GOOD PREPARATION PRACTICES
AUTOLOGOUS PLATELET-RICH PLASMA
(PRP-A)
FROM THE RECIPIENT'S BLOOD
Daphné V. DIERMAN, PhD Pharmacist, Antoine TURZI, CEO RegenLab.
INTRODUCTION
New cell therapies characterized as autologous (organic substance whose donor and recipient is the same individual) are coming onto the market, their preparation dependent on the use of medical devices certified by an accredited organization, enabling them to minimize the risks of contamination (infection), standardize the steps in a closed circuit and demonstrate therapeutic efficacy.
We will discuss the preparation of human blood-derived biological products for therapeutic purposes, and specifically the preparation of autologous platelet-rich plasma (PRP-A).
PREPARATION OF AUTOLOGOUS PLATELET-RICH PLASMA (PRP-A)
IVD tubes are intended for diagnostic use in vitroIn addition to the fact that they are not produced in a controlled environment (clean room) like medical devices for human use, with a therapeutic indication demonstrated in published clinical studies, using them for therapeutic purposes is an alteration of the authorized intention of use.
COMPLIANCE WITH STANDARDS
Among these requirements we find Compliance with ISO10993 standards (Biological Evaluation of Medical Devices) in which numerous tests are listed, such as biocompatibility, pyrogenicity and chemical characterization.
- In order to be used in a patient for therapeutic purposes, a Medical Device must comply with current European regulations on medical devices: "The European Medical Device Regulation (MDR)" 2017/745, which became 100 % mandatory on May 26, 2024.
This is why one of the leading manufacturers of in vitro diagnostic tubes, Becton & Dickinson, has published an official communication stating that the preparation of PRP must be carried out using medical devices that comply with the above international regulations.
FOR THE SAFETY OF A BIOLOGICAL PREPARATION DERIVED FROM HUMAN BLOOD, USING MEDICAL DEVICES SUCH AS REGENPRP-A, THE MEDICAL DEVICE (MD) MANUFACTURER MUST COMPLY WITH THE FOLLOWING REQUIREMENTS:
" A. Have a Quality Management System compliant to ISO 13485: 2016, meeting the requirements of MDR 2017/745, where applicable a grace period notified by the notifying body.
- Since 2019, a company with international activities must certify its quality system according to the MDSAP program (Medical Device Single Audit Program), following the CIH (International Harmonization Conference set up in 2001!).
- This unique audit program for Medical Devices is recognized by the authorities of the 5 participating countries: Australia, Brazil, Canada, Japan and the United States.
- As of January 1, 2019, Canada has made MDSAP mandatory. The United States of America, Brazil, Australia, Japan are expected to follow suit. Europe is currently only an observer of this program.
" B. Certify Medical Devices according to European Regulation MDR-EU 2017/745 which replaces Directive 93/42 CE MDD.
The MDR maintains the requirements of the MDD and introduces new ones. The MDR is more focused on safety. This word appears 290 times in the MDR (40 times in the MDD).
- For each medical device, provide a technical file (Technical File) compliant with the new MDR 2017/745 requirements that includes the Device's technical and functional specifications, and a clinical evaluation report (CER) carried out with its medical device(s), enabling proof of their therapeutic efficacy/s and safety for the patient in recognized therapeutic indications.
- Set up a Post-Marketing Surveillance Plan (Post-market Monitoring) concerning the safety of the Medical Device throughout its life cycle.
This plan also includes the follow-up of clinical studies (Post Market Clinical Follow up) who will have to continually monitor and demonstrate certified clinical claims.
" C. Requirements for the preparation of the biological product (e.g. autologous Platelet Rich Plasma), i.e. :
- Sterile medical devices designed and certified by a notified body in accordance with MDR 2017/745/EEC.
- A closed-circuit preparation system, with minimal handling and at the patient's bedside (extemporaneous use), in compliance with strict asepsis techniques to guarantee sterile sampling and administration, whatever the indication of use.
- PRP must be used in a single medical procedure, not stored or prepared elsewhere at a third-party facility.
- The collection procedure must be performed by or under the supervision of a physician, and the PRP injections must be performed by a physician.
According to the French public health code, legislative parts, articles L1211-8 and 1242-1, autologous blood sampling for therapeutic purposes is authorized on condition that the samples are taken in compliance with the rules of Good Preparation PracticeThe concept of bioequivalence cannot be applied to biological preparations derived from human blood for therapeutic purposes, as each medical device has its own performance in terms of cell isolation and therapeutic performance.
According to the French public health code, legislative parts, articles L1211-8 and 1242-1, blood samples for autologous therapeutic purposes are authorized provided that the samples are taken in compliance with the rules of Good Preparation Practices.
█ D. Taking into account these various regulations and international standards, the preparation of blood-derived products, and more specifically the preparation of platelet-rich plasma, can only be carried out using class IIb or III Medical Devices, certified and validated for this use.
█ D. Thus, preparations using Diagnostic devices In Vitro - IVD (devices intended for use only in vitro for the examination of biological samples to provide patient information) subject to the new IVD 2017/746 standard, are prohibited for the preparation of autologous PRP:
- 1) IVDs are not subject to biocompatibility and pyrogenicity tests in accordance with ISO 10993-1 to 23.
- 2) IVDs cannot be promoted or used in medical use as they do not comply with the safety and clinical evaluation prerequisites according to MDR 2017/745. Their contents, even if sterile, cannot be re-injected into the patient.
IN CLINICAL PRACTICE
Medical devices for the preparation of Platelet-Rich Plasma are being used more and more frequently for a variety of indications, from skin care to musculoskeletal and joint care.
Autologous PRP, with its high presence and secretion of growth factor, stimulates tissue regeneration by boosting collagen production and stimulating fibroblast proliferation, a biological stimulation that has been reported in numerous studies, resulting in tissue renewal and improved skin quality.
From a therapeutic point of view, PRP has also demonstrated numerous benefits for certain pathologies such as androgenic alopecia.
