WEBVTT 00:00:00.000 --> 00:00:02.120 You probably use medical devices every single 00:00:02.120 --> 00:00:04.540 day, maybe from a simple bandage to perhaps something 00:00:04.540 --> 00:00:07.860 a bit more complex, like an oximeter or even 00:00:07.860 --> 00:00:10.919 an implanted device. But have you ever stopped 00:00:10.919 --> 00:00:13.720 to think about how these vital tools are regulated 00:00:13.720 --> 00:00:17.260 to ensure their safety and effectiveness? It's 00:00:17.260 --> 00:00:19.179 quite a complex world behind the scenes, isn't 00:00:19.179 --> 00:00:22.059 it? It absolutely is. And, well, it all starts 00:00:22.059 --> 00:00:24.719 with how these devices are defined and classified. 00:00:25.339 --> 00:00:27.480 That initial decision, as we're about to sort 00:00:27.480 --> 00:00:30.730 of dig into, isn't just paperwork, it's really 00:00:30.730 --> 00:00:34.109 a strategic pivot point for innovation and, crucially, 00:00:34.359 --> 00:00:37.439 patient safety. Exactly. So our mission today 00:00:37.439 --> 00:00:39.539 is to take a deep dive into that foundational 00:00:39.539 --> 00:00:42.320 first step of medical device regulation here 00:00:42.320 --> 00:00:45.060 in the United States, basically how the FDA defines 00:00:45.060 --> 00:00:47.140 and classifies these essential tools. That's 00:00:47.140 --> 00:00:49.600 right. And by the end of this deep dive, you'll 00:00:49.600 --> 00:00:52.060 hopefully have a clear understanding of the FDA's 00:00:52.060 --> 00:00:54.979 risk -based classification system, why it matters 00:00:54.979 --> 00:00:57.460 so much, and how it really shapes the entire 00:00:57.460 --> 00:00:59.960 development roadmap for medical devices. Yeah, 00:01:00.100 --> 00:01:02.299 we'll be pulling insights from, you know, the 00:01:02.299 --> 00:01:04.459 official code of federal regulations, expert 00:01:04.459 --> 00:01:06.900 analysis, and plenty of real -world examples 00:01:06.900 --> 00:01:09.180 to guide us. Okay, let's unpack this. Where do 00:01:09.180 --> 00:01:12.879 we start? The definition. Yes, exactly. What's 00:01:12.879 --> 00:01:15.219 crucial to understand right from the outset is 00:01:15.219 --> 00:01:18.260 that the FDA legally defines a medical device 00:01:18.260 --> 00:01:21.700 very differently from a drug. The core distinction 00:01:21.700 --> 00:01:24.060 really lies in their primary mode of action. 00:01:24.409 --> 00:01:27.310 So devices achieve their intended purpose through 00:01:27.310 --> 00:01:30.030 physical or mechanical means. Oh, okay. So think 00:01:30.030 --> 00:01:32.969 of something like a stethoscope or maybe a pacemaker. 00:01:33.569 --> 00:01:35.709 Precisely. They work through physical presence 00:01:35.709 --> 00:01:38.329 or mechanical function within the body. They 00:01:38.329 --> 00:01:40.129 aren't achieving their primary purpose through 00:01:40.129 --> 00:01:42.870 chemical action within or on the body or being 00:01:42.870 --> 00:01:45.250 metabolized. Right, right. That's the key drug 00:01:45.250 --> 00:01:47.109 differentiator. They're not being metabolized. 00:01:47.489 --> 00:01:49.769 Exactly. So this distinct regulatory framework 00:01:49.769 --> 00:01:52.769 for devices really emphasizes product safety, 00:01:53.040 --> 00:01:55.840 performance and quality throughout the device's 00:01:55.840 --> 00:01:57.959 entire life cycle. It makes perfect sense, really, 00:01:58.099 --> 00:02:00.719 for ensuring safety. It does. And here in the 00:02:00.719 --> 00:02:03.739 U .S., the FDA primarily oversees medical device 00:02:03.739 --> 00:02:06.239 regulation through its Center for Devices and 00:02:06.239 --> 00:02:10.250 Radiological Health, or CDRH. CDRH. Got it. They're 00:02:10.250 --> 00:02:12.169 the main players. They're basically the central 00:02:12.169 --> 00:02:14.949 hub for all things medical device at the FDA. 00:02:15.150 --> 00:02:17.909 So once the FDA has this definition, how do they 00:02:17.909 --> 00:02:20.270 categorize devices? I mean, I imagine not all 00:02:20.270 --> 00:02:22.930 devices pose the same level of risk, right? Yeah. 00:02:23.090 --> 00:02:24.669 And that must fundamentally change the whole 00:02:24.669 --> 00:02:26.629 process. You've absolutely hit on a critical 00:02:26.629 --> 00:02:29.389 point. Devices are sorted into three main classes, 00:02:29.530 --> 00:02:32.169 class one, two, and three. And it's all based 00:02:32.169 --> 00:02:34.550 on their potential risk to patients and the level 00:02:34.550 --> 00:02:36.949 of control needed to ensure safety and effectiveness. 00:02:37.150 --> 00:02:39.819 OK, three classes. And you're right. control 00:02:39.819 --> 00:02:41.960 the requirements, they increase significantly 00:02:41.960 --> 00:02:44.300 as you go from Class I up to Class III. So this 00:02:44.300 --> 00:02:46.319 sounds like a really foundational decision. It 00:02:46.319 --> 00:02:49.300 dictates the whole path forward for a company 00:02:49.300 --> 00:02:52.560 and its product. It truly is. This initial classification 00:02:52.560 --> 00:02:55.639 determines the entire regulatory pathway. It 00:02:55.639 --> 00:02:57.560 dictates what testing is required, whether you 00:02:57.560 --> 00:02:59.819 need clinical trials, which pre -market submission 00:02:59.819 --> 00:03:02.939 type you'll use, like a 510K, a PMA, or maybe 00:03:02.939 --> 00:03:05.539 a de novo request. Wow. This isn't just about 00:03:05.539 --> 00:03:08.080 ticking a regulatory box. It's a fundamental 00:03:08.080 --> 00:03:10.909 strategic decision. I mean, choosing to classify 00:03:10.909 --> 00:03:14.310 your device as Class 3, for instance, might mean 00:03:14.310 --> 00:03:16.729 committing to years of clinical trials, potentially 00:03:16.729 --> 00:03:19.610 hundreds of millions in R &D. Yeah, that fundamentally 00:03:19.610 --> 00:03:22.030 shapes your budget, your timeline, even your 00:03:22.030 --> 00:03:24.110 market entry strategy. It's where innovation 00:03:24.110 --> 00:03:27.349 meets, well, practical business reality. Exactly. 00:03:27.430 --> 00:03:29.349 And it sounds like risk management is just built 00:03:29.349 --> 00:03:31.969 into this entire process from day one. How deeply 00:03:31.969 --> 00:03:34.469 integrated is it? Oh, it's absolutely foundational. 00:03:34.650 --> 00:03:37.569 The FDA expects risk management, often guided 00:03:37.569 --> 00:03:41.349 by international standards like ISO 14971, to 00:03:41.349 --> 00:03:44.030 be embedded in both the design and the manufacturing 00:03:44.030 --> 00:03:46.810 stages. Okay. It's a systematic approach. You 00:03:46.810 --> 00:03:49.430 identify hazards, estimate and control the risks, 00:03:49.469 --> 00:03:52.009 and this ties directly into device validation. 00:03:52.229 --> 00:03:54.409 It guides decisions on changes or complaints 00:03:54.409 --> 00:03:56.689 throughout the device's entire lifecycle. It's 00:03:56.689 --> 00:03:58.710 really a continuous loop of ensuring safety. 