Regulatory Tips & Pointers from a Former FDA Reviewer

As some veteran FDA reviewers leave and new ones are hired, knowledge is not always passed on seamlessly... To that end, regulatory professionals are often left to their own devices to find the guidance, support, and resources they need to fulfill their important roles in the medical device industry.

In this episode of the Global Medical Device Podcast, Jon Speer talks to Allison Komiyama, a former FDA reviewer who is an expert in regulatory submissions, quality systems, and biocompatibility evaluation.

Listen to Allison share her thoughts on what she wishes she had known as an FDA reviewer, providing valuable insights for regulatory professionals in the medical device industry.

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Some highlights of this episode include:

• New FDA reviewers are trying to navigate what’s important by asking questions because they have been working from home, never been onsite, and haven’t met their manager or other team members.
• FDA managers are trying to make sure that their teams get the training and mentorship that they need, but it is difficult and challenging.
• Deficiencies: What is four-part harmony? How are they written? List what was provided, what’s missing, what needs to be provided, and why is it needed?
• It’s not only the lead reviewer looking at the submission, but a team of people. Review the deficiencies and manage the additional information (AI) letter to ask relevant questions.
• To improve the speed of review and the time it takes for files, it’s important to support the reviewers and resources during that process.
• There’s just not enough time for FDA reviewers to read through and understand all the guidance documents put out by the FDA. Include guidance documents in files to help the reviewers and express how regulations are being followed.
• Recommendations for new reviewers: There’s what the regulation states, the legal definition, but how do you interpret the regulation? What does it mean, and how does it apply?
• There are different risks to different devices. For most questions, there are multiple correct answers that are acceptable for what the FDA wants. As a reviewer, you feel a huge burden of wanting to make sure nothing bad happens.

Links:

Allison Komiyama on LinkedIn

Acknowledge Regulatory Strategies

Regulatory Science Forum

FDA - Medical Devices

FDA - Guidance Documents

Breakthrough Devices Program (BDP)

Safer Technologies Program (STeP)

510(k) Submission Process

Premarket Approval (PMA)

Emergency Use Authorization (EUA)

David Pudwill (a.k.a. Mr. Regulatory) 

Code of Federal Regulations (CFR) Title 21

Medical Device User Fee Amendments (MDUFA)

Use of ISO 10993-1 Biological Evaluation of Medical Devices

Greenlight Guru Academy

Greenlight Guru YouTube Channel

MedTech True Quality Stories Podcast

Greenlight Guru

Memorable quotes by Allison Komiyama:

“We’re kind of dealing with a lot of new reviewers who are trying to navigate being a new reviewer and what’s actually important. We can see that reflected in some of the questions that we’re getting.” 

“I think the managers at FDA are doing an amazing job trying to make sure that their teams get the training and the mentorship that they need while they are there. But it’s hard.” 

“Sometimes that knowledge doesn’t get passed on as seamlessly as we all would want. From the industry perspective, one of the most beneficial things that we can do to improve the speed of review and improve the time that our files take to go through that process is really to support the reviewers.”

“One of the things she didn’t realize when she was a new reviewer was how diligent a lot of us in industry are at keeping up on guidance and the changes in regulations because that’s my job. That’s what we do.”

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.

Jon Speer: All right. I think my next guest knows this. But, regardless, I'll say it anyway. Allison Komiyama. Every time I talk to her, I just have a great time. I mean it's hard to imagine that somebody makes regulatory science fun. She seems to be successful at doing so. Allison is the owner at Acknowledge Regulatory Strategies. Checkout their website, acknowledge-rs.com. But on this episode of The Global Medical Device Podcast, she shares some thoughts. If you didn't know her background, there was a period of time in her career where she was a reviewer at FDA. And now that she's sort of on the other side of the equation so to speak, she recently had said something in a conversation that we were having, " And I wished I knew that back when I was an FDA reviewer." " All right, pause, let's record our conversation and talk about those sorts of things." So she shared some of these tips and pointers. So I hope you enjoy this episode of The Global Medical Device Podcast. Hello, and welcome to, The Global Medical Device Podcast, streaming to you live... or, actually not live, it's recorded. Streaming to you via audio and video. So if you're listening to us, as you normally do that's great. If you want to watch these episodes, they're on video now. So go to YouTube, check it out at the Greenlight Guru Channel. Be sure to subscribe to the channel, hit the thumbs up and the like, and the bells, and all those sorts of things that you do on YouTube. So that way you'll keep notified of that. But either way, if you'd just rather listen to us as you're walking your dog and taking out your trash, that still works too. So, I thank you. But, joining me on this episode of The Global Medical Device Podcast is Allison Komiyama. Allison is the owner of Acknowledge Regulatory Strategy. So, Allison, welcome back.

Allison Komiyama: Thank you Jon. It's so nice to be back with you, and also we get to see each other this time, so it's crosstalk.

