How To Avoid Major Common Mistakes During the FDA 510(k) Process with Michael Drues

November 20, 2015


In episode #8 of the Global Medical Device Podcast we welcome back Michael Drues, president of Vascular Sciences. As many of our listeners may recall, Mike does consulting for medical device companies, the FDA, Health Canada and other regulatory bodies.

Today Jon and Mike talk about 510(k)'s and some of the major mistakes some companies make when they get FDA 510(k) clearance. Specifically, they talk about companies that get 510(k) clearance but don’t have design controls, risk management and don’t have a quality system.

And it’s chuck full of actionable advice and takeaways.



Like this episode? Subscribe today on iTunes or Spotify.


Some highlights of this episode include:

  • When a 510(k) isn’t necessary

  • Reasons for rejection of a 510(k)

  • “Lead don’t follow, tell don’t ask.”

  • Design controls

  • Multiple Predicate Strategy / Split Predicate Strategy

  • Risk Mitigation

  • Regulatory checks

  • Corrective Action/Preventative Action Plan

The FDA’s mission is to make sure the products we bring to market are safe and effective. The 2 areas of 510(k) submissions that are getting the most scrutiny are the substantial equivalents argument and the risk mitigation strategy. If you don’t have a rock solid argument and a bulletproof strategy you will probably be rejected. Early and frequent communication with the FDA is the key to success. 

What can a company do if they’ve been approved for market but aren’t prepared? Conduct a gap analysis, figure out what you have, figure out what’s missing, fill in what’s missing and be upfront about it.


Memorable quotes from this episode:

“Design controls are nothing more than a synonym for prudent engineering.” - Mike Drues

“Physicians can kill patients one at a time but an FDA reviewer can kill patients thousands at a time.” - Mike Drues

“70-75% of 510(k) and PMA submissions are rejected the first time.”- Mike Drues

Ask for help if you need it. Go to the experts. There is so much more we can do to help before, rather than cleaning up problems later, but, “It’s never too late to do the right thing.” - Jon Speer



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.


Jon Speer:

Hello, this is Jon Speer, the founder and VP of Quality and Regulatory at Greenlight Guru.



Welcome to today's episode of the Global Medical Device Podcast. Hey, it's a good one too. We've brought back Mike Drues. Mike is the President of Vascular Sciences. In this episode, Mike and I dive into the topic of 510(k). Specifically, we get into some of the issues that Mike and I have seen firsthand all too many times, some of the major mistakes that some companies actually make when they get 510(k) clearance. Some of the things that they need to take care of before going to market.



So if you want to save yourself potentially hundreds of thousands of dollars, you probably need to spend the next 25 minutes and dive into this episode of The Global Medical Device Podcast.



Hello. Welcome to the Global Medical Device Podcast. This is Jon Speer, Founder and VP of Quality and Regulatory at Greenlight Guru. Today, I have Mike Drues. Mike is the President of Vascular Sciences. Mike does consulting for medical device companies. He does consulting for FDA. He does consulting for Health Canada and other regulatory bodies. Look him up. Last name D-R-U-E-S. He writes articles, blog posts, podcasts. If you need help with regulatory matters, and you're a medical device company, you need to call Mike.



Mike, welcome.


Mike Drues:

Thank you Jon. It's a pleasure to be with you today.


Jon Speer:

Well Mike, we're going to dive into a topic that's been kind of hot and heavy on my end, and it's been on the news a little bit too. You and I have been quoted on some recent articles on a similar sort of topic, and here it is. 510(k), companies that get 510(k) and yet they don't have design controls. They don't have risk management, and they don't have a quality system. Have you ever come across that scenario before?


Mike Drues:

I have, Jon. There's several situations where that can be the case. First of all, there are some medical devices that are not required to have a 510(k) and are not required to follow design controls. These typically are the lowest of the low-hanging fruit in terms of risk, but as you and I have discussed in the past, I really think that design controls is nothing more than a synonym for prudent engineer. These are things that we all are supposed to have learned to do in engineering school because they're the right thing to do.



Another possibility are there are a small number of companies, not many, who bring a device through the FDA via a 510(k), but do not have an intention to market it, or at least not right away. There are a couple of companies that I work with, for example, that have brought 510(k) products through the FDA, but are specifically sitting on them waiting to release a next generation and to do that as a label expansion.



