technology to change the practice of medicine and raise the standard of care. Fortunately, we were able to get the meeting under control and re-focus on the device in the limited application described in the pre-submission documentation package. Do not make superlative statements when seeking 510(k) clearance as substantially equivalent to an existing predicate device.
2. Overloading The Room
A second idea that could have a negative impact on your pre-sub meeting is having too many people involved, whether on a teleconference or meeting in person at FDA headquarters. Now, it is certainly necessary to include your experts (e.g., physicians, designers, clinicians, statisticians, etc.) as appropriate, but realize that the FDA will match you. They will strive to include an expert of their own, in each applicable area, to ask and answer questions.
This can make for a very large gathering, leading to delays in scheduling and eventually resulting in an unwieldy meeting. A director of regulatory affairs with whom I once worked wanted to make an impression of how important the pre-sub meeting was to her organization. She planned to have a dozen members of her team on the teleconference. FDA responded in kind with an impressive team, and introductions alone took nearly a quarter of the meeting. Even worse, though the dialogue was productive, so many individuals were weighing in on each question, only half of the agenda was covered by the end of the one-hour meeting. There is absolutely no need to try to show strength or importance in planning for a pre-sub meeting. You cannot overwhelm the FDA, but if you want to impress them, have the right people in the room, and no one else.
3. Winking At The FDA
I really wish I was joking, but this actually happened: I was attending an in-person pre-submission meeting at FDA headquarters, acting as a consultant to a medtech CEO and his team. The company had scheduled the meeting to get feedback for its next 510(k) submittal, covering an updated version of its device. The complicating factor was that the company’s currently-marketed device had come under fire in a recent FDA inspection, and was under threat of recall. In talking about the new submission for the next-generation device, the CEO brought up his company’s current compliance problem, and commented how the new design wouldn’t have the problems of the current product. Then, he winked across the table at the FDA representatives and asked if they would put in a good word for the company with field compliance staff. Awkward…I wanted to crawl under the table. Remember, there are no favors from the FDA. Each device must be safe and effective of its own merit, or be removed from the market.
The FDA Weighs In
I’m not the only one with some advice on pre-subs. FDA has shared its thoughts on some bad ideas in the above-mentioned guidance document. The agency provides these examples of general questions it considers NOT conducive to a productive discussion during a pre-sub meeting:
• Will the information outlined in my pre-sub support a substantial equivalence determination?
• Are the results of my bench testing acceptable?
• Is the clinical data collected sufficient?
In preparing for the pre-sub meeting and putting the data package together, we need to do enough work to be able to ask the FDA questions that they can answer either yes or no. For example, if we gather clinical data at three sites, with 30 patients at each site, and statistically 95 percent of the subjects have a successful outcome as defined in the study plan, will the FDA agree that we will have adequately demonstrated clinical utility for the device? The value of the FDA’s feedback to us is directly related to our effort in asking the right questions.