WEBVTT 00:00:00.000 --> 00:00:02.399 Welcome to the deep dive. Today, we're going 00:00:02.399 --> 00:00:04.660 to be tackling something I bet you interact with 00:00:04.660 --> 00:00:07.480 every day, but probably rarely think about. Oh, 00:00:07.599 --> 00:00:10.019 yeah. It's the regulations that govern those 00:00:10.019 --> 00:00:12.240 little pills in your medicine cabinet. You're 00:00:12.240 --> 00:00:14.400 absolutely right. We often take medications for 00:00:14.400 --> 00:00:16.719 granted, but there's a whole world of regulations 00:00:16.719 --> 00:00:19.739 ensuring that every single pill you swallow is 00:00:19.739 --> 00:00:21.820 safe and effective. It's kind of mind blowing 00:00:21.820 --> 00:00:24.120 when you think about it. It really is. So imagine 00:00:24.120 --> 00:00:26.760 you're a scientist. You just developed this potentially 00:00:26.760 --> 00:00:29.280 life saving new drug. Right. What would be the 00:00:29.280 --> 00:00:31.620 first hurdle you'd have to clear? Well before 00:00:31.620 --> 00:00:34.880 any human testing can even begin, you have to 00:00:34.880 --> 00:00:39.219 submit an IND. an investigational new drug application 00:00:39.219 --> 00:00:43.320 to the FDA. And this document, it's not a quick 00:00:43.320 --> 00:00:47.280 form. It's a massive compilation of preclinical 00:00:47.280 --> 00:00:50.240 data manufacturing processes and the proposed 00:00:50.240 --> 00:00:53.880 clinical trial plan. Think of it like a detailed 00:00:53.880 --> 00:00:56.380 roadmap for the entire drug development journey. 00:00:56.659 --> 00:00:58.939 A roadmap, that's a great way to put it. So the 00:00:58.939 --> 00:01:00.479 FDA basically wants to know everything about 00:01:00.479 --> 00:01:03.409 the drug. From its chemical makeup to how it's 00:01:03.409 --> 00:01:06.269 made before they'll even let you test it on humans. 00:01:06.769 --> 00:01:10.069 Exactly. It's all about protecting patients and 00:01:10.069 --> 00:01:12.769 ensuring that only thoroughly researched and 00:01:12.769 --> 00:01:15.269 potentially beneficial drugs make it to clinical 00:01:15.269 --> 00:01:17.810 trials. That makes sense. Now let's say your 00:01:17.810 --> 00:01:20.510 IND gets approved and you're ready to start clinical 00:01:20.510 --> 00:01:23.609 trials. I bet the FDA isn't just hands off at 00:01:23.609 --> 00:01:26.359 that point, are they? Absolutely not. There are 00:01:26.359 --> 00:01:29.079 different phases of clinical trials, each designed 00:01:29.079 --> 00:01:31.819 to answer specific questions about the drug's 00:01:31.819 --> 00:01:34.620 safety and effectiveness. And the FDA is involved 00:01:34.620 --> 00:01:37.420 every step of the way, providing continuous oversight 00:01:37.420 --> 00:01:40.359 to make sure everything is done according to 00:01:40.359 --> 00:01:42.459 strict guidelines. So it's not just a one -time 00:01:42.459 --> 00:01:45.060 check, it's constant back and forth. Precisely. 00:01:45.180 --> 00:01:47.959 The FDA reviews the data from each phase of the 00:01:47.959 --> 00:01:50.180 trials before allowing the company to move on 00:01:50.180 --> 00:01:53.209 to the next. I see. It's a rigorous process designed 00:01:53.209 --> 00:01:56.670 to catch any potential problems early on. That's 00:01:56.670 --> 00:01:58.989 good. Yeah. And speaking of those phases, I've 00:01:58.989 --> 00:02:01.370 always been curious what they actually entail. 00:02:01.530 --> 00:02:03.250 Like, what's the difference between, say, a phase 00:02:03.250 --> 00:02:05.349 I trial and a phase III trial? That's a great 00:02:05.349 --> 00:02:08.229 question. So phase I trials are the first time 00:02:08.229 --> 00:02:11.449 the drug is tested in humans. OK. And they usually 00:02:11.449 --> 00:02:13.610 involve a small group of healthy volunteers. 