Examining FDA’s Refusal to Accept (RTA) Policy and Guidance

After three “Refusals To Accept” Guidance Documents from the FDA, why are there still so many submission issues? Who’s to blame? Learn from other people’s mistakes. 

In this episode of the Global Medical Device Podcast, Jon Speer and Etienne Nichols talk to Mike Drues of Vascular Sciences about the FDA’s Refusal to Accept (RTA) policy and guidance.

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Some highlights of this episode include:

• After the FDA receives a 510(k), De Novo, Pre-Market Approval (PMA), or any other submission, the 2-step process is to conduct an administrative and then a substantive/scientific review.

• If a submission is rejected on the administrative review, it is completely the company’s fault, not the FDA’s. If the substantive review is rejected, however, there’s room for negotiation with the FDA.

• Most of the FDA’s acceptance checklists have been available for more than a decade, but companies submissions are still commonly rejected on administrative review.

• Electronic tools and software platforms, such as eSTAR, are supposed to help and facilitate the preparation process of submissions. The problem is, this is contingent on what information is entered.

• Potential hangups for companies using tools like eSTAR for the submission process are that they do not evaluate the quality of the content entered. That said, they do require a Table of Contents and the use of most current forms.

• Never leave any sections of your submission blank. At the very least, enter Not Applicable (N/A) and explain why - or risk the FDA rejecting the submission. It’s a company’s responsibility to make sure the FDA understands their device.

• The draft guidance documents have been published for a reason - don’t ignore them and risk a rejection for what could easily have been avoided.

Links:

How To Avoid Having Your FDA Submission Rejected (And What To Do If It Is)

Guidance: Refuse to Accept (RTA) Policy for 510(k)s

Guidance: Acceptance Review for De Novo Classification Requests

Guidance: Acceptance and Filing Reviews for Premarket Approval Applications (PMAs)

Acceptance Checklists for 510(k)s

Medical Device User Fee Amendments (MDUFA)

FDA - Voluntary eSTAR Program

What is the eSTAR Pilot Program and How Will it Improve FDA's 510(k) Review Process?

Mike Drues on LinkedIn

Greenlight Guru YouTube Channel

MedTech True Quality Stories Podcast

Greenlight Guru Academy

Greenlight Guru Community

Greenlight Guru

Memorable quotes from this episode:

“If a submission gets rejected on an administrative review, that is 100% the company’s fault, it is not FDA’s fault.” Mike Drues

“Approximately 60% of 510(k)s are rejected on RTA part of the administrative review.” Mike Drues

“An eTool should help facilitate the process. However, caveat—it still is contingent on humans entering information.” Jon Speer

“I would like the FDA to be just as careful with the claims that they put on their own website as they are when they are evaluating claims on a device coming in for a submission.” Mike Drues

“One of the most common reasons why submissions are rejected is because a particular section is left out. Put yourself in the shoes of the reviewer. They have no idea why you are leaving out that section.” Mike Drues

Transcript

Announcer: Welcome to the Global Medical Device Podcast, where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge, direct from some of the world's leading medical device experts and companies.

Etienne Nichols: Hey everyone. Welcome back to the Global Medical Device Podcast. Today with me is Jon Spear, the founder of Greenlight Guru as well as Mike Drues, a familiar face on the podcast. Today we're going to be talking about a refusal to accept and specifically, and we may dance around this question a little bit, but after three refusal to accepts, the different guidances from the FDAs. We still have submission issues. We still have problems with submissions due to the RTA. So maybe to kick us off, Mike, could you summarize the FDA's review process? What happens after the FDA receives a submission?

Mike Drues: Yeah. Great question. And as always, thanks for the opportunity to have this discussion with you and your audience. So basically when FDA receives a submission, whether it's a 510(k), a Denovo, a PMA, whatever it is, it's basically a two step review process. The first step is the administrator review and then that's followed by what FDA calls the substantive or what I call the scientific review. So in a nutshell what happens in those two portions of the review process, starting out with the administrator review, basically a bean counter at FDA is sitting down with your submission on one side of their desk and their version of the RTA checklist on the other side of their desk. And they're going through, section by section, part by part to make sure that you have all the different sections that they're present, you have the signatures present, you have the pages numbered, and so on and so on. So all of that occurs at the administrative review. And then if you pass administrative review, the next part is the substantive or what I call the scientific review. And in my opinion, that's much, much more important than the administrative review because that's when FDA will actually evaluate the substance of your submission. In other words, they will read your device description, they will look at your statistical analysis, your benchtop testing, your clinical testing if you've done that, and so on and so on. The RTA, the refuse to accept checklist, which is the topic of today's discussion, that focus is primarily on the administrative review. In other words, do you have all the sections present? Do you have the signatures in place? Do you have the pages numbered? And so on and so on. And if you don't get through the administrative review, FDA will not go on to review the substance, the scientific portion of your submission. So the RTA and the administrative review is important, but only to the point that it gets you to the most important part and that is the substantive review. And then the last thing that I'll mention real quick and then Jon, please feel free to add whatever I may have forgotten. If a submission gets rejected on administrative review, that is 100% the company's fault. It is not FDA's fault. It is 100% the company's fault. If the submission has a problem on substantive review, in other words, FDA doesn't agree with your statistical analysis or thinks you should have done different testing or something. Okay. That's fair game. That's FDA doing their job and that's when you start the negotiation, what I call the poker game. But if your submission has problems on administrative review, that is 100% your fault. Jon, would you agree or am I being overly harsher here?