00:03:58.849 --> 00:04:01.330 A continuous loop. Okay, so let's start at the 00:04:01.330 --> 00:04:03.610 bottom then. The lowest risk category. What is 00:04:03.610 --> 00:04:05.969 that? what does it mean for manufacturers? That 00:04:05.969 --> 00:04:09.370 would be class one. These devices pose the lowest 00:04:09.370 --> 00:04:12.229 potential risk to patients. They're subject to 00:04:12.229 --> 00:04:15.490 what the FDA calls general controls. General 00:04:15.490 --> 00:04:17.509 controls. OK, what does that mean practically? 00:04:17.730 --> 00:04:21.009 These are the basic regulatory requirements applicable 00:04:21.009 --> 00:04:24.310 to all medical devices, things like registering 00:04:24.310 --> 00:04:26.930 your establishment, listing your devices, proper 00:04:26.930 --> 00:04:30.170 labeling, and adhering to the quality system 00:04:30.170 --> 00:04:32.550 regulation, though with some exceptions. And 00:04:32.550 --> 00:04:34.600 what about getting them to market? What do these 00:04:34.600 --> 00:04:37.180 general controls mean for pre -market submission? 00:04:37.360 --> 00:04:39.680 Is there a lot of, you know, red tape? Surprisingly 00:04:39.680 --> 00:04:42.319 little for most of them. Most class I devices 00:04:42.319 --> 00:04:44.620 are actually exempt from pre -market submission. 00:04:44.939 --> 00:04:48.230 Exempt. So no 5 and 10K, no PMA. For the majority, 00:04:48.290 --> 00:04:50.110 that's correct. They don't require that level 00:04:50.110 --> 00:04:52.449 of pre -market scrutiny because the risk profile 00:04:52.449 --> 00:04:54.750 is considered low and managed by those general 00:04:54.750 --> 00:04:57.029 controls. OK. So give us some real world examples 00:04:57.029 --> 00:04:59.589 then from the sources. What falls into this lowest 00:04:59.589 --> 00:05:01.970 risk category? Maybe something that might surprise 00:05:01.970 --> 00:05:04.970 us. Sure. Think of everyday items like bandages 00:05:04.970 --> 00:05:07.589 or manual stethoscopes. Those are classic class 00:05:07.589 --> 00:05:10.769 I. Right. Makes sense. But also some more specific 00:05:10.769 --> 00:05:15.350 devices, like a staphylococcal -typing bacteriophage. 00:05:15.569 --> 00:05:19.089 Whoa, a bacteriophage? A virus? That's class 00:05:19.089 --> 00:05:22.170 Y. Yep. It's a bacterial virus used to identify 00:05:22.170 --> 00:05:25.709 pathogenic staph bacteria, mostly for epidemiological 00:05:25.709 --> 00:05:28.930 information. Because its intended use and risk 00:05:28.930 --> 00:05:32.269 profile fit, it lands in class 1. Wow, OK. That 00:05:32.269 --> 00:05:34.269 definitely broadens my understanding of what 00:05:34.269 --> 00:05:36.839 low -risk can mean. It's not just simple tools. 00:05:37.480 --> 00:05:39.800 Indeed. Other examples include things like an 00:05:39.800 --> 00:05:42.699 erythrocytic glucose -6 -phosphate dehydrogenase 00:05:42.699 --> 00:05:45.379 assay that measures enzyme activity for diagnosing 00:05:45.379 --> 00:05:48.500 a type of congenital anemia. OK. Or a galactose 00:05:48.500 --> 00:05:50.899 test system used for diagnosing galactosemia 00:05:50.899 --> 00:05:54.459 in infants. Even beta or gamma counters for clinical 00:05:54.459 --> 00:05:56.860 use, which detect radiation in clinical samples, 00:05:57.040 --> 00:06:00.029 can be class I. Huh. Any dental examples in this 00:06:00.029 --> 00:06:01.589 category? I know you mentioned dental earlier. 00:06:02.069 --> 00:06:04.310 Absolutely. An electro gel for pulp testers that's 00:06:04.310 --> 00:06:06.470 applied to a tooth surface to help conduct electrical 00:06:06.470 --> 00:06:08.910 current, that's class on. I was a dental x -ray 00:06:08.910 --> 00:06:11.149 film holder. Or a cement dispenser, which is 00:06:11.149 --> 00:06:13.329 like a non -powered syringe device for placing 00:06:13.329 --> 00:06:16.209 bone cement into surgical sites. Right. So even 00:06:16.209 --> 00:06:19.170 a relatively simple tool, if it has a specific 00:06:19.170 --> 00:06:22.050 medical purpose, gets classified. Exactly. And 00:06:22.050 --> 00:06:24.529 we've touched on the quality system regulation, 00:06:24.709 --> 00:06:28.620 the QSR before and other deep dives. incredibly 00:06:28.620 --> 00:06:31.740 robust. How early does that framework kick in 00:06:31.740 --> 00:06:34.000 even for these lower -risk devices? That's a 00:06:34.000 --> 00:06:36.620 good question. While some non -sterile class 00:06:36.620 --> 00:06:38.860 I devices might get a pass on certain parts of 00:06:38.860 --> 00:06:42.720 the QSR, that's 21 CFR part 820, they still can't 00:06:42.720 --> 00:06:45.319 skip the basics. Oh, OK. They are still required 00:06:45.319 --> 00:06:47.779 to adhere to general record keeping requirements, 00:06:48.139 --> 00:06:51.720 section 820 .1A0, and maintain robust complaint 00:06:51.720 --> 00:06:56.399 files under 820 .198. So accountability is definitely 00:06:56.399 --> 00:06:58.579 expected across the board, even for the lowest 00:06:58.579 --> 00:07:01.649 risk class. Got it. Accountability from the start. 00:07:02.310 --> 00:07:04.209 OK, so we've covered the basics of class one. 00:07:04.509 --> 00:07:06.970 But what happens when a device steps up the risk 00:07:06.970 --> 00:07:09.430 ladder a bit? What new layers of scrutiny does 00:07:09.430 --> 00:07:12.490 the FDA add for these class two devices? Right, 00:07:12.649 --> 00:07:14.850 class two devices. These pose a moderate risk 00:07:14.850 --> 00:07:17.129 to patients. For these, general controls alone 00:07:17.129 --> 00:07:19.089 aren't considered sufficient to assure their 00:07:19.089 --> 00:07:21.209 safety and effectiveness. OK, so they need something 00:07:21.209 --> 00:07:24.040 more. Yes, they require what are known as special 00:07:24.040 --> 00:07:26.620 controls. These are specific measures tailored 00:07:26.620 --> 00:07:29.620 to the particular risks of that device type going 00:07:29.620 --> 00:07:32.160 beyond the basic regulatory requirements. Special 00:07:32.160 --> 00:07:33.800 controls. Can you give an example? What might 00:07:33.800 --> 00:07:36.180 that actually involve? Sure. So for instance, 00:07:36.240 --> 00:07:38.879 for an oximeter, a special control might be a 00:07:38.879 --> 00:07:41.379 mandatory performance standard dictating its 00:07:41.379 --> 00:07:44.779 accuracy under various conditions or maybe specific 00:07:44.779 --> 00:07:47.060 labeling requirements or even a requirement for 00:07:47.060 --> 00:07:49.600 post -market surveillance like tracking patient 00:07:49.600 --> 00:07:53.250 outcomes. So more tailored oversight for specific 00:07:53.250 --> 00:07:57.550 risks. What's the typical pre -market submission 00:07:57.550 --> 00:08:01.129 pathway for these moderate risk devices? Most 00:08:01.129 --> 00:08:03.790 Class II devices typically require a pre -market 00:08:03.790 --> 00:08:06.810 notification, which is commonly known as a 510K 00:08:06.810 --> 00:08:09.550 submission. 10K, right. This is where a manufacturer 00:08:09.550 --> 00:08:12.709 demonstrates substantial equivalence to a legally 00:08:12.709 --> 00:08:15.569 marketed device already on the market, a predicate 00:08:15.569 --> 00:08:17.490 device. Substantial equivalence. So it doesn't 00:08:17.490 --> 00:08:20.050 have to be identical, but just as safe and effective. 