Mastering PRESUB FDA Pre-Submission for the MedTech Industry

Hello! Hello! Welcome! Welcome everyone to mastering presub FDA pre submission for the Med tech industry. I'm really excited. This is truly a master class in FDA communication with our expert Michelle lot from Lean RA. Qa. We have a great program lined up for you today. There's gonna be some poll questions. Feel free to use the chat. If you have questions, please submit them not saying that we're gonna get to them today, but would try to follow up with everyone. And yeah, let's go ahead and kick it off, Michelle. It's over to you.

Michelle Lott, RAC: Alright. Michelle Lott, RAC: There we go. Michelle Lott, RAC: Okay. Michelle Lott, RAC: are we? You could see my screen and everything. Michelle Lott, RAC: Okay. Michelle Lott, RAC: So today, we're gonna talk about pre submission master class. We you guys probably all know me by now, but I've been in Raqqa for over 20 years. I've assisted more than 150 Co. Companies. But I've also been on the FDA. Good manufacturing Practices advisory Committee. I served a term as the industry representative there. Michelle Lott, RAC: This is my executive team. Michelle Lott, RAC: So today, we're gonna go through a crash course and pre submissions. We are going to also cover different types of queue submissions like the 5 13 g. The breakthrough device requests the safer technologies, program and lessons learned and hopefully, at the end of the course, you'll be able to differentiate between them. And what's the best to use for your purpose.

Michelle Lott, RAC: So let's get started with presubmissions. Michelle Lott, RAC: So pre submissions can be a really powerful tool. And the opportunity to ask very specific questions. Of the FDA and make the FDA really up more of a partner to you than an adversary. So it kinda gets them involved early on in your technology as part of the problem solving team about how is this product gonna move through the FDA Michelle Lott, RAC: they're really valuable. If you have a anything new or novel about your technology, especially if you are trying to get something that's similar, but different from your possible predicate. Through the FDA via 5, 10 K.

Michelle Lott, RAC: Oftentimes FDA has got maybe a draft guidances, or maybe there's something political happening behind the scenes Michelle Lott, RAC: could also be. Other devices are about to be cleared or granted to Denovo. There can be things happening that you don't have visibility to. That will reflect FDA's current, thinking that may give you a challenge. When you are in submission. If you haven't had a presub to learn what those things are Michelle Lott, RAC: and so, of course, this is having this kind of inside perspective is going to help make you more successful in your submission.

Michelle Lott, RAC: It's also important to know that these are non binding technically. But the FDA does consider intend to honor them their opinion if their current thinking is not changed between your presubbing your submission. Michelle Lott, RAC: Most importantly, it is still free. So it's it's free, and they're pretty good about hitting their timelines. So there's there's really nothing lost by doing your pre submission. Michelle Lott, RAC: So we talked about this Michelle Lott, RAC: that not if if you have anything that's new or novel.

Michelle Lott, RAC: any first of this kind that can be more than just a technology that can also include expanding an indication or a patient population. I work with a lot of devices where they want to make them on specific pediatrics. FDA does consider that a new indication. Michelle Lott, RAC: And then, while they are non binding you have to rem the FDA will remember them, and so, if you make changes between the time you do your pre submission and the time that you go into your submission, you still need to address those questions in the pre submission, even if they're not relevant anymore because of the changes you made to your product or or indication.

Michelle Lott, RAC: You need to to say that and address them directly, or the FDA will ask you. Michelle Lott, RAC: So this is an opportunity to build your story, and a true story to the FDA and inform them and help for formulate their position in their review. Michelle Lott, RAC: So this is again an opportunity to to tell a story around your product. So creative writing is very critical task Michelle Lott, RAC: to the pre-submission you need to focus on 3 to 4 critical topics in a single presub. Now, even though these might be only 3 to 4 questions, they could be multi-part questions associated with a single or specific topic.

Michelle Lott, RAC: You need to be straightforward. Your your questions don't need to be open ended. They need to almost make a statement and then ask for FDA's concurrence Michelle Lott, RAC: and don't include everything under the sun in your submission. As far as the context or background, but make sure that you balance that where the FDA isn't overwhelmed with data or information. Michelle Lott, RAC: but they've got enough information to thoroughly understand the questions you asked.

Let's go ahead and do poll number one. We may.

Michelle Lott, RAC: Short.

Can everybody see that? Can you see it, Michelle? Yes, okay. Good. So the question is, are you planning to do an FDA pre submission in the next 12 months, including pre submission. 5, 13 g, breakthrough or safe attack program. Yes. Now, we're uncertain. So you can keep going. If you want. We're just gonna let this run for a little bit.

Michelle Lott, RAC: Art. Michelle Lott, RAC: So common topics for pre submission include asking specific questions about your regulatory strategy? Again, particularly if you have anything new or novel, or different from your predicate Michelle Lott, RAC: the regulatory pathway. If your device doesn't fully fall in you're not sure if it fully falls in a particular maybe product code, or how the FDA would feel about predicate strategy compared to a Denovo. Michelle Lott, RAC: It is also very helpful to get buy in from the FDA. If they agree that your significant risk or non significant risk and your overall clinical strategy.

Michelle Lott, RAC: and then also to ask specific questions about your plan performance, testing about both the plan and then in the future, the protocols. Michelle Lott, RAC: And then again, this is a way for FDA to get just get familiar with your technology. So just that background and your your technology will help update FDA, advance your submission more efficiently through the agency.