Jon Speer: No. I don't think you're being overly harsh because it does amaze me. Sometimes I hear a comment from somebody that their submission got kicked back at the RTA or the refuse to accept stage of the review process and they're surprise. And I'm like," What was the question? What was missing? What were they asking for that you didn't provide?" And like 100% of the time, it's something that was known. It's something that a section of the 510( k) that was missing or folks note, there's not a secret here. The FDA publishes the refuse to accept checklist. The very checklist. I believe it's the exact very same checklist that they're going to use when they get your submission. That's a publicly available template and there's no excuse for you not to go through that template. In fact, what I advise folks who are preparing those submissions is to make a copy of that RTA checklist and add in a reference, a page number, a section, whatever the case may be of where that specific item on that checklist is addressed. And if you as the submitter have not done that or cannot point to where that's specifically called out in your submit, then yeah, that's 100% in your control.

Etienne Nichols: This is funny because when I was in college, this is a dumb example, but bear with me for a minute. I was actually a TA, the teacher's aid, unbeknownst to my other classmates. I was supposed to be an anonymous TA. And so I was grading homework and it was an easy throw. I would flip through that, anyone who forgot their name I'd throw that homework out because it was an automatic zero. That was easy and there was always like half a dozen people who did that. And that's what makes me think. I didn't realize with the RTA, you have this broken down from you have the substantive, which I like your word scientific better I think. Make it a little bit more sense to me, but versus the simply administrative section. That makes a lot of sense.

Jon Speer: I mean, it's a provision. And then this is as far as things FDA are related anyway. I mean, it's older than I realized after seeing some of the notes, but it is still a newer practice, I would say in the agency, at least with respect to the 510(k), but I like this step because to me, when I was in the practice of preparing 510( k) submissions, it gave me a little bit of clarity as to," Okay. This is a fairly black and white list of things that above and beyond the table of contents that give me a little bit guidance as the preparer of that submission." But it also gave me a point in time, because when you submit a 510(k), at least back in the olden days, back when I didn't have white and gray hair, sometimes you'd submit a 510( k) and there was no exchange. There was no dialogue and that sort of thing. There was kind of silence for sometimes weeks upon weeks upon weeks. So at least with the RTA step, you get confirmation that says," Yeah. Everything we expected in this submission, we've got it. We've confirmed that. And now we're moving to that scientific review stage of the review process." So yeah. I like this step.

Mike Drues: And Etienne and I would just point out that metaphor that you just shared about your TA experience. It's a very good metaphor because there are specific line items in the various RTA checklists. Remember, there's not just one, there's several of them, with that level of granularity. In other words specifically, did you number your pages? Do you have a table of contents? Now I would like to think that for people that have graduated from elementary school, we wouldn't need that level of micromanagement. But as many of our audience know, I also work as a reviewer for the FDA, as a consultant for the FDA. So I see these issues from both sides. Some of the submissions that I see come into the agency, some of them are terrific. Some of them are literally painful to read and if they don't have page numbers or if they don't have the person's name on the paper, what other kinds of information do they not have that is much more important? So that's a good point.

Etienne Nichols: Yeah. It really reduces the confidence and the quality of the content itself. I can totally see where you're coming from. So there's multiple guidances out there from the FDA. How should those be used, the different guidances that have been published?

Mike Drues: Yeah. Great question. So there are three guidances that I would point out to the audience to be aware of and we can put references on the links of the podcast.

Etienne Nichols: Sure.