00:08:20.279 --> 00:08:22.699 Essentially, yes. You need to show it has the 00:08:22.699 --> 00:08:25.959 same intended use and similar technological characteristics. 00:08:26.620 --> 00:08:28.680 Or if the characteristics are different, that 00:08:28.680 --> 00:08:30.879 those differences don't raise new questions of 00:08:30.879 --> 00:08:33.379 safety and effectiveness. It's about proving 00:08:33.379 --> 00:08:35.940 it performs comparably to something already cleared. 00:08:36.259 --> 00:08:38.879 OK. Can you give us some examples of Class II 00:08:38.879 --> 00:08:41.399 devices? What kind of technology falls into this 00:08:41.399 --> 00:08:44.779 moderate risk category? Certainly. Common ones 00:08:44.779 --> 00:08:47.200 include things like powered wheelchairs or infusion 00:08:47.200 --> 00:08:50.419 pumps. Endoscopes are another big category. More 00:08:50.419 --> 00:08:52.860 specialized examples are things like that oximeter 00:08:52.860 --> 00:08:55.399 we mentioned, which transmits radiation through 00:08:55.399 --> 00:08:58.580 blood to measure oxygen saturation, or an auto 00:08:58.580 --> 00:09:01.080 -transfusion apparatus used to collect and re 00:09:01.080 --> 00:09:03.440 -infuse a patient's lost blood during surgery 00:09:03.440 --> 00:09:06.139 or trauma. It's interesting how diverse the devices 00:09:06.139 --> 00:09:09.399 are within this single class. from something 00:09:09.399 --> 00:09:11.940 very visible like a wheelchair to something highly 00:09:11.940 --> 00:09:14.080 technical like that auto -transfusion device. 00:09:14.220 --> 00:09:16.860 They really are. We also have automated differential 00:09:16.860 --> 00:09:19.639 cell counters for immature or abnormal blood 00:09:19.639 --> 00:09:22.440 cells. These often combine electronic particle 00:09:22.440 --> 00:09:25.519 counting or optical methods. In the dental world, 00:09:25.700 --> 00:09:28.200 a base metal alloy used for crown and bridge 00:09:28.200 --> 00:09:32.519 restorations is Class II. Even clubziella serological 00:09:32.519 --> 00:09:35.639 reagents, used to identify clubziella bacteria 00:09:35.639 --> 00:09:38.639 from cultured isolates for diagnosis, fall into 00:09:38.639 --> 00:09:41.039 this class. What about some of the newer, maybe 00:09:41.039 --> 00:09:43.940 more tech -driven examples? ones that integrate 00:09:43.940 --> 00:09:46.700 software. Good point. A self -fitting air conduction 00:09:46.700 --> 00:09:48.919 hearing aid, one that includes software allowing 00:09:48.919 --> 00:09:51.220 users to program it themselves. That's class 00:09:51.220 --> 00:09:54.799 two. Ah, interesting. Also, a telephone electrocardiograph 00:09:54.799 --> 00:09:56.960 transmitter and receiver, which conditions an 00:09:56.960 --> 00:10:01.220 ECG signal for transmission, or an electrocardiograph 00:10:01.220 --> 00:10:03.759 software device for over -the -counter use, one 00:10:03.759 --> 00:10:07.019 that creates and displays ECG data and can help 00:10:07.019 --> 00:10:09.759 identify arrhythmias, but importantly, not for 00:10:09.759 --> 00:10:12.159 actual diagnosis by the lay user. That's a key 00:10:12.159 --> 00:10:14.690 distinction. OK, now for diagnosis. And any implanted 00:10:14.690 --> 00:10:17.269 devices in Class II? Yes. For example, an elbow 00:10:17.269 --> 00:10:19.590 joint radial polymer prosthesis, so a partial 00:10:19.590 --> 00:10:22.149 elbow replacement, can fall into Class II. Right. 00:10:22.389 --> 00:10:25.169 Now, what happens if there's a truly novel device, 00:10:25.490 --> 00:10:28.029 something moderate risk, but there's just nothing 00:10:28.029 --> 00:10:30.669 like it already on the market? No predicate for 00:10:30.669 --> 00:10:33.710 that 510K comparison. How does the FDA handle 00:10:33.710 --> 00:10:36.230 that kind of innovation? That's exactly where 00:10:36.230 --> 00:10:38.450 the de novo classification pathway comes in. 00:10:38.700 --> 00:10:41.559 It's specifically designed for novel, first -of 00:10:41.559 --> 00:10:44.340 -a -kind devices that are generally low to moderate 00:10:44.340 --> 00:10:47.860 risk but have no existing predicate device. So, 00:10:48.440 --> 00:10:51.220 a manufacturer submits a de novo request. If 00:10:51.220 --> 00:10:53.480 granted, the FDA creates a new classification 00:10:53.480 --> 00:10:56.259 for that device type, classifying it as either 00:10:56.259 --> 00:10:59.100 Class 1 or Class 2, and establishes any necessary 00:10:59.100 --> 00:11:01.500 special controls right then and there. Ah, so 00:11:01.500 --> 00:11:04.379 it sets the standard. Exactly. Once that de novo 00:11:04.379 --> 00:11:06.399 is granted and the classification regulation 00:11:06.399 --> 00:11:09.240 is created, subsequent similar devices can then 00:11:09.240 --> 00:11:11.860 use the 510k pathway by referencing that newly 00:11:11.860 --> 00:11:13.960 classified device as their predicate. I see. 00:11:14.019 --> 00:11:16.039 So it helps pave the way for future innovation 00:11:16.039 --> 00:11:18.200 by establishing a new benchmark that makes sense. 00:11:18.500 --> 00:11:20.820 It's a pathway specifically designed to bring 00:11:20.820 --> 00:11:23.899 truly new, but not necessarily high -risk, technologies 00:11:23.899 --> 00:11:26.919 to market safely. Okay. Now, what about the top 00:11:26.919 --> 00:11:30.240 tier, Class 3? These are the highest risk, right? 00:11:30.440 --> 00:11:32.059 What kind of devices are we talking about here? 00:11:32.100 --> 00:11:34.460 And what scrutiny do they face? Correct. Class 00:11:34.460 --> 00:11:37.179 III devices pose the highest potential risk to 00:11:37.179 --> 00:11:39.820 patients. These are typically devices that are 00:11:39.820 --> 00:11:42.740 life -sustaining, life -supporting, or are implanted 00:11:42.740 --> 00:11:45.779 devices. Or they could just present a potential 00:11:45.779 --> 00:11:49.340 unreasonable risk of illness or injury. For these, 00:11:49.559 --> 00:11:51.740 general controls and even special controls are 00:11:51.740 --> 00:11:54.519 simply insufficient. They require the most rigorous 00:11:54.519 --> 00:11:57.220 level of regulatory review. So what's the pre 00:11:57.220 --> 00:11:59.200 -market submission for Class 3? I'm guessing 00:11:59.200 --> 00:12:02.039 it's the most stringent, demanding a huge amount 00:12:02.039 --> 00:12:04.980 of data. Absolutely. Most Class 3 devices require 00:12:04.980 --> 00:12:08.639 pre -market approval, or PMA. A PMA application 00:12:08.639 --> 00:12:11.460 involves the most stringent scientific and regulatory 00:12:11.460 --> 00:12:14.379 review by the FDA. It requires comprehensive 00:12:14.379 --> 00:12:16.919 data, non -clinical laboratory studies, animal 00:12:16.919 --> 00:12:19.440 studies, and, crucially, clinical investigations 00:12:19.440 --> 00:12:21.860 involving human subjects to demonstrate safety 00:12:21.860 --> 00:12:24.200 and effectiveness. So extensive clinical data 00:12:24.200 --> 00:12:27.379 is usually a must. Almost always for PMA. The 00:12:27.379 --> 00:12:30.159 FDA needs robust evidence that the benefits outweigh 00:12:30.159 --> 00:12:32.379 the risks for these high -risk devices. They 00:12:32.379 --> 00:12:35.440 may even refer the PMA to an advisory panel of 00:12:35.440 --> 00:12:37.700 external experts for review and recommendation. 