Thank you, Scott, and thank you to the AANA and to Biologics Association for the opportunity to share some perspective with you. I don't see patients anymore. I haven't seen patients in 30 years directly, but I'm happy to talk about product development and how to stay safe here. My disclosures are of ‑‑ is this not working? Thank you. My disclosures are on the AAOS website, but I show this to indicate that we work with a large variety of firms in helping them navigate the product development pathway. Well, this product development pathway really reflects, I think, a change in the AAOS's emphasis on orthobiologics. You can see here they're really embracing the future. There's sessions like this. There have been sessions all week on orthobiologics. This is a book that just became available this week. I had the pleasure of co‑editing this book with, in fact, my undergraduate thesis advisor, Dr. Roy Aaron from 40 years ago, and many of the authors who contributed chapters are here in the audience and even on the podium today. This has led to an enormous business that I've had the pleasure of working with for the last 30 years, and you can see the overall orthobiologic business on the right‑hand side of the slide at $5 billion really represents almost 10 percent of the worldwide orthopedic product sales market, and it's growing faster at 15 percent year over year than the overall orthopedic market, so it's outstripping the growth rate of orthopedics overall, and what this means is that particularly on the right‑hand side of the slide, the 43 percent or $2 billion is really the result of 200 companies, each making about $10 million of revenue, and that means with so many companies out there, it can sometimes drive bad behavior. The other element of this $5 billion that you see here is that the HCTP market that we're talking about most frequently lately, PRP, BMAC, adipose tissue, really only represents about $250 million, and that means the rest of this is visco‑supplementation and bone grafting and cartilage repair. So one question that I get is, where do you look to understand the rules and regulations? This is information that's available on the FDA website. It hasn't really changed since 2017. There are these final guidance documents. They're a little tedious to get through, I'll admit, but the content is rather clear still, and this really guides how sponsors develop products. There are some aspects here in the FDA that guide how physicians can use them, but the FDA does not regulate the practice of medicine. That's very important. Too many physicians believe that the FDA regulates how you practice medicine. They do not. They regulate how sponsor companies make products available. Now there is this documentation, a guidance around minimal manipulation and homologous use. I urge people to read this carefully because it describes products that are eligible for FDA exemption if they are minimally manipulated and used in a homologous fashion. Forgive me, that sounds a little bit of jargon. You best read about it inside. Homologous use means like for like. So if you're a bone tissue, you can't use bone to recreate cartilage and call that homologous use, for example. There are tissues that are allowed. So adipose tissue that you minimally manipulate, that means not creating stromal vascular fraction or isolating stem cells. You can read through this that matrix amniotic membranes when used as a layer or a wound protector, those are allowable, but you can't grind up or sponsors can't grind up and sell amniotic tissue and inject it into joints. You can't have culture expanded cells or exosomes. My friend Dr. Rodio referred to the IND that he is participating in an investigative new drug product. This is the kind of product that has to be evaluated under the registration of an FDA trial. Lastly here about bone marrow and PRP, we know that the devices exist for the preparation of these products that can be used at your discretion, how you see fit based on your clinical judgment. But importantly, there's no therapeutic claim that you can make about the use of PRP or bone marrow. Now I'll also say agency has issued hundreds of letters and those letters are to physicians, those letters are to sponsors. One of the things the agency did, and I'm not going to play this video, you can search it on YouTube, but the upshot of this is that there are no approved stem cell therapies in orthopedics. How many of you had patients come in saying, I want that stem cell therapy, I need a stem cell therapy? Raise your hand. I consider this an educational opportunity. Don't call it stem cells. Nobody here is delivering stem cells, I guarantee you, unless you are involved in an IND or IDE study. Even in that case, they're not coming asking for it in that way. Now it's not just the FDA. The authorities are stepping up their surveillance, I'll call it. It's FTC, Federal Trade Commission. It's the Center for Medicare and Medicaid Services and even the academy and other societies. So I'm not here to act as the police. I've never turned anybody in. The goal here is to think of what I'm telling you as radar detection, how to stay out of trouble. One of the problems is that the people that turn you in may be your competitors, may be your surgeon competitors down the street, may actually be the patients themselves, because they are financially motivated to turn you in. And I'll explain that in a moment. So as I said, these agencies are stepping up their enforcement. FDA is really focused on the companies themselves more so than the physicians. But if you have a side laboratory, you've converted an exam room into a laboratory, and you're preparing PRP and BMAC and you do it properly, that's completely fine. Donnie Buford is a great example and has a great story about