the CEM Program Committee for having me here. First and foremost, if everyone could raise their hand if in the audience you treat patients with biologics in some way, shape, or form. For those of you who do that, if you could keep your hands up, who has it figured out? If you don't have it figured out, lower your hand. Okay, so no one, so we're all in the same boat. So practical utilization of biologics in your practice is very difficult and that's because we don't fully understand biologics yet. Now a lot of what we just heard is going to help us better understand biologics. So I'll give you my level five advice and experience on how to practically utilize biologics in your practice, but as we're all experiencing, it can be challenging. What are our options? We've heard about a few of them here. We consider VSCO as a biologic as well as blood-based products, cell-based therapies, placental tissue-derived therapies, and isolated growth factors. How do we utilize biologics in practice? For me, it comes down to these four things. Number one, clinical indications. Number two, regulations and safety, and is the product FDA approved? And even if it's not FDA approved, it doesn't necessarily mean we can't use it, but we do need to understand what the risks and implications are. Number three, clinical logistics. How does it work in your clinic flow? And number four, the cost. And we're gonna hear about the business side from Dr. Rodeo in just a little bit. So let's talk about indications. Well, when you look at mainstream media, biologics can be used for everything. And I'm talking about everything, not just orthopedic conditions. In fact, biologics can take this subluxated, bone-on-bone degenerative hip and with a few cash-paid treatments, turn it into a normal hip. It's just that easy, except not that fast, because biologics are not the answer to everything, and certainly bad things can happen, such as complications, infections, even cancer can occur from ill use, ill proper use of biologics. So we have to be careful. So to sum it up, because this is not an indications talk, but we have to understand, just because we can treat a patient with PRP or a biologic of choice, doesn't mean that we should. So what are the indications? Well, in my mind, they're constantly evolving. Science, like we've heard today, helps us better understand what we can and should do, but they're consistently inconsistent. You can find a paper to support PRP for knee OA, and then you can find another one published last month in a major journal to negate it. And they're two different PRPs, so we're talking about apples and oranges, but what we see at the end of the day is conflicting evidence. So consistently inconsistent. In my practice right now, I use PRP for what I think are appropriately indicated patients with mild to moderate knee OA, tendinitis particularly of the elbow, and as a surgical augment for certain procedures, including meniscus repair. With cellular treatments in my current practice, this is more of an operative procedure to augment surgical reconstructions and techniques. So the bottom line is it's not entirely clear when it comes to indications, and we all think we know the literature, but the literature's so challenging that it's tough to really say if what we're making our clinical decisions based on is accurate. What do patients really wanna know? This is, for me, I put this slide in every biologics talk I give, because it's so important. They wanna know how long does the treatment last, when can they get back to sport or CrossFit, or if I do nothing, is that okay? Our job as clinicians is to manage their expectations under promise and ideally over deliver. What about safety and regulation? So when we talk about regulation, it's important to understand where biologics fall into this mix, and biologics are not easy to understand because we don't fully understand what they are. So there's two categories, according to the FDA, of increasing risk, largely related to the risk of communicable disease transmission, and the goal of this is not to torture us, although it seems like that. The goal of these two pathways is to assure safety, integrity, and function, as well as efficacy of the product and make sure it's maintained after processing. And so products fall into the HCT slash P pathways of 361 and 351. 361 products are lower risk. They are registered in the FDA as a manufacturer, and no clinical study is needed. So you can have a 361 product, go to market, and start using it. Examples of this include allografts, whole blood, collagen, possibly adipose, bone marrow, et cetera, but these definitions are evolving and we need to make sure we understand what we're telling our patients before we inject or place. 361 classification rules suggest that these products have to be, not suggest, mandate, that these products have to be minimally manipulated and intended for homologous use. The big question is, is adipose that I take from my flank or my belly, and I certainly have a lot of that, is that the same as an MSC that's in my knee? Am I using that in a homologous state? And some people may argue yes, and some people may argue no. We have to make sure if they fall into 361 that these products are not combined and there's no systemic effect. It's only a local effect at that location. If the product does not meet all of these criteria, it is regulated and considered a drug under FDA 351. If you're a 351 product, drug, device, biologic, et cetera, you have to go through clinical trial applications and marketing applications. What does this all mean? Big dollars. Why is this important? Because if we want the studies, we need the funding. If we want the funding, we have to write good protocols and do good research, and it's kind of a vicious cycle because one can't occur without the other. But the bottom line is to get a 351 product, it's got to go through a lot of processes. Those include pre- and post-market requirements. Those include IND applications, phase one, two, and three clinical trials, and then they ultimately get submitted for safety and efficacy as part of the BLA. This turns into years, if not decades, and by the time the research is done, a new product is available. So it makes it really challenging for any company or any researcher to want to put a product in 351, and 361 is thus much more attractive. Okay, we're all clinicians, or most of us are clinicians. What does this all mean in terms of utilizing biologics in your practice? Two take-home slides. What is allowed, at least in the United States right