I had a pre-submission meeting
so I went down to Silver Springs.
I took documents, and drawings,
and lots of other things.
They said, “Go home, boy.
Wait until the telephone rings.”
I got the Regulatory Blues.
About to lose my mind.
I’m waiting on some data
no one can seem to find.
Now my 510(k) submission
is running three months behind.
I got a call last week.
Said they were coming for an inspection.
Someone down at the hospital
got a real bad infection.
Now they’re telling me
I got to recall the whole collection.
Tried to renew my registration.
I just sent it in the mail.
Because every time I went online,
their website would fail.
Now they’re putting me in handcuffs,
and taking me to jail…

Joe Hage: I’ve been doing this for six years, Bob. That was a first. Thank you very much.

Bob Marshall: Well, thanks very much [laughs].

New FDA Guidelines

So, I’m going to talk to you today a little bit about new FDA guidelines. Some things to think about, some of it from experience and exposure to the industry.

We’re going to cover two things: We’re going to look at the 2017 guidance, some of those in detail, that were issued in fiscal year 2017 – some of those impacts and things to think about and learn from. And we’re also going to take a sneak peek at some things that are coming in this fiscal year, that we’ll also have to adapt to.

Real world evidence

The first thing I want to talk about is real-world evidence. This is an interesting thing because we have FDA, in a very progressive way, starting to understand that every time we bring a new device out, we don’t have to do a new trial. There’s a lot of data, right? We’re moving toward a whole world of Big Data.

I think that’s a really good thing. But if you look at the standard and when they came out with it — I actually did an article on this because it’s almost talking out of both sides of your mouth — it’s like saying that there are situations where we could look at this and we may have data that is the same as or even better than what you could come up with through a trial, but at the same time, nothing is going to change our evidentiary requirements. So that’s an interesting challenge, to deal with both sides.

But, I have seen it effective. I recently talked to Stryker, and it was interesting that they had recently submitted a product – it’s part related. It’s dealing with stroke, so heart and brain related – and, in that process, they did not have to do a clinical trial related to the function of the catheter for that specific application. And it was cleared within 30 days.

But part of the issue was they had good bench data. They had pre-clinicals, but they also had real-world data from very similar other applications that they could lean on. So, it worked out very well for them and, I’m sure, others potentially.

It’s something we have to get used to, which is a positive. It doesn’t mean every device that may be of a Class II level or Class III is necessarily going to require a full clinical trial. So, there’s still a lot to learn in testing this, but it does seem that they’re pretty open to it. So, it’s certainly something to think about.

Reporting age, race, and ethnicity data in clinical studies

For a long time in clinical trials, we’ve not done a good job covering gender, ethnicity, and other issues in having a good population to represent the end users. And, they put out guidance to talk about how they want to see this being different. And, I think it certainly is time.

I think we’re always a little worried with trials to get a little too involved with different splits of patient population. But in the guidance, they give us pretty clear guidance. And, it’s really based on that differentiation, potential risks, different types of effects for those different populations.

So, it doesn’t mean you necessarily have to do that, but you have to think about what those effects might be if you’re dealing with something different for men and women, “how does that work?”

Some of the examples they used in the guidance were interesting. There were several studies that had been done for, I think, knee implants. For a long time, generally, the patient population was men. But as women were having them, they were having many more complications after being implanted for some time. And they really weren’t properly represented in the initial clinical studies related to that implant. So, it’s definitely something that is important to cover all of those issues.

Drug/device classification issues

We’re blurring lines everywhere within the regulatory space. And this is one that has been there for a while. I do think the Office of Combination Products at FDA does a great job. But, then again, part of the reason is because, ultimately, it’s not their problem.

All they’re going to do is guide you in the direction to go. And at times when I’ve had the involvement with engaging them, they were extremely helpful. So, I think that’s a real good part of this.

But, in reality, they did try and come through and deal with some of the issues around that specific classification and “how should we do that? How do we deal with that?”