Jon Speer: I know, it's been a bit. I mean, we were just catching up before the show about the last time that we connected. And it's hard to believe it's been over a year and a half ago. That just doesn't seem right. But I know we're all probably excited to get back and doing face- to- face things. We'll get into the show here in a moment, but you have an in- person event coming up later this year too if I recall, right?

Allison Komiyama: That is right. I'm hoping you'll come. It's going to be the Regulatory Alliance Forum in August. So-

Jon Speer: All right. I'm-

Allison Komiyama: ...it's in- person. And we're doing a smaller size, we can stay socially distanced and follow all the guidelines. But all the speakers were like, " Yeah, we want to be in- person. Let's all be vaccinated and be there." So I'm excited.

Jon Speer: Cool. All right. And we'll end a link to all the details about that event and the notes that accompany the show. But, you and I were on a call the other day. So Greenlight Guru, we recently formed a regulatory advisory board. You were so gracious to be willing to be part of that, so thank you for that first and foremost. And this group of people, which, I'm in awe in this group. Like, if you look at the backgrounds and the experience of these people, hey, I am like, it sounds weird maybe, but a kid in a candy store as far as regulatory is concerned. It's like, I feel like I'm at the All- Star game of regulatory viewers, maybe that's a better way to... I get autographs from all these people, and hear their insights and their wisdom. It's just a great group. But you said something the other day, I'm like, " Oh, that's a good topic." And the thing you said is, " Man," and I'm paraphrasing maybe, maybe it's a direct quote, but something along the lines of, " Man, I wish I knew all of these things back in the day when I was an FDA reviewer." And I'm like, " Let's talk about that." So, you used to be an FDA reviewer.

Allison Komiyama: For a very short period of time. I would not-

Jon Speer: This counts.

Allison Komiyama: ... it was nota very... People are there 15, 20 years, oh my God, I can barely hold a candle to that. But yeah, it counts, thank you, it counts.

Jon Speer: It counts. I mean, you were an infant for a very short period of time, but you still were an infant.

Allison Komiyama: That's true, well said, yeah.

Jon Speer: All right. So when you were there, I mean, if I recall too you were like a biocompatibility expert, right?

Allison Komiyama: Yeah, yeah. I was the bio- nerd that worked as a consult on different files, which I loved.

Jon Speer: And just in order of magnitude, not that it really matters, but how many submissions were you part of reviewing in your period of time at FDA?

Allison Komiyama: I mean...

Jon Speer: Hundreds?

Allison Komiyama: Not as a lead reviewer. No, I wouldn't say-

Jon Speer: Not as a lead reviewer, but hundreds probably?

Allison Komiyama: Probably 50 to 100, somewhere in there, yeah.

Jon Speer: Okay, so you saw a lot of things, a lot of things.

Allison Komiyama: crosstalk saw a lot of things. I mean, I would say on any given day most reviewers will have 10 files that they're working on actively. But you also have consults. It's a lot of the smaller projects that you work on. And I was also doing research. So I was farmed out to the folks over in OCEL which I loved. It was like a mini-postdoc that I got to do when I was there.

Jon Speer: Yeah. So, now fast forward, a few years later at Acknowledge Regulatory Strategies, I mean, you're doing a lot of regulatory strategy, submission preparation, I guess-

Allison Komiyama: It's in the name, yeah.

Jon Speer: Well okay, duh. But sometimes it's not obvious. But I mean, what types of services are you providing to companies these days?

Allison Komiyama: Sure. So we really stay on the premarket side of things. So we do a lot of regulatory strategy. So we work with mostly smaller startups, anywhere from like 1 to 10 people on their staff. And try and help them figure out, " Okay, what does your future regulatory pathway look like?" It's not always clear, right? There could be five different pathways, and do you do a precept first, did you go through breakthrough designation first? Should you forego all that and just go straight to your premarket submission. So we do a lot of 510( k) s, a lot of precepts, you know, recently breakthrough designation requests. Working on a couple secret technology program applications as well at the moment.

Jon Speer: Nice. All right. So the comment you made, man, I wish I knew these things when I was a FDA reviewer. I don't know if you have a top 3, 5, 10, 38, but what is one of those things that you wish you knew?

