On 24 April 2024, the European Parliament formally adopted the Regulation on Standards of quality and safety for Substances of Human Origin (SoHo) intended for human application (the SoHO Regulation). On the same date, the European Commission published a Questions & Answers (Q&A) document on the SoHO Regulation. Then on 27 May 2024, the EU Council adopted the new rules. For the final step in the legislative process, the new Regulation is due to be published in the Official Journal shortly.
The SoHO Regulation aims to introduce new and innovative measures to help ensure that high standards of safety and quality for SoHO are maintained across the EU and that SoHO activities are appropriately regulated. A key goal is to facilitate cross-border exchanges and access to SoHOs across the EU, while ensuring high levels of health for donors, recipients and offspring from medically assisted reproduction. A more harmonised approach to the regulation of SoHO across the EU is envisaged, which will be welcomed by industry. However, Member States may still diverge and include more stringent measures under their national laws. The extent to which one Member State's authorisation of a SoHO Entity, SoHO establishment or SoHO preparation is really "EU wide" therefore remains to be seen. Furthermore, the success of the SoHO Regulation is reliant upon cooperation and coordination between Member States, including the use of the SoHO Platform and seeking opinions from the SoHO Coordination Board on borderline issues. This will require continuous contact between Member States and a good understanding of the ever-developing and innovative uses of SoHOs. Guidance accompanying the new rules, as well as what measures need to be put in place from the outset, will need to be informative, clear and proportionate for the SoHO Regulation to make the differences it is intended to achieve.
The text adopted by the European Parliament and Council is largely unchanged since the initial Commission proposal for a SoHO Regulation, details of which can be found in our previous blog. Below, we provide a summary of some of the key elements introduced by the SoHo Regulation and the changes agreed by the Parliament.
Broad scope
The SoHO Regulation contains a broad definition of SoHO, covering any substance collected from the human body whether or not it contains cells, in all manners, excepts solid organs for transplantation, which remain regulated under the Organs Directive (Directive 2010/45/EU). It includes additional substances not covered under the current regime (e.g. human breast milk and intestinal microbiota). The definition of 'SoHO' is intended to cover substances that may be applied to patients in the future, without requiring amendments to be made to the SoHO Regulation. Furthermore, the SoHO Regulation contains clear provisions on when the rules will apply to substances collected with the purpose of manufacturing a product (e.g. medical devices or medicinal products).
Additionally, certain definitions have been extended (e.g. 'human application') or introduced (e.g. 'release', 'import' and 'export') compared to the current SoHO regime, to ensure coverage of all uses of SoHOs and to enhance clarity.
The SoHO Regulation refers to "SoHO activities", which are activities that have a direct impact on the quality, safety or effectiveness of SoHO (e.g. processing, storage, or clinical-outcome registration).
Protecting Innovation and Improving Safety
The Regulation introduces an EU-wide authorisation procedure for SoHO preparations, simplifying requirements for companies using SoHOs. Such authorisations will be granted by SoHO competent authorities, designated by Member States. However, the SoHO Regulation contains a caveat that authorisations by one SoHO competent authority may be declined by another Member State that has more stringent measures in place concerning SoHOs until compliance with those measures have been demonstrated.
SoHO preparations are SoHOs subject to processing and, where relevant, one or more other SoHO activities, with a specific clinical indication and intended for immediate application to a recipient or for distribution. Assessment of SoHO preparations will be risk based, including a review of all activities affecting the safety, quality and effectiveness of the preparation, followed by clinical outcome data collection requirements proportionate to the identified risks.
There may be mutual recognition of an authorisation granted to another SoHO Entity, provided that safety, quality and efficacy results are proven as equivalent. Existing preparation processes authorised and lawfully used under the current regimes remain valid.
The text adopted by the EU parliament no longer refers to a requirement for conditional authorisations where clinical outcome data is required. Instead, when data is found insufficient or the risk associated with a SoHO is found more than negligible, SoHO Entities will be required to submit a clinical-outcome monitoring plan (designed to evaluate safety and effectiveness of SoHO preparations), which will need to be approved by the SoHO competent authority.
The adopted text provides that, in cases of identified moderate and high risk, carrying out a SoHO clinical study on a pre-defined number of SoHO recipients is required to assess pre-defined clinical end points. Non-authorised SoHO preparations used in these clinical studies must adhere to the requirements and standards provided in the SoHO Regulation. Before commencing a clinical study in case of identified high risk, SoHO Entities must obtain a favourable opinion from an ethics committee, and obtain approval of the clinical-outcome monitoring plan.