Mike Drues: The first is the refuse to accept or RTA policy for 510(k)s. The second is similar, an acceptance review for Denovo's, and the third is acceptance and filing reviews for premarket approval applications or PMAs. So between those three, the 510(k) and the PMA and the Denovo, we're covering the vast majority of the medical device universe. So there's plenty of guidance out there. There are checklists out there, as Jon alluded to earlier, that we could use. If we parse those a little bit more, if we look for example within the 510(k) RTA guidance, there are three checklists within that guidance. One for traditional 510(k)s, one for special 510(k)s, and one for abbreviated 510( k) s. Interestingly enough, FDA has not caught up. Jon, you may remember we've done some other podcasts on the safety and performance based 510(k), sort of the new version. I'm hesitant to use this word, but the resurrected version of the abbreviated 510( k), which we now call the safety and performance based 510(k). That's not in the RTA guidance yet. I personally don't think that it's necessary to have an RTA for an SP 510(k), but that's a topic of a different discussion. I would point out though that looking at the three RTA guidances, you guys might find this interesting. The traditional 510(k) RTA checklist is 34 pages long. Just the checklist alone is 34 pages long. Special 510(k) RTA checklist is 11 pages. Okay. That makes sense. But the abbreviated 510(k) checklist is 35 pages long. The abbreviated RTA checklist is actually longer than the traditional 510(k) RTA checklist. So abbreviated doesn't necessarily mean what a lot of people might think that it means. It's kind of like, to quote a famous politician," It depends on what your definition of is is." Anyway. Just a little bit of regulatory trivia for those in our audience. And ironically, the PMA checklist, just to complete the comparison here. So the 510( k) checklists are between 11 and 35 pages long, depending on which version of the 510( k) you're talking about. The Denovo checklist is about 18 pages long. So a Denovo checklist is shorter than the traditional 510( k) checklist and yet the Denovo, more complicated usually than a traditional 510( k), but here's the irony. The PMA checklist is 17 pages long. The PMA checklist is roughly half the length of a traditional 510(k) checklist. So I'm only pointing that out just simply because of when you look at the numbers, it's kind of interesting or ironic, but that doesn't say anything about the substance. These checklists have all been around for a very long time. As a matter of fact, with the exception of the Denovo, the 510( k) and the PMA checklist have been around for more than a decade. And yet, as we'll talk about when we get to the statistics, there's still a lot of companies that get submissions rejected on administrative review. As a matter of fact, here's one statistic for you and then Jon, I would love to hear your thoughts. Approximately 60% of 510(k)s are rejected on RTA part of the administrative review. Approximately 60%. And as I said before, when a submission has problems or is rejected on administrative review, that's 100% the company's fault. Jon, your thoughts.

Jon Speer: Well, I'm actually excited about what you just said in a weird, twisted sort of way, but let me explain. I remember Mike, you and I, when we talked about 510( k) s getting rejected quite a few years ago, I think that number was north of 75% we're getting rejected. So industry relations just made an improvement, but it's still over 60%. That's still crazy, for something that is 100% in your control, right? We're not talking you getting kick back during the scientific review. We're talking about at the administrative. That's still crazy that six out of 10 are being rejected because they're inadequate.

Mike Drues: Jon, would you like to know the current statistics because I actually looked them up for the purposes of today's call. So according to the most currently available MDUFA statistics, this is through February of this year. So roughly about a month and a half prior to our recording of today's. 65% of 510( k) s are rejected. They result in additional information requests.

Jon Speer: Yeah.

Mike Drues: 65%. Now, if you look at over the last five years, that number has been pretty constant. It's fluctuated between 64 and 66%. So two- thirds of 510(k)s are continuing to be rejected over the last five years.

Jon Speer: Wow.

Mike Drues: The average review time for 510(k)s from receipt by the FDA to MDUFA decision is 302 days. So that's on the 510( k) side. On the PMA side of the universe, 83% of PMAs are being rejected first time out of the box and resulting in what we call major deficiency letters. And if you look at over the last five years, there's been more fluctuation there. Roughly between 63% and 91% of PMAs are being rejected over the five years. The total review time for those submissions is about... oh, I'm sorry. I think I gave the wrong number for the 510(k). The total review time for the 510(k) is about 108 days. The total review time for the PMA, about 302 days.

Jon Speer: Yeah. That makes sense.

Mike Drues: So bottom line, these numbers, although they do fluctuate a little bit, although the 510( k) really doesn't fluctuate much at all in years. They're still not very good.

Etienne Nichols: Just trying to make-

Jon Speer: No they're not.

Etienne Nichols: Make sure I understand. So you're saying, has it gone down, the rejection rate, or just a little?