So it looks like over half of the attendees are planning on doing a submission this year. That's great news. So we're gonna close the thingy let me know what goes away. Yep.

Michelle Lott, RAC: So I mentioned that pre submissions can be you know, a a little bit of creative writing again, you're telling a true story, but the way you phrase your questions is really critical to see your success. Michelle Lott, RAC: So you need to focus your efforts on issues that are most relevant to moving your project forward for the phase that it's at. Michelle Lott, RAC: You need to ask clear and objective questions. And you and this is important, because I see a lot of people that are in love with their own science and technology. And you don't need to be making assumptions that FDA is going to think the same things as as you do about your product or your technology and its needs in the marketplace.

Michelle Lott, RAC: You need sufficient background and information and supporting documents and avoid the extraneous information that can be counterproductive. Michelle Lott, RAC: And because it's easy to maybe distract the FDA if you inundate them with information, and then your questions need to guide FDA to a desired outcome. Michelle Lott, RAC: So it it all comes down to the power of phrasing, and there are ways that are more most productive to ask questions. Michelle Lott, RAC: For example, if you include protocols and ask questions on strategy, an example of this would be, does FDA agree that the non clinical test strategy is sufficient to demonstrate performance evaluation for the proposed device.

Michelle Lott, RAC: But you don't ask the FDA to review actual data. They will not review data in a pre-submission Michelle Lott, RAC: so, for example, does FDA agree that my data is sufficient for a pre submission. I have seen companies, particularly companies that are outside of the Us. That might have already done studies for one purpose or another in another country, and they did the study without getting FDA to review the protocol in advance to see if FDA would acknowledge the results of that. And they're like Michelle Lott, RAC: insistent on turning that in. And there's presumption. And FDA, just.

Michelle Lott, RAC: you know, shuts that down very quickly, and they will not look. Look at data. So even if you're gonna do. Oh, us studies or testing, I would still submit the protocols in advance to make sure you can get most the most mileage and reuse out of Michelle Lott, RAC: out of data that you may obtain prior to going into your FDA submission. Michelle Lott, RAC: So also you can ask specific questions on the suitability of maybe your study or test design. So does the FDA agree that statistical sample size, calculation, method of the Statistical Analysis plan Michelle Lott, RAC: is appropriate for the proposed clinical study

Michelle Lott, RAC: as opposed to asking the FDA a question around your study or test protocol. That may be more open, ended. And just ask the FDA what they think like, how many subjects should be. Should my clinical study have. Michelle Lott, RAC: I see this a lot with people who just randomly pick a number like they'll say does, you know, is a hundred people enough for my clinical study Michelle Lott, RAC: without Michelle Lott, RAC: including that statistical analysis of how did they come to that number? They just kind of picked the number out of the hat, and it thought FDA would validate it.

Michelle Lott, RAC: So there are several ways to get feedback. You can get feedback written feedback, only you can get teleconferences, or FDA is now back to in person meetings. Michelle Lott, RAC: Now, the differences here is that, you know, written feedback. Only you are going to get a letter from FDA. That's that's actually very comprehensive. They're gonna thoroughly answer each question you asked. Michelle Lott, RAC: And then in written, I've had a lot of luck with written feedback only where they said. You know, we're gonna answer your questions. But here are some additional things we're thinking or questions we may have or point you towards specific guidance documents for your consideration.

Michelle Lott, RAC: and to me written feedback only is often the best place to start, because it's it's a more comprehensive response. It's written in FDA's own words. Michelle Lott, RAC: whereas with both the teleconference and in person meetings, you're going to get Michelle Lott, RAC: a limited amount of written feedback in advance to help prepare you for the meeting, but it's not gonna be to the extent that written feedback is, and in both the teleconference and the the in person meeting you, somebody on your team is going to have to take notes in their own words of how they heard and interpreted the FDA.

Michelle Lott, RAC: Then you're gonna have to submit those notes to the FDA for their concurrence, and then for them to do the final edits. Michelle Lott, RAC: And then Michelle Lott, RAC: and it's I see all the time that people that that are taking notes and then submitting minutes. Michelle Lott, RAC: The FDA says, Oh, that's not what we said, or that's not what we meant, and we'll make corrections. So, at least for that that first round of interaction with the FDA. It could often be helpful to ask that written feedback, because for all 3 of these you've got an opportunity to ask clarification questions after you've had the initial feedback or meeting.

Michelle Lott, RAC: So an example of there was one where I had written feedback, only Michelle Lott, RAC: it had, pretty extensive feedback in the written feedback only. But we could tell that the FDA had misunderstood an aspect of the technology. So I just submitted an informal email to the reviewer, I said, Hey, we wanna clarify Michelle Lott, RAC: these points. Does that change your written feedback? If I got a response in email through an informal discussion that was as comprehensive Michelle Lott, RAC: as my written feedback. Only so, Michelle Lott, RAC: just know that there are all those kind of dynamics in play around. Why you pick what? What type?

Michelle Lott, RAC: So? Michelle Lott, RAC: Another advantage of having a having a teleconference or a meeting is, or at least an in person meeting is that you've got the advantage of seeing the body language of the FDA, which can kinda help maybe read how they're positioning on teleconferences. You may or may not. People may or may not have their their Michelle Lott, RAC: cameras on, but also know that with teleconferences and meetings that these are hard stops at 60 min, so you've gotta manage this on the nose to Michelle Lott, RAC: to make sure that you're very efficient with your communication.