00:12:38.340 --> 00:12:41.179 It's a very thorough process. Okay. What are 00:12:41.179 --> 00:12:44.139 some classic examples of class 3 devices, the 00:12:44.139 --> 00:12:47.360 kind that really illustrate this high -risk profile? 00:12:47.740 --> 00:12:49.929 Well, Casemakers and implantable heart valves 00:12:49.929 --> 00:12:52.509 are definitive class three devices, life -sustaining 00:12:52.509 --> 00:12:55.450 implants. Other examples include an implanted 00:12:55.450 --> 00:12:58.129 electrical urinary continence device intended 00:12:58.129 --> 00:13:00.610 to activate pelvic muscles or sphincters to treat 00:13:00.610 --> 00:13:04.669 incontinence, or a sorbent hemoperfusion system 00:13:04.669 --> 00:13:06.950 which is used for treating specific conditions 00:13:06.950 --> 00:13:09.750 like hepatic coma or certain metabolic disturbances 00:13:09.750 --> 00:13:11.769 by filtering the blood. And what about other 00:13:11.769 --> 00:13:13.590 implanted prostheses? You mentioned an elbow 00:13:13.590 --> 00:13:15.549 one was class two. Right, the classification 00:13:15.549 --> 00:13:17.610 depends on the specific device and its risk. 00:13:17.480 --> 00:13:20.179 So, for example, a single -lumen silicone gel 00:13:20.179 --> 00:13:23.200 -filled breast prosthesis implanted for augmentation 00:13:23.200 --> 00:13:26.700 or reconstruction is Class III. Also, a finger 00:13:26.700 --> 00:13:30.000 joint metal polymer constrained cemented prosthesis 00:13:30.000 --> 00:13:33.559 or a hip joint metal constrained cemented or 00:13:33.559 --> 00:13:36.659 uncemented prosthesis. These are implanted joint 00:13:36.659 --> 00:13:39.000 replacements designed specifically to prevent 00:13:39.000 --> 00:13:42.279 dislocation, adding complexity, and risk they 00:13:42.279 --> 00:13:45.350 fall into Class III. Constrained. That sounds 00:13:45.350 --> 00:13:48.029 like a key factor there. It often is. These are 00:13:48.029 --> 00:13:50.490 devices that live inside the body, often performing 00:13:50.490 --> 00:13:53.250 critical functions. So the risk profile demands 00:13:53.250 --> 00:13:55.970 the highest level of proof for safety and efficacy 00:13:55.970 --> 00:13:58.450 before they reach patients. Makes sense. So once 00:13:58.450 --> 00:14:01.830 a device is defined, classified, and that regulatory 00:14:01.830 --> 00:14:03.929 pathway is clear, especially for these higher 00:14:03.929 --> 00:14:06.169 risk class two and three devices, what about 00:14:06.169 --> 00:14:08.429 the human studies, the clinical trials? When 00:14:08.429 --> 00:14:11.320 do those come into play? That brings us to Investigational 00:14:11.320 --> 00:14:14.159 Device Exemptions, or IDEs. These are outlined 00:14:14.159 --> 00:14:16.940 in the regulations, specifically 21 CFR Part 00:14:16.940 --> 00:14:20.559 812. IDEs. An approved IDE allows a device that 00:14:20.559 --> 00:14:22.639 would normally require pre -market approval or 00:14:22.639 --> 00:14:24.940 clearance, like a Class 3 device, or sometimes 00:14:24.940 --> 00:14:27.000 a Class 2 needing clinical data to be shipped 00:14:27.000 --> 00:14:29.179 lawfully for investigational purposes. So it 00:14:29.179 --> 00:14:32.269 lets you test it in people. Primarily, yes. It 00:14:32.269 --> 00:14:34.669 allows the sponsor to conduct clinical investigations 00:14:34.669 --> 00:14:37.169 on human subjects to gather the necessary safety 00:14:37.169 --> 00:14:39.350 and effectiveness data needed for that eventual 00:14:39.350 --> 00:14:43.049 PMA, or sometimes even a 510K or de novo. And 00:14:43.049 --> 00:14:45.690 I imagine, similar to the device classes, not 00:14:45.690 --> 00:14:47.889 all device studies carry the same risk for the 00:14:47.889 --> 00:14:49.929 participants. That's a key distinction the FDA 00:14:49.929 --> 00:14:52.330 makes. They differentiate between significant 00:14:52.330 --> 00:14:55.230 risk and non -significant risk device studies. 00:14:55.490 --> 00:14:59.179 Okay, SR versus NSR. Exactly. A significant risk 00:14:59.179 --> 00:15:01.860 or SR device study involves an investigational 00:15:01.860 --> 00:15:04.419 device that poses a potential for serious risk 00:15:04.419 --> 00:15:06.600 to the health, safety, or welfare of a subject. 00:15:07.139 --> 00:15:09.960 Think implants, devices supporting or sustaining 00:15:09.960 --> 00:15:12.779 life, or those used for diagnosing or curing 00:15:12.779 --> 00:15:15.870 serious conditions. Right. High stakes. For these 00:15:15.870 --> 00:15:18.490 SR studies, the sponsor or investigator must 00:15:18.490 --> 00:15:21.370 submit an IDE application directly to the FDA 00:15:21.370 --> 00:15:24.289 and get approval before starting the study. It's 00:15:24.289 --> 00:15:26.450 a very high bar involving detailed protocols 00:15:26.450 --> 00:15:31.009 and safety monitoring plans. a non -significant 00:15:31.009 --> 00:15:33.509 risk, or NSR. Then the study is considered to 00:15:33.509 --> 00:15:36.269 have IDE status without formal FDA submission, 00:15:36.710 --> 00:15:38.889 but it still requires approval and oversight 00:15:38.889 --> 00:15:41.970 from an institutional review board, or IRB. The 00:15:41.970 --> 00:15:44.950 IRB still plays a crucial role. Absolutely. Even 00:15:44.950 --> 00:15:48.129 without formal FDA IDE oversight for NSR studies, 00:15:48.330 --> 00:15:50.289 the basic principles of protecting participant 00:15:50.289 --> 00:15:52.870 safety, rights, and welfare, including informed 00:15:52.870 --> 00:15:55.870 consent, must be followed. The IRB ensures that. 00:15:56.330 --> 00:15:59.169 So while the pathway might differ slightly, Patient 00:15:59.169 --> 00:16:01.730 safety is always paramount. We've talked a lot 00:16:01.730 --> 00:16:03.990 in past deep dives about good clinical practice 00:16:03.990 --> 00:16:07.110 or GCP for pharmaceuticals, often referencing 00:16:07.110 --> 00:16:10.370 the ICH E6 guideline. Is there a similar standard 00:16:10.370 --> 00:16:13.070 specifically for device trials? There is, and 00:16:13.070 --> 00:16:14.710 this is another key difference from the drug 00:16:14.710 --> 00:16:17.990 world. While pharma trials largely follow ICHE6, 00:16:18.409 --> 00:16:20.730 medical device clinical trials primarily adhere 00:16:20.730 --> 00:16:24.629 to ISO 1 .55 .20 swanier for good clinical practice. 