Module 1: PRP & Orthobiologics 101 for the Clinical Sales Professional
Learning Objectives
By the end of this module, you will be able to:
- Define "orthobiologics" and explain where platelet-rich plasma (PRP) fits within the current treatment landscape for knee osteoarthritis (OA)
- Differentiate PRP from other biologic therapies, particularly stem cells and microfragmented adipose tissue (MFAT), using FDA-compliant language
- Identify the most common, evidence-supported clinical applications for PRP in musculoskeletal medicine
- Communicate the clinical context of PRP to providers in a vendor-neutral, evidence-based manner, managing expectations ethically
1. What Are Orthobiologics? A Framework for Clinical Conversations
In the field of joint care, "orthobiologics" are substances derived from biological sources used to help the body heal musculoskeletal injuries. This is a rapidly growing area of medicine, but one that requires precise, compliant language, as clinical use has often outpaced the evidence base.
Orthobiologics are not curative therapies for advanced osteoarthritis (OA), a progressive degenerative disorder involving cartilage loss and inflammation. For severe, "bone-on-bone" arthritis, total joint arthroplasty remains the definitive surgical treatment. Orthobiologics are primarily positioned as non-surgical interventions for patients with earlier stages of disease, aiming to provide symptomatic relief and potentially delay the need for surgery.
The main orthobiologics you will encounter in the sports medicine/orthopedic market include:
- Platelet-Rich Plasma (PRP): An autologous blood product concentrated with platelets and plasma, which is rich in growth factors. It is often considered the "entry point" biologic due to its simple preparation, safety profile, and the growing body of clinical evidence supporting its use
- Bone Marrow Aspirate Concentrate (BMAC): Contains a small number of progenitor cells, platelets, and plasma. While it has theoretical advantages, head-to-head clinical trials have not shown BMAC to be superior to PRP for knee OAand this is a highly experimental modality suitable for academic medicine and research
- Microfragmented Adipose Tissue (MFAT): Processed fat tissue containing the stromal vascular fraction
- Emerging Products: This category includes alpha-2 macroglobulin (A2M), interleukin-1 receptor antagonist protein (IRAP), and exosomes, all of which are still investigational and primarily suitable for academic medicine and research
Sales Professional Tip: Position PRP as an autologous option within the broader orthobiologics category that is accumulating clinical research evidence every year. Avoid comparing it to therapies that have higher regulatory hurdles or less clinical evidence, and if asked, immediately refer to your company's medical affairs scientists.
Regulatory Reality Check: PRP is a blood-derived autologous product prepared with FDA-cleared devices. Devices are cleared for preparation, not for any specific applications. Physicians determine clinical use, which is considered off-label but within the "medical practice" domain. Medicare nationally covers PRP only for chronic non-healing diabetic wounds for up to 20 weeks when prepared by devices cleared for wound management. There is no national Medicare coverage for PRP in knee OA.
2. What is PRP? The Science You Need to Know
PRP is a fraction of a patient's own blood that is centrifuged to achieve a higher concentration of platelets than baseline whole blood.
- Whole Blood: Contains approximately 150,000–350,000 platelets/µL
- (Centrifuged Fraction Containing) PRP: Typically contains a platelet concentration 2–5 times above baseline, although this varies significantly between preparation systems
The Fascinating Evolution of PRP: From Cardiac Surgery to Orthobiologics
PRP’s journey through medicine is a story of clinical curiosity and innovation. The first widely documented medical use came in 1987, when Ferrari and colleagues introduced platelet-rich plasma as an autologous transfusion component to reduce the need for donor blood after open-heart surgery. That application was far removed from today’s common use in joint and tendon injections.
Orthopedics and sports medicine began to explore PRP seriously in the early 2000s, particularly for tendon injuries. Landmark studies on chronic elbow tendinosis (tennis elbow) in the mid-2000s provided some of the earliest controlled evidence of benefit. High-profile use among professional athletes soon attracted major media attention, accelerating interest across the sports medicine community.
The growth of the scientific literature has been striking: from fewer than 100 PubMed-indexed studies before 2005 to well over 5,000 publications today, covering specialties ranging from orthopedics and sports medicine to dentistry, dermatology, and maxillofacial surgery.
In musculoskeletal medicine, PRP’s credibility was built first in tendinopathy, particularly lateral epicondylopathy (tennis elbow). These successes opened the door to broader exploration. By the late 2000s, clinical studies were underway in cartilage and joint applications, following earlier preclinical work in the mid-2000s.
Unlike many medical technologies, where strong evidence is required before widespread use, PRP followed a different path. Clinical innovation often preceded robust randomized trial data. Practitioners experimented in the field, especially in sports and regenerative medicine, with the evidence base gradually catching up over the next two decades. This trajectory illustrates how clinical intuition and patient demand can sometimes drive research rather than follow it.