They really realized that some previous guidance they had given was going to be problematic, specifically related to things around chemical action. They initially had said, “There can’t be any chemical action or it’s not a device.” And so, they’ve taken those couple of things and really, specifically in this guidance, backed those things off. It’s good because there were definitely concerns that those things could be problematic, certainly, if someone gets pushed down a drug path when they’re actually a device.

That’s a small part of it. So, they’ve looked at a better way to determine whether, “Is that chemical action almost coincidental or is it the main part of how the product achieves its results?” So, I think that’s an interesting piece to look at in trying to understand what we have here.

Pre-submission process

How many folks have been involved in a pre-sub? [Show of hands] And did you generally find it to be helpful and positive? Yes. Okay. Hands are up.

So, it’s interesting — and I wrote about this, too — because there seem to be two camps in this. There are folks who see it as a natural follow-on to transparency at the agency and the desire toward collaboration in the industry.

But, some folks are just hard-set against it. It’s like, “Don’t go down there. Don’t ask them any questions. Just do your best to interpret the regulations and go.” But as it gets ever more complex, it’s difficult to do that. And so, I really think there’s an opportunity there.

Personally, I’m a big fan. Prior to doing what I do in writing for Med Device Online and organizing the content, I was a consultant for seven years and, in the device industry, for 15 more before that.

I’ve been there a lot of times and I think they were all positive. I can’t think of anything that went bad. One or two times, on our end, people we were working with and representing didn’t do some things that were probably the best for their desired outcome. But in general, it’s been a good process, I think.

But it’s interesting that folks I generally see not recommending this process are usually folks that are ex-FDA. I don’t know if that’s just a small data set, but it seems like maybe they’ve seen the inside and they’re like, “Don’t mess with that. Don’t waste your time.”

And I think that’s unfortunate because I think there’s a lot of good there and, as I said, I think that the results have been great.

It’s important to keep in mind, though, they gave us very clear guidance on what that pre-submission should look like. And a couple of the things that are really important – the device description is critical.

You’re explaining something new or different, at least, to the FDA. They don’t have any frame of reference on this. You may have been developing this thing for two years. And, to you, it’s second nature. You really need to describe it well, so they can understand what it is, and they can get comfortable with whatever it is you hope to do.

So, that part is really key. I think it’s also really important to make sure that you are very good with your specific questions. Don’t go down and ask them, “What kind of clinical trial should we have for this?”

We can all guess what the answer to that would be, right? There’ll be so many sites and so many patients that we can’t afford it.

So, it’s important to frame that carefully. Do your homework. We come up with a reasonable plan, “We think, if we have three sites and we have 30 patients at each site, that we can demonstrate the intended outcome for this product. Do you agree or disagree?” It’s always important to put those into a yes-or-no type question.

I think it’s a process that we’re all getting used to. I think there’s a lot of value in it. It’ll be interesting to hear the continued experience of the group with it.

De Novo submissions

These are coming more and more forward. These have been around for quite some time. In the late ‘90s, early 2000s, they were getting, maybe, 10 a year, And the general word on the street was, “Just stay away from it. It’s just a wormhole. You’re going to get lost in the process.”

But the idea is, if we have something that’s not classified, and we don’t really know where it belongs, it’s an automatic Class III. But there are devices that are clearly not major risk. They’re minor or moderate risk. And so, this is the way to do that.

It’s a little bit quicker in theory. FDA is trying to say they’ll get them done in 150 days and working the percentage of them being done that way up over the next five years. It’s a good effort to do that. Much better than having to go down the PMA path, if it works for you.

They put that guidance out and they gave some guidance about what to have in that submission. It’s important to pay attention to these things. They don’t do it for no reason.

It is a newer process, but the numbers are starting to come up. Sometime into the 2010-ish timeframe, we were getting toward 25 a year.