00:16:24.850 --> 00:16:27.950 ISO 14155, okay. It's an international standard 00:16:27.950 --> 00:16:30.789 that covers device, trial design, conduct, performance, 00:16:31.149 --> 00:16:33.330 monitoring, auditing, recording, analysis, and 00:16:33.330 --> 00:16:35.789 reporting. The FDA recognizes this standard, 00:16:36.009 --> 00:16:38.830 so data gathered under ISO 14155 can support 00:16:38.830 --> 00:16:41.850 regulatory submissions in the U .S. And the investigator's 00:16:41.850 --> 00:16:45.049 role, still critical. Hugely critical. The clinical 00:16:45.049 --> 00:16:47.529 investigator holds significant responsibility, 00:16:47.809 --> 00:16:49.490 not just for conducting the trial according to 00:16:49.490 --> 00:16:52.090 the plan, but for supervising the entire research 00:16:52.090 --> 00:16:55.110 team, ensuring participant safety, obtaining 00:16:55.110 --> 00:16:58.409 proper informed consent, and maintaining robust, 00:16:58.750 --> 00:17:01.429 accurate data integrity. OK, so we've gotten 00:17:01.429 --> 00:17:04.869 our device defined, classified, maybe run human 00:17:04.869 --> 00:17:09.130 trials under an IDE adhering to ISO 14135. Right. 00:17:09.390 --> 00:17:11.930 But the story of patient safety doesn't end when 00:17:11.930 --> 00:17:14.309 the device gets approved or cleared, right? The 00:17:14.309 --> 00:17:16.789 FDA's commitment to quality must extend throughout 00:17:16.789 --> 00:17:19.230 the entire life cycle. Absolutely. It has to. 00:17:19.410 --> 00:17:21.150 And that's where the quality system regulation, 00:17:21.349 --> 00:17:24.349 or QSR, comes back into play in a big way. That's 00:17:24.349 --> 00:17:28.250 21 CFR Part 820 again. The device EGMP. Exactly. 00:17:28.369 --> 00:17:30.549 It serves as the equivalent of current good manufacturing 00:17:30.549 --> 00:17:33.329 practices, but specifically for devices. It mandates 00:17:33.329 --> 00:17:36.750 a robust quality management system, or QMS. QMS. 00:17:37.000 --> 00:17:39.960 And this QMS has to encompass pretty much everything. 00:17:40.539 --> 00:17:43.319 Design, purchasing, manufacturing, packaging, 00:17:43.559 --> 00:17:46.059 labeling, storage, installation, servicing, and 00:17:46.059 --> 00:17:48.660 post -market activities. The goal is to ensure 00:17:48.660 --> 00:17:50.859 devices consistently meet their specifications 00:17:50.859 --> 00:17:53.829 and safety and effectiveness standards. And is 00:17:53.829 --> 00:17:55.829 there an international standard that aligns with 00:17:55.829 --> 00:17:58.650 this QSR, maybe helps global manufacturers? Yes. 00:17:59.089 --> 00:18:03.009 ISO 13485 .20 Sunstein provides an internationally 00:18:03.009 --> 00:18:05.710 recognized framework for a medical device QMS. 00:18:06.390 --> 00:18:08.589 Many regulators around the world, including the 00:18:08.589 --> 00:18:12.150 FDA to a large extent, recognize or have harmonized 00:18:12.150 --> 00:18:15.289 their requirements with ISO 13485. It's really 00:18:15.289 --> 00:18:17.630 the global benchmark for device quality systems. 00:18:18.029 --> 00:18:21.569 OK, ISO 13485. So what are the most critical 00:18:21.569 --> 00:18:24.369 elements of this QMS? this quality system, let's 00:18:24.369 --> 00:18:26.029 maybe start back at the beginning how devices 00:18:26.029 --> 00:18:28.329 are designed and developed. Design controls are 00:18:28.329 --> 00:18:30.329 absolutely fundamental. The QMS guides the whole 00:18:30.329 --> 00:18:32.029 design and development process through structured 00:18:32.029 --> 00:18:34.450 documentation and rigorous risk controls. This 00:18:34.450 --> 00:18:36.730 includes having detailed design plans upfront. 00:18:36.970 --> 00:18:39.529 And define what the device needs to do. Precisely. 00:18:39.710 --> 00:18:42.549 That's covered by design inputs. These are all 00:18:42.549 --> 00:18:44.990 the physical and performance requirements. They 00:18:44.990 --> 00:18:47.809 come from user needs, regulatory requirements, 00:18:48.150 --> 00:18:50.190 industry standards, everything that dictates 00:18:50.190 --> 00:18:53.579 what the device must achieve. And how do manufacturers 00:18:53.579 --> 00:18:56.279 make sure the design is actually going to work 00:18:56.279 --> 00:18:59.380 as intended before they start making thousands 00:18:59.380 --> 00:19:01.559 of them? That's where design verification and 00:19:01.559 --> 00:19:04.480 validation come in. Verification is about confirming 00:19:04.480 --> 00:19:07.519 that the design outputs the drawings, specifications 00:19:07.519 --> 00:19:10.599 meet the design inputs. Basically asking, did 00:19:10.599 --> 00:19:13.319 we design the device right? This usually involves 00:19:13.319 --> 00:19:16.500 tests, inspections, analyses. OK, verification. 00:19:16.799 --> 00:19:19.319 Did we design it right? Then there's design validation. 00:19:19.640 --> 00:19:21.819 This then shows that the final finished device 00:19:21.819 --> 00:19:24.259 actually meets the user's needs and its intended 00:19:24.259 --> 00:19:27.480 uses. So asking, did we design the right device? 00:19:27.819 --> 00:19:30.740 This often involves testing under actual or simulated 00:19:30.740 --> 00:19:33.140 use conditions and very often includes data from 00:19:33.140 --> 00:19:35.500 clinical trials. Right, validation. Did we design 00:19:35.500 --> 00:19:37.779 the right thing? Exactly. And all of this history, 00:19:37.980 --> 00:19:40.720 the whole chronological story of the design process, 00:19:41.220 --> 00:19:43.920 is meticulously documented in a design history 00:19:43.920 --> 00:19:48.380 file, or DHF. The DHF. The design story. It's 00:19:48.380 --> 00:19:51.579 the full narrative, yes. So the DHF is the design 00:19:51.579 --> 00:19:55.299 story. What are the actual how -to for manufacturing 00:19:55.299 --> 00:19:57.920 once the design is locked? That's where the Device 00:19:57.920 --> 00:20:01.440 Master Record or DMR comes in. The DMR is essentially 00:20:01.440 --> 00:20:04.299 the definitive recipe or blueprint for manufacturing 00:20:04.299 --> 00:20:07.039 the device. It's derived directly from the design 00:20:07.039 --> 00:20:10.079 specifications in the DHF. And for production 00:20:10.079 --> 00:20:13.299 and process controls, the QMS ensures devices 00:20:13.299 --> 00:20:15.759 are manufactured precisely according to that 00:20:15.759 --> 00:20:18.960 DMR recipe. This means documented instructions, 00:20:19.660 --> 00:20:23.000 standard operating procedures, SOPs for every 00:20:23.000 --> 00:20:26.059 step. SOPs for everything. Pretty much. It also 00:20:26.059 --> 00:20:28.259 includes stringent control over all the inspection, 00:20:28.539 --> 00:20:30.980 measuring, and test equipment used. And crucially, 00:20:31.519 --> 00:20:33.559 process validation. Process validation. What's 00:20:33.559 --> 00:20:35.779 that? That means establishing documented proof. 00:20:35.950 --> 00:20:38.829 that a specific manufacturing process will consistently 00:20:38.829 --> 00:20:41.569 produce a product meeting its predetermined quality 00:20:41.569 --> 00:20:43.910 specifications. You have to prove your process 00:20:43.910 --> 00:20:46.789 works reliably every single time. Prove the process. 