Mike Drues: So just to be clear, the statistics that I just shared with you, and again, these are coming right out of the MDUFA statistics from the FDA. FDA is required to track these by Congress. For the 510( k) universe over the last five years, it's only fluctuated between 64 and 66%. So that's pretty-

Jon Speer: Etienne, number I mentioned, so Mike and I have been conversating about, well a lot of things regulatory for quite a few years and I think the 75% number, it could be an incorrect memory, but that was-

Mike Drues: No it's not an incorrect memory, Jon. That's the number in the past that I would just-

Jon Speer: Yeah okay. Okay. Yeah.

Mike Drues: Kind of carry around in mind. So right now we've dropped about 10 percentage points, but still, we're still talking-

Jon Speer: So high.

Mike Drues: Two- thirds of 510(k)s, and even greater for PMAs, in spite of the fact that these RTA guidances have been around for more than a decade. So now to be fair, one second, to be sure. It doesn't necessarily mean that all of these rejections are coming on the administrative review.

Etienne Nichols: Right.

Mike Drues: Roughly the MDUFA statistics do not include that directly, but if you do some indirect comparison, some back of the envelope kind of calculation, approximately 60% of newly filed 510(k)s are refused under the RTA under administrative review.

Jon Speer: Yeah.

Etienne Nichols: And that's still, I guess sometimes I am optimistic, silver lining kind of guy. So from when we talked about this maybe more than five years ago to now, there's been some improvement, but to your point, it's still two- thirds. Two- thirds for-

Mike Drues: And in the PMA universe, even more.

Etienne Nichols: To your point, the guidance has been out for about 10 years. Pre- submission should be more invoked these days as well. So if we're utilizing the RTA guidance documents, if we're utilizing opportunities like pre- submissions, it still kind of is sad that two- thirds are getting kicked back. It's inexcusable really.

Mike Drues: Well look, I don't want to use our time to bash on the FDA. There's too much of that. I don't want to use our time to bash on our industry and ourselves. I think maybe what would help the audience here is to talk about some specific examples of what can lead to this and how can we avoid it?

Etienne Nichols: And there's two things I wanted to ask. So let's focus on the dropdown and I know, for every silver lining there's a dark cloud, but I'm with Jon. I prefer to focus on the silver lining, but there are eTools out there now. Is that helping or is that advantageous to use those or the pros and cons? Is that helping as opposed to the RTA themselves? Thoughts there and then I would like to get in some specific examples.

Mike Drues: Sure. Jon, do you want to take a first stab at that one?

Jon Speer: Well, I have a little bit of experience with a couple of software platforms that are out there that are supposed to help with the preparation process. I wish I could sit here and tell you I have statistics on their success rate and how it compares to the MDUFA numbers. I don't have that. I'd like to believe that any tool should help facilitate the process. However, caveat, it still is contingent on humans entering information. Now some of these eTools, they do have the added benefit, like for example, the intended use statement. I think this is a good example. It probably finds its way in your 510( k) submission. I haven't counted recently, but at least a half dozen times in multiple different. And you would think this is a no brainer, can never happen thing that I'm about to say, but you would be surprised how often that statement is different within a single submission. This section it might say this and this other section might have other words. That's a common bonehead mistake that people make. So the eTools try to help facilitate it and mitigate that issue. So I got to believe those are working and I know FDA has, oh, what's the program called? The eSTAR and I think that's it, but I don't know how that's helping or hurting, but I got to believe if it's done properly, it should assist a little bit, but I think that's only going to reduce the rejections by a small fraction of the percentage.

Mike Drues: Well Jon, that example that you just shared on the high level labeling, specifically the indications for use, there is no better way to guarantee that your submission is going to get thrown right back in your face than when you repeat the high level labeling, but you do not repeat it exactly the same way each time.

Jon Speer: Yep. Right?

Mike Drues: As a matter of fact, just one of my customers yesterday admitted to me that she had submissions rejected in the past for exact same reason.

Jon Speer: Yeah.

Mike Drues: So electronic tools, whether you're talking about the eSTAR version, which is the FDA's version or some of the commercial versions, they will help you do that. They will help you minimize those kinds of problems, but just taking a step back, so coming back to the original question, we do now have eTools available to help us with the submission process. On the FDA side, there's the voluntary, what's called the eSTaR program. Basically this is an interactive PDF file. You can get it right off of their website. We can put a link on the podcast page-

Etienne Nichols: Sure.

Mike Drues: For our audience to help make sure that you have all of the sections in place and the information and so on. According to FDA's website, and this is a direct quote," It's intended to enhance the incoming quality of submissions for a wide variety of medical devices by helping to ensure submitters provide quality comprehensive data for the CDRH's premarket review." That's right from FDA's website and I could not disagree with it more. Disagree with it more. As a matter of fact, I would, with all due respect to my many FDA friends, I would like FDA to be just as careful with the claims that they put on their own website as they are when they're evaluating claims on a device coming in for a submission. What do I mean by that? All of these tools, including eSTAR, they will help, as Jon just described, with the organization of your submission. Making sure that you have all the sections, make sure that you have the labeling repeated exactly the same, make sure you have the signatures in place, but they will do absolutely nothing in terms of evaluating the content, the substance of your submission.