Allison Komiyama: Sure. And I'll start with saying, I actually went and asked a few folks that are either still at FDA or since left FDA as well, what their take was on this. Because I said, " I've been thinking a lot about new reviewers that are at FDA." And we've had quite a few as our lead reviewers on files recently, where they've never actually been in the building. They are really new employees, they're working from home, they've never met their team in person. Their manager sometimes they haven't met in person. So we're kind of dealing with a lot of new reviewers who are trying to navigate being a new reviewer, and what's actually important. And we can see that requested in some of the questions that we're getting, I think the managers at FDA are doing an amazing job trying to make sure that their teams have the training and the mentorship that they need while they're there. But it's hard. And it's hard when you're there in person. I remember sitting down and looking at files, but I'm like, " What am I doing here? What is four- part harmony?" So that's actually one of the first things I was thinking about is, deficiencies and how deficiencies are written. You're usually trained... or you're supposed to be trained to provide what's called four- part harmony in each deficiency that you write. And you're supposed to list, what was provided in the file, what's missing? What needs to be provided to answer this question or answer this deficiency, and why do they need it? What is the regulatory or science of the question that it's going to address? So, its becoming very savvy at understanding how to craft those deficiencies in that AI letter that gets sent to sponsors. And the other piece is also, how do you manage your team, your consults on the file? You know, it's not just the lead reviewer that's looking at your submission, it's a team of people. And so oftentimes, what I found one of the most challenging things, is to take the deficiencies that are coming back from these various consults, that is my team that's helping me to review this file. And to look at their deficiencies and make sure that I'm managing the entire deficiency letter. I think what can happen is, the lead reviewer will collect all the deficiencies and then just compile and send it out. When really, in best practice it's going through, making sure all of your consults are asking relevant questions. Is this really an important question? Is it truly something that is deficient about the file? And then having that conversation with our consult. And I think, it's hard to back down after you've sent that AI letter out, once you've asked those questions, to say, " Oh, actually, never mind, that's not important." Right?

Jon Speer: Yeah.

Allison Komiyama: You kind of have to keep moving forward. So yeah, I think that's one of the big ones that I've felt, " Wow, I really wish I had just had been trained more on what that needs to look like."

Jon Speer: Yeah. Well, and I'm sure you've got a few other things that are top of mind for you or through your connections and network. But part of what I'm curious about too, I mean you just mentioned that a lot of these reviewers, they've never been in the FDA office. They've worked their entire time at FDA has been remote. And sometimes they haven't even met the teams and their colleagues from FDA. I think there's that. And that's probably a huge factor in this. And then, I was just catching up with another peer the other day. And she was sharing with me... we were talking about breakthrough and STeP as you mentioned. But she was talking about some branch or some divisions are no longer receiving pre- subs for the rest of the year. I think one of them was the IVD side of them, like, "What? It's the middle of the year, still a lot of 2021 left." And then we talked a little bit further, it was like, " Oh, well they've been so inundated with EUAs on the IVD side of things, that they're borrowing resources from other groups within the agency too." So I got to imagine that all of these sorts of things are creating some of the challenges that our industry is seeing right now.

Allison Komiyama: Absolutely. I think, they called it surge review, or there were different groups that were borrowing reviewers from other branches that weren't as impacted by COVID. And it was tough. I mean, I do not envy what they have had to deal with in the past year and a half. I think, there are a lot of people that have left. A lot of people said, " You know, this is the right time for me to retire now." And so they're seeing a lot of the veteran reviewers and people that have been there a long time leaving, and then also trying to hire. And sometimes that knowledge doesn't get passed on as seamlessly as we all would want. I think from industry's perspective, I often feel like one of the most beneficial things that we can do to improve the speed of review, and improve the time that our files take to go through that process is really to support the reviewers. I think we often will see upper management making decisions or putting guidance out there and saying, " Hey, this is a great idea. This is a program that we're hearing industry wants, and we're going to roll it out." And the reviewers are there trying to scramble and understand, " Okay, what does that actually do? How does that actually impact my day- to- day review and the resources that I have available to me." I think that's a disconnect. And I wish that industry could say, " Okay, how do we support the reviewers so that we can help them manage those two voices that are coming at them-

Jon Speer: Yeah. Well, I mean, you mentioned guidance documents, and I've heard this before, and I don't know, I've not sat in the seat. But in a particular submission somebody was sharing that they had sided or followed a particular guidance document for their product or whatever the case may have been. But they got a lot of questions from the reviewer that were counter to what was in the guidance document. And it's like, now you got to dance this dance. It's like, " Ah, me as the submitter of this information, I'm trying to... I've got this guidance and it's from FDA." And here this reviewer is saying things that are the opposite of that guidance document. And it's like a head scratcher. Like, how do guidance documents... Do reviewers get this information? Do they not get this information? How can I help if I'm submitting, say, " Hey, here are these guidances from FDA that we follow." I mean, is that a realistic scenario that happens often, or do you know?

Allison Komiyama: Absolutely. Yeah, it's funny you bring it up. Last year at the Regulatory Alliance Forum, one of the former directors of one of the groups who will remain unnamed, she said, " I have to be honest. I didn't read most of the guidance documents. They were very long, there's one every day that seems to come out right now. I don't have the time to go through them." So you have all these files sitting on your desk that you need to review, when do you have time to go read the breakthrough guidance document? When do you have time to go crosstalk in-

Jon Speer: Yeah, I mean, your already late.

Allison Komiyama: Exactly, right? So, yeah, I think that could be something that FDA could work on. How do you make sure that the reviewers are really up to speed on all the guidance documents that you're pumping out there all the time. I think, from my perspective now, one of the ways we do it is try to incorporate the guidance documents into our files, to make sure we say, " Hey, this is what you said. This is from certain press releases. We're getting this language from you."