00:02:13.770 --> 00:02:17.039 Got it. The focus is on safety, figuring out 00:02:17.039 --> 00:02:19.300 the right dosage range, and understanding how 00:02:19.300 --> 00:02:22.099 the drug is absorbed and metabolized by the body. 00:02:22.300 --> 00:02:25.180 So like how the body processes it. Exactly. Then 00:02:25.180 --> 00:02:27.840 phase two trials expand to include a larger group 00:02:27.840 --> 00:02:29.960 of patients who actually have the condition the 00:02:29.960 --> 00:02:32.719 drug is intended to treat. OK. The goal there 00:02:32.719 --> 00:02:35.000 is to gather preliminary data on whether the 00:02:35.000 --> 00:02:37.740 drug is effective and to identify any potential 00:02:37.740 --> 00:02:39.479 side effects. So you're starting to see if it 00:02:39.479 --> 00:02:41.900 actually works. Yeah. And then phase three trials 00:02:41.900 --> 00:02:44.840 are the largest and most comprehensive, enrolling 00:02:44.840 --> 00:02:47.280 hundreds or even thousands of patients across 00:02:47.280 --> 00:02:50.879 multiple locations. This phase confirms the drug's 00:02:50.879 --> 00:02:52.879 effectiveness, monitors for side effects in a 00:02:52.879 --> 00:02:55.400 larger population, and compares the new drug 00:02:55.400 --> 00:02:58.219 to existing treatments. So each phase builds 00:02:58.219 --> 00:03:00.479 on the previous one, gathering more and more 00:03:00.479 --> 00:03:02.759 data about the drug's safety and effectiveness. 00:03:03.400 --> 00:03:06.099 It's a step -by -step process, and the FDA is 00:03:06.099 --> 00:03:08.340 right there with you at each stage, making sure 00:03:08.340 --> 00:03:10.580 everything is done by the book. Now, I know we've 00:03:10.580 --> 00:03:13.020 all heard about these mysterious acronyms like 00:03:13.020 --> 00:03:16.520 NDAs and BLAs. What exactly are they? Those are 00:03:16.520 --> 00:03:19.240 the big kahunas, the new drug application, NDA, 00:03:19.759 --> 00:03:23.129 and the biologics license application. These 00:03:23.129 --> 00:03:25.909 are the massive submissions a company sends to 00:03:25.909 --> 00:03:28.509 the FDA to get final approval for a new drug. 00:03:28.610 --> 00:03:31.889 Huge. They contain years of research data, clinical 00:03:31.889 --> 00:03:35.150 trial results, manufacturing details, and a whole 00:03:35.150 --> 00:03:38.300 lot more. Think of it as the final exam for a 00:03:38.300 --> 00:03:40.900 PhD in drug development. That sounds incredibly 00:03:40.900 --> 00:03:43.199 intense. So even after a drug makes it through 00:03:43.199 --> 00:03:45.719 all those phases of clinical trials, there's 00:03:45.719 --> 00:03:48.240 still this mountain of paperwork and scrutiny 00:03:48.240 --> 00:03:50.080 before it can actually hit the market. That's 00:03:50.080 --> 00:03:52.680 right. The FDA reviewers meticulously analyze 00:03:52.680 --> 00:03:55.360 every piece of data. Wow. To make sure the drug 00:03:55.360 --> 00:03:57.960 is safe, effective, and manufactured to the highest 00:03:57.960 --> 00:04:00.280 standards. So even after a drug is approved, 00:04:00.580 --> 00:04:02.419 the FDA isn't just waving goodbye and moving 00:04:02.419 --> 00:04:04.659 on. Absolutely not. The journey continues with 00:04:04.659 --> 00:04:07.180 post -marketing. surveillance. The FDA keeps 00:04:07.180 --> 00:04:09.039 monitoring the drug's performance in the real 00:04:09.039 --> 00:04:11.639 world, looking for any unexpected side effects 00:04:11.639 --> 00:04:14.219 that might not have shown up in the smaller clinical 00:04:14.219 --> 00:04:16.740 trial populations. So it's really a continuous 00:04:16.740 --> 00:04:19.360 process from the lab bench to the pharmacy shelves 00:04:19.360 --> 00:04:22.480 and beyond. And I'm starting to get a sense of 00:04:22.480 --> 00:04:25.019 just how intricate this whole process is. I know 00:04:25.019 --> 00:04:26.920 there's a lot of talk about good practices in 00:04:26.920 --> 00:04:29.360 the pharmaceutical world. What exactly does that 00:04:29.360 --> 00:04:32.509 mean? Good practices are essentially a set of 00:04:32.509 --> 00:04:34.970 guidelines and regulations that ensure the quality 00:04:34.970 --> 00:04:37.129 and consistency of every step of the process. 