The SoHO Regulation (EU) 2024/1938 will merge into one single piece of legislation the rules applicable to human blood, tissues, and cells that were previously split between the Blood Directive 2002/98/EC and the Tissues and Cells Directive 2004/23/EC (the specificities of these regulated substances will be taken into account in the technical standards issued by expert bodies).
The SoHO Regulation will apply to all substances of human origin (SoHO) intended for human application, as well as those used to manufacture medical devices and medicinal products. It will also regulate SoHO activities from the early steps of donor registration and history review, testing and collection, to distribution, human application and outcome monitoring. Provisions for the protection of SoHO donors, SoHO recipients and offspring from medically assisted reproduction are also included.
Learning lessons from the COVID-19 pandemic, the SoHO Regulation also sets out new rules on supply continuity, including the establishment of national emergency plans and certain obligations for entities dealing with critical SoHO.
Various other measures are introduced to address the shortcomings of the previous BTC Legislation. Here is an overview of some of the main ones:
Extended scope
The Blood Directive applies to whole human blood and blood components, while the Tissues and Cells Directive covers human tissues and cells. The SoHO Regulation, however, has a wider scope, covering not only these but all SoHO, defined as any substance collected from the human body, whether it contains cells or not and whether those cells are living or not (and also including preparations resulting from the processing of that substance). This will capture, among others, substances such as human breast milk, intestinal microbiota and blood preparations not used for transfusion that were outside the scope of the BTC Legislation. Organs continue to be excluded and remain regulated by Directive 2010/53/EU on standards of quality and safety of human organs intended for transplantation.
The SoHO Regulation only applies to the extent that SoHO are intended for human application or for the manufacture of medical devices or medicinal products. This includes investigational medicinal products used in the context of clinical trials governed by Regulation 536/2014 (Clinical Trials Regulation). It does not cover however SoHO intended for research that does not involve application to the human body (e.g., in vitro research or research in animals).
For SoHO collected to manufacture medical devices or medicinal products (including investigational ones), only the provisions of the SoHO Regulation concerning donor registration, donor history review and medical examination, testing of SoHO donors, collection and release will apply. The provisions on storage, distribution, import and export apply only insofar as they relate to SoHO up to and including their distribution to a pharmaceutical or medical devices manufacturer.
Requalification of blood and tissue establishments
Blood and tissue establishments under the BTC legislation will be requalified under the SoHO Regulation into SoHO entities and SoHO establishments, depending on the SoHO activities that they undertake. As a consequence of the extended scope of the SoHO Regulation (see above), other entities not previously qualified as tissue or blood establishments (e.g., organizations operating in the faecal microbiota transplants and human breast milk sectors) will now also be captured by this new qualification of entities.
All SoHO entities will need to be registered following the instructions of their respective competent authorities before commencing any SoHO activity. SoHO establishments will also need a SoHO establishment authorization, granted by the respective national competent authority and valid throughout the EU.
Advisory mechanism on the regulatory qualification of substances, products or activities
The SoHO Regulation creates a new coordination body composed of representatives of all EU Member States - the SoHO Coordination Board (SCB). Among other tasks, the SCB will be responsible for providing opinions on the regulatory status of substances, products or activities. While the ultimate responsibility for the regulatory qualification remains with national competent authorities, in case of questions they may (and in certain cases shall) submit requests for opinion to the SCB.
The SCB will also be responsible for keeping an updated list, called the SoHO compendium, of decisions taken at the Member State level, and opinions issued by national competent authorities and by the SCB, on the regulatory status of specific substances, products or activities. The SoHO compendium will be made publicly available in the also new EU SoHO platform.
This new SCB consultation mechanism is intended to bring increased legal certainty and regulatory coherence across the EU, hopefully reducing the cases of diverging qualifications of the same substance, product or activity by different competent authorities. Moreover, the fact that such decisions and SCB opinions will be made publicly available through the EU SoHO platform will be helpful for developers to determine the regulatory status of their innovative SoHO therapies, as well as for competent authorities to take into account previous qualification decisions.
