Rev Esp Cir Ortop Traumatol. 2014;58(2):65---67

Revista Española de CirugíaOrtopédica y Traumatología

www.elsevier.es/rot

EDITORIAL

Can I continue to use platelet-rich-plasma on mypatients? How do I use it legally?�

¿Puedo seguir aplicando plasma rico en plaquetas a mis

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Professionals who have been using PRP for decades in theirpractices and others who wish to use it to treat their patientsare faced with these and other questions. In this editorial weattempt to shed some light on the most controversial aspectsof the use of PRP and comment some possible solutions forthe successful application of the treatment, considering itslegal framework.

It is generally known that, in recent years, the applica-tion of ‘‘growth factors’’ in all their forms, and specificallyplatelet rich plasma (PRP), for multiple pathologies hasundergone a boom, leading to their indiscriminate use inmany cases. It is also true that, due to this considerableincrease, there is a lack of scientific evidence regard-ing the benefits of this product and the standards forthe best method of obtaining it. Therefore, there is sig-nificant controversy in both aspects. This situation hasled numerous professionals, represented by their scientificsocieties (Sports Traumatology professionals representedby SETRADE and the TERCEL Cell Therapy Network), toaddress the Spanish Agency for Medicines and Health Prod-ucts (AEMPS) in order to request clarification on the useand application of PRP. Following consultations, the finaldecision was to elaborate a joint report (between AEMPStechnicians and professionals harboring concerns about themisuse of PRP) which attempted to clarify and define the‘‘Autologous use of Platelet Rich Plasma’’.1 This report clar-ified data and established criteria for the use of autologousPRP, hitherto diffuse and in a limbo in which it seemedthat everything was acceptable. The report ‘‘gathered the

framework for the autologous use of PRP in Spain, theobligations to be met by manufacturers and the mini-mum information to be given to patients undergoing the

� Please cite this article as: Fernández Santos M. ¿Puedo seguiraplicando plasma rico en plaquetas a mis pacientes? ¿cómo hacerlolegalmente? Rev Esp Cir Ortop Traumatol. 2014;58:65---67.

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1988-8856/$ – see front matter © 2014 SECOT. Published by Elsevier Espa

reatment’’.a Nevertheless, there still remain some unre-olved issues and we are currently going through an activeeriod of collaboration between experts and scientific soci-ties involved in the preparation and application of PRPherapies and AEMPS, in an attempt to answer and resolvell the doubts which continue to appear regarding the nec-ssary facilities, the regulations to be met in all cases, theefinition of pathologies in which this product is applicable,he publication of more scientific studies which support these of these products, etc.

Even taking into account the doubts inherent to themplementation of new legislation in a complex field, somessues are already very clear. In the report, AEMPS classifiesRP as a drug for human use, according to the definition ofirective 2001/83/EC, of 6 November, establishing a EU coden drugs for human use, and Law 29/2006, from July, on theuarantees and rational use of drugs and healthcare prod-cts, with different regulatory aspects which are directlypplicable and must be enforced. Among them, we shouldote that the use of PRP must be prescribed by a physician,entist or podiatrist within the scope of their respectiveompetencies, with prescription by other healthcare or non-ealthcare professionals not being permitted. Therefore,he choice of product that best suits the condition beingreated and the best way to obtain it remain the respon-ibility of the prescriber. Furthermore, this professionalhould have experience in the treatment being applied.ince the drug should only be dispensed under a restrictededical prescription, it may only be used in specific and

pecialized facilities: healthcare centers or services, whichre duly authorized to carry out such activities in accor-ance with the applicable regulations of each Regional

a The report does not address the allogeneic use of PRP (plasmarom a different donor). The use of this type of product should beubject to consultation with experts from AEMPS about the require-ents that must be met in each case.

ña, S.L. All rights reserved.

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overnment, assisted by technicians and specialists fromEMPS, the authority which will ultimately issue the autho-ization. The objective for the coming months will be toork on defining the types of facilities required to obtain

quality product, the contents of the product, a list ofpplications, methods of application, etc.

Another important aspect to consider is that, like anyther prescription medication, any type of advertisingegarding the product and the pathologies to be treatedhich targets the general public is prohibited. The lat-

er is important because of the numerous establishments,linical and non-clinical, which advertise these treatmentsith great fanfare. We only need to enter the term into an

nternet search engine and, within seconds, we will be over-helmed by a vast amount of advertising about it, most of

t misleading.Always bearing in mind that PRP is a medicine, the report

stablishes the minimum guarantees required for its use.e will attempt to present these assurances as clearly asossible.

inimum quality assurance in production

ince there are different techniques to obtain PRP (produc-ion), a minimum quality assurance should be established forhese processes. In this sense, there are significant doubtsegarding the minimum facilities required. The report fromEMPS groups these techniques into two main categories:pen and closed, giving different guidelines about the nec-ssary facilities required to use one or the other. In bothases, the prescribing physician will be ultimately respon-ible for ensuring that the process employed, despite beingerformed by a third party, complies with these guarantees.