Jon Speer: It's a good tip.

Allison Komiyama: Not to make them feel bad or today you rub it in their faces, it's more-

Jon Speer: Just to help them out.

Allison Komiyama: ...yeah. Like, here, let's talk about what your agency has said and what we're trying to follow, we're trying to follow your lead. And one of the comments that came back from one of my buddies, she said, " You know, one of the things..." She didn't realize when she was a new reviewer, was how diligent a lot of us in industry are at keeping up on guidance and the changes in regulations. Because that's my job, right?

Jon Speer: Yeah, that's what we do.

Allison Komiyama: So my company... that's what we do. And in my company, every Thursday we have a journal club. And the journal club, it's kind of like when I... It goes back to my days in academia, we'd have journal club. We'd talk about cool journal articles. And that's what we do. We take the guidance document that's new. One of us will go through it and try to distill it and provide an output, saying, " Here's what I take away from it and what we should all keep on task." And actually, David Pudwill, he is Mr. Regulatory, I know you've interviewed or you've had him on this as well. Fantastic service. I mean, he has the Mr. Regulatory Guidance Digest. And he really makes it easy to understand and walks you through. So, you know, what new guidances are out. So, can't speak highly enough about what he's providing. And I hope, and I believe that FDA reviewers are also consuming some of this content. And I know that they listen to your podcast.

Jon Speer: Well, I mean, maybe this is the craziest thing I've said, probably not, but maybe it's the craziest thing I've said today. Have you ever thought about, when you do your review, your journal club, your guidance review club, have you ever thought about just like setting up a camera and recording it, and then publishing it? Because I mean, that might be good stuff, right? I mean especially for regulatory nerds.

Allison Komiyama: crosstalk. Yeah. I have thought about it actually. I think the hardest thing is, we talk oftentimes very candidly about how does this impact the current clients. So we'd probably have to have-

Jon Speer: Yeah, all right, that's-

Allison Komiyama: ...like an open session, and then a closed door session. Or have everybody under a big NDA. So, you're making me think, Jon. This is quite crosstalk.

Jon Speer: Yeah, anyway. And then you just get it to all the reviewers at FDA and they're like, " Oh, well let's listen to Allison and her team review crosstalk standards and guidances."

Allison Komiyama: ...to go part of the training that they do.

Jon Speer: Seriously. I mean, it seems to me like in the past, certainly two years, but recently for sure, that the volume of guidance that is coming is crazy to me. I don't know why. And it's like, well if there's so much emphasis and time... somebody's writing those things, you know? There's so many resources that are being spent preparing these things, somebody thinks they're important for some reason. It seems like that would be worth at least knowing more about, or doing a better job. I mean, I don't know, that's probably a whole different topic for a whole different day.

Allison Komiyama: That's a great point. I mean, how do you... it's supposed to be FDAs current thinking, right, when a guidance document comes out. But we've seen it-

Jon Speer: It's just confusing when it's not.

Allison Komiyama: Right. Yeah, because there are separate different groups at FDA and they say, " Well, we see that guidance and we read the guidance. Maybe they didn't read the guidance. But that's not how our current thinking at our branch. Which I know is not supposed to be how it works. But that is true. And there are different risks to different devices, right?

Jon Speer: Sure. Absolutely.

Allison Komiyama: I'm mean, there are some very low- risk class II devices in my opinion. And then there's some very high risk class II devices. And to try and say that they're equivalent in risk and how you need to review it, and what are the biocompatibility effects of those things? It's just not possible. So I know that, yeah, it's not a one- size- fits- all for all the different branches of the FDA. You know, I had a really great conversation. There's a person who just left FDA a week or two ago, and we just had a conversation. And one of his comments, I asked him the same question like, " What recommendation would you give if you're inaudible. Oh, you know one of the biggest things that he really focused on was, there's what the regulations say, right? There is the legal definition, and here's what 21 CFR says. But really, how do you interpret the regulations? What is the spirit of the regulation? What does it mean and how does it apply? I think there are a lot of new reviewers, or just reviewers in general that will just go to the letter of the law, right?

Jon Speer: Yeah.

Allison Komiyama: Another consultant I talked to, he said, " You know, I was reviewing things my first year, I've just been trying to make for substantial equivalents. You're just trying to make sure everything's identical. Identical to the predicate. Because that's what I was told, it has to be equivalent to the predicate." But the whole point of the 510( k) program, or one of the points of the 510( k) program is that there are going to be differences.

Jon Speer: There's gray.

Allison Komiyama: crosstalk pathology. There's got to be some design improvements over time. And it can be slow improvements over time. But the question is, is that an appropriate predicate? And is the clinical use of this new method, does it raise different questions in safety and effectiveness? Those are the questions. And you know, I'm trying to interpret the flowchart, right, the 510( k) flowchart, and trying to understand again, what does the regulation mean? How does it apply to the device? And how do you ask relevant questions? How do you really understand the fundamentals of the device? And what does that mean with regard to risk?? And is it clearable, right? I think for most devices, and I think when they do them inaudible, or they're talking about their goals at FDA, what are the shared goals? How are they asking the right questions? And I think a big part of that is, understanding the regulations and really understanding a sphere of the regulation page.