00:20:47.250 --> 00:20:49.269 And I imagine keeping track of each individual 00:20:49.269 --> 00:20:51.549 device produced is vital, like a unique record 00:20:51.549 --> 00:20:54.549 for every unit. Absolutely essential. A device 00:20:54.549 --> 00:20:57.589 history record, or DHR, must be maintained for 00:20:57.589 --> 00:21:00.190 each individual device, or sometimes each batch 00:21:00.190 --> 00:21:03.869 or lot. The DHR. This record contains all the 00:21:03.869 --> 00:21:06.690 details. The manufacturing dates, the quantity 00:21:06.690 --> 00:21:09.529 manufactured, the quantity released for distribution, 00:21:09.930 --> 00:21:11.990 all the acceptance records showing it met the 00:21:11.990 --> 00:21:15.269 DMR specifications. It's the individual device's 00:21:15.269 --> 00:21:17.630 production story providing traceability. Sounds 00:21:17.630 --> 00:21:19.769 like a lot of documentation. And what about all 00:21:19.769 --> 00:21:21.869 the equipment used in manufacturing? How does 00:21:21.869 --> 00:21:24.650 the QMS ensure that machinery itself is reliable 00:21:24.650 --> 00:21:27.450 and consistent? Equipment management is critical. 00:21:27.730 --> 00:21:29.869 Every piece of equipment used from mixers to 00:21:29.869 --> 00:21:32.430 testing machines must meet specified requirements. 00:21:32.849 --> 00:21:35.109 It needs to be appropriately designed, constructed, 00:21:35.450 --> 00:21:37.950 placed, and installed in a way that facilitates 00:21:37.950 --> 00:21:40.630 maintenance, adjustment, cleaning, and proper 00:21:40.630 --> 00:21:42.970 use. So it's not just about plugging it in? Oh 00:21:42.970 --> 00:21:45.789 no. There's often a formal qualification process, 00:21:45.789 --> 00:21:49.609 sometimes called DQ, IQ, OQ, PQ design, installation, 00:21:49.930 --> 00:21:52.630 operational, and performance qualification. It's 00:21:52.630 --> 00:21:55.329 a multi -step process to rigorously prove that 00:21:55.329 --> 00:21:57.710 the equipment is designed correctly, installed 00:21:57.710 --> 00:22:00.630 right, operates as intended, and consistently 00:22:00.630 --> 00:22:03.589 performs as needed within the process. Wow. DQ, 00:22:03.609 --> 00:22:06.809 IQ, OQ, PQ. Plus, regular calibration against 00:22:06.809 --> 00:22:09.009 certified standards is crucial for measurement 00:22:09.009 --> 00:22:11.269 equipment. And proper preventative maintenance 00:22:11.269 --> 00:22:14.309 schedules are key. All of this calibration, maintenance, 00:22:14.509 --> 00:22:17.329 repairs needs meticulous documentation, usually 00:22:17.329 --> 00:22:19.730 in equipment log books. Risk management plays 00:22:19.730 --> 00:22:21.670 a role here, too, in forming things like cleaning 00:22:21.670 --> 00:22:24.230 procedures to prevent cross contamination and 00:22:24.230 --> 00:22:26.410 setting those maintenance schedules. It really 00:22:26.410 --> 00:22:28.970 sounds like the absolute mantra here is, if it 00:22:28.970 --> 00:22:30.970 isn't written down, it didn't happen. for the 00:22:30.970 --> 00:22:32.930 entire process. It truly is the bedrock of the 00:22:32.930 --> 00:22:35.470 whole system. Documentation and record keeping 00:22:35.470 --> 00:22:38.430 are paramount under the QSR. Detailed records 00:22:38.430 --> 00:22:41.150 provide that complete, traceable history of how 00:22:41.150 --> 00:22:43.769 a product was designed, made, tested, released, 00:22:44.269 --> 00:22:48.250 everything. Personnel training records, supplier 00:22:48.250 --> 00:22:51.029 evaluations, complaint files, audit reports. 00:22:51.470 --> 00:22:54.349 It's comprehensive. And in today's world, electronic 00:22:54.349 --> 00:22:56.769 records and signatures are common governed by 00:22:56.769 --> 00:23:00.430 21 CFR Part 11. Part 11, right. Which has its 00:23:00.430 --> 00:23:02.849 own stringent requirements for validation, audit 00:23:02.849 --> 00:23:05.410 trails, security, and ensuring data integrity 00:23:05.410 --> 00:23:09.029 based on principles often called ALCOA plus HUE. 00:23:09.200 --> 00:23:12.640 L is C -O -A plus E -A. Attributable, legible, 00:23:12.839 --> 00:23:15.380 contemporaneous, original, accurate, plus complete, 00:23:15.799 --> 00:23:18.480 consistent, enduring, and available. It's all 00:23:18.480 --> 00:23:20.640 about ensuring the electronic data is trustworthy 00:23:20.640 --> 00:23:22.980 and reliable. That's thorough. OK, what about 00:23:22.980 --> 00:23:24.799 the labeling and packaging, the part the user 00:23:24.799 --> 00:23:27.200 actually sees? Are there strict QSR rules for 00:23:27.200 --> 00:23:29.240 that, too? Absolutely. Labeling and packaging 00:23:29.240 --> 00:23:31.819 fall under the QSR and also have their own specific 00:23:31.819 --> 00:23:35.400 regulation. 21 CFR Part 801. Labels need adequate 00:23:35.400 --> 00:23:37.940 directions for use, warnings, contraindications, 00:23:37.980 --> 00:23:40.839 and so on. Clear information. Yes. And they must 00:23:40.839 --> 00:23:43.019 comply with the Unique Device Identification, 00:23:43.240 --> 00:23:46.220 or UDI, rules for traceability throughout the 00:23:46.220 --> 00:23:49.460 supply chain. Labels have to be legible, securely 00:23:49.460 --> 00:23:53.299 affixed, and meticulously for accuracy before 00:23:53.299 --> 00:23:55.480 any device is released for distribution. It's 00:23:55.480 --> 00:23:57.940 a critical control point. UDI for traceability. 00:23:58.500 --> 00:24:00.599 Makes sense. Now what if something goes wrong 00:24:00.599 --> 00:24:03.019 after a device is out on the market? How does 00:24:03.019 --> 00:24:05.880 the QMS handle that? Say a safety issue emerges 00:24:05.880 --> 00:24:08.700 or customer complaints start coming in. This 00:24:08.700 --> 00:24:11.599 is a critical part of the QMS post -market activities. 00:24:12.240 --> 00:24:14.700 Manufacturers must have robust procedures for 00:24:14.700 --> 00:24:16.980 identifying, investigating, and dealing with 00:24:16.980 --> 00:24:19.380 non -conforming products, whether caught internally 00:24:19.380 --> 00:24:21.960 or reported from the field. Crucially, they need 00:24:21.960 --> 00:24:24.420 solid systems for handling complaints. Complaints 00:24:24.420 --> 00:24:26.740 aren't just problems. They're valuable feedback 00:24:26.740 --> 00:24:29.160 that can identify potential quality issues or 00:24:29.160 --> 00:24:31.920 emerging risks. The investigation has to be thorough 00:24:31.920 --> 00:24:34.380 and documented. And if a serious issue is found, 00:24:34.599 --> 00:24:37.380 a recall. If a manufacturer initiates a correction 00:24:37.380 --> 00:24:40.099 or removal action to reduce a health risk posed 00:24:40.099 --> 00:24:43.000 by a device or to remedy a violation of the act, 00:24:43.259 --> 00:24:45.660 they generally have to submit a written report 00:24:45.660 --> 00:24:50.400 to the FDA under 21 CFR Part 806. Recalls themselves 00:24:50.400 --> 00:24:53.119 are classified by the FDA based on the severity 00:24:53.119 --> 00:24:55.940 of the potential health risk, Class I being the 00:24:55.940 --> 00:24:58.960 most serious involving potential death or serious 00:24:58.960 --> 00:25:02.000 injury. That classification then guides the urgency 00:25:02.000 --> 00:25:04.259 and scope of the recall communication strategy. 