Etienne Nichols: Yeah.

Mike Drues: That's the problem that I have with the way that that's written, but there are some advantages of using eSTAR over the commercial programs. Because of the automatic verification that's been built into eSTAR, CDRH does not intend to conduct RTA review of submissions that go in under the eSTAR program. So that could be a possible advantage for a company. ESTAR is now available for 510(k) and Denovo submissions. It's not available for PMA submissions, at least not yet. Perhaps in the future. I kind of doubt it because even though, as I said earlier, the checklist for the PMA is ironically much shorter than for 510(k), a PMA is much more complicated than a 510(k). And Jon, you mentioned, we actually did a podcast, we can put this up on the website as well, specifically on the eSTAR program almost two years ago when the eSTAR program was first announced. So that's available on the FDA side. On the commercial side, there are a couple of commercial packages that I'm aware of that basically do the same thing. One of the companies likes to use the metaphor, like TurboTax for 510(k)s. It helps you fill in the information, make sure that it's in the proper place, but the reason why I like that metaphor is because TurboTax is not a substitute for a good accountant. In other words, TurboTax will help you make sure that you have the right forms and you have the numbers and the forms and so on, but when it comes to evaluating the quality of the information, the numbers that go into the boxes, TurboTax is of no benefit. So eSTAR and the commercial programs are very, very good, very useful tools when they're used by someone who knows what they're doing. But when they're used by somebody who doesn't know what they're doing, you can cause a lot of damage.

Jon Speer: Still garbage in, garbage out.

Mike Drues: Garbage in, garbage out. There you go.

Jon Speer: Yeah.

Etienne Nichols: You said one thing. So if you use eSTAR, you said FDA does not intend for it to go through the RTA process. So it's almost if the RTA guidance sort of built into the eSTAR process. Did I hear you correctly.

Mike Drues: I think that's the theory. ESTAR is still relatively new. I've been involved now in a few submissions where we've used the eSTAR. So I'm sort of holding back my final opinion, but I think that's exactly the theory. They've built the checks into the eSTAR program, such that you couldn't complete and submit the application if you didn't pass it. Kind of like TurboTax. I should be careful what I say here, but I just finished my taxes this past weekend. TurboTax would not let me submit it to the IRS until I had the information filled out properly. It doesn't evaluate the quality, the accuracy of your information. It fills it out, make sure that you have all the right forms, and so on. So that's why I like the metaphor.

Etienne Nichols: So one thing, when I'm thinking about the RTA and the possibility that eSTAR could prevent me having that process taken care of, maybe it would be beneficial to see some very specific examples of submissions being completed and if you think about that Gaussian curve, let's leave out the long tails where someone left their entire name off, but what are some things that you can see as being potential hangups for companies?

Mike Drues: Yeah. Great question. And to transition from our eSTAR discussion, when I say that eSTAR is not intended or designed to evaluate the content of your submission, if I typed into, literally, in the device description field, my device is a piece of crap, then eSTAR will accept that. It has your device description. It will accept it. The other commercial programs will accept it. So it's not evaluating the content of that infor... of course I'm using an extreme example to illustrate, but you understand my point. Okay. So more importantly, let's take a look at some specific examples starting out with some of the more trivial and then getting into the more interesting ones. So one of the things on the 510(k) RTH checklist is to make sure that you have a table of contents. Well, a few years ago I had a three page submission that was rejected because we did not have a table of contents. I was miffed. I said to the company, because I wanted to make a statement here. I said to the company," Okay. Add one line to the submission. Table of contents, submission pages one through three." I did not even want to kick it to a fourth page because I was miffed. I wanted to make a statement. Then we also, I said to the review team, I said," Look, I understand that rules are important and we have to follow the rules and so on. But can we use a modicum of common sense? Does a three page submission really need a table of contents?" And the reason why it was so miff is because by the time it gets rejected out of FDA system and sent back to the company and the company deals with it and so on, you're talking about many weeks, maybe a few months of delay just because of that. That's one example. Another example is to make sure that you're using the current forms. One of the things that I do with some of my customers before they make their submission is they'll ask me to review it. My FDA reviewer had on temporarily review it. And when I was reviewing it, I happened to notice, purely coincidentally, that the rev date on the bottom of the 510( k) cover sheet was not the most current version of that form. And I said to the company," You should update it." And by the way, I had a graduate student working for me at the time. I had them do a comparison previous version and the current version, there was no difference between the forms. No difference. It was exactly the same. The only difference was the date on the bottom of the form. I still said to the company," Update the form before you submit it." They said," Why Mike? It's the same form." Because I can envision a scenario where some bean counter at FDA is sitting down with their RTA checklist. Do they have this section? Check. Do they have that section? Check. Are they using the current form? Nope. Gets thrown out of the system, gets sent back to the company. And again, you're talking about weeks, maybe even months of delays. One of the most common reasons why submissions are rejected is because a particular section is left out. Put yourself into shoes of the reviewer. They have no idea why you're leaving out that section. In other words, are you leaving out-