00:04:37.170 --> 00:04:40.209 OK. We have CGMPs, which stand for current good 00:04:40.209 --> 00:04:43.769 manufacturing practices. Got it. And CDCPs, which 00:04:43.769 --> 00:04:46.649 are current good clinical practices. So CGMPs 00:04:46.649 --> 00:04:49.329 for manufacturing CGCPs for the clinical trials, 00:04:49.629 --> 00:04:51.209 they're all about doing things the right way. 00:04:51.370 --> 00:04:53.850 Exactly. It's about creating systems where quality 00:04:53.850 --> 00:04:56.389 is built into every step of the process, from 00:04:56.389 --> 00:04:58.829 the raw materials used to make the drug to how 00:04:58.829 --> 00:05:00.519 the cli - clinical trials are conducted, it's 00:05:00.519 --> 00:05:02.259 not just about the final product, it's about 00:05:02.259 --> 00:05:04.959 the entire journey. And all of these good practices, 00:05:05.100 --> 00:05:07.199 the clinical trials, the NDAs, this isn't just 00:05:07.199 --> 00:05:09.519 a US thing, right? You're right, the pharmaceutical 00:05:09.519 --> 00:05:11.860 industry is global, and that's where the ICH 00:05:11.860 --> 00:05:15.139 comes in. The International Council for Harmonization 00:05:15.139 --> 00:05:17.480 of Technical Requirements for Pharmaceuticals 00:05:17.480 --> 00:05:20.019 for Human Use. Wow, what a mouthful. The ICH 00:05:20.019 --> 00:05:22.639 develops guidelines that are adopted by regulatory 00:05:22.639 --> 00:05:25.600 bodies worldwide, including the FDA. So it's 00:05:25.600 --> 00:05:27.759 like a global network, ensuring that no matter 00:05:27.759 --> 00:05:30.699 where a drug is developed, it meets certain standards. 00:05:31.279 --> 00:05:33.860 Exactly. The ICH guidelines cover everything 00:05:33.860 --> 00:05:37.079 from manufacturing processes to the format of 00:05:37.079 --> 00:05:38.699 those applications we talked about, like the 00:05:38.699 --> 00:05:42.240 NDA. The FDA incorporates these guidelines into 00:05:42.240 --> 00:05:45.379 the Code of Federal Regulations, or CFR. OK. 00:05:45.420 --> 00:05:48.439 So we have the ICH setting the standards globally, 00:05:48.439 --> 00:05:51.519 and then each country like the US with its FDA 00:05:51.519 --> 00:05:54.199 adapts those standards into their own specific 00:05:54.199 --> 00:05:57.500 regulations. Precisely. It's a complex but important 00:05:57.500 --> 00:06:00.319 system that ensures consistency and quality in 00:06:00.319 --> 00:06:02.439 drug development around the world. So we've talked 00:06:02.439 --> 00:06:05.339 about these NDAs, these huge applications companies 00:06:05.339 --> 00:06:07.899 have to file. Right. But what about generic drugs? 00:06:08.079 --> 00:06:10.620 Okay. I imagine the process is a bit different 00:06:10.620 --> 00:06:12.600 for them since they're essentially copies of 00:06:12.600 --> 00:06:14.519 already approved medications. You're right. The 00:06:14.519 --> 00:06:16.939 pathway for generic drugs is a bit different. 00:06:16.939 --> 00:06:19.220 Instead of an NDA, they file what's called an 00:06:19.220 --> 00:06:22.680 NDA. An abbreviated new drug application. So 00:06:22.680 --> 00:06:24.060 abbreviated because they don't have to start 00:06:24.060 --> 00:06:25.839 from scratch like a brand new drug. Exactly. 00:06:25.879 --> 00:06:28.899 With an NDA, the focus is on proving that the 00:06:28.899 --> 00:06:31.279 generic drug is essentially the same as the brand 00:06:31.279 --> 00:06:33.660 name drug in terms of active ingredient dosage 00:06:33.660 --> 00:06:36.199 form strength and how it's absorbed and used 00:06:36.199 --> 00:06:39.339 by the body, what we call bioequivalence. Bioequivalence. 