now? Products that are FDA 361 HCT slash B pathway products, which means they're minimally manipulated and intended for homologous use, and they can't be more than minimally manipulated or put in a place that's not considered homologous. They currently, unless they're part of a trial that's been approved, or potentially outside the United States where there are different rules and regulations, you currently cannot take these products and culture them, take them out of the procedure room or OR and bring them back, sort them, add growth factors or enzymes. Again, if you read a paper that talks about this, you have to understand if that group is in a study that's allowed by the FDA, or if they're overseas outside the US, and it may not be applicable to your regular practice. Okay, let's talk about logistics. I think this, for me, is the most important part of the practical utilization of biologics in the clinic, because it sounds great. Let's give some PRP here, let's give a little bone marrow here, let's give a little adipose. But if you're running a 60-patient clinic in your office and you, say, for example, have an MA or an ATC or an RN to help you run that clinic, perhaps you have a PA or an NP to work with you, perhaps you have a resident or fellow, which sometimes helps and sometimes hurts, just depends, and no offense to any of the residents or fellows, I was just one. So it just depends on your clinic flow. So the questions become, from a logistical approach, who does it? Are you the surgeon doing it? Is it a non-surgeon physician? Is it a PA, an NP, is it someone else? When are you doing it? Is it going to be in the middle of your morning when you're potentially 30 minutes behind because you had a difficult patient or a surgical complication? Is it going to be at the end of the day when your staff just wants to go home and no one's there to draw the blood, and so you might have to draw it, and you've not done that in 20 years? Or is it in a separate biologics clinic that you've set up with your office, with your PA or NP? When do you do this, and do you have a room? Do you pay rent and overhead for that room? How does this logistically work in your clinic flow? And then do you do it as the surgeon, or is that not valuable use of your time? Do you have your PM&R and more procedural-based colleagues, PM&R, primary care, family practice, internal medicine, ER, et cetera, pediatrics, do these procedures because, number one, they're good at it, and number two, they're not doing surgery, so they may have time to offer these procedures in their clinic where you as the surgeon may not. And then how do you do it? Are you drawing your own blood? Do you have an MA? Do you have an ATC? For example, for PRP, which is probably the most common biologic that we use. Are you collecting cash upfront because we know these are not paid for by insurance? Are you giving an NDA to the patient? Are you having them sign and form consent every time? Are you using an ultrasound? Do you have a procedure room? Does your hospital have COVID policies with how many procedures you can perform in a given day? If yours doesn't, mine does, and that's a very fun component to add to the clinical application of biologics in your clinic because those were not rules or regulations that we had pre-pandemic, but now we do. So here's how we do it, or here's how I do it. In my practice, my PA will do biologics, namely PRP, in a separate clinic, or we will refer to one of our non-op partners who's an expert in ultrasound-based procedures. If the patient requests me, Dr. Frank, I love you, I want you to do it, then we make time to do it at the beginning or end of my clinic day, but I do not do these in the middle of the clinic day. I have found that it disrupts the flow, and we don't need that in a busy clinic. When do we do it? Again, separate PA clinic or at the first or last appointment of the day. Very resource-dependent. I'm sure everyone's experiencing short staffing. We are too. We need people to draw the blood so I can see patients, and we need people to be able to set up the ultrasound machine, type in the patient's medical record number, save the information, et cetera, and so it all depends on ultrasound and centrifuge availability. And so in the middle of a clinic, and I've learned this the hard way, less than ideal. Cost, we're gonna hear about the business side of biologics in just a sec, so I'm not gonna go through too many details of this, but these are important considerations, and this is the first thing I bring up to the patient. This is an out-of-pocket expense, and I can't promise you it's going to make any difference. Those are the first two things I say, and oftentimes that stops the conversation right there. Patients didn't realize it was gonna cost X, or that I can't prove that PRP's gonna cure their arthritic hip into a normal hip. So in the clinic, there's a facility fee. If you work in a hospital-owned facility, there's a technical fee, there's the equipment and kit fee, and then in the OR, there's the all of the above plus the anesthesia fee if your system allows or mandates that. My practical Level 5 experience, these are kind of the take-home slides when it comes to applying biologics in your practice indications. I use these for knee osteoarthritis, tendonitis, especially lateral epicondylitis, and as a surgical adjunct. Regulations, I give full disclosure to patient. I am brutally honest. I tell them what I know, and more importantly, what I don't know, and I try to under-promise and over-deliver. Logistics, I've mentioned my PA or our non-op colleagues perform these when they're in the clinic unless the patient requests me. And in the OR, I'm doing these, of course, by myself. Cost in our system, full disclosure, PRP costs $9.50 cash for the patient, but you get a discount if you want both knees, it's $10.50. And then the cell-based treatments cost around $5,000. My Level 5 advice for anyone trying to figure this out, and if you have it better than me, please tell me. Be transparent and upfront with your patients. Disclose any financial relationships. It's critical to make sure that if you're a consultant, that's not a bad thing, but the patient should know about it. Be careful with marketing certain things. You cannot market that you're doing because they're not FDA approved. Understand product safety and efficacy, and certainly recognize what's on-label versus what's off-label. With that, thank you very much. Thank you.

biologics utilization

clinical indications

regulations and safety

clinical logistics

cost