And a third possibility are companies, especially very small or start-up companies that are looking for funding, so oftentimes there's a tremendous amount of pressure to get the product through the FDA, that is get the 510(k) with a sort of minimal amount of work that they absolutely can, and all of the other issues, like quality and this design controls, and so on, can wait until later when they have more money.



So those are some of the scenarios that I've been involved with Jon, how about yourself?


Jon Speer:

Well, I've seen a few of those type of scenarios as well. Some of the other scenarios that I see are actually funded companies, usually skewed toward the start-up side of things, but they have necessary funding. It just seems like sometimes they're not aware of the regulatory environment. They don't know what they're supposed to do, but they do know this 510(k) thing that they have to do, and then put together a submission, and they get the clearance.



Short story, I had a company call me recently, and they got their 510(k) clearance, and they were ready to go to market, and they had one of these moments, "Oh crap, I don't have a quality system. Oh crap, I don't have a design history file. I don't have risk management." And they called me, and asked me to look over things.



It's interesting to me because they shared their 510(k). I started going through it, and I started pointing out content within their 510(k) that actually were design control elements and started to educate them on that.


Mike Drues:

Well that's a good example, Jon, because regardless of what the regulation says or does not say, in that particular case, the folks, it sounds like, they were doing what they should do, what a prudent engineer would do, and maybe they just didn't realize that that was also in the regulation.



I had ... You shared a situation, Jon, from your experience. I'll share one of mine. I had a company come to me. They wanted to get a 510(k) in, literally at all cost. In other words, they really didn't care about getting it right or not. They just wanted to get a 510(k) submitted to FDA even if it came back with a whole bunch of deficiencies because that was one of the milestones they needed to show their potential investors that they were making progress.



I tried to work with them. I tried to encourage them. Look, I understand the importance of getting it submitted, but we also want to make sure that we get it submitted right, because here's an interesting statistic to share with the audience. 70% to 75% of 510(k) and PMA submissions today to FDA, 70% to 75% of them are rejected first time out of the box. We have an industry full of people who are essentially treating the FDA as if they are our teacher in a class, and they're grading our homework assignment and marking it out what's wrong, what's missing and so on, and I just don't see it that way. We should-


Jon Speer:

Yeah, I don't either. I don't either. I mean, that's an interesting statistic. Sorry to jump in there Mike. 70% to 75% are rejected. So, give me a few examples of why those are rejected by FDA because you're right. FDA is not in the role of educator. They're in the role of, a better descriptor might be gate-keeper. Would you agree with that?


Mike Drues:

Yeah, they are a gate-keeper in the sense. That's a good metaphor because the FDA's mission is basically to make sure that the products that we bring to market are safe and effective, and that's certainly an important job, and as one of my friends who used to be a senior reviewer at CDRH was fond of saying, "Physicians can kill patients one at a time, but an FDA reviewer can kill patients thousands at a time." This is something that I think that more folks in our industry need to remember.



In terms of examples of why FDA might reject these applications, of course, there are tons and tons of examples, but specifically-


Jon Speer:

Pick your favorite three.


Mike Drues:

So specifically within the 510(k) world, the two areas of the submission that are getting the most scrutiny these days, and you can chime in with your experience as well, Jon, but the two areas of the 510(k) that are getting the most scrutiny are the substantial equivalence argument and the risk mitigation strategy. Bottom line, and I say this in many of my presentations. I don't care if you fill out all the forms correctly. I don't care if you dot all your i's and you cross all your t's. If you don't have a rock-solid substantial equivalence argument, and if you don't have a bullet-proof risk mitigation strategy, you are probably not going to be successful with your 510(k), certainly not first time out of the box.



A lot of my regulatory friends, they tell me their goal is to get their 510(k) cleared or the PMA approved. That has never been my goal because quite frankly, anybody can do that. My goal is to get my 510(k) cleared or my PMA approved, ideally, the first time out of the box if I can. Or if I can't, with the minimum number of ping pongs of Q&A going back and forth. Am I successful 100% of the time? No, but I can tell you that I'm in that 20% to 25%, not in that 70% to 75%, and there's as lot of ingredients in my secret sauce, but the most important ingredient is early and frequent communication with the FDA. There is nobody that is a bigger fan of communication with FDA than I am.



As a matter of fact, I've said publicly now, several times recently, there is absolutely no excuse whatsoever for anybody to ever have a 510(k) deemed not substantially equivalent. That is totally avoidable, 100%.