The orthobiologic rationale is that platelets are depots of bioactive proteins and growth factors that have normal functions in wound- and tissue repair. Key growth factors you may hear healthcare providers talk about include:
- Platelet-Derived Growth Factor (PDGF)
- Transforming Growth Factor-beta (TGF-β)
- Vascular Endothelial Growth Factor (VEGF)
- Insulin-like Growth Factor-1 (IGF-1)
Healthcare providers interested in having in-depth conversations relating to specific components in PRP and hypothesized cellular processes should be connected with your company's medical affairs scientists.
You may hear about two formulations of PRP from clinicians based on availability of leukocytes in the generated PRP. The FDA requires manufacturers to report whether their systems produce leukocyte-rich or leukocyte-poor PRP, leaving clinical interpretation about leukocytes to physicians.
- Leukocyte-Rich PRP (LR-PRP): Contains a higher concentration of white blood cells (leukocytes). Physicians hypothesize that this may be beneficial for tendon injuries but can be pro-inflammatory
- Leukocyte-Poor PRP (LP-PRP): Contains fewer white blood cells. Increasing evidence supports this formulation for intra-articular injections, such as in knee OA, to minimize inflammatory reactions.
3. Critical Distinction: PRP is NOT Stem Cell Therapy
This is a crucial point for both ethical communication and regulatory compliance. Direct-to-consumer marketing often conflates these treatments, leading to patient confusion, and a growing number of FDA warning letters and regulatory enforcements in the PRP market.
- PRP: An autologous blood product prepared at the point of care from a simple blood draw. It is regulated by the FDA as a blood product, and the devices used for preparation are cleared via the 510(k) pathway. It does not contain stem cells
- Stem Cell Therapy: This term typically refers to therapies involving mesenchymal stem cells (MSCs) that are isolated and often culture-expanded (grown in a lab). These are regulated by the FDA as biologics (HCT/Ps under section 351) and require extensive clinical trials and a Biologics License Application (BLA) prior to marketing. No such products are currently approved for routine musculoskeletal use in the U.S.
Compliance Alert: Claiming PRP is a "stem cell therapy" is a
significant regulatory violation. It misrepresents the product and creates unrealistic patient expectations of cartilage regrowth, which is not supported by evidence.
4. Clinical Applications: Where Does the Evidence Stand?
Clinicians are using PRP across musculoskeletal medicine, but the strength of evidence varies for this orthobiologic. For this reason, clinicians often have questions about clinical evidence on specific applications with PRP. When encountering these questions, focus conversations on the availability of peer-review published high-level evidence (i.e., exists or does not yet exist) for healthcare providers' specific query, then immdiately refer additional questions and discussions to your company's medical affairs.
- Knee Osteoarthritis: Peer-reviewed, published, high-level (Level I) evidence exists.
- Lateral Epicondylopathy (Tennis Elbow): Peer-reviewed, published, high-level (Level I) evidence exists.
- Plantar Fasciitis: Peer-reviewed, published, high-level (Level I) evidence exists.
Other orthobiologic applications of PRP are considered investigational, with less consistent clinical evidence. The American Academy of Orthopaedic Surgeons (AAOS) acknowledges that PRP "may reduce pain and improve function" for symptomatic knee OA, but still gives this a "limited" strength of recommendation due to heterogeneity in studies and products. Availability of high-level clinical research evidence DOES NOT automatically translate into standards of clinical practice.
Comprehensive Regulatory and Payer Landscape
FDA Regulatory Framework:
- Device Clearance: PRP preparation systems (centrifuges and kits) are typically brought to market via the FDA's 510(k) pathway. This means the device is cleared for preparing an autologous platelet concentrate, not that the resulting PRP is approved for treating specific conditions like knee OA
- Off-Label Use: The use of PRP for knee OA is considered "off-label" from a device instruction-for-use (IFU) standpoint
- Blood Product Classification: PRP itself is regulated as a blood product, not a drug, biologic, or HCT/P, and is exempt from certain regulations under 21 CFR 1271 when used autologously (e.g. recipient of blood product is donor of same blood product)
Reimbursement Reality:
- PRP for musculoskeletal indications, including knee OA, is generally not covered by Medicare or most commercial insurance payers
- Payers often classify PRP and other orthobiologics as "investigational" or "not medically necessary"
- Patients typically pay out-of-pocket, with costs reported to be over $700 per treatment course
Professional Society Positions: The Complex Landscape
Despite reviewing similar evidence, major medical societies have reached different conclusions about PRP, reflecting the complexity of interpreting emerging evidence:
- American Academy of Orthopaedic Surgeons (AAOS): States PRP "may reduce pain and improve function," with a "limited" strength of recommendation due to heterogeneity in studies and products
- American Association of Hip and Knee Surgeons (AAHKS): Does not recommend routine use of PRP for advanced hip or knee OA due to lack of data showing significant benefit over existing therapies and due to high out-of-pocket costs.