00:06:39.379 --> 00:06:42.079 So they need to show that the generic acts the 00:06:42.079 --> 00:06:44.399 same way in the body as the brand name drug. 00:06:44.680 --> 00:06:47.300 Precisely. We do this through studies comparing 00:06:47.300 --> 00:06:50.180 how both drugs dissolve and how they appear in 00:06:50.180 --> 00:06:52.339 the bloodstream over time. They don't have to 00:06:52.339 --> 00:06:54.259 repeat all the original clinical trials that 00:06:54.259 --> 00:06:56.560 were done for the brand -name drug, which saves 00:06:56.560 --> 00:06:58.779 a lot of time and resources. That makes sense, 00:06:58.779 --> 00:07:00.759 especially when we're talking about making medications 00:07:00.759 --> 00:07:03.779 more affordable and accessible. Exactly. The 00:07:03.779 --> 00:07:06.699 NDA pathway is crucial for bringing generic drugs 00:07:06.699 --> 00:07:09.199 to market quickly and efficiently. We've touched 00:07:09.199 --> 00:07:11.439 on the FDA's role as an oversight body. We hear 00:07:11.439 --> 00:07:14.399 about these Form 483 sometimes. What are those 00:07:14.399 --> 00:07:17.420 all about? Think of a Form 483 as a wake -up 00:07:17.420 --> 00:07:20.519 call from the FDA. They conduct inspections of 00:07:20.519 --> 00:07:22.740 drug manufacturing facilities, and if they find 00:07:22.740 --> 00:07:25.180 something amiss, maybe a deviation from those 00:07:25.180 --> 00:07:28.120 CGMPs we talked about, they'll issue a Form 483. 00:07:28.160 --> 00:07:30.300 So it's like a warning letter pointing out areas 00:07:30.300 --> 00:07:32.259 where the company needs to improve its practices. 00:07:32.500 --> 00:07:34.079 Exactly. It doesn't necessarily mean the drug 00:07:34.079 --> 00:07:37.290 is unsafe. But it indicates that the FDA has 00:07:37.290 --> 00:07:39.870 identified potential issues that need to be addressed. 00:07:40.050 --> 00:07:41.589 And I imagine the companies take these forms 00:07:41.589 --> 00:07:44.170 very seriously given the FDA's authority to take 00:07:44.170 --> 00:07:46.949 further action if those issues aren't resolved. 00:07:47.230 --> 00:07:50.089 Absolutely. Receiving a Form 483 usually triggers 00:07:50.089 --> 00:07:52.889 a flurry of activity within the company to investigate 00:07:52.889 --> 00:07:55.829 the findings, implement corrective actions, and 00:07:55.829 --> 00:07:58.050 prevent similar issues from happening again. 00:07:58.350 --> 00:08:00.250 It really highlights the critical role of the 00:08:00.250 --> 00:08:02.769 FDA in ensuring that drug manufacturing meets 00:08:02.769 --> 00:08:04.449 those high standards we've been talking about. 00:08:04.680 --> 00:08:07.720 It does. The FDA's oversight is vital for maintaining 00:08:07.720 --> 00:08:10.139 public trust in the safety and quality of medications. 00:08:10.379 --> 00:08:12.480 OK, so we've covered a lot of ground here. We've 00:08:12.480 --> 00:08:18.019 talked about INDs, NDAs, BLAs, CGMPs, the ICH, 00:08:18.319 --> 00:08:21.339 the FDA. It's quite a complex world. It is. But 00:08:21.339 --> 00:08:23.519 when you break it down, it's all about ensuring 00:08:23.519 --> 00:08:26.879 that the medications we rely on are safe. effective 00:08:26.879 --> 00:08:29.300 and consistently manufactured to the highest 00:08:29.300 --> 00:08:31.439 standards. And that's a journey that starts long 00:08:31.439 --> 00:08:33.919 before a drug ever hits the pharmacy shop. Absolutely. 00:08:34.059 --> 00:08:36.120 It's a journey that starts with the spark of 00:08:36.120 --> 00:08:39.240 scientific discovery. winds its way through years 00:08:39.240 --> 00:08:41.960 of research and rigorous testing, and ultimately 00:08:41.960 --> 00:08:44.580 ends with a medication that can improve or even 00:08:44.580 --> 00:08:47.200 save lives. And along that journey there are 00:08:47.200 --> 00:08:50.639 countless checkpoints, regulations, and dedicated 00:08:50.639 --> 00:08:53.799 individuals working tirelessly to ensure that 00:08:53.799 --> 00:08:56.519 every step is taken with the utmost care and 00:08:56.519 --> 00:08:58.570 attention to detail. That's what makes this field 00:08:58.570 --> 00:09:01.710 so fascinating. It's a delicate balance of scientific 00:09:01.710 --> 00:09:04.889 innovation and regulatory oversight, all driven 00:09:04.889 --> 00:09:07.549 by the ultimate goal of improving human health. 