Jon Speer: Yeah, I'm sure. I'm sure. I want to take a quick break. I want to remind folks I'm talking with Allison Komiyama. Allison is with Acknowledge Regulatory Strategies. You heard her share a little bit about what her and her team do, and how they help companies. You can learn more about their products and services by visiting their website acknowledge-rs.com, and I'm sure they'd be thrilled to have a conversation with you and leverage some of their expertise. And speaking of companies that are here to help, this is what we do at Greenlight Guru. We're here to help as well. So, we have the only medical device quality management success platform on the market today, designed by actual medical device professionals for medical device companies. Novel concept, I know. But we've got workflows to help you manage your design and development, document and records management, as well as postmarket quality events, postmarket surveillance, things of that nature. And that's a big deal. You need to be able to manage that total product lifecycle of your medical devices. So, check it out, learn more. Go to www.greenlight.guru, and we'd be thrilled to have a conversation with you, and see if we might be able to help meet your needs and your requirements. So, Allison, you said something a moment about about that review process. And one of the things that's sort of always been intriguing to me is that, it feels like, or has felt like in my past... and maybe this has hopefully changed, or maybe this is... you haven't had this experience. But it's always felt like, that me as a submitter of 510( k), whatever, pre- sub, whatever the case may be, that I was struggling to communicate with the reviewer. I felt like we were just reading from a different book, or speaking a completely different language. And I remember one thing in particular, it drove me crazy. But I'll open that wound up a moment and share. But I was working on a 510( k), this is a little bit of the way back machine. And the product had a material that we weren't making this material, we were purchasing it. And there was like three suppliers in the world for this particular material. And there's a complete master file on file at FDA. It wasn't a drug, it was a polymeric material that had a full battery of everything for this specific indication for use. And now, I didn't see the contents, the company is proprietary. But the company did send me a letter and say, " Hey, yes. FDA can access this file. We give you our permission for the FDA to access this on your behalf. Can't share with you." But then I was asked to do the full battery of tests anyway. And I was like, "That just didn't make any sense to me at all." And I wonder if it was one of those moments where there was like this literal interpretation of something that was written and not necessarily thinking about, " Okay, well, we already have this body in knowledge from the supplier on this material for everything that would be needed for that body contact and duration." I don't know, that was a... I didn't really do a good job of asking a question there. Hopefully you're tracking with me, and I-

Allison Komiyama: Yeah, I'm with you, man.

Jon Speer: ... kind ofcrosstalk. So, listen I'm just grabbing my plug here, I'm going to die in the middle of this thing.

Allison Komiyama: Oh, at least then talking to myself, it was your crosstalk.

Jon Speer: I should've planned ahead, I just didn't do a very good job of that. But does anything I just said make any sense at all as far as like-

Allison Komiyama: crosstalk them, yeah. Gosh. I feel like you just kind of reiterated something that happened a couple weeks ago, something I was working on. Like, wow. So history repeats itself. I think the-

Jon Speer: Well, and I think product compatibility is one of those topics in particular. It's just like people need to have... I mean, I believe the regulation is clear. It says, I'm paraphrasing extremely here but, " Oh, if there's evidence that you can provide to support that it's already been addressed then you don't need to redo it." But that doesn't seem to be the case. But anyway, I cut you off, go ahead.

Allison Komiyama: No, I think BioComp's a really good example. Because I think there's a clear standard, ISO 10993, or dash one, and that's the overarching standard for all of the subparts that's standard. And FDA has a guidance on how to use 10993, and they came out with an additional website recently that says, " Here's how to look at your device and how to decide what sort of testing you need." And as a person who was a consult, a BioComp consult on many of these files, I could say that that's... I sort of went through as a checklist. I used it more as a checklist for the early files that I worked on. And it pains me to say that. Because I feel like, I know seeing it from this side, gosh, it shouldn't be, right? It really is supposed to be a risk- based approach. You're supposed to use the wealth of information that you have maybe on the material to decide whether or not additional testing is needed. I feel like FDA comes out with, they want to reduce the amount of animals that they're using in testing. There's a global effort to try and reduce animal testing. For sensitization testing for example, I talked recently to a lot of different test labs, three or four of them. And I said, " How many times have you seen a sensitization test come back positive with a bad result?" And they said, " This many." Every single ones that you know. That test, everyone's got to do it. If you have something that's touching-

Jon Speer: I had a theory and I'll explain it here in a moment. But go ahead.

Allison Komiyama: Yeah. They've all said, " Nope." How sensitive is that sensitization test? And also how relevant is it to demonstrate that there's really going to be biocompatibility concern. This is a bigger conversation than for us.

Jon Speer: Oh yeah, yeah.