00:25:04.539 --> 00:25:08.029 Class, I recall most serious. Got it. I've also 00:25:08.029 --> 00:25:10.029 heard about post -market surveillance, where 00:25:10.029 --> 00:25:12.250 companies might be required to actively monitor 00:25:12.250 --> 00:25:14.829 devices after approval. How does that fit into 00:25:14.829 --> 00:25:17.509 the QMS? Right. Sometimes the FDA requires manufacturers 00:25:17.509 --> 00:25:19.450 to conduct post -market surveillance studies, 00:25:19.710 --> 00:25:21.950 often through what's called a 522 order under 00:25:21.950 --> 00:25:25.670 21 CFR Part 822. 522 order. This usually happens 00:25:25.670 --> 00:25:28.529 for higher risk devices or when specific long 00:25:28.529 --> 00:25:31.150 -term questions remain after approval. It's about 00:25:31.150 --> 00:25:33.309 proactively monitoring the device's performance 00:25:33.309 --> 00:25:35.970 and safety in the real world across a broad patient 00:25:35.970 --> 00:25:38.980 population. Proactive Monitoring And separate 00:25:38.980 --> 00:25:42.000 from that, but related, are the medical device 00:25:42.000 --> 00:25:46.339 reporting or MDR requirements under 21 CFR part 00:25:46.339 --> 00:25:50.279 803. Manufacturers and importers and device user 00:25:50.279 --> 00:25:52.740 facilities are required to report certain adverse 00:25:52.740 --> 00:25:55.720 events to the FDA. What kind of incident? Particularly 00:25:55.720 --> 00:25:57.680 if they become aware of information suggesting 00:25:57.680 --> 00:25:59.700 that one of their devices may have caused or 00:25:59.700 --> 00:26:02.980 contributed to a death or serious injury or if 00:26:02.980 --> 00:26:05.099 a malfunction occurred that could lead to death 00:26:05.099 --> 00:26:08.210 or serious injury if it were to recur. It's about 00:26:08.210 --> 00:26:11.250 mandatory vigilance for safety signals. Mandatory 00:26:11.250 --> 00:26:13.950 vigilance. Yeah. It really sounds like this whole 00:26:13.950 --> 00:26:16.269 quality management system isn't just about ticking 00:26:16.269 --> 00:26:18.710 boxes for compliance, but it's fundamentally 00:26:18.710 --> 00:26:21.089 designed for continuous improvement. It absolutely 00:26:21.089 --> 00:26:23.329 is, or at least that's the goal when implemented 00:26:23.329 --> 00:26:26.490 effectively. A robust QMS supports continuous 00:26:26.490 --> 00:26:28.869 improvement in several ways. It standardizes 00:26:28.869 --> 00:26:31.269 processes, which reduces variability and human 00:26:31.269 --> 00:26:33.849 error. It leverages tools like audits, internal 00:26:33.849 --> 00:26:36.069 audits, supplier audits, and preparing for regulatory 00:26:36.069 --> 00:26:38.029 inspections to provide an independent assessment 00:26:38.029 --> 00:26:40.470 of compliance and system effectiveness. Audits 00:26:40.470 --> 00:26:42.809 help identify potential risks or weaknesses before 00:26:42.809 --> 00:26:45.329 they cause major problems. Catching things early. 00:26:45.390 --> 00:26:48.250 Exactly. And then there's the corrective and 00:26:48.250 --> 00:26:50.410 preventive action, or KPA system. system. KPA 00:26:50.410 --> 00:26:52.630 is crucial for investigating the root causes 00:26:52.630 --> 00:26:55.109 of problems, implementing effective corrections, 00:26:55.430 --> 00:26:57.430 and importantly, putting preventive measures 00:26:57.430 --> 00:27:00.150 in place to stop them from happening again. It's 00:27:00.150 --> 00:27:02.890 meant to be a cycle of identifying issues, fixing 00:27:02.890 --> 00:27:05.150 them, and learning from them to refine the system 00:27:05.150 --> 00:27:07.430 constantly. A cycle of learning and refining. 00:27:07.470 --> 00:27:09.690 That makes sense. So that's the extensive U .S. 00:27:10.009 --> 00:27:12.589 landscape under the FDA and the QSR. But, you 00:27:12.589 --> 00:27:14.369 know, medical devices are a global business. 00:27:14.730 --> 00:27:17.049 Are there international efforts to maybe harmonize 00:27:17.049 --> 00:27:20.450 regulations? Or are manufacturers just facing 00:27:20.450 --> 00:27:21.990 entirely different rule books everywhere they 00:27:21.990 --> 00:27:23.890 want to sell? That's a great question. There 00:27:23.890 --> 00:27:25.950 are significant efforts towards harmonization, 00:27:25.950 --> 00:27:28.910 yes, but it's still a complex global tapestry. 00:27:29.650 --> 00:27:31.710 International bodies like the International Medical 00:27:31.710 --> 00:27:36.210 Device Regulators Forum or IMDRF work on developing 00:27:36.210 --> 00:27:39.740 converged regulatory practices. But different 00:27:39.740 --> 00:27:42.099 regions still have their own specific requirements. 00:27:42.660 --> 00:27:45.359 A major one, for example, is the European Union's 00:27:45.359 --> 00:27:48.859 medical device regulation, the EU MDR regulation 00:27:48.859 --> 00:27:53.359 2017 745. It replaced older directives and now 00:27:53.359 --> 00:27:56.460 governs device approvals across the EU. EU MDR. 00:27:57.180 --> 00:27:59.640 Okay, so how does that EU system compare to the 00:27:59.640 --> 00:28:02.170 FDA system we've been discussing? What are some 00:28:02.170 --> 00:28:04.650 of the key differences, maybe philosophical or 00:28:04.650 --> 00:28:06.730 practical, that manufacturers need to grasp if 00:28:06.730 --> 00:28:09.309 they're aiming for both U .S. and EU markets? 00:28:09.730 --> 00:28:11.529 Well, one of the most fundamental differences 00:28:11.529 --> 00:28:14.170 is the regulatory body itself, or rather the 00:28:14.170 --> 00:28:16.839 structure. the EU uses what are called notified 00:28:16.839 --> 00:28:19.319 bodies. Notified bodies. Yes, these are independent 00:28:19.319 --> 00:28:22.180 third -party organizations accredited by national 00:28:22.180 --> 00:28:24.599 competent authorities. They are the ones who 00:28:24.599 --> 00:28:26.839 actually audit the manufacturer's quality management 00:28:26.839 --> 00:28:29.440 system, review the technical documentation for 00:28:29.440 --> 00:28:31.799 most devices, and assess conformity with the 00:28:31.799 --> 00:28:34.119 MDR requirements. If everything checks out, they 00:28:34.119 --> 00:28:36.799 issue the CE mark certificate. Ah, so it's third 00:28:36.799 --> 00:28:38.839 -party auditors doing the review, not the government 00:28:38.839 --> 00:28:41.700 agency directly like the FDA. For most devices, 00:28:41.940 --> 00:28:45.119 yes. This contrasts sharply with the FDA's model, 00:28:45.119 --> 00:28:47.960 where FDA's own scientists and reviewers conduct 00:28:47.960 --> 00:28:50.579 that centralized scientific review of the pre 00:28:50.579 --> 00:28:53.640 -market submission, like the 510k or PMA. That's 00:28:53.640 --> 00:28:55.579 a huge difference in approach. It really is. 00:28:55.640 --> 00:28:58.539 In Europe, getting that CE mark indicates compliance 00:28:58.539 --> 00:29:01.019 and allows marketing across the EU member states. 