Michelle Lott, RAC: so you might can dive deeper and get a broader perspective, because FDA is gonna come with a a legion of people for these meetings, and you might get a verbal perspective of from a couple of different perspectives. Michelle Lott, RAC: And so this is great to like capture, maybe some more nuanced information. Or for FDA to speak. Michelle Lott, RAC: you know, verbally speak things that might have been difficult to convey in writing Michelle Lott, RAC: so recently. FDA has launched the prestar it is still voluntary, but for

Michelle Lott, RAC: for you to be able to submit your pre submission to the FDA. There's a section to you can either, you know, request submissions, or I mean, request a meeting or request written feedback, depending on your selections from the dropdown menus Michelle Lott, RAC: and then that OP starts to Michelle Lott, RAC: open up or close down different elements of the presart template. Michelle Lott, RAC: So for those of you who don't know or haven't worked in it, prestar is an interactive Pdf form intended for to be a dynamic Pdf, that can automate the Pre, the submission process because it predefines the content and structure, and it is complementary to the Cdh internal review templates

Michelle Lott, RAC: and then it also integrates multiple FDA resources like guidance documents, databases help text, and then it guides you through the construction for each section of the submission, and then at the end, it has a automatic verification where you can tell did you fully complete the the sections Michelle Lott, RAC: in in a way that the FDA might perceive them as technically complete as well, and so go from red to green. Michelle Lott, RAC: You have to have a specific software and operating system configurations you have to have a Pdf editor like a acrobat pro and windows or fox it.

Michelle Lott, RAC: and mandatory that as of 20 October 2023 Sda, it's only accepting 5, 10 k submissions via the e star format Michelle Lott, RAC: and right now pre submissions 5, 13. G's de novos and pmas are still voluntary. Underneath the E star. But pre submissions I anticipate are going to be the next that are going to be required in the Eastar prestar tip late, followed by 5, 5, 13 g's. Michelle Lott, RAC: So the advantages of prestar for the FDA is that it's to enable more efficient and consistent reviews. Again. Your information that you submit, and your prestar template is supposed to get uploaded and integrated to their internal it's called smart review template

Michelle Lott, RAC: and it's supposed to increase the productivity and the evaluation of applications for devices that pro pose the highest potential risk to patients. Michelle Lott, RAC: And then, importantly, it fulfills a Medofa commitment that the FDA made to ensure patients have more timely access to safe and effective devices. Michelle Lott, RAC: And it's supposed to do that by making the the streamline that that initial process and the initial the and the way that the FDA internal process works.

We take. Do the second poll question.

Michelle Lott, RAC: Sure.

So one person asked for a certificate of attendance or completion of the webinar. I thought that was a nice idea. So we're gonna go ahead and make a certificate. If you drop your name and email address into the participant chat I'll make one for you as well, please write your name the way that you would like it to appear. I thought that was kind of a neat idea. So the second question is around your program experience. Have you previously completed? FDA. Pre submission and a like? No, it's pulling it ahead, Michelle, I'll let you keep talking.

Michelle Lott, RAC: So again, the the pre start template aligns with FDA. Internal review templates. And the one nice thing about it is that it integrates the guidance document. Expectations. So it's got Michelle Lott, RAC: dropdowns that include help text. So you once you fill in and you get some sections opened up and you're not. Maybe you're not sure what they mean by that question. You can click the help text. They'll give you an overview of their expectation, and then often, they will point you to a specific guidance document. If you have additional questions about that Michelle Lott, RAC: about, where did that question come from? Or you need additional context.

Michelle Lott, RAC: Okay, it looks like Michelle Lott, RAC: like, like, close to 60 have not done a pre submission before. So that's great. We're getting a lot of background context here. And then we're gonna go into some more specific examples. So hopefully, this will all be helpful. Michelle Lott, RAC: Another helpful thing is that the prestar has error messages that pop up if the responses don't make sense. So maybe you a asked to answered a question earlier on that you didn't have software. Michelle Lott, RAC: But then, later on, you, you talk about wireless technology. And so it says, like, maybe you indicated that your system had wireless technology. But you didn't indicate it has software. So these things are a disconnect to the FDA within this template.

Michelle Lott, RAC: So it kind of really helps Prescreen for the FDA that the submission is complete. Michelle Lott, RAC: Which is why they don't have the refuse to accept process anymore, though, that they do have a technical documentation review. Michelle Lott, RAC: So once you select early on in the template. You have to tell it what topics that you want to ask questions about, and you can notice that they have said, select up to a maximum of 4 topics Michelle Lott, RAC: which I think is interesting, because in that pre submission, guidance document or the Q sub guidance document rather, that discusses pre submissions. They do recommend like a handful, these 3 to 4 questions. Then you pick which areas you want to ask the questions in

Michelle Lott, RAC: I I I guess. Which topics. So all that kind of lines up with the expectations there. Michelle Lott, RAC: So the FDA it auto also automatically generates applicable guidance documents. So once you put in the classification information that you believe is pertinent to your device. Say, in this case we have an infusion pump we wanna ask about? Well, then, it it will open up a new section and it says, Hey, this product code has this product specific guidance document in it Michelle Lott, RAC: that you need to be aware of. That you are. You're also that that you will need to be able to answer questions about from a technological perspective.

Michelle Lott, RAC: So you select your application type. Again, you can request the written feedback or the meeting an initially based off of that first dropdown. Michelle Lott, RAC: and then later on, when you start filling in your questions, it's going to ask you to identify her question, what Michelle Lott, RAC: what topic category from that initial 3 or 4 topics that you selected would be Michelle Lott, RAC: appropriate. So you can see how selecting selecting different information earlier on, you know, is going to affect the the formatting and options that you have available in the rest of the Pre. Start template.