Jon Speer: Sorry, but especially at this phase of the review process.

Mike Drues: Exactly correct Jon. Thank you. Exactly correct. Are you leaving that section out because it's not applicable and I'll give you some examples of that in a moment or are you leaving it out because you just forgot about it? The reviewer has absolutely no idea. They're not in your head. They have no idea why that section is missing. So never leave a section out, never leave anything blank. At the very least, put not applicable. And then I often take it a step further. I will say," Not applicable and here are the reasons why." I'm not saying to create a 300 page Ph. D dissertation, but a sentence or a couple of sentences explaining why it's not applicable. Now, some companies will take that approach. Other companies won't. Some companies will take the approach of," We only want to give FDA as much information as we have to and not one bit more." So in that case, we only want to say not applicable. And the defense of that position is why beta potential problem where a problem doesn't exist if you're giving more information. Other companies will say," Let's try to prevent a problem. Let's try to prevent the question coming back," Hey. You marked this not applicable. Why is this not applicable?" So this is sort of the risk benefit analysis that you have to do when you're filling these sections out. And again, I'm not talking about a five year Ph. D dissertation. Just a few seconds or a few minutes of mental time. I take what are the benefits of just saying not applicable versus the risk and what are the risk and benefits of adding a sentence or a couple of sentences of explaining why this is not applicable. I have a few other examples I can share, but maybe Jon, do you want to add something at this point?

Jon Speer: Yeah. I'll just enhance what you just said. Like Mike's examples of sometimes there are sections that are not applicable. Some of you are probably like," Yeah. I already know what those are." Others maybe like," What do you mean? Can you give me a more specific example?" So if you're making a purely mechanical device, there's a section of a 510( k) that has to do with, I think it's electromagnetic safety.

Mike Drues: Yep.

Jon Speer: Well if it's a purely mechanical device, that section probably doesn't apply because you don't have electronics. So state," Not applicable. Device has no electronics." I mean-

Mike Drues: There you go.

Jon Speer: Pretty simple, right?

Mike Drues: That's a perfect example.

Jon Speer: Pretty simple.

Etienne Nichols: And the idea of just getting things through quickly. You talked about the time for review sort of being reduced. I'll give just a real world example that I think everybody who's now flying. I have global entry. I went to the TSA precheck, but it wasn't on my ticket. I get up to the counter and I started having a sinking feeling. He said," You're not TSA precheck. Get out of here." And I said," Well I'm global entry." He said," Those are two different things. Get out of here." Well, global entry covers TSA precheck, but I'm not going to argue with the TSA guy. And someone else said," Are you upset?" I'm like," Well, he's got a lot of his mind. I want him to focus on what he's got to focus on." Maybe I was a little upset, but it's the same thing. People are, it's an expedite process and we should be thankful for that.

Mike Drues: Well I'm impressed because I have TSA pre, but I do not have global entry.

Etienne Nichols: Maybe I shouldn't say that on here.

Mike Drues: I won't argue with TSA because that serves me no good, but I will argue with FDA. That's part of my job.

Etienne Nichols: Yeah.