- American College of Rheumatology (ACR): Recommend against PRP for hip OA; knee recommendations are not supportive
- International Olympic Committee (IOC): Supportive of PRP use for mild OA in "sports medicine contexts".
| Therapy |
Source |
Key Components |
Regulatory Status |
Common MSK Uses |
| PRP |
Autologous blood |
Platelets, plasma, growth factors |
Devices are FDA-cleared for preparation. Clinical use in OA is off-label |
Knee OA (K-L grades 1-3), tendinopathy, plantar fasciitis |
| BMAC |
Bone marrow aspirate |
Progenitor cells, platelets, plasma |
Not regulated as an HCT/P if it meets specific criteria (e.g., same surgical procedure exception) |
Research, some MSK applications |
| MFAT |
Autologous adipose tissue |
Stromal vascular fraction |
Regulatory status is complex and carries a higher risk; often considered more than minimally manipulated |
Investigational |
| Stem Cells (Cultured) |
Cultured marrow/adipose |
Mesenchymal Stem Cells (MSCs) |
Regulated as a Section 351 biologic; not cleared or approved for routine MSK use |
Clinical trials only |
Most Common Adverse Events:
Based on systematic literature review through January 2024, PRP demonstrates a generally favorable safety profile when proper protocols are followed. However, all healthcare providers should be aware of documented adverse events to ensure appropriate patient selection and informed consent.
The 2024 systematic review of PRP adverse events reveals that most infection complications occur during preparation rather than from the autologous blood itself, emphasizing the critical importance of sterile technique and functionally closed preparation systems.
Post-operative Infections (Most Frequent):
- Staphylococcus aureus infections
- Spondylodiscitis (Cutibacterium acnes)
- Septic arthritis (Streptococcus mitis)
Severe Complications (Rare but Documented):
- Irreversible blindness (cosmetic glabellar injections)
- Exuberant synovitis and severe local inflammation
- Allergic reactions including serum sickness
- Nodule formation and cutaneous sarcoidosis
5. The Clinical Conversation Framework
When discussing PRP with healthcare providers, focus on key features of a PRP system (volume of blood draw, time required for centrifugation, ease of preparation) that facilitates clinical decision-making for a particular system. Avoid discussing clinical benefits or biological effects even if solicited/prompted by clinicians: these are beyond the use specifications (off-label) of PRP systems.
Scenario 1: The Stem Cell Question (Medical Affairs Trigger)
Physician: "I have a patient asking about stem cells and if PRP contains stem cells. Does your kit contain stem cells?"
Appropriate Response: "That's a common question, and a frequent point of confusion about these modalities. PRP is prepared from the patient's own blood to concentrate platelets. True stem cell therapies involve growing cells and are regulated differently by the FDA, typically available in clinical trials and academic medicine. What responses have worked to best educate your patients?"
Medical Affairs Triggers: The following physician questions require immediate medical affairs engagement due to FDA off-label/unapproved use implications:
- Requests for specific treatment protocols or dosing recommendations
- Questions about PRP efficacy compared to specific competitors
- Inquiries about PRP for conditions other than those with published evidence
- Questions about combining PRP with other therapies
- Requests for unpublished study data or internal efficacy claims
Scenario 2: The Protocol Question (Medical Affairs Trigger)
Physician: "What's your recommended injection protocol for PRP in knee osteoarthritis? How many injections should I give?"
Appropriate Response: "That's an excellent clinical question that involves treatment protocols, which fall under the practice of medicine and are beyond my scope as a sales professional. Let me connect you with our medical affairs team—they can discuss the published literature on various approaches and help you access the clinical evidence that informs these decisions. I can have Dr. [Medical Affairs Contact] reach out to you this week. Are there questions about the features of the PRP system that may help with your selection process?"
Scenario 3: The Comparative Efficacy Question (Medical Affairs Trigger)
Physician: "How does PRP compare to hyaluronic acid injections for pain relief?"
Appropriate Response: "Comparative effectiveness questions are really important for clinical decision-making, and they require a thorough review of the published literature. Our medical affairs team is best positioned to discuss the available evidence from published studies. I'd be happy to arrange a call or a (virtual) meeting with our medical affairs team. Would either of those options work for you?"
Scenario 4: Safety Discussion
Physician: "I'm concerned about infection risk since this involves blood processing. What should I know about safety?"
Clinical Sales Response: "That's an important safety consideration. While PRP uses the patient's own blood, which reduces immunogenic risk, infections have been reported in the literature, likely occurring during the preparation process rather than from the blood product. The key is following sterile technique throughout the entire process. Published reports show the most common adverse events are post-operative infections, which highlights the importance of sterile preparation protocols and functonally closed PRP systems. I can connect you with our medical affairs scientists for an in-depth discussion."
Device-Specific Focus Areas Safe to Discuss
- Device reliability and consistency
- Ease of use and workflow integration
- Technical specifications and performance
- Customer support and training
- Published clinical outcomes (factual reporting)
- Cost-effectiveness and efficiency