We’re actually starting to get the list of recent clearances. I get a lot of requests from people that say, “Hey, you know, we’ve got our new device released.” And they want Med Device Online to cover it.

There are actually, now, some de novos that are coming in. And they were under the radar, I think, because they happened infrequently. So, it’s a new pathway and it’s important to keep an eye on that.

Breakthrough Devices Program

So, breakthrough devices are unified here. We had some different access pathways in the past, but they’ve laid this out and explained – which I think was necessary – how we can use this.

I’ve seen a lot of people wanting to get in the program, obviously, because it gets quick attention and rapid response. And that’s good in two ways. As we were talking earlier, the idea is that you want to help people, and a company wants to get in business.

I put up a couple of examples here. These were actually cleared through the expedited access pathway which is now replaced by Breakthrough. But it is happening.

It’s good for patients everywhere and it’s good for the businesses, but it has to truly be that type of need that is going to do some very necessary things and help folks, so certainly a good thing to have.

Submissions involving cybersecurity

We’re all very aware of a lot of things that are going on. The incident recently in Atlanta caused a lot of concern just on the commercial side. But we all worry about those types of things in the medical device space.

So, here, they’ve given us guidance of what they are looking for. That really means that you need to evaluate your product or systems vulnerability, understand what risks there are and what things you’re going to do about it.

And the interesting thing is, it doesn’t end there. They really want you to discuss how things will be updated over time because we know software changes all the time and is easily changed. But, you have to think about this impact as well as the functional impact that it could have.

They’ve given some really clear guidance as to what they want to see when that is a part of your product. And the big thing is, they want to see that you are thinking about that part of the product. If it’s connected, as so many devices are today, we really need to think about potential cybersecurity threats.

Medical device accessories

Medical device accessories, for a long time, have been an interesting challenge. It was, if you were an accessory to a device, then you were a device and you were in the same class as the device you were connected to.

But they’ve really come out and turned on that a little bit. And I think that’s actually a good thing for industry because they’re trying to look at the accessory on its own merit – what really is this thing doing?

When I saw this, the first thing I thought of was the simple example of a respiratory mask. The mask is typically and traditionally classified by what it is used with. It’s not used by itself, but it can be used on a CPAP to help somebody. It could be used on a ventilator that is helping to keep them alive.

It depends on what your use is. It can be a Class II, it can be a Class III. So, those kinds of things make it important to be able to consider it on its own and not connected to the device.

You need to evaluate its risk level and how it could potentially interfere with the function of the device. But, it’s nice to see them open that door for us as well. So, those are the key pieces there.

Coming distractions

We’ll do a quick look forward here, relative to what I call coming distractions. So, these are the 2018 draft guidance documents. The interesting thing is the list of draft is, for this fiscal year, much longer than the ones for final.

And the ones that will be final guidance are specific and complicated, but I won’t read those to you. You can obviously see them. But I’ve got a couple of quick comments on them.

The Third-Party Review has been bandied about for quite some time. The program has been around for 20 years or more. They did put out some guidance in 2016, and it was a draft, but they’re coming back around next year to visit it again. So, I don’t know exactly what the bee is in their bonnet, but that one seems to be something that’s staying there.

They’re going to actually come around, again, with the pre-submission. They’re going to talk more about Q-Sub, probably give us more direction on it. So, I think that’s interesting as well to look at.

The abbreviated 510(k), which has not been used a lot except by companies for very simple follow-on products. So, all of these things are important things to be aware of and to stay on top of.

I know everybody’s already got a full plate, but it’s definitely an important thing to do.

So, I’m going to draw it to a close there. That is the end of what I had to present and the end of my time.

Joe Hage: Well, I have a question for you, and this is a way for us to help you.

As editor of Med Device Online, I suspect that you love scoops and good content. I suspect some of you here in the audience have good content to share that you’d like some visibility on Med Device Online? Show of hands? Meet the editor.

Bob, thank you very much. Let’s hear it for Bob.