Michelle Lott, RAC: So witnesses of the pre start template signatures are complicated because oftentimes you will have several different people that need to sign, and the person that is compiling the the pre submission may or may not be the official correspondent for the company or the person that needs to make certain declarations. Michelle Lott, RAC: I have had people that just still physically sign a P piece of paper scan it and upload that as their signature which defeats a little bit of the electronic purpose of of the star templates. Michelle Lott, RAC: So also, and this is a big one in practice. File collaboration, is likely has got to occur out of pre start because the pre start template does not track changes.

Michelle Lott, RAC: File sharing of the pre start template is extremely difficult. You have to upload and download, and it takes a long time. And there's a lot of information for a lot of opportunities for information to be lost. Michelle Lott, RAC: And then, if you rely on that iterative editing or editing with multiple people. Across your organization. That using that, this solely the prestar is complex and diff difficult, not only because it doesn't track changes, but in areas where you need to enter, maybe long sections of information like, maybe the device description. Michelle Lott, RAC: the actual box that's available for you to view. That text is only about 3 or 4 lines, and you've got to scroll and scroll and scroll to be able to read the whole section because you're only going to be able to read 3 sentences at a time

Michelle Lott, RAC: for 3 lines. Michelle Lott, RAC: So let's look at the timeframes. Michelle Lott, RAC: So it starts with the FDA's receipt of of the submission Michelle Lott, RAC: they are gonna either do a refuse to accept or a technical review, because, remember, prestar is still optional. So if you do a traditional E copy, they will still do a refuse to accept. But if you do a prestar, it still goes through what's called technical review about. Do they believe that you answered your questions correctly, and that the attachments appear to go with the Michelle Lott, RAC: questions where they expect attachments

Michelle Lott, RAC: between day, 30 and 40. If you have requested a teleconference or in person meeting, they're going to reach out to you to schedule it. Michelle Lott, RAC: Then by day 70, you should have your FDA initial feedback. If you're gonna have a meeting or your rep written feedback is due by day, 70 and do in full. Michelle Lott, RAC: Now, one thing that's important, like FDA does run pretty close to their predicted timelines for Michelle Lott, RAC: for pre-submissions Michelle Lott, RAC: by day. 75. Michelle Lott, RAC: You should have your meeting with the FDA conducted and done Michelle Lott, RAC: at this meeting. You're going to take your notes.

Michelle Lott, RAC: and then by day 90 you are going to provide those notes and the minutes to the FDA for their final edits and approval. Michelle Lott, RAC: and by day 1 20, the FDA will give you your your revisions to the meeting minutes, if needed. If you accept their revisions, there is no further communication unless you guys go back and forth with the edits to the or revisions to meeting minutes. Michelle Lott, RAC: So just notice, especially if it's your first pre submission this whole timeline to getting, you know, FDA concurrence on everything that happened. Michelle Lott, RAC: you know, if you get written feedback, only, you know for certain at day 70 about where they're standing. And you still have opportunities to ask clarifying questions, whereas you know you, it's not till day 1 20 that you know for certain FDA stands, and how to move forward

Michelle Lott, RAC: if you do a meeting. Michelle Lott, RAC: so if you do a meeting. Here is your checklist. Make sure that you prepare a slide deck to guide the conversation in the FDA Michelle Lott, RAC: Decide ahead of time. Who's taking the meeting minutes, and it's important to take really good notes. I always dedicate one person from my team, and usually somebody that's not even involved with that project to take the notes because they can focus and they're not going to be worried about, you know how to respond or who's responding, or the whole dynamics of the meeting. Michelle Lott, RAC: Choose who is the presenter for each slide or each topic you want to cover. And they should. Their content should be limited and they should have practice.

Michelle Lott, RAC: They're both. They're Michelle Lott, RAC: what they want to say and what they anticipate. The FDA asking and how that interaction is is going to go. Michelle Lott, RAC: Make sure that you're ready to listen Michelle Lott, RAC: and compromise and value their time because you're gonna have 60 min on the dot Michelle Lott, RAC: in terms of meeting management. Michelle Lott, RAC: The meeting minutes should be a summary, not a transcript of the meeting. You have to provide these to the FDA within 15 days. Michelle Lott, RAC: There are no recordings allowed either video or audio. That's another reason why you do not need to turn in something that feels like a transcript to FDA

Michelle Lott, RAC: and then you submit the minutes as a minute amendment to the queue. So through the appropriate document Control Center within 15 days document control centers. If you do the E copy they do accept them through the portal. The last time I I did one if you did the prestar. Michelle Lott, RAC: So it's important to remember if you are having a meeting, do not repeat your presub comment. Michelle Lott, RAC: Everybody has read your con your presub ad nauseam at this point, and and you are going to waste your time. If you tried to give any background or context that had already been discussed in your pre submission.

Michelle Lott, RAC: Don't expect FDA to consult on your pre submission. They will not tell you what to do, or necessarily tell you their opinions, that are not directly related to the quest, the topics under discussion. Michelle Lott, RAC: Don't introduce new topics to that point, Michelle Lott, RAC: or questions. As so. This is not the time to ask clarification questions, and it's not the time to broach new subjects. You will have to do all that in a subsequent pre submission. Michelle Lott, RAC: and then don't let the inventor talk too much if you have got. If your inventor Michelle Lott, RAC: insist on being at the meeting, you know again I mentioned something earlier about being in love with your own science, and that can derail a conversation with the FDA. Because, again, these are supposed to be very pointed. Follow up questions and topics specifically related to information that you have already provided, and responses that they've already given.