Mike Drues: So Jon, let me take that electrical example and build onto that a little bit further because I have a few other specific examples. I don't want to talk in generalities of latitudes. I want to give as many specific examples as possible and these are real examples. Not that I experienced, but real reasons why submissions were rejected by the FDA. Failure to state whether a condom was patient contacting. Failure to state whether a condom is patient contacting. Now, I never assume that FDA understands anything that I tell them. Don't assume that FDA understands your device. One of the most poorly written sections of the submission, in my opinion, is the device description. And the reason why I say that is because the vast majority of questions that I see coming back from reviewers across the board, the vast majority of questions is indicative of the fact that they don't understand the device, what it does, how it works, it's mechanism of action, and so on. It's not the job of the FDA to make sure that they understand your device. It's the job of you to make sure that FDA understands your device. So my advice to companies is I find it interesting. So many people, they think about measuring the efficacy of their device, but they don't think about measuring the efficacy of their submission, specifically the device description. So here's my recommendation. Take your device description, give it to somebody who's not familiar with their device, ask them to read it, and then literally yank it out of their hands, ask them to describe to you what they just read. If they describe to you, if they paint a verbal picture of something that looks like your device, then great. You know you're communicating. But if they paint a picture that looks nothing like your device or worse, they're so confused that they can't paint any picture, then you know you're not communicating. Right? So this is so basic to me it's common sense, but it's amazing to me how few people actually do this. So measure the efficacy of your device description. Here's another example. Failure to comply with a draft guidance document. Failure to comply with a draft guidance document. Well, first of all, I think Jon, as you and I have talked about in the past, even though FDA continues to use the verbiage draft versus final in the context of guidance documents, it really doesn't matter. There's no such thing as a draft or a final guidance document and that's a topic of a different discussion, but here's the thing. Whether you're going to follow a guidance document or not, you've got to justify what you do. So as part of your submission or better, as part of your pre- submission meeting, you need to make sure that you explain and get FDA to understand and agree that we're not going to do what's in the guidance. We're going to do something else and here are all the reasons. One last example and then I would love to hear you guys thoughts on this. Failure to indicate vinyl gloves do not contain software or meet electrical safety requirements. This is the example that you shared a moment. Vinyl gloves. Failure to indicate that vinyl gloves do not contain software or meet electrical safety requirements. This is the quintessential example of do not leave a section out. If your device is something like vinyl gloves, which clearly does not involve electrical safety or software, don't just leave those out. Say," Not applicable," and even step further, say," Not applicable because it's a vinyl glove you idiot. It doesn't contain a risk of electrical safety or software or something like that." And last and very last, typos, misprints, duplicate pages, and so on. Do I really need to say more? I mean, proofread your submission. And it sounds like a very common sensical thing and it is, but it's amazing to me how many people don't do this and here will be my last piece of pragmatic advice on this point and then Jon, I would love to hear your thoughts. Why does so many companies treat the FDA as their beta tester? In other words, the first people to see their submission outside of their own company is the FDA. To me, that makes absolutely no sense. One of the things that I do with a lot of my customers, I don't mean to be self- serving. I'm just simply trying to share some of my best practices. Before a company submits their submission or has a meeting at the FDA, they'll ask me to come in, temporarily put my FDA reviewer head up because I work as a consultant for the agency, sit through their presentation, read through their submission, and if I could be a bit brash here, bash the hell out of it. Because the idea is if they're going to make a mistake, better for them to make a mistake in front of me. After all, what do I-

Jon Speer: Absolutely.

Mike Drues: I don't matter, as opposed to the FDA. I don't want to go so far as to say that if a company can get what it is that they're trying to sell through me, if they can get me to buy it, then the FDA will buy it. I'm not going to go quite that far. But on the other hand, I can make a reasonable surrogate for the FDA. And I think a good regulatory professional or a good regulatory consultant, not an average one, a good one, should be sort of a surrogate or a proxy for the FDA. If you can get your submission through your own regulatory consultant or your own regulatory professional, you should be in good shape. But unfortunately, there's a lot of average regulatory professionals out there. In my opinion, Jon, maybe you disagree. There's a lot of good ones. What do you think?

Jon Speer: Yeah. Well I agree with that last statement. Yeah. I want to remind people too. I mean, you and Etienne have touched on this a little bit so far, but this submission that you're preparing and sending to FDA, you don't know who on the FDA side of thing is going to get it per se. I mean, you may have a pretty good idea, but to make an assumption that that person that's getting this understand," Oh. Not applicable. Oh. Vinyl glove. Makes sense." Making those kind of assumptions without an explanation, there's a little bit of risk to that. The other thing is this submission, in some respects it's a reflection of you, the preparer, but definitely a reflection of the company that you and this mission represents and it's your story. Make that story as easy to follow as you possibly can. Provide the pagination, the table of contents, just some basic things where the reviewer can find the information that they're looking for as easily as possible. Also keep in mind, a lot of submissions, they're divided. Some person over here is going to review, with a toxicology background, may review the ability information. The electro mechanical expert's going to look at electrical safety and so and so forth. There's a chance it's going to be parsed out to different people. And if it is confusing to follow or you keep pointing back and forth and here and there, you're just making that reviewer's job more and more difficult. And if you're going to make somebody's job more difficult, I guess, do you think that's going to make your life easier?