how to do that. There are others. Jason has set up a similar process. But if you're doing things like culture expanding cells or even isolating fragments of complex cell populations and delivering that, you are now acting as a biologic manufacturing facility. And if you do that, you need a biological license. And the agency can come in and the federal authorities can come in and put yellow tape around your building. And this has happened. I don't recommend it. I'll also say I know some people are taking pictures. If you go to our website, you can find video lectures, a repeat of things that I've done and articles that I've written about this. So you may not need to take pictures. I don't care if you do, but I think the society cares. As far as your promotional and marketing materials, that's subject to FDA and FTC scrutiny, so false advertising. Your testimonials have to comply with the labeling. It doesn't matter if Mrs. Jones came in and couldn't barely get off the couch before you treated her, and now she climbed Mount Everest. You can't put her on, if you put her on your website saying that, you're subject to some serious scrutiny and possible prosecution. That's not consistent with the labeling. Of course, ethical guidelines you need to follow. And the DOJ is, in fact, following through with clawbacks. They're going after a billion dollars of inappropriate submitted claims, and that is happening. So many of you know me as a physician and a scientist. I am not an attorney. My attorney tells me it's illegal for me to provide any legal counsel, so consider this just wise guidance. Naturally, the question is, how do you use this in your practice? Well, I'm going to repeat this again. You can use any product that has any legal basis for commercial sale, based on your clinical judgment, based on your experience, based on experience of colleagues, best if based on publications. There are billions of dollars worth of products being sold and used that are legal today. However, as I've said, keep your promotional materials on label, and don't use any products at the bottom of this list in the context of a traditional practice setting. If you're involved in an FDA registration study, that's fine. You can use those products, but you can't use them on patients that are not enrolled in the study. So if you look at the bottom two sets of bullets, raise your hand if you've had a rep in your office in the last six months trying to sell you some of this stuff. Well, that's really good, because I only see a few hands going up. You've got to throw those reps out of your office. You should ask them for all of the documentation. Here's an example of some false advertising. I'm going to try and fly through this. This center started out really good with what they describe as their regenerative medicine unit. Then they start talking about adult mesenchymal stem cells. This is bad. This is very bad. Don't do that. And if you're a small clinic, for example, don't brand yourself as a stem cell therapy group. And on the right-hand side of this slide, don't say that you can treat any of these conditions, because first of all, stem cells are not legal in the United States. And second of all, none of these approaches are taking care of these kind of conditions. This is an example of the impact on birth tissues. You can see the list here of products that were withdrawn from the market. These are no longer legitimate. And I'll say that I've been quickly fly through this to say that I have been called in the last few years the chicken little of orthobiologic compliance, because I've been saying, you're going to have to manage yourself. Authorities are going to come in here and tell you what to do. People didn't necessarily believe me. But now I've received a subpoena from the Department of Justice. If you've never seen one, this is what it looks like. It's not redacted. I had to redact it. Here's what it says, that I am being engaged essentially to provide testimony, sadly, in an awkward situation against former clients and even attendees at meetings. Wow, it got quiet. Who are not listening to the things that I'm saying. And so that's a very awkward place for me to be. The companies have come in and done terrible things. DOJ does an investigation on them. They find that we were supporting them. We told them what to do. And now they're subpoenaing me to ask to find out why the company is no longer following what I told them to do. So it's not fun when they show up at your door unannounced with a taser and a gun. And then you have to go through thousands of emails. And then you get invited down to the Thurgood Marshall Courthouse and you sit in a room and six U.S. attorneys stand there with you for six or seven hours asking you hundreds of questions. It's not fun. And I'm not even at risk. So I feel bad for those who might be at risk. So what I learned is they take it very seriously. It's a lot of money they're going after. They've got very smart people who have a lot of patience. It's expensive. I'm not at risk. And I've spent $10,000 already on this. Never mind the hundred hours that I have had to spend dealing with all of this. So it's very distracting. And I think I'll close by saying as a student of this for 40 years, I'm a huge fan that biology can make an impact. We're going to solve these pathologies. You can use any product you want that's legally available if you can justify it. Use on-label claims only. Don't use the list of bad products. You can find it on our website. You can find it on the FDA website and challenge the reps. If you build for Medicare tissues, build Medicare for birth tissues or exosomes, I think you need to have legal counsel. Thank you, Scott. Thanks very much.

orthobiologics

product development

regulations

FDA

enforcement