Is a poll question showing on the screen or not.

Michelle Lott, RAC: No.

No. I messed that one up. Okay.

Michelle Lott, RAC: Do you like to redo it now.

Gonna try. Sorry. Oh, I see.

Michelle Lott, RAC: Charles.

Yeah, it won't launch okay? Well. that's weird.

Michelle Lott, RAC: Just shovel troubleshooting, and then I'll I'll just keep going here.

Yeah. Sorry to interrupt.

Michelle Lott, RAC: No problem. Michelle Lott, RAC: So the FDA never forgets. So don't try to hide or ignore any previous pre submissions with the FDA, and don't try to resubmit old. Well, obviously, old data, because they don't look at data, but maybe old protocols or old ideas or questions, because and the reason this this is important. I have gotten there. We go. There's the next full question.

You can just talk over the poll question. Awesome.

Michelle Lott, RAC: So. I have gotten customers that were new to me, but they had been in business, you know, one of those famous, you know, 1010, 15 year old startup situations. Michelle Lott, RAC: And they had. I found out during the the data and document dump that they gave me, that they had had not one, not 2, but 3 pre submissions with the FDA over those course of years before they hired me. Michelle Lott, RAC: They did not mention this when they hired me or in our initial kickoff meetings. And then when I found these pre submissions, I'm like, what's going on here, guys, and they're like, well, we didn't think that they were relevant anymore.

Michelle Lott, RAC: Because, we have made changes to the product, to the technology, to the intended juice. So we don't feel like, we need to address those anymore. Michelle Lott, RAC: Okay. Michelle Lott, RAC: like, there are a lot of people who are new to this process Michelle Lott, RAC: newer early on in their experiences. Michelle Lott, RAC: So Michelle Lott, RAC: so so yeah, so we did the best we could. Kind of, you know, picking this up midstream and trying to move it forward, based off of. Michelle Lott, RAC: you know the constraints given by the client. Michelle Lott, RAC: and we tried to address those things to the best we could at this point. But the FDA

Michelle Lott, RAC: knew about every one of those 3 pre submissions along the way, and blew the dust off of them, pull them back out, and asked them about every question that the client told me, was now irrelevant, because they expected that the client had addressed their previous feedback, and if they feel like it was irrelevant why, it was irrelevant. They also felt like, well. Michelle Lott, RAC: some of the context of our concerns are still relevant. Even if you've changed your technology, we still want that question answered about your product now. So, Ju, just be aware of that. If you get feedback that you you didn't like, and you go and you make changes.

Michelle Lott, RAC: you're that that that's context, for the FDA is not going to go away. Michelle Lott, RAC: So, moving on to 5, 13 G's. Or requests for information. Michelle Lott, RAC: Now, this is like a pleasant to the pre submission. Michelle Lott, RAC: 5, 13. G's functionality was added just recently to the prestar template and in March of this year it is still voluntary. Michelle Lott, RAC: In this case you will select request for feedback or information. So the Rfi. And then you can request the type of Michelle Lott, RAC: submission or or yeah, the type of submission that you you're looking for.

Michelle Lott, RAC: So when to do Rfi or a 5 13, G, well, you would typically do it when it's difficult to find an exact predicate. And you don't feel like you have a good argument for for a predicate device. But or you don't feel feel like you clearly fit in with an existing product code or FDA regulation. Michelle Lott, RAC: So in that case it might be Michelle Lott, RAC: appropriate to do this request for information, because that's the pathway where FDA does more specific designation requests. And so there are 2 mechanisms depending on what you're looking for option. One is kind of quick and informal. You send an email with some specific but abbreviated information to device determination@fdahhs.gov.

Michelle Lott, RAC: Option 2 is to submit a formal 5, 13. G. Request that that is a much more specified content, different level and detail of the content. This. This does have a fee. It is a CC. 2, 50 for normal businesses and 32 64 for small businesses for this fiscal year. Michelle Lott, RAC: Now, option one. While it might sound intriguing, you know. Just be prepared, that the information you get out of this may or may not be of any type of level of detail or decision to be helpful, and at the end of it they may just say, Hey, submit a 5, 13 g. If you really want to know.

Michelle Lott, RAC: So types of questions that could be appropriate. To ask Michelle Lott, RAC: is is the product subject to FDA regulations at all? You know in this case, it might be. Michelle Lott, RAC: is it a device or not? A device? Is it general wellness, you know, looking for so Michelle Lott, RAC: some kind of formal determination around that. What is the appropriate regulatory pathway is the product exempt for 5, 10 k. You would ask this question in the event like, Say, maybe you had something that the product code that exists, for it is Class 1, 5, 10, Kent. Michelle Lott, RAC: But maybe you have different technological features. Or you added software, or something of that nature or an indication, and that might have taken you out of what FDA intended for the exemptions around that product

Michelle Lott, RAC: is the product subject to FDA regulations. Michelle Lott, RAC: At all. Michelle Lott, RAC: So what is the program? I need to edit all that. Michelle Lott, RAC: So Michelle Lott, RAC: an example of a question that we have asked in 5 13 g. Is, does the FDA concur. That marketing the device only under this specific product code is appropriate with a proposed revised intended use statement Michelle Lott, RAC: along with other revisions indicated above Michelle Lott, RAC: without further submission to the FDA. The FDA does not concur. Could the agency please explain? So Michelle Lott, RAC: here we like make a little. We pose the questions with some context and a little bit more of a statement.

