On 14 July 2022, the European Commission published a Proposal for a Regulation on standards of quality and safety for substances of human origin intended for human application (the “SoHO Regulation”). Once adopted, the SoHO Regulation will repeal the around 20 years old Blood Directive (Directive 2002/98/EC) and Tissues and Cells Directive (Directive 2004/23/EC) and merge them into one single act. These two Directives currently set out the main requirements applicable in the EU for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues, cells, blood and blood components for human application.

The standards of quality and safety for human organs intended for transplantation will still be provided by the Organs Directive (Directive 2010/45/EU), which is not affected by the new SoHO Regulation.

This proposed Regulation is the result of a process started in 2019 with an evaluation of the EU legislation on blood, tissues and cells. This evaluation identified various shortcomings and gaps in the existing legislation, including the fact that the legislation was not up to date in light of the scientific and epidemiological developments and divergent implementations of the two Directives by EU Member States created unequal levels of protection and a lack of trust between national competent authorities.

Some of the objectives of the new SoHO Regulation include:

• Ensuring the safety and quality of SoHO therapies for patients and their protection against avoidable risks linked to SoHOs (such as the risks of communicable and non-communicable disease transmission from donors to recipients and the cross-contamination of donations);

• Harmonising the supervisory activities among EU Member States (which explains Chapters II and III of the SoHO Regulation, fully dedicated to competent authorities and supervisory activities);

• Creating a legal framework that is future proof, agile and crisis resistant (namely by introducing measures to ensure the continuity of the supply of SoHOs and mitigate the risk of shortages).

Highlights

• Extended scope: the SoHO Regulation will cover all substances of human origin intended for human application. A SoHO is defined as “any substance collected from the human body in whatever manner, whether it contains cells or not and whether those cells are living or not” (Article 3(5)). This includes all substances meeting the definition of tissues, cells, blood and blood components under the Blood Directive and Tissues and Cells Directive, but also other substances that currently fall outside the scope of these definitions (e.g., human breast milk, intestinal microbiota, blood preparations not used for transfusion and other SoHO that may be developed in the future). Like the previous Directives, however, the SoHO Regulation will continue to regulate only substances that are intended for human applications (excluding for example any uses in the context of in vitro research).

• SoHO activities: similarly to the current legal framework, the SoHO Regulation is intended to cover the whole process-flow of SoHOs from donor to recipient, including recruitment, testing, collection, processing, storage, distribution, import and export and human application (Article 2(1)).

• Balance between harmonisation and flexibility: to make the SoHO Regulation future proof, the proposed Regulation sets out only high-level technical standards for SoHO donors and recipients protection (Articles 53, 54, 55 and 58). The European Commission will be empowered to adopt, where necessary, implementing acts describing particular procedures to be followed and applied to meet such technical standards. For all aspects that are not addressed by any implementing act, entities carrying out SoHO activities (SoHO entities) shall apply the most recent technical guidelines published by the European Centre for Disease Prevention and Control (ECDC) and the European Directorate for the Quality of Medicines and Healthcare (EDQM). This represents a significant change in comparison with the current legislation and ensures that the requirements for SoHO activities will be quickly adapted to scientific and technical developments.

• SoHO entities and SoHO establishments: entities qualified as blood establishments or tissue establishments under the Blood Directive and Tissues and Cells Directive will be requalified under the SoHO Regulation as “SoHO entities” and “SoHO establishments”. Entities carrying out both processing and storage of SoHOs will be qualified as “SoHO establishments” (a sub-set of SoHO entities).

• SoHO Coordination Board: a SoHO Coordination Board will be established under the new Regulation. This new body will be chaired by the European Commission and consist of representatives from the EU Member States. It is intended to support EU Member States in coordinating the implementation of the Regulation. Additional responsibilities include exchanging best practices and supporting joint inspections of SoHO entities (Article 68). The SoHO Coordination Board will also be entrusted with preparing opinions on the regulatory status of a substance, product or activity under the SoHO Regulation.

• EU SoHO Platform: the new Regulation also envisages the establishment of a new IT platform called “EU SoHO Platform” for the exchange of information concerning SoHO activities. Among other features, this platform will gather the registration information of SoHO entities and SoHO establishment authorisations, as well as information on the suspension or withdrawal of any authorisations (such information to be publicly available).

• Single European Code (“SEC”): the SoHO Regulation continues to provide for the application of the SEC to SoHO preparations distributed for human application. The European Commission shall adopt implementing acts concerning the format of the SEC and the requirements related to its application (Article 46(3)).