00:09:07.870 --> 00:09:10.090 It's amazing to think about the sheer complexity 00:09:10.090 --> 00:09:13.000 of bringing a new drug to market. It is. We've 00:09:13.000 --> 00:09:15.320 talked about the science, the regulations, the 00:09:15.320 --> 00:09:17.679 global collaboration. Right. But what about the 00:09:17.679 --> 00:09:19.759 human side of this equation? Where do patients 00:09:19.759 --> 00:09:21.740 fit into all of this? That's a crucial point. 00:09:21.799 --> 00:09:23.320 Patients are at the heart of everything we've 00:09:23.320 --> 00:09:25.700 discussed today. All of these regulations, all 00:09:25.700 --> 00:09:28.080 of this research, it's ultimately about ensuring 00:09:28.080 --> 00:09:30.620 that patients have access to safe and effective 00:09:30.620 --> 00:09:33.480 medications. So while the FDA might seem like 00:09:33.480 --> 00:09:37.000 this distant regulatory body, their role is fundamentally 00:09:37.000 --> 00:09:39.500 about protecting patients. Exactly. And patients 00:09:39.500 --> 00:09:41.600 themselves play a crucial role in this process. 00:09:41.480 --> 00:09:44.139 us to. How so? Well, it's important for patients 00:09:44.139 --> 00:09:47.279 to be informed about their medications, to understand 00:09:47.279 --> 00:09:50.200 the potential benefits and risks, and to be active 00:09:50.200 --> 00:09:52.600 participants in their healthcare decisions. So 00:09:52.600 --> 00:09:54.679 it's not just about passively taking whatever 00:09:54.679 --> 00:09:57.379 the doctor. prescribes. Not at all. Patients 00:09:57.379 --> 00:09:59.899 should feel empowered to ask questions, to discuss 00:09:59.899 --> 00:10:01.820 their concerns with their health care providers, 00:10:01.960 --> 00:10:04.899 and to report any unusual side effects they experience. 00:10:05.059 --> 00:10:06.879 It's a two -way street then. Open communication 00:10:06.879 --> 00:10:09.299 between patients and their doctors is key. Absolutely. 00:10:09.399 --> 00:10:11.200 And let's not forget the role of pharmacists. 00:10:11.320 --> 00:10:13.580 They're a wealth of information about medications 00:10:13.580 --> 00:10:16.620 and can provide valuable guidance to patients. 00:10:16.759 --> 00:10:19.200 It sounds like being an informed patient is almost 00:10:19.200 --> 00:10:21.600 as important as having a good doctor. I'd agree 00:10:21.600 --> 00:10:23.679 with that. The more patients understand about 00:10:23.679 --> 00:10:26.080 their medications, the better equipped they are 00:10:26.080 --> 00:10:28.679 to make decisions that are right for them. This 00:10:28.679 --> 00:10:31.480 deep dive has really opened my eyes to the complex 00:10:31.480 --> 00:10:34.620 world of pharmaceutical regulations. It is complex. 00:10:34.720 --> 00:10:37.080 It's a world that's often hidden from view, but 00:10:37.080 --> 00:10:39.639 it's so important for all of us. It is. And it's 00:10:39.639 --> 00:10:41.039 something we probably don't think about very 00:10:41.039 --> 00:10:43.940 often. Right, until we need it. Exactly. Yeah. 00:10:44.899 --> 00:10:46.740 Well, it has been a fascinating journey learning 00:10:46.740 --> 00:10:48.899 about all of this. It has been a pleasure sharing 00:10:48.899 --> 00:10:51.309 this journey with you. To you, dear listener, 00:10:51.450 --> 00:10:53.350 we hope you've gained a new appreciation for 00:10:53.350 --> 00:10:55.730 the intricate process that goes into making those 00:10:55.730 --> 00:10:58.570 pills in your medicine cabinet. It's a world 00:10:58.570 --> 00:11:01.230 of science regulations and dedicated individuals 00:11:01.230 --> 00:11:04.110 all working together to ensure that the medications 00:11:04.110 --> 00:11:08.190 you rely on are safe, effective, and truly make 00:11:08.190 --> 00:11:11.289 a difference in your life. Until next time, keep 00:11:11.289 --> 00:11:14.009 exploring the world around you and never stop 00:11:14.009 --> 00:11:14.950 asking questions.