Michelle Lott, RAC: And then do you concur Michelle Lott, RAC: if the FDA does not concur? What type of 15 K in which product code would be needed to submit to meet the requirements. Michelle Lott, RAC: 5, 13 G's are also perfect for combination products. Where you might have a drug and device device and biologic. Or you know, the trifecta drug device and a biologic. And in this case Michelle Lott, RAC: this is gonna end up, you know, kind of through the Ocp for them to determine who's gonna be the lead reviewer? For these types of products the lead reviewer is gonna depend on the primary mode of action, which is the primary way that the product accomplishes is therapeutic action.

Michelle Lott, RAC: So it's possible for a product to include a drug. But the primary mode of action, for the product Michelle Lott, RAC: is a device as opposed to the therapeutic action of the drug. So that's when 5 13 G's could also be appropriate. Michelle Lott, RAC: So in their timeline, the FDA's Ca clock days or 60 calendar days and then once the FDA makes a determination, if they determine that that there is a suitable regulation number and a product code, and you can bring your product to market underneath this particular pathway. Your device is then going to be eligible to serve as a predicate once it gets through whatever the appropriate submission pathway is.

Michelle Lott, RAC: benefits of the 5 13 g. Is that the decision is binding with the FDA, and it can be leveraged in future submissions. Should the subsequent review pathway be in question? Michelle Lott, RAC: So, however, if you receive feedback that you you didn't want that could present a challenge for your future pathway. Michelle Lott, RAC: Here are some some references around the 5 13 g. For your future. Michelle Lott, RAC: Now, here's something interesting about the 5 13 g. Versus the pre-submission program. Michelle Lott, RAC: So we do have fees around 5 13 G's, we're around pre submissions. We do not.

Michelle Lott, RAC: however, around presubmissions, even though they are free. Michelle Lott, RAC: The they. They have a metric associated with them Michelle Lott, RAC: to where the FDA, because of the Medusa commitments gets measured on. How often do they meet their timelines for their the pre submission commitments? There are no metrics for 5 13 G's, even though you're paying them good money in which they could re they have funding to resource themselves for these reviews. Michelle Lott, RAC: So because there's no internal metric, our experience with 5 13 G's is that these are running 10 to 12 months for a review time, and they're supposed to be 60 days.

Michelle Lott, RAC: So that just tells you the good old fashion or the classic statement, what what gets measured gets managed Michelle Lott, RAC: and what gets measured gets done. Michelle Lott, RAC: So Michelle Lott, RAC: just keep that in mind if you're doing a 5, 13 g.

Launched a last poll question. appreciate everyone's participation, as I mentioned earlier somebody had the brilliant idea of handing out certificates of attendance. And so if you drop your name and email address into the chat, then I'll make sure that you got one thought that was cool. yeah. Show. Let's just let this run a little bit longer, and then we'll get back to your regularly scheduled program. Michelle. It looks like there are 18 questions in the QA. Oh, wait. and a lot of people have requested a certificate. So

for us going to be busy. Okay.

Michelle Lott, RAC: Well, I'll I'll kind of pick up the pace a little bit here, so I can take the the questions. Michelle Lott, RAC: So let's let's see here. Michelle Lott, RAC: how confident are you? Michelle Lott, RAC: Okay? Most people are somewhat confident. We've got a handful that are very confident, and then a a few that are are not confident. Hopefully, we'll be building those confidence levels by the time we finish here. Michelle Lott, RAC: So the breakthrough devices requests or Bd versus safer technologies program or step. Michelle Lott, RAC: Let's compare and contrast those. Michelle Lott, RAC: So first, we have to UN understand the FDA's definition of novel technology is, it has the potential to lead to clinically a clinical improvement and the diagnosis cure, treatment, prevention, mitigation of a life threatening or irreversibly delicate, debilitating disease or condition.

Michelle Lott, RAC: This is how they describe novel technology, which is the foundation of the breakthrough device request. Michelle Lott, RAC: The breakthrough device is designed to streamline the market clearance and approval process for novel medical devices as per that definition we just talked about. Michelle Lott, RAC: It is a two-step process. Michelle Lott, RAC: The process got started in 2,015 and the program is gaining popularity and maturing over the years, and you can see that when it initially, this is the number of breakthrough devices granted when it initially got kicked off, was a very slow start, and then covid it kind of shot up, and then it's kind of mellowing back out post, Covid.

Michelle Lott, RAC: as far as who's getting breakthrough designations. You know, it's primarily cardiovascular, neurologic, and orthopedic review divisions. Michelle Lott, RAC: So is your device eligible. The first criteria you have to demonstrate is that the device provides for more effective treatment of that life, threatening and irreversibly debilitating condition. Michelle Lott, RAC: There are 4 criteria, and you have to prove at least one. But you need to make a case for as many as you possibly can in your argument. Michelle Lott, RAC: That that's my recommendation, at least. But one has to be really, really solid.

Michelle Lott, RAC: So they are. It represents that breakthrough technology for the definition we just discussed. There are no approved or cleared alternatives. Michelle Lott, RAC: It offers significant advantages over existing approved or cleared alternatives Michelle Lott, RAC: or the device. Availability is in the best interest of patients. Michelle Lott, RAC: and you have to meet both criteria. Michelle Lott, RAC: So what happens if your breakthrough is denied. Well, you can go about your merry way and do the standard filing of whatever you were gonna do before, be it novo or pma, or possibly, if you feel like there could be an argument for the safer technologies program, you can go that method that way and then proceed with your submission.