00:29:01.559 --> 00:29:03.779 This difference means manufacturers often need 00:29:03.779 --> 00:29:05.900 different strategies for engaging with regulators 00:29:05.900 --> 00:29:08.539 interacting with multiple notified bodies versus 00:29:08.539 --> 00:29:10.759 interacting centrally with the FDA. OK. What 00:29:10.759 --> 00:29:13.529 about classification? class one, two for FDA. 00:29:13.690 --> 00:29:16.569 Is it similar in the EU? It's similar in concept 00:29:16.569 --> 00:29:18.750 risk -based, but with some key differences in 00:29:18.750 --> 00:29:22.309 the details. The EU uses four main classes, class 00:29:22.309 --> 00:29:24.829 one, lowest risk, class C, class I, and class 00:29:24.829 --> 00:29:28.609 three, highest risk. Four classes, I, IA, IB. 00:29:29.049 --> 00:29:31.369 Right. And the specific classification rules 00:29:31.369 --> 00:29:35.049 can differ. For example, under EU MDR, many devices 00:29:35.049 --> 00:29:37.589 previously in lower classes got upclassified. 00:29:37.970 --> 00:29:40.130 And something like a sterile class I device in 00:29:40.130 --> 00:29:42.579 Europe, often requires notified body involvement 00:29:42.579 --> 00:29:45.400 for the sterility aspects, making its pathway 00:29:45.400 --> 00:29:47.680 look a bit more like a class two device pathway 00:29:47.680 --> 00:29:50.720 in the US context. So you can't just assume your 00:29:50.720 --> 00:29:53.119 FDA class translates directly. You really have 00:29:53.119 --> 00:29:55.519 to assess classification separately for each 00:29:55.519 --> 00:29:57.819 region. Absolutely critical for a global launch 00:29:57.819 --> 00:30:00.579 strategy. And what about the pre -market review 00:30:00.579 --> 00:30:03.140 process itself? What's the main difference there 00:30:03.140 --> 00:30:06.839 beyond the notified body versus FDA staff aspect? 00:30:07.000 --> 00:30:09.920 Under the EU MDR, for most devices above Class 00:30:09.920 --> 00:30:12.640 1, the Notified Body Review focuses heavily on 00:30:12.640 --> 00:30:15.380 the manufacturer's technical documentation, proving 00:30:15.380 --> 00:30:17.799 the device meets safety and performance requirements 00:30:17.799 --> 00:30:20.599 in their quality management system, often including 00:30:20.599 --> 00:30:24.299 that ISO 13485 audit. The emphasis is really 00:30:24.299 --> 00:30:26.559 on ensuring the manufacturer can consistently 00:30:26.559 --> 00:30:29.019 produce a safe and effective device, and verifying 00:30:29.019 --> 00:30:33.720 the clinical evidence supporting it. Yes, and 00:30:33.720 --> 00:30:36.539 the EU MDR significantly increased the requirements 00:30:36.539 --> 00:30:38.759 for clinical evidence for almost all devices, 00:30:39.039 --> 00:30:41.880 even established ones. Now, contrast that with 00:30:41.880 --> 00:30:45.640 the FDA's pre -market review. A510K is focused 00:30:45.640 --> 00:30:48.769 on that substantial equivalence comparison. A 00:30:48.769 --> 00:30:51.710 PMA is a deep scientific dive into the device's 00:30:51.710 --> 00:30:55.569 specific data by FDA's own experts. While a QMS 00:30:55.569 --> 00:30:57.869 inspection happens eventually, and often pre 00:30:57.869 --> 00:31:00.650 -PMA approval, it isn't always the primary focus 00:31:00.650 --> 00:31:03.730 of the initial 510 -K clearance decision itself. 00:31:03.910 --> 00:31:05.789 So different focus points in the review. EU, 00:31:06.309 --> 00:31:08.930 maybe more QMS -centric up front for CE marking? 00:31:09.650 --> 00:31:12.410 FDA, more data -equivalence -centric for clearance 00:31:12.410 --> 00:31:14.349 approval? That's a reasonable simplification, 00:31:14.549 --> 00:31:17.200 yes. Both demand strong data and quality systems, 00:31:17.440 --> 00:31:19.559 but the review structure and emphasis can feel 00:31:19.559 --> 00:31:21.839 quite different. Manufacturers really need to 00:31:21.839 --> 00:31:23.980 understand both systems thoroughly if they plan 00:31:23.980 --> 00:31:26.619 to operate globally. Wow. OK. We've really covered 00:31:26.619 --> 00:31:28.660 a lot of ground here, digging into the intricate 00:31:28.660 --> 00:31:30.980 world of medical device regulation. From the 00:31:30.980 --> 00:31:32.799 FDA's core definition, that crucial difference 00:31:32.799 --> 00:31:34.900 from drugs. Right. The physical versus chemical 00:31:34.900 --> 00:31:38.619 action. to the fundamental risk -based classification 00:31:38.619 --> 00:31:41.359 system, class one, two, and three, and how those 00:31:41.359 --> 00:31:44.700 decisions really ripple through the entire development 00:31:44.700 --> 00:31:48.059 lifecycle. Dictating the testing, the clinical 00:31:48.059 --> 00:31:50.740 trials needed, the submission pathway. Yeah, 00:31:50.839 --> 00:31:52.980 you've really shown that classifying device isn't 00:31:52.980 --> 00:31:54.960 just some administrative step you check off. 00:31:55.220 --> 00:31:57.740 It's a truly strategic foundation for everything 00:31:57.740 --> 00:32:01.089 that follows. Absolutely. And I think Understanding 00:32:01.089 --> 00:32:03.430 this landscape really highlights the immense 00:32:03.430 --> 00:32:05.910 effort and the rigorous standards that go into 00:32:05.910 --> 00:32:08.569 every medical device you might encounter. It 00:32:08.569 --> 00:32:10.849 helps ensure that the tools we rely on for our 00:32:10.849 --> 00:32:13.210 health, from the simplest tongue depressor you 00:32:13.210 --> 00:32:16.109 mentioned, right up to the most complex implanted 00:32:16.109 --> 00:32:19.130 heart valve, are reviewed for safety, effectiveness, 00:32:19.430 --> 00:32:21.890 and reliability. It's kind of an unspoken promise 00:32:21.890 --> 00:32:24.309 of quality and patient safety woven into the 00:32:24.309 --> 00:32:26.750 fabric of this industry. An unspoken promise. 00:32:27.069 --> 00:32:29.230 I like that. So thinking ahead then, what does 00:32:29.230 --> 00:32:31.599 this all mean? for the future. But technology 00:32:31.599 --> 00:32:33.799 isn't standing still. We're seeing more software 00:32:33.799 --> 00:32:35.880 integration, artificial intelligence, personalized 00:32:35.880 --> 00:32:38.059 medicine approaches getting built into devices. 00:32:38.279 --> 00:32:40.480 Huge changes happening. Right. So how do you 00:32:40.480 --> 00:32:43.700 think regulators like the FDA or their counter 00:32:43.839 --> 00:32:46.980 parts globally will need to adapt these classification 00:32:46.980 --> 00:32:49.299 systems and their oversight models. How do they 00:32:49.299 --> 00:32:51.799 keep pace with that rapid innovation while still 00:32:51.799 --> 00:32:53.920 maintaining the highest standards of safety and 00:32:53.920 --> 00:32:56.039 efficacy? That's the multi -billion dollar question, 00:32:56.059 --> 00:32:58.920 isn't it? Yeah. What new categories or maybe 00:32:58.920 --> 00:33:01.880 regulatory pathways might need to emerge, especially 00:33:01.880 --> 00:33:04.240 as those lines between medical devices, wellness 00:33:04.240 --> 00:33:07.140 products, and consumer tech continue to blur? 00:33:07.559 --> 00:33:09.940 It seems like a really fascinating and critical 00:33:09.940 --> 00:33:12.039 challenge for the future of health care regulation. 00:33:12.180 --> 00:33:14.930 It absolutely is. safety paramount while enabling 00:33:14.930 --> 00:33:17.369 beneficial innovation, that's the ongoing balancing 00:33:17.369 --> 00:33:17.670 act.