Using one technique or the other for the processing of PRPemains a decision for the prescriber. The person respon-ible should be aware that open techniques are those inhich any of the products is exposed to ‘‘open air’’ during

he process (opening of peripheral blood tubes, pipettingo collect different types of plasma, etc.). In this case,he competent authority must be requested to conduct annspection in order to verify that the facilities are optimalor obtaining a quality product. When closed techniques aresed, usually with disposable kits, it will not be necessaryo obtain a certificate of appropriateness of the facilities,rovided that the kits are CE marked for their intended usend that they are truly closed, that is, that at no stage in therocess is the product exposed to open air (opening of con-ections, tubes, etc.). Inspections by the authorities will beerformed when they are considered appropriate by thosesing these techniques. In both cases, EU good manufactur-ng practices (GMP) will be taken as a reference in order toaintain quality assurance.Considering the quality of the product obtained, there

ust be some kind of analysis which determines whetherr not the product meets the prescriber’s requirements inrder to ‘‘repair’’ the lesion, including a specific number of

latelets, product sterility, etc. These characteristics muste defined by the prescriber and will help to carry out aetter analysis of the effectiveness of the product used inach treatment.

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EDITORIAL

ffectiveness assurance

s previously discussed, PRP is a commonly used treatmentn a wide range of medical specialties. However, there areo clinical trials of sufficient quality to demonstrate efficacyn any of them. Hence, AEMPS, in collaboration with thexperts and scientific societies involved, will develop a listf the different applications in which there is some evidencef a positive benefit/risk to patients and those where well-esigned clinical trials are required to establish levels ofvidence which support the use of different PRPs in each ofhe pathologies studied.

raceability assurance

ince these products are derived from blood, despite beingutologous they require control, monitoring and traceabil-ty measures which prevent the transmission of infectiousiseases. The prescribing physician will be responsible foromplying with these measures. In practical terms, the pre-criber must comply with Royal Decree 1088/2005, of 16eptember, which establishes the technical requirementsnd minimum conditions for blood donation and transfu-ion services and centers,2 in addition to conducting theandatory analytical tests on patients (donors) described innnex III of Royal Decree 1088/2005. Blood group determi-ation is excluded in the present scenario (patient---donor ofRP), with the focus being on the identification of infectiousgents.

harmacovigilance assurance

he prescriber should monitor every patient fol-owing treatment with PRP, promptly notifying anyuspected adverse reactions that may have beenaused by the drug to the Pharmacovigilance Centersf the appropriate Regional Government. Informa-ion about how to report these adverse reactionsan be obtained through the AEMPS website: http://ww.aemps.gob.es/vigilancia/medicamentosUsoHumano/ome.htm (in Spanish).

nformation assurance

ince PRP does not have a technical data sheet or a prospec-us authorized by the AEMPS, the prescribing physician wille responsible for providing adequate information to eachatient in order to ensure compliance with the require-ents regarding product quality, effectiveness aspects for

he pathology being treated, advantages of using this prod-ct over any other existing alternatives, known risks andethods for reporting any adverse reaction. In this sense

here is a commitment by AEMPS, along with the scientificocieties involved, to determine and publish minimum infor-ation criteria for each indication.In conclusion, we can continue to apply PRP to our

atients, but we must not forget that it is a drug, so we mustomply with existing legislation. If we harbor doubts, weust study the product to be applied and for what condition,hat facilities are available and what we need to obtain the

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Directora de la Unidad de Producción del HospitalGregorio Maranón, Instituto de Investigación Sanitaria

EDITORIAL

product, considering whether we should request authoriza-tion or not. Since the legislation is new, it would be usefulto have a roadmap which reflected all the legal aspects andsteps to be followed in relation to the request and autho-rization for the processing and application of PRP, as wellas the minimum criteria for processing facilities for each ofthe assumptions that would be necessary to use autologousPRP as a treatment, while complying with all the require-ments established by the V1/23052013 report published byAEMPS. This information will certainly become available inthe coming months through the different scientific societies.However, until we have this information, we must appealto ethics and good clinical practice which, by definition,should always be applied by professionals employing thesetreatments. We must never forget that the person primarily

responsible for the correct preparation, implementation andmonitoring of this drug is the prescriber, who should placethe clinical benefit that the patient may obtain through itsuse before any other benefit.

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eferences

. Informe de AEMPs sobre el uso de plasma rico en plaquetas.Informe/IV/23052013. Available from: http://www.aemps.gob.es/medicamentosUsoHumano/medSituacionesEspeciales/docs/PRP-AEMPS-DEF-mayo13.pdf

. Real Decreto 1088/2005, de 16 de septiembre, por el quese establecen los requisitos técnicos y condiciones mínimasde la hemodonación y de los centros y servicios de trans-fusión. Available from: http://www.msssi.gob.es/profesionales/saludPublica/medicinaTransfusional/legislacion/docs/RD1088-2005.pdf

M.E. Fernández Santos

Gregorio Maranón, Madrid,Spain