Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine

Abstract

Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions.

Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital

“…Importantly, as the present study focused on the attributes of the final autologous PRP products and specifically on the platelet concentration factors characterizing the obtained PRP, the aforementioned systematic accuracy issues within platelet enumeration bear virtually no consequences (i.e., use of a relative value or platelet ratio, and not absolute values) and have not resulted in any kind of systematic clinical failures. However, this important element constitutes a prime real-world and experience-based example of the current need for additional standardization of manufacturing and control activities for PRP products [ 44 , 77 , 78 , 79 , 80 ]. Specifically, this could technically be performed by optimizing sample preparation workflows (i.e., primary containers, anticoagulant type, and analytical timelines) or by using and validating platelet enumeration methods, which are not only precise but also accurate in a variety of clinical settings.…”

A Comprehensive Review of Platelet-Rich Plasma and Its Emerging Role in Accelerating Bone Healing

“…Consistency in injection techniques not only enhances the precision and efficacy of PRP therapy but also minimises the risk of variations in treatment outcomes. Standardisation in injection techniques is integral to promoting best practices, reducing the likelihood of procedural errors, and optimising the therapeutic benefits of PRP across diverse clinical applications [ 35 ].…”

A Comprehensive Review on Platelet-Rich Plasma Activation: A Key Player in Accelerating Skin Wound Healing

“…Sterilization verification ensures that PRP preparations are free from contaminants that could lead to adverse patient reactions or infections. Robust quality control measures instill confidence in both healthcare providers and patients regarding the safety and reliability of PRP therapy, contributing to its responsible and effective use in clinical practice [ 61 ].…”

“…By defining the standards for facility infrastructure, staff competence, and patient selection criteria, regulatory agencies contribute to the safety and quality of PRP therapy. This oversight also helps protect patients from unscrupulous providers and substandard practices, ensuring that they receive treatment that adheres to established best practices and safety measures [ 61 ].…”