There was a company that I worked with recently, an in-vitro diagnostic company. They made a submission to FDA, a 510(k). 11 months later, that submission was deemed not substantially equivalent. They were delayed nearly a year, and that was a very amateurish mistake.


Jon Speer:

I can understand that. I've heard some similar horror stories. There's a little bit of difference with Mike Drues picks up the phone to call FDA versus start-up who has no credibility or rapport with the agency. Do you agree with that?


Mike Drues:

That's very flattering, Jon, but really I don't think so. The bottom line, FDA works for all of us, all of us here in the United States that pay income tax every year. So anybody, whether it's myself or you or anybody else has an expectation to be able to interact with the agency, and that could be the topic of a whole other conversation.



The last thing I'll about communication with FDA, as I said, I'm a huge fan of communication with FDA, but there's a caveat to that, and that is lead, don't follow. Tell, don't ask.



It's amazing to me, Jon, and perhaps you've seen it as well, how many people go to the FDA and essentially ask them, "What should we do?" And that's a terrible strategy for several reasons. First of all, it's not FDA's job to tell us what to do. It's our job to determine what to do. That's number one. But more importantly, number two, when you ask FDA what to do, you're opening up a Pandora's box, and you have absolutely no idea what you're going to get in return.


Jon Speer:

You may not like the answer. Careful what you wish for.



It's interesting to me. When I hear a company say they've got a 510(k), but they don't have design controls, to me, those things are like part and parcel with one another. You have to go through a design control process in my opinion, my experience, to even put together a 510(k) because so much of that design control, those activities, that verification and all your requirements and so on, all of that stuff actually feeds into a section in a 510(k) submission, so that's what's confusing me at times.



The industry or the start-up world knows what a 510(k) is because there's sometimes funding milestones that are tied to that sort of event, but they don't always get funded for having a good design history file.


Mike Drues:

That's correct. As a matter of fact, I don't think, and I work with a lot of VC's and angel groups. I actually am on retainer for several investment groups as a regulatory consultant. I don't think anybody [inaudible 00:11:33] invested in a company because they have good documentation of one kind or another.


Jon Speer:

So let's talk a little bit about ... You mentioned substantial equivalents, a good predicate, as an issue. If you don't have a good predicate, that's not going to go well for your 510(k), and I think that's important for the audience to understand. Have a good predicate.



So what do you mean by that? I know once upon a time you used to be able to kind of paint a picture from a 510(k) where your intended use was sort of like this device and sort of like this device and sort of like this other device, and you may list all three of those as predicates. Is that a practice that's accepted today in the agency?


Mike Drues:

Well Jon, what you're describing in that latter part is what is called either the multiple predicate strategy or the split predicate strategy, and those two things are actually not the same. I won't get into that level of detail.



Bottom line, the substantial equivalents rationale if you will, the regulation requires us to have a predicate. The regulation does not say we can only have one predicate. We can certainly have more, and the regulation does not say how close or alternatively how far away that predicate needs to be.



Again, this could be the top of a whole different podcast, but basically, what we have to do is we have to choose the predicate or a combination of predicates that we think is going to make our case the most strongly.



One other thing, the 510(k) regulation, the essence of the 510(k) really has not changed since it was created in 1976. FDA has put out a number of guidances. As a matter of fact, just last summer, there were five new guidances that came out in the general area of the 510(k). Next year, we will be celebrating the 40th anniversary of the 510(k) for better or for worse, and we're still trying to figure this out.



Everybody thinks that substantial equivalence is so simple, but it's really not. That's something that we really need to give thought to.



I'll leave you with one more interesting thought on this, Jon, and that is there are a number of medical devices that have come to market under the 510(k) here in the United States, say 10 years ago, even five years ago. If that same medical device with the same submission were to come to FDA today, it might not get through. So, the question is, what has changed during that time? Has the regulation changed? Well, really in my opinion, no. It really has not changed since 1976, but what has changed is the level of scrutiny, if you will, that FDA is paying to certain parts of the submissions like, for example, the substantial equivalence argument.


Jon Speer:

Right. The other thing you mentioned is risk mitigation, and so when I hear risk mitigation, I automatically start thinking ISO 14971 Risk Management. So can you expand a little bit about what you meant about risk management as another reason for rejection?