Allison Komiyama: But you know, so yeah, I mean, how do you leverage master file information? How do you use real- world evidence, or clinical testing that you've gathered? And also looking at, what are the reports on... If it's a consumer product, right? If there actually a material that's used regularly on a consumer product, is that causing sensitization or irritation? So there's a lot of information out there. And I would say to my earlier self, that if I had been working at FDA, like don't use it as checklist. Like, really try to understand, what are the important questions? Is there something that could be toxic on the material that's a residual left behind? If that likelihood is low, or if that risk is low, do you need to go off and kill a bunch of guinea pigs. You know, those are the questions that I feel like younger Allison hopefully would have been receptive to.

Jon Speer: Well, I mean, here's what I've learned through my life, and it's taken me a while to figure this out. Is that, for most questions, there are multiple answers that are acceptable. And I think though that it's a human nature thing. And I think industry is guilty of this too. I think industry is super guilty of, " Well, what does FDA want? What do they want for this? What do I need to include?" Blah, blah, blah. So they're asking to be spoonfed, except that sometimes when they're being spoonfed, they don't like how it tastes. And it's like, " Well, think for yourself, step back," but you know, I think that's a big lesson. Sometimes there is more than one right answer. But the sensitization test that I had back in the day that failed, we had an antibiotic impregnated catheter that was impregnated with.... I was trying to think, those shares aren't proprietary, but this is all public domain... that was impregnated with two antibiotics, Rifampin and Minocycline. One of them I can't remember had a orange rusty color in the nature, and the catheter itself, once it was impregnated, had that color. So it was a hideous looking catheter. But it was impregnated with antibiotics to prevent catheter related bloodstream infections. And my memory could be off. I've had a lot of bourbon since this happened, and beer, and I'm old. But, I think sensitization, isn't that the one where there's like a color component to the pass/ fail criteria? If you look at the color of the serum in the vial or something like that?

Allison Komiyama: I mean, you're supposed to always look at the changes in coloration. crosstalk I'm not sure how that impacts the sensitization, yeah.

Jon Speer: Well, in this case when they did the extraction, the color of the vial looked like the color of the antibiotic. So it was like, instead of being... it's supposed to be like clear, colorless, or slight tint. Well, ours were coming like clear, but bright orange, rust color. And so that was a failed test. So then it was like, now that created a different challenge. Like now we had to explain why this test was not valid, or this particular product. But you know, it's a challenge. All right, so-

Allison Komiyama: You know, I just want to... at a point, when I know I've been telling to any manufacturers that do any of the extract testing, ask the test lab to make sure they're taking measures of it. Because oftentimes it'll come back and they'll say it's tan, or it's orange, or it has particulate. And oftentimes having the image of what that actually means is very valuable for if and when FDA asks questions about it. So-

Jon Speer: For sure.

Allison Komiyama: ...just said, got it. Because we do get questions like that from FDA. I think your point earlier about, just right before you were talking about the sensitization test. I was thinking about, as a reviewer, you feel a huge burden of wanting to make sure that nothing bad happens on your watch, right? Like, I think there is a huge, you live by the mission, to protect and promote. And I felt so strongly that I didn't want anything on my tenure while I was reviewing something, to go off and injure someone and cause damage. No one wants that to happen, right? And so, you ask the questions, and you ask a lot of questions. Or if there are things that you don't think quite meet your standards or meet the... I'm sorry, the standards that FDA sets, and that meets the substantial equivalents if you're doing a 510( k). I think there's got to... I will say, of all the 510(k)s that were submitted, De Novo's resubmitted, I've only ever had one that had zero questions back, right? Every crosstalk.

Jon Speer: Yeah, it is a rare-

Allison Komiyama: Right? And as you say, industry wants to know, " Well, what's FDA going to ask?" How do we manage... and I want to submit a perfect file. Like how do I do it? I don't want them to ask any questions. Now like, that's just an impossibility. I've one had one, again, once. And that was a pretty straightforward file, and I couldn't believe it. It just got cleared. We didn't even know who the reviewer was. And there's this-

Jon Speer: And like I tell people all the time too... sorry to cut you off but-

Allison Komiyama: Yeah.

Jon Speer: ... whatI tell people, if I could predict what questions the FDA were going to ask, don't you think we would put that in the submission. And if I could predict such things, you would never know me. Because I would already have an island somewhere. Because I would have already made a bazillion dollars selling my trade secrets to people.

Allison Komiyama: Exactly, bye, I want to go inaudible island.

Jon Speer: Yeah, there's going to be questions. I mean, I think it's just good preparation, mental preparation for those who are submitting, you will have questions. And there will be things that you haven't thought of, just know that. Some of them will be simple, and maybe just clarifications. Others might not be. So, you just got to prepare for that.