The Regulation establishes safety standards for SoHOs and includes a chapter on 'SoHO Donor Protection' and 'Protection of SoHO Recipients and Offspring', which include requirements to mitigate the transmission risk of communicable and non-communicable diseases, including pathogens, toxins, and genetic conditions. Member States could decide to introduce more stringent requirements.
Registration of SoHO Entities and SoHO Establishments
SoHO Entities are entities that carry out SoHO activities, including the import and export of SoHOs. They must be registered with their national competent authorities, nominate a responsible person for release of SoHOs for clinical use, and comply with the relevant obligations to their activities. SoHO Entities must carry out a self-assessment of whether they are a "critical SoHO Entity" (a SoHO Entity that carries out activities contributing to the supply of critical SoHO) and communicate the result; however SoHO competent authorities may also impose this status on SoHO Entities, meaning certain additional obligations apply.
SoHO Establishments have been more broadly defined in the amended text, as a subgroup of SoHO Entities handling SoHO processing and storage, release, import or export. SoHO Establishments must obtain a specific authorisation, implement a quality management system, and designate a responsible physician for tasks such as procedures and policies on SoHO donor eligibility criteria and the allocation of SoHOs, as well as clinical data collection. The SoHO Regulation provides competent authorities with the ability to decide whether SoHO Entities that do not fall under the definition of SoHO Establishments, but with significant influence on SoHO safety and quality or involvement with multiple SoHO Establishments, nevertheless need such an authorisation.
A transitional regime has been introduced for establishments already accredited under the current regime before the coming into force of the SoHO Regulation, ensuring legal clarity and continuity. SoHOs collected and stored before the SoHO Regulation's implementation date can still be used for a specified period.
SoHO Entities must report annual activity data to prevent supply issues and notify competent authorities of sudden drops in supply when dealing with critical SoHOs. Entities will also be required to implement emergency plans to support supply resilience. The SoHO Regulation aims to provide measures to monitor and support the sufficiency of the supply of SoHO that are critical for the health of patients.
Compensation and reimbursement of donors
The current regimes uphold the principle of voluntary unpaid (altruistic) donations. However, this has not effectively prevented shortages caused by supply disruptions. The principle is applied at national level, resulting in varying approaches across the EU.
The SoHO Regulation harmonises these divergent approaches with the principle of 'financial neutrality', meaning that no financial gain or loss will be incurred by the SoHO donor, as recommended by the Council of Europe Committee on Bioethics. The SoHO Regulation allows Member States to authorize SoHO Entities to compensate or reimburse donors for their incurred losses during donations through fixed rate allowances, with an upper limit set in national legislation.
Oversight
SoHO Entities will be subject to oversight, with such requirements being proportionate and risk-based. Supervision will be the SoHO competent authorities' responsibility.
A new SoHO Coordination Board (SCB), hosted by the European Commission and made up of EU Member States representatives, will promote and support the implementation of the SoHO Regulation and national coordination during emergencies. The Commission will publish on the SoHO Platform rules on procedures of the SCB, agendas for meetings and meeting minutes, provided these do not undermine the protection of any public or private interests. The SCB will exchange best practices, support joint inspections of SoHO Entities, and clarify the regulatory status of borderline products upon SoHO competent authorities' request. The SCB will cooperate with advisory bodies established under other EU laws, to assess the regulatory status of substances, products and activities, and may also seek input from experts.
Additionally, an EU SoHO Platform will be created to support information sharing between SoHO competent authorities and SoHO Entities, facilitating the timely submission of data and reports and the exchange of data (including decisions of the regulatory status of substances, products or activities) and best practices (for instance, those published by the SCB on SoHO supervisory activities), enabling communication and transparency. The platform will allow collection and publication of data on donations, clinical use and possible adverse reactions, under clear governance and in line with data protection rules. The European Commission will use this Platform to periodically review monitoring indicators, serving as a central hub for access to information on registrations, authorisations and technical guidelines. The Platform will provide public access to information, including, among others, on approved SoHO clinical studies and authorised SoHO preparations, registries of SoHO Entities, and the work of the SCB and national authorities.
SoHO competent authorities may use the secure communication channel on the SoHO Platform with SoHO Entities for the exchange of documents relating to authorisation applications. It also allows for the compilation of the annual reports submitted by the SoHO Entities and provide the SoHO competent authorities with an annual aggregated report with the activity data from their SoHO Entities.
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