Mike Drues:

Well that's a good question, Jon. This is something that I put out in one of my columns earlier this summer, and I think you and I have talked about before. Risk has many different connotations, and suffice it to say, risk in the design control sense of the word is not quite the same as risk in the regulatory submission sense of the word.



I see sometimes companies, they will take their risk management plan from their design controls and literally copy and paste it into their regulatory submission, 510(k) or whatever it is, as their risk mitigation strategy.



Right away, without even reading it, I know that it's wrong simply because the design control sense of risk, and again, I won't get into the details of it, but in the design control sense, we're looking at risk only in the sense of what I call the probability of direct harm. That is the harm caused directly by using that device.



But in a regulatory submission, we need to consider other forms of risk as well. What example, what I call the probability of not use. What is the harm if we don't use the device. Or, the probability of providing the wrong information if you're making a diagnostic kind of a device, an imaging device, in-vitro diagnostic, an EKG monitor or something like that. If you are providing the wrong information, a false positive, for example. Tell the patient that they have cancer when, in fact, they do not. Or False negative, telling the patient they don't have cancer, when in fact they do.



These are contexts of risk that we don't take into account in the design control sense of the word, but we do, or at least we're supposed to take them in account in our risk mitigation strategy, in our regulatory submission. This is important in all regulatory submissions, but the part that it's the most important in, of course, is the De Novo. Because in the De Novo, it's only about risk mitigation and nothing else.


Jon Speer:

Right, and we'll leave the audience hanging on what is the De Novo thing because we can talk about that again in a whole separate podcast. Do you go De Novo?  Do you go 510(k)? And so on.


Mike Drues:



Jon Speer:

If you want to know more about De Novo, we'll just let you know right now that the best person to talk to on that is Mike Drues.


Mike Drues:

Well thank you, Jon.


Jon Speer:

I'm sure you can provide a lot of guidance and direction to companies that want to go down that path.


Mike Drues:

So Jon, before we wrap this up, let me ask you a question. Do you think there needs to be some sort of a requirement or provisions or some sort of a check within the 510(k) regulation, maybe adding it to the Refuse to Accept checklist that there needs the elements of the quality system and the design control as part of your regulatory submission?


Jon Speer:

It's a really good question, and one that I've thought about often because if you're bringing your product to market in Europe, for example, really those provisions, the need from a quality system and design control and risk, those are almost defacto requirements, more or less, before you get that CE mark in Europe for example.



To me, I think adding that as a provision is interesting because companies are a little naive from time to time because they get that 510(k), and if they don't ask the next question, or they don't take the time to educate themselves on what are the FDA Quality System Regulations, they could be in for a big surprise a couple years later when that FDA inspector shows up and says, "All right, we're here to do our inspect. You've got a Class 2 device, and this is a requirement, and we're going to inspect your facility. We're going to look at your quality system." And if a company didn't think about or didn't address design control and risk and quality system, they're going to get a lot, lot, lot of [inaudible 00:18:26] observations. It's going to be a painful activity.



I think if there were a check in place, that could be a good thing. However, I think the check is already in place. It's called, hey, you're a med device company. Look up 21 CFR, part 820. Follow the regulations. What do you think, Mike?


Mike Drues:

Well, largely I agree with you Jon. You're obviously a very well recognized expert in quality and design controls and related issues. You mentioned that some companies are naive. I guess, to be honest, I'm a bit naive as well. I would like to think that these are things that we, as companies, would do anyway, and that we don't need any regulation, or we don't need our government telling us to do these things.



But of course, I did not just fall off the turnip truck yesterday, and sometimes companies don't do these things either because they don't know they're supposed to or perhaps some other reason, and so maybe we do need to have that in the regulation. I would like to think that we don't need it, but clearly because there are people that don't do it, maybe we do.



I probably shouldn't say this, but more than 70% of my business is coming in and cleaning up after somebody else's mess.


Jon Speer:

I was just going to ask you that, Mike. If a company finds themselves in this predicament where they've got that magic 510(k) clearance letter from the FDA saying they can go to market, but yet they realize they don't have a design history, or they don't have their quality system in place, is there anything that they can do? How should they address that situation?