Allison Komiyama: There is strategy, right? There's strategy to what you submit. And I feel like, all my friends that were FDA reviewers that are not in industry, the unanimous thing that they all say is like, " I wish I had known what was actually important. Because there are some questions you're like, " Oh my gosh. Would I have cared about that one detail?" Probably not anymore. This was the big burning question, and this really shouldn't have held the file back from getting clearance. I might have asked a question about it. But really, what were the major deficiencies? And we all joke about, " Gosh, wouldn't it be nice if we could say,'Listen FDA, I'm sending this file in, and here are the two sections I really think you should focus on, and where I anticipate you're going to have the biggest questions,'" but of course, I have clients that crosstalk.

Jon Speer: Don't want to lead the witness, right?

Allison Komiyama: Exactly.

Jon Speer: But I think it's like the whole process... and I know it's gotten better in recent years. But I mean, back when I started it was definitely a throw it over the wall and cross your fingers type of process. Where you didn't have any dialogue, or collaboration, or interaction with the agency. You did what you thought, and largely it was informed by the success or failure from the last time that you did this. And then you send it in, and you waited. And you didn't have any confirmation. I think the mail center probably sent a note that said, " Yep, got it." But you didn't really have any confirmation, and definitely no interaction until day 60, sometimes day 90 you get a list of questions. And you're like, " Oh my God." But then you did it all. There was no communication. It was just static things back and forth. And it's still kind of like that. It seems to me that, " Whoa, can we just take a page out of the pre- sub book when it comes time for the 510( k)?" At least get everybody in the room after all the reviewers and the consults have had a chance to review. And then, bring any and all questions and let's talk through them, and let's figure out together as submitted and reviewer, maybe we can figure out what's the big deal and what's not the big deal? That way we can both be on the same page. It just seems like there's an opportunity there, but that may not be that pragmatic.

Allison Komiyama: I agree. I think the most successful files we've had in the past two years, especially since COVID, because everyone's working remotely, is that anytime where we can get the reviewer on the phone... like there are times when it's just like, " Oh my gosh, the emails back and forth, and especially FDA has said, put it under preset, put in a preset." It was like, " Oh, if you'll just get on the phone with us. Honestly, it'll take 5 to 10 minutes, and we can get so much accomplished." And I think a lot of reviewers are very hesitant to do that. They think they're going to be put on the spot. They think that the CEOs going to get on and yell, you know, at FDA. And that's really not the case. It's like, help us understand what you need. Because I think one of the misconceptions at FDA, and I felt it, it was, " Gosh, industry is... they're going to try and pull one over on us," or, " They're all shady." I didn't feel that way. But you know, you'd be like, " Oh, gosh, I'm here to protect and promote public health, and that's my job." But I think what you forget is, that's also industry's job. I don't have any client that I can say that-

Jon Speer: Yeah, I know.

Allison Komiyama: ...however said, I have no clients that feel like this is just a big business enterprise, I don't care about patients, I'm doing this for money. That's never like... I guess that I don't bring those clients on to my crosstalk portfolio, but I might. Everyone has so much crosstalk.

Jon Speer: Those people exist.

Allison Komiyama: Yes, there's a crosstalk.

Jon Speer: I mean, those people exist. But I mean, I was talking to somebody the other day about, they were new to the industry and they had mentioned some negative thing that they heard. I'm like, "Well, okay. I'm not naïve, certainly these things happen." But I surround myself, or throughout my career I've been very blessed that the people that I interact with, the medical device professionals that I interact with, they care about improving the quality of life. And they put that at the top. That's like their North Star. That's the main thing that guides them in their day- to- day. And I think that there's always bad apples, but I think generally speaking, that's who we're dealing with in this. And there's some people that actually care, you know?

Allison Komiyama: Yeah. Yeah. Absolutely. And that's what's so heartbreaking sometimes. Is when it comes to benefit risk a device, or it comes down to the last push to get something cleared, or granted, or approved is, " Gosh, are we going to deny something, or deny this technology getting out there that is found to help a lot of people because of one small thing?" And you know, it might, again, we have to make sure we answer all the questions, right?

Jon Speer: Sure.

Allison Komiyama: We have to make sure that we've made every consult and the lead reviewer happy on the file. It's just weighing those different things. Again, we get back to the guidance documents. FDA has done a fantastic job providing guidance on benefit risk and how to use it in-

Jon Speer: Yes they have.

Allison Komiyama: ... inregulatory decisions, right? And I had a reviewer recently who said, " Oh gosh, could you put some of that additional information into your response? And that should be really helpful." And I don't know if she had read that guidance or even knew it existed. Yeah, so, I'm happy to do it. That's the stuff that, if that makes her sleep easier at night and feel comfortable making the final positive decision, absolutely.

Jon Speer: Yeah. And you know, I guess I'll say this for both industry as well as agency, if you're listening. We try to on a global medical device podcast, we try to cover quite a bit of things regulatory related, submission related. Allison mentioned the Mr... Or, Mr Pud... well, all I can say is Mr. Pud. Well, David Pudwill, Mr. Regulatory, he has a YouTube channel that he goes through some guidances and different aspects of regulatory. You guys at Acknowledge, you're pretty prolific on the writing side of things, right?