Mike Drues: Absolutely not. Absolutely not. One of my most important jobs is I want to make the reviewer's job as easier as I can. I guarantee that your submission is going to be reviewed by a lot of people, a lot of different subject matter experts at FDA. That goes without saying and Etienne, I know we got to wrap this up soon.

Etienne Nichols: Sure.

Mike Drues: But Jon, I love your metaphor of telling a story. What we should be doing, not just in regulatory submissions and pre- subs and all of these kinds of documents that we're sending to the FDA, we should be doing exactly that. We should be telling a story. This is a story of my medical device. This is a story of how it was developed, how I tested it, how I know that it's safe, effective, and so on and so on. So I love that metaphor of telling a story. I think that's something that I do in most of my documents. I think it's something that other people can try as well. It should be non- fiction though.

Etienne Nichols: One thing this makes me think of is, so when I was a manufacturing engineer, GDP was a big deal, good documentation process. That's why you always had to cross a box out that was blank. And if you didn't, you go to have it approved or circulated, somebody invariably would say," What happened here?" You don't want to have to retell that story every time because that's obviously a red flag in an audit. You're going to have to tell that story again and that's never a place you want to be. So we come back to the true quality side of an engineer's life that doing a good job for this form, this is something that should be ingrained in our everyday life anyway already. Getting away from the philosophical idea, I have one other question before we do wrap it up. Suppose I'm rejected for an RTA, what are some of the options that we have if we've been rejected for this?

Mike Drues: Yeah. Great question. And it depends on what was the nature of that rejection. In other words, if you were rejected on a straight review, then chances are it's something relatively minor like you forgot a signature or you omitted a section. Those kinds of problems can usually be resolved fairly quickly. But on the other hand, if it's rejected on scientific review, then if FDA has a difference in opinion in the testing that you've done, in your statistical analysis, what have you, those things can be more difficult to resolve, especially at the point of the submission. That's why, Jon, as you and I have talked about many times and it's no secret, I'm such a big fan of the pre- submission process because problems that occur in the substantive review or what I call the scientific review of the submission, can almost always be mitigated if not completely eliminated with a good pre- sub beforehand. So administrative review problems, those can usually be fixed, but they shouldn't happen anyway if you're following the guidance, you're using one of these eTools. Substantive review problems can usually be minimized or avoided with a good pre- sub. That would be my best there. Jon, anything you would add to that?

Jon Speer: No. Nothing to add.

Etienne Nichols: All right. That might be a mic drop, but any other pieces of information that are important in this topic?

Mike Drues: No. Just to wrap this up, look, we have the three guidances now for RTA checklists. Within the 510(k) we have three RTAs checklists and that. So there's a litany of resources out there that are freely available. And yet in spite of that, or maybe because of that, companies still run into problems. It's difficult to understand. So as Jon and I both have talked about, whether we should have these kinds of guidances or not, it's a moot they exist. So since they exist, you might as well Jon said, I always like to use it as a checklist or even include that checklist as part of my submission. Tick those boxes, even though Jon, I think, you and I both are not fans of the box ticking mentality, but in this particular case, maybe it's an exception to the rule. So use those. And perhaps most importantly, don't blame FDA or anybody else. Learn from other people's mistakes. I've tried to, in as specific detail as I can in today's discussion, give some very specific, very concrete examples of what happened and why and how it could have been avoided. So learn from those mistakes. There's other resources out there. A lot of people like Jon and myself that have a lot of experience playing this game. You don't have a lot of experience with this, then get somebody on your team to help you. I think that's the most important thing.

Etienne Nichols: One of my favorite lines that you said so far, I'm going to try to remember it. I don't know if I'll have it verbatim, but the FDA's job is not to understand your device. It's your job to make sure the FDA understands your device. I thought that was a great line. I guess that's encoupled with, if you have an RTA rejection, it is your company's fault, not the FDA's fault. Those kind of go hand in hand I suppose, but I thought that was really good.

Mike Drues: Thank you.

Etienne Nichols: Jon, anything to add or takeaways in your mind?

Jon Speer: No. Well, I guess one thing to add. Folks, we still have a long way to go. I mean, you heard Mike share the statistics over the past few years. Two- thirds are still being rejected. We got some work to do. So we're moving in the right direction, but there's no reason why two- thirds of 510(k)s should be rejected. There's just no reason. None at all.

Etienne Nichols: All right. So we have specific guidances for each one of these submissions. Whichever one you're working with, you can definitely check those out in the show notes. We will add those. And you've been listening to the Global Medical Device podcast. Thank you. If you're interested in learning more about the Global Medical Device success platform, the only success platform that can help you get to market faster because it's built by medical device professionals for medical device professionals, go over to www.greenlight.guru to find out more. We will see you next time.

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