Mike Drues:

Well, that's a great question, Jon, and I'll chime in, and then I'd love to hear your thoughts as well. So, simply put, there's an awful lot that they should do, and they should do it soon rather than later because coming to FDA and say, "Look, we realize that we have some gaps." However you want to phrase it. "But these are things that we're doing to fix them." Maybe even starting an internal CAPA, a corrective active and preventative action plan. That's the essence of a CAPA whether you think about it that way from a regulatory perspective or not.



I'm a huge fan of being honest and acknowledging this is where we are. I see this happen, by the way, when sometimes a large company will acquire a small company or a start up, and when they acquire them, they might have a 510(k), but they might not have all of the other documentation in place, and so what you need to do is you need to do a gap analysis, figure out what you have, figure out what's missing, fill in what's missing, and most importantly to me, be honest about it.



I have seen, occasionally, companies, and I have to be a little careful what I say here. They will recreate documentation and make it appear as if it was created in the past, and I have a problem with that because that defeats the whole purpose of what it is that we're trying to do.



So simply put, my best recommendation, whether you're in a large company that's acquired a small company or whether you're working in a small company yourself. Be honest. Be aware of what you know, but more importantly, be aware of what you don't know. If these are things you can't do yourself, ask for help from somebody like yourself or somebody like me to help you put in place what you need. That's my best recommendation, Jon. How about you?


Jon Speer:

I'll echo that. It's never too late to do the right thing, and if a company finds that they have some gaps or they don't know what they don't know, pick up the phone and call Mike. Pick up the phone and call Jon. Just give us a ring. Ask us some questions. Yeah, you may not like the answers that we're going to tell you, but we're going to help get you on the right path to make sure that you're addressing the requirements and the regulations for your particular product and company.



I can promise you that if you have an FDA inspection, that's going to be a tense enough event in and of itself even if you do have your ducks in a row. If you don't have your quality system buttoned up, if you don't have a design history file, then it is going to be a painful, painful experience, and it's going to cost you tens, maybe hundreds of thousands of dollars to address any [inaudible 00:22:56] observations for fixing your quality system or for fixing your design controls.



Sure, if you want to call Mike and me after your FDA inspection to come clean it up, we'll happily let you do that, but actually I think both Mike and I would ... Mike you can confirm this, but I think we would both prefer that you call us sooner rather than later so that we can provide a little bit of guidance and direction to help make your life a little bit easier.


Mike Drues:

I agree with you 100%, Jon, and just to wrap this up, my final thought/recommendation for the audience, and this is, by no means, meant to be self-serving, but there's so much more than Jon or I can do for you or with you in advance, that is before somebody comes knocking on your door and says, "Hey, there's some problems here." It is so much faster and cheaper and easier to solve these problems before they go to that point than after.



I can't tell you how many times companies come to me, they're in a hole, and they ask me to help them come and get out of that hole, and I say, "Sure, I'd be happy to help you do that, but I also have to tell you, if you would have called me six months ago or 18 months ago, we might not be in this hole to begin with."



So please, I understand, especially for people in start-up in small companies where cash is a premium. I understand the challenges of managing the finances, and I can be very creative in working with companies as I know you can be as well, Jon. But please don't be penny wise and pound foolish. Saving a few cents today might actually cost you a ton of time and money later on.


Jon Speer:

I can't say it any better than that, so we'll let that be the final word today.



Did you know that the Greenlight Guru Global Medical Device podcast, it's on iTunes. It's also on Sound Cloud, and we also have a page dedicated on our website just for the podcast. You can hear past episodes where Mike and I talk about things like designer views and other regulatory matters as well as other podcasts about other industry topics. So please be sure to check that out. The domain again is Greenlight Guru.



Again, you can find Mike Drues Vascular Sciences, and you can also look up Mike on LinkedIn. That's a good place to find him. Again, if you search for his name, you're going to find all kinds of wonderful content that's going to help you stay out of hot water with the regulatory bodies across the world.



This has been Jon Speer with my guest, Mike Drues. Mike, thanks for joining us today, and look forward to the next Global Medical Device Podcast.


About The Global Medical Device Podcast:

The Global Medical Device Podcast powered by Greenlight Guru is 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.

Like this episode? Subscribe today on iTunes or Spotify.

FDA 510(k) Submission Webinar

Nick Tippmann is an experienced marketing professional lauded by colleagues, peers, and medical device professionals alike for his strategic contributions to Greenlight Guru from the time of the company’s inception. Previous to Greenlight Guru, he co-founded and led a media and event production company that was later...

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