Allison Komiyama: Yeah. We love... so we'll have like medical device Mondays which we love. And that talks about cool new devices that FDA has recently cleared or approved. And we just kind of geek out. I mean, none of crosstalk. It's just stuff that we've seen come off the FDA press, news press and that. But the other one... we'll have another one coming up shortly to your, FDA Friday, it's been fun to interview former FDA reviewers and just see... You know, ask them questions like this. Ask them questions about, " What was your experience like at FDA? What was the good? What was the bad?" And I love that. And actually, a lot of FDA reviewers read it. They have some... When I was at an FDA pre- sub meeting a year and a half ago now, someone said, " Oh, you're the inaudible the blog lady." I was like, " Oh, am I?" Yeah, that's some crosstalk.

Jon Speer: The blog lady, that's what I'm going to call you. That's what I'm going to call you from now on, the blog lady.

Allison Komiyama: The blog lady. It was nice. I feel like that's... I am so impressed with the Greenlight Guru has been able to accomplish-

Jon Speer: Thank you.

Allison Komiyama: ... and the amount of content thatyou are able to put out. Because it impacts, it helps industry. Because people can better understand, you know, what's the difference between intended use and indications for use? What's going on in cybersecurity and software? And I know that FDA consumes that content as well. Because it's good for them to know industry's perspective on what they're doing in- house.

Jon Speer: Yeah. And thank you. To me, that's the most important thing that we do at Greenlight Guru. Yeah, we have an awesome software platform, but we get to collaborate with people like Allison Komiyama, and many, many other experts in this industry. And we are fortunate that we have a large subscriber network, folks that are consuming. But you know, I've been through it. I know how frustrating it is to read a guidance or regulation and be like, " Okay, I know what all of those words that I just read mean. But when you put them in the combination in the way that they were put, I have no idea what that means." So sometimes it's helpful to have somebody that can say, " Oh, okay, well here's what that means, and why it means that way. And here's some supporting evidence to corroborate that." So I think that's a really important objective that we try to do at Greenlight Guru. So I appreciate the comment. Wrapping things up today. Any last minute thoughts, tips, pointers, advice, anything that fits into that bucket?

Allison Komiyama: Just on to the last point. I think the most successful reviewers in my perspective, the ones that I see nailing it and getting their files off the table and getting things done and prepared. The ones that are willing to pick up the phone, or the ones that are willing to be collaborative. I had a conversation recently with someone from the breakthrough designation, by the breakthrough program. And their comment to me was, " The most effective use of the program is when it is collaborative." When the reviewers team and the industry team can see eye- to- eye, see the value of the program, and work collaboratively to move things forward. Otherwise, you have designations, but it doesn't benefit you. And the reviewers just say, "Oh gosh, it's just more resources, and I'm too busy to actually review and do sprint discussion." But I see that across the board. Anytime that it can be an open dialogue, that's it going to be, " Hey, help us understand what it is you actually need," and not to recommend a pre- sub for every single interaction. Those are the ones that really get done quickly. And it goes back to those shared goals, right? It actually reduces the amount of time that a file actually takes to review.

Jon Speer: Yeah, it's a good tip.

Allison Komiyama: So, I'm optimistic. There's a lot of new reviewers at FDA. They think scientifically, and I'm just excited that maybe we'll be able to go back in a year or so, to go to meetings and some in- person-

Jon Speer: That'd be great, yeah. I mean, I know FDA reaches out to industry from time to time for folks to come in and provide training and this of that nature. They had a program there a couple of years ago, I can't remember the name of it, but hopefully that comes back. Because I think those were great opportunities for industry to share with the agency. Allison, thank you. We should do this more often. I know we say this every time we do this, but this time we're going to make sure that we do this more often. I know you have lots of insights, nuggets, and all sorts of wisdom that you can share. Although it was only for a short period of time, you've been on both sides of the fence. So that knowledge is invaluable. Plus even though you may have only been there a short time, you're connected with this whole network of folks who also used to be with the agency. You have conversations with them on the regular. And I know that you're extracting additional nuggets of wisdom and all sorts of knowledge from them as well. So, thank you. And folks, check out Acknowledge Regulatory Strategies, acknowledge-rs.com. Attend their upcoming event, or at least, I think you can do it virtually, even if you can't do it in person, right? If I remember, the Reg AF event?

Allison Komiyama: Yeah. If you're not going to be vaccinated, there is the option to attend virtually. Yeah.

Jon Speer: All right. So we'll get you all that information so you could check it out. As always, thank you for being listeners and watchers of The Global Medical Device Podcast. Again, hit that subscribe, click the bell, thumbs up, whatever is applicable and appropriate in this case, do all of that. So that way you get up to date information about when new episodes are live. And as always, this is your host and founder at Greenlight Guru, Jon Speer. And you have been listening to The Global Medical Device Podcast.

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