Prepare to meet thy regulator

Manufacturers stand to gain time and cost benefits if they can facilitate a successful pre-submission meeting with the FDA prior to making their final medical device application submission. Sandi Schaible, senior director of analytical chemistry and regulatory toxicology, WuXi AppTec, and Michelle Lott, founder and principal of lean RAQA, advise how to squeeze the most out of these one-time-only meetings. 

The more a manufacturer can collaborate with regulators, the better the manufacturer can identify submission expectations and potential challenges. An effective way to do so is through a successful pre-submission meeting with the US Food and Drug Administration (FDA). These meetings allow manufacturers to work with the FDA to review their medical device testing plans and address concerns before final submission. 

Facilitating a pre-submission meeting with a regulatory reviewer is a critical resource for a manufacturer trying to get a device cleared with the FDA. Currently, there is no similar pre-submission pathway available in the European Union (EU) as notified bodies (NBs) are not available for consultive purposes. Competent Authorities are inconsistently interpreting and applying the EU Medical Device Regulation (MDR), creating a wide difference in what each NB will accept. 

An effective pre-submission meeting can reduce time and money spent preparing the submission and increases the chance of gaining approval. There are three forms of feedback manufacturers can request from the FDA: written responses only, a 60-minute teleconference or an in-person meeting. In light of the pandemic, meetings are held in a digital format via video or teleconferencing. No matter what they choose, manufacturers must come prepared to make the most of their time. Understanding how to best leverage a pre-submission meeting can set companies and their device up for successful regulatory submission.

Getting started

Manufacturers must have a detailed understanding of their device before initiating a pre-submission meeting. This includes knowing the intended use, features, functions, testing strategy, along with how it compares to a predicate. 

In addition, it is critical to develop clarifying questions on FDA’s initial response to send to the FDA before the meeting. These questions should be sorted by priority and consider regulatory updates and other high-risk topics that need addressing before final submission. Once the FDA responds to the questions, this feedback will guide the specific talking points for the meeting. 

What to expect 

The reviewers will only come prepared to discuss their responses to the questions submitted by the manufacturer ahead of the meeting. Anything outside the preliminary topics should not be addressed during the pre-submission meeting. 

The pre-submission process allows manufacturers to work with the FDA directly to gain their insight. Based on the responses provided before the meeting, manufacturers can follow up and pinpoint specific areas of their plan where they would like greater detail about the reviewers’ feedback. Prioritize potential talking points to improve the testing plan and minimize additional information requests. 

Keep in mind that this meeting is not the time to negotiate or barter. Even if the feedback is unexpected or not ideal, essential factors such as patient safety and submission approval may be at stake if manufacturers don’t take the feedback seriously. Manufacturers should work with the team offline to provide potential follow-up questions for the final call.

Making the most of the pre-submission meeting 

Prior to attending the pre-submission meeting, manufacturers should understand that the FDA will not be leading the conversation. In this meeting, they can discuss their clarifying questions in detail and provide rationale. Reviewers will voice if they agree, disagree or have further questions. 

With only an hour, manufacturers should not repeat the same content addressed in the pre-submission document that the FDA has already reviewed in detail. Instead, come with a high-level outline of thoughts on the responses, prioritized by most significant concerns. For example, if a manufacturer’s device uses a novel material or manufacturing method, the biocompatibility test strategy may be particularly complex. The manufacturer may want to focus on more complex topics rather than a line-by-line review of the FDA’s feedback. In short, prioritize topics and prepare direct follow-up questions. 

And finally, practice. With an established team, prepare what each attendee is going to address and when. A point person should lead the call and direct questions to the appropriate team members. As for any important presentation, it’s essential to rehearse and ensure roles are understood. Remember, there’s only one opportunity for this meeting. 

Those who attend are crucial to the meeting’s success. Considering team expertise can help determine who should attend the meeting. Everyone in attendance should have defined areas of expertise relevant to questions already posed to the FDA. Attendees should be designated to speak one at a time to those topics and should otherwise remain silent.

After a pre-submission meeting

If a manufacturer involves a laboratory testing partner or consultant in their submission process, the partner(s) may attend the pre-submission meeting. If they do attend, they cannot be the sole expert guiding the discussion. The manufacturer will need to drive the conversation. The FDA will bring their in-house expert counsel. Manufacturers should consider inviting testing partners and consultants to provide any additional support to the team and interpret any feedback as needed.

If the testing partner does not attend, it is critical to relay the exact feedback from the meeting to them. Do not interpret or paraphrase when communicating the results received from the FDA. Any misinformation can affect testing decisions and potentially put the entire submission at risk.

Since preparation may change after the pre-submission meeting, manufacturers need to re-evaluate their testing and submission timelines to be realistic. 

Reap the benefits

Facilitating a pre-submission meeting before moving forward with medical device testing will provide the solid foundation manufacturers need for a successful submission. The more input from regulators a manufacturer can receive early on, the smoother their submission experience will be. 

Testing and submitting a medical device for regulatory approval is not the time for trial and error. When approaching the pre-submission meeting, manufacturers must focus on detail, be open to feedback and allocate enough time to incorporate any changes to their plan. Doing this work upfront not only saves money and time later on, is also sets manufacturers up to get their submission right the first time.