Michelle Lott, RAC: So the safer technologies program is a bit like a fraternal twin to the breakthrough device. The arguments are are very similar with a different nuance. So this is fo focused on the device. Offers significant safety benefits for non life, threatening or re reasonably reversible conditions that are less serious than those that are intended for the breakthrough devices program. Michelle Lott, RAC: We look at the data. There's not as much data around the step authorizations. It is a newer program than the breakthrough device. So the information we have is from the Crih annual report, as of October 2023. There are total of 35 devices in the step, program since it's inception. And of those 35 15 were enrolled in 2023,

Michelle Lott, RAC: and only 2 of the 35 have made it through the step process. And we're authorized for marketing. So that just shows you, you know, companies think that the step and the breakthrough are going to be maybe a faster program for them. Michelle Lott, RAC: Well, if that was true, you would think that we would have more of the those 20 devices that were in the program prior than prior to 2023 should have been made it out of that queue. More than 2 should have made it out of the queue by the end of the fiscal year Michelle Lott, RAC: is your device eligible for a step. Michelle Lott, RAC: So the first criteria is you are not eligible through the breakthrough devices pro program. Be that because you were denied for it, or you just know that you don't meet that life threatening, debilitating definition, or the definition of novel.

Michelle Lott, RAC: The second criteria is is similar, but slightly different in that it focuses on a reduction in the occurrence of like serious adverse events, device failures, use errors, or an improvement in the safety of an alternative device or intervention which could include even a drug intervention. Michelle Lott, RAC: The process for application for both of them is the say the same. You start with that queue submission. Both of them are free. You go through your application process. You address your 2 criteria Michelle Lott, RAC: and then the within 30 days from the receipt of the request, FDA supposed to ask you for additional information that they may need to factor into their decision. Then within 60 days

Michelle Lott, RAC: they are supposed to make a decision on. If your pro, your device meets the criteria by the program. Michelle Lott, RAC: if it's granted, you move through your submission process, and you go on but with the special tools that you get through one of these programs, if it's denied you just Michelle Lott, RAC: you can apply for step, or you can. Just move, move through your submission. Strategy like you would have without having this program Michelle Lott, RAC: the special program fee features that you can request in the scope of your Bdd or Step application include a sprint discussion, a data development plan. And then there are other handful of very specific things that you can request. But the clinical protocol agreement is only an option if you have a Bd.

Michelle Lott, RAC: so the advantages just in general of the program is that this includes regular updates from the FDA during your submission and your submission development more informal and timely interactions with the FDA. And then so this is supposed to lead to the potential for the shorter time to market than your standard review process. Michelle Lott, RAC: So those strategic advantages of those benefits are that. The FDA intends that this. These programs are gonna provide a high level of engagement between FDA and innovators where there are no good alternatives to patients, and at the end of the Bd process, when you finally get granted, or clearance or approval, whatever pathway you ended up on FDA like puts out an actual kind of press release of FDA worked with this

Michelle Lott, RAC: company to bring this important technology to market. So it could be really good for marketing purposes. Michelle Lott, RAC: So this is just for your reference later, to compare the 2 technologies and the benefits. Michelle Lott, RAC: So here's here's some of my lessons learned. Michelle Lott, RAC: When is it appropriate to have multiple presubs. Michelle Lott, RAC: Well, when you have multiple really in depth, com Michelle Lott, RAC: topics to cover like clinical bench and regulatory strategy. So, combining these might compromise the depth or quality of review that you are seeking. So I would typically break this up where maybe I submit like a test plan or my test selection confirmation, and why I selected those. Get Fba to concur with the test plan.

Michelle Lott, RAC: and then, at a later date, submit the test protocols and say, Hey, remember, we've already got to buy in with the test plan itself. Do you agree that these test methodologies and acceptance criteria are going to be appropriate to meet your needs, and then I would do clinical questions in a totally separate Michelle Lott, RAC: so I would typically not put clinical with any other type of question, because it requires such specific feedback and the FDA from the F from the FDA reviewers and specific group. That I would kind of keep that when segregated from the other types of questions I'm asking.

Michelle Lott, RAC: This is really important to know there is an FDA guidance document on queue subs, and in an appendix to talks about example, presub questions. And it it tells you how to specifically like these are concepts that are going to lead to the most valuable feedback from the agency. So it gives you kind of a structure of how this structure your presub. Michelle Lott, RAC: It also has very specific questions, and by reading the question of in a huge number of topics that are just ideas of questions that you could ask that would be lead to a profitable discussion with the FDA. Michelle Lott, RAC: And so you can kind of read between the lines about how the question structured, what type of attachments need to be

Michelle Lott, RAC: it included for appropriate discussion with the FDA. Michelle Lott, RAC: So just again, more examples of of questions here. Michelle Lott, RAC: This guidance document is being revised. It is in draft as of March of this year. One of the more interesting new sections in it is that there's a clarification on Michelle Lott, RAC: informal interactions that could occur outside the queue submission program. And some of these are examples are fascinating. They even have. Questions. I don't know why you would ask this question. That is their example in there of things that you could ask the FDA in just an email or a one off types

Michelle Lott, RAC: type of of Michelle Lott, RAC: interaction. And some of this is all new content in this draft. Michelle Lott, RAC: So it also talks about written feedback versus clarification meetings, and it specifies, even though FDA is kind of doing this in practice, that a clarification email or clarification call are separate than your formal written feedback. Michelle Lott, RAC: But and it has several examples of those. But but the problem is, if you don't already have a lead reviewer, and you want to ask one of these informal questions, it's not clear who to Michelle Lott, RAC: who? Who? To send that question to? And again, there are no metrics for response time here, so not only do we not know who to send it to. But when to expect the response.