• Proportional approach to SoHOs for autologous use: the SoHO Regulation recognises that the autologous use of SoHOs generally presents less risks, and so it provides that the Regulation is not applicable to SoHOs used without any manipulation, processing or storage. For SoHOs that are processed but not stored before application, only a limited number of provisions of the SoHO Regulation will apply (Article 2(2)).

• Continuity of supply and shortages management: the SoHO Regulation introduces the definition of “critical SoHO”, meaning a SoHO for which an insufficient supply will result in serious harm or risk of harm to patients (Article 2(41)). SoHO entities carrying out activities contributing on a significant scale to the supply of critical SoHOs (“critical SoHO entities”) will be required to have a SoHO entity emergency plan and to launch a SoHO supply alert in case of a significant supply interruptions (Articles 63 and 65).

Impact for ATMPs and medical devices

SoHOs or SoHO preparations can be used to manufacture medicinal products (or as the starting and raw material thereof), especially Advanced Therapy Medicinal Products (“ATMPs”) (currently regulated by Regulation 1394/2007, the “ATMP Regulation”). SoHOs or SoHO preparations can also be used to manufacture medical devices (or as the starting and raw material thereof) regulated by the Regulation 2017/745 on medical devices (the “MDR”).

Delineation of borderline products

The SoHO Regulation does not bring any changes in the delineation of the borderline with the legal framework for medicinal products or medical devices. The delineating criteria that define when SoHOs or SOHO preparations become medicinal products or medical devices are still defined in the pharmaceutical and medical devices legislation and are not affected by the SoHO Regulation.

In principle, competent authorities of each EU Member State shall decide on a case-by-case basis on the regulatory status of a substance, product or activity under the SoHO Regulation. However, national competent authorities may also request the opinion of the SoHO Coordination Board (Article 14(2)). The European Commission will also be empowered, in order to ensure consistent decisions across all EU Member States with regard to borderline cases, to adopt implementing acts to determine the regulatory status of a particular substance, product or activity under the SoHO Regulation (Article 14(4)).

Scope of application

For SoHOs that are used to manufacture medicinal products (mainly ATMPs) or medical devices, or as the starting and raw material thereof, only the following provisions of the SoHO Regulation apply (Article 2(3) SoHO Regulation):

• SoHO donor recruitment;
• Donor history review and eligibility assessment;
• Testing of donors for eligibility or matching purposes; and
• Collection of SoHOs from donors or patients.

The SoHO Regulation also applies to the following activities insofar as they relate to SoHOs prior to their distribution to an operator regulated by the legislation on medical devices and medicinal products:

• SoHO release;
• Distribution of SoHOs;
• Import and export or SoHOs.

Where SoHOs, SoHO preparations, or products manufactured from SoHO are exclusively for autologous use, only the provisions of the SoHO Regulation that concern the collection of SoHOs from patients shall apply (Article 2(3) 2^nd paragraph).

Transitional provisions

The SoHO Regulation is expected to apply two years after its entry into force. During this transitional period, the national laws implementing the Blood Directive and Tissues and Cells Directive will continue to apply.

Blood and Tissue establishments designated, authorised, accredited or licensed under the two Directives shall be deemed to be registered as SoHO entities and authorised as SoHO establishments (or registered as SoHO entities only, if they don’t meet the definition of SoHO establishment). Tissue establishments authorised as importing tissue establishments under the Tissues and Cells Directive shall also be deemed to be authorised as importing SoHO entities in accordance with the SoHO Regulation.

There are also transitional provisions for existing SoHOs. SoHOs distributed before the date of application of the SoHO Regulation and kept under appropriate control conditions until that date will not subject to the SoHO Regulation. SoHOs that were already released for distribution before the date of application will also not subject to the SoHO Regulation, provided that they are distributed within 1 year after the application of the SoHO Regulation.

Next steps

The proposal needs to be adopted by the Council and the European Parliament. Amendments of the text are still possible at this stage. The proposal is open for feedback until 8 September 2022.

Please do not hesitate to contact our team should you have any questions concerning this proposal for the SoHO Regulation.

Authored by Fabien Roy, Cláudia Mendes Pinto, and Carolin Mieczkowski

This article is the eleventh in our 2022 series, “Trends in Cell, Tissue, and Gene Therapies,” which aims to help you stay informed about the broad array of legal and regulatory issues affecting companies operating in the regenerative medicine space. From clinical studies, to obtaining patents, to scaling up manufacturing, our global team will discuss novel issues arising in all parts of the world, including unique deal-making, litigation, and inspections concerns for CTGT companies. Ensure you are subscribed to Hogan Lovells Engage to receive these new insights weekly!