In addition, the SoHO Regulation also provides mechanisms for SoHO competent authorities and the SCB to communicate and consult with equivalent national authorities and advisory bodies in adjacent regulatory fields (such as organs, medical devices and medicinal products). It remains to be seen if these open consultation mechanisms will achieve the purpose of improving the cross-sector regulatory consistency and provide more legal clarity for developers of borderline and combination therapies, as well as remove some of the challenges to cross-border exchanges of SoHO within the EU.
Risk-based authorization of SoHO preparations
A SoHO preparation is a type of SoHO that: (i) has been subjected to processing and, where relevant, to one or more other SoHO activities; (ii) has a specific clinical indication; and (iii) is intended for application to a SoHO recipient or is intended for distribution. The release of SoHO preparations is subject to a SoHO preparation authorization, which is granted by the relevant national competent authority and is valid throughout the EU (SoHO intended to be distributed for the manufacture of medical devices or medicinal products are exempted from this authorization requirement).
One of the objectives of the SoHO Regulation is to facilitate the development of innovative BTC therapies. For this purpose, a risk-based authorization model was introduced, requiring developers to provide sufficient clinical evidence to demonstrate the safety and efficacy of SoHO preparations in a manner that is proportional to their level of innovation and risk.
Applicants need to perform a benefit-risk assessment and, where scientific and clinical evidence is not sufficient, or the risk is greater than negligible, implement (subject to approval by the competent authority) a clinical outcome monitoring plan for gathering further evidence for the authorization of a new SoHO preparation or for a new indication for an existing one. This plan shall include the following:
Reinforced role of scientific guidelines (ECDC and EDQM)
The SoHO Regulation provides the principles and standards for the protection of SoHO donors, SoHO recipients, and offspring from medically assisted reproduction. However, how these legal principles and standards are implemented has now changed, with technical requirements removed from EU legislation and replaced by technical guidelines published by expert bodies, notably the European Centre for Disease Prevention and Control (ECDC) and the European Directorate for the Quality of Medicine & Healthcare (EDQM). These guidelines incorporate the latest scientific evidence and are subject to regular updates, which shall allow the SoHO legal framework to keep pace with technological advancements and evolving risks.
In the absence of EU legislation describing particular procedures to be observed, SoHO entities shall now apply the following hierarchy of technical guidelines:
- The most recent technical guidelines of ECDC and EDQM;
- Other guidelines adopted by EU Member States; or
- In cases of detailed technical issues for which neither the ECDC and the EDQM, nor other guidelines, have defined a technical guideline or rule, SoHO entities should apply other guidelines or technical methods that are in line with relevant internationally recognized guidelines and available scientific evidence and are appropriate to mitigate any identified risk.
This new hierarchy of technical guidelines will make EDQM and ECDC standards, which are already widely applied in the sector, the primary means to meet the SoHO Regulation standards.
Application and transitional provisions
The SoHO Regulation will apply from 7 August 2027. Until that time, the national laws implementing the BTC legislation remain in effect, giving time for stakeholders to transition to the new regime.
Blood and Tissue establishments authorized under the BTC Legislation before 7 August 2027 will be deemed to be registered as SoHO entities and, if applicable, authorized as SoHO establishments. Tissue or cell preparation processes authorized under the Tissues and Cells Directive before 7 August 2027 will also be deemed to be authorized as the corresponding SoHO preparations.
There are also transitional provisions in place to avoid the unnecessary discard of existing SoHO: SoHO already in storage before 7 August 2027 shall not be subject to the relevant obligations under the SoHO Regulation provided those SoHO are released and distributed before 8 August 2029; the SoHO Regulation will also not apply to SoHO which have been distributed before 7 August 2027 and kept under appropriate control conditions until that date.
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Please get in touch with a member of our team should you wish to discuss how this legislative development may affect your business activities in the EU.
Authored by Cláudia Mendes Pinto.