Michelle Lott, RAC: here's another recommended of mine recommendation of mine. Use the FDA originated verbiage. So if you can possibly quote something out of the guidance document to support your case. Michelle Lott, RAC: Be that a queue, submission, guidance, document, a product, specific guidance, document, or a feature specific guidance, or a standard like for stability packaging, so on, so forth. Do that. The FDA specifically told me in a review, we really need you to use our our own word. So we know how you meet our requirements. Michelle Lott, RAC: Here's an example where? And this is a difference where we had written feedback. And then we had. We were able to have a subsequent clarification meeting where the the reviewers actually showed up. Not just an email

Michelle Lott, RAC: in the re written feedback. We got kind of a odd response that said silicone was carcinogenic. And all these things and that we recommend that you just said, justify this material with bio compatibility testing. Michelle Lott, RAC: And so it's like, Okay, we already propose bio compatibility testing, what else do you want? And it turned out that the reviewer who gave gave this question was anesthesiologist practicing anesthesiologist. Michelle Lott, RAC: not the bio compatibility or toxicologist expert on the team, and in the meeting the actual FDA, reviewer was like, Yeah, we understand. But yes, the way testing you proposed is appropriate to mitigate that concern. And the FDA said, We understand, and we don't have any further clinical concerns specifically about that statement from that reviewer, that clinical reviewer.

Michelle Lott, RAC: This is another interesting one where I ran up against, you know the F 2 2 different things about this one. Michelle Lott, RAC: First, the FDA said. Well, we disagree with your choice of the pro kit, because internally we have information that's not publicly available Michelle Lott, RAC: to so that you would not know that we don't think that that's an appropriate predicate. Michelle Lott, RAC: Well, how what are we supposed to do for a substantial equivalence argument. When we're we're bound to the information that's that's publicly available. Michelle Lott, RAC: The other feedback that we got on this particular one is that the feedback came from a particular group of clinical doctors that only practiced in women's anatomy.

Michelle Lott, RAC: And this product was specific to men's anatomy, and the clinical experts we had on our side. We're all for men's anatomy, and they're like, well, the FDA people said, well, we learned about men's anatomy and school doesn't matter that we hadn't practiced in it. So just be aware that there could be these, these challenges of your review team. If you get some Michelle Lott, RAC: squirrely feedback Michelle Lott, RAC: multi offices, office interactions can be challenging especially if you've you know, Fba is going through a lot right now between, you know, what are they gonna do with the Ivd Division versus the device Division, and some we've seen them kind of duke it out within a pre submission where we were like kind of flies on the wall watching it all go down.

Michelle Lott, RAC: This is important. Michelle Lott, RAC: I have gotten a lot of feedback lately. When I've done presubmissions that we really think this would have been more appropriate to ask Michelle Lott, RAC: in a 5, 13 g. Instead of a pre submission? And they said this, even when I, verbatim took the question out of the the suggested questions for appropriate interactions, or feedback from the agency. Michelle Lott, RAC: So if you get something like this where it it specifically contradicts a Michelle Lott, RAC: a something that is in the FDA guidance document. Be aware there are a lot of new reviewers. That don't really know these guidance documents as well as somebody in industry that does as many of these a year as we do and you might need to get their supervisor involved, or the Ombudsman involved and escalate this if it's not following FDA policy and procedure.

Michelle Lott, RAC: So your secrets to success. Michelle Lott, RAC: Plan out not just your submission strategy, but your pre-submission strategy. How do you want to group your questions? How many of them do you want to have. How does it affect your timelines? Michelle Lott, RAC: Don't rely on pre-submissions alone as the only tool to get your Michelle Lott, RAC: your the feedback that you need with a new pathways that have opened up, and don't expect to get the feedback that you expected, especially all under one pathway or avenue. Michelle Lott, RAC: Be clear on who is your contact person, especially if you're using a consultant because I've seen the FDA copy one group of people and not the other group of people. Then the first group of people didn't board it to the second group of people. And it it led to some complicated interactions

Michelle Lott, RAC: and then don't overload your pre-submission with too many topics or questions. Michelle Lott, RAC: Here are the helpful links for your reference for everything we talked about today. Michelle Lott, RAC: And then you can visit my website. If you want some of my tools and tips and tricks and resources that are available Michelle Lott, RAC: shall Michelle Lott, RAC: now we can.

That's great. Thank you so much, Michelle. We have 26 questions. We got to none of them. And we've run a little bit over. So I know people have other things to do. But I wanna thank you again. And I wanna thank everyone who attended, as I mentioned in the chat. we'll try to get back to the questions we will create those certificates this first time I've ever done this. So please be patient with me. And yeah, is that, are we done? We're done.

Michelle Lott, RAC: Yeah. So I will answer all your questions and follow up via email, so I do apologize. It was a action packed hour, and I just want to be respectful of everybody's time. Going forward. But I will add, answer your questions.

Thank you so much, Michelle. Take care everyone have a great day.

Michelle Lott, RAC: Thank you.