In Austria, almost 1,000 units of stored blood are needed every day; in Germany, it is around 15,000 units. Blood is an important emergency medication in the event of accidents, childbirth, surgeries or serious illnesses. It has a shelf life of only 42 days and cannot be produced artificially.
In recent years, there has been an increasing and often criticised shortage of blood donations throughout Europe. A continuing decline in plasma donations is also making it more difficult to provide therapies and produce medicines. Plasma, in particular, often has to be imported from third countries like the United States. This jeopardises the reliability of the European health care system in both (emergency) medical care and pharmaceutical production, increases competition for these substances between companies and organisations involved and affects the attractiveness of the European Union as business location for companies.
Currently, effective incentives for potential donors are very limited at best and subject to national law. The demand for blood and blood components is at odds with donor protection and vice versa. This is also subject of ongoing political discussions. Austria is currently, based on a Supreme Court decision of 2020 (4 Ob 183/20w), one of the few Member States permitting lump-sum compensation for plasma donors and additional bonuses for repeated plasma donations, thereby encouraging donations. On the other hand, for further donor protection, the Austrian Ministry of Health intends to adapt the Blood Donor Regulation (Blutspenderverordnung) based on new scientific studies in fall 2024: The maximum amount of blood donated per person per year is to be reduced significantly to prevent potential iron deficiency. To (at least partly) counter the expected reduction in blood donations, the regulation now allows for all people, regardless of their gender identification, to donate in accordance with the medical guidelines provided.
The result of EU-wide intense discussions on this issue is the Regulation (EU) 2024/1938 on standards of quality and safety for substances of human origin intended for human application (“SoHO Regulation”), which was published on 17 July 2024 in the Official Journal of the European Union. This regulation seeks to harmonise and enhance the protection of donors and recipients of substances of human origin as well as children born from medically assisted reproduction and to facilitate cross-border circulation of those substances to increase supply reliability. Also, scientific and technical innovation should be promoted by increasing legal flexibility. It will enter into force on 7 August 2027, with an extra year for certain provisions.
1. Background
According to the European Commission’s data from 2023, each year 15 million people donate blood and plasma, 4.6 million units are transfused to patients, more than 200,000 babies are born from medically assisted reproduction and 36,000 stem cell transplants for blood cancers are carried out.
The existing Directives 2002/98/EC and 2004/23/EC on blood, blood components, tissues and cells resulted from increasing transmission of communicable diseases in the 1980s and 1990s. Considering the data above and the still increasing need for SoHO, this legal framework is no longer up to date, meaning that patients, donors and children born from donated eggs, sperm or embryos are not fully protected from avoidable risks. Additionally, divergent national supervisory systems often hinder cross-border exchanges of substances of human origin and related innovations. A sufficiently solid, transparent, up-to-date and sustainable legal framework was required.
On 19 July 2022, the European Commission presented the long-awaited proposal for a regulation on quality and safety standards for substances of human origin for human use, also taking lessons learned from the recent COVID-19 pandemic into account. The SoHO Regulation was then adopted by the Council on 27 May 2024, approved by the European Parliament on 24 April 2024 and officially published on 17 July 2024. The SoHO Regulation is going to replace both directives.
2. What does “SoHO” mean?
Due to scientific and technical innovation, donation and human application of substances other than human blood, blood components, tissues and cells are increasingly common. Thus, the SoHO Regulation broadens its scope to substances of, generally, human origin (“SoHO”), meaning any substance collected from the human body, whether it contains cells or not and whether those cells are living or not, including SoHO preparations resulting from processing such substances. As a result, it also covers donated breast milk, intestinal microbiota, blood preparations that are not used for transfusion and any other substances that might be applied to humans in the future. The latter enables a future-proof, automatic adaption to technological advancements, without requiring amendments to the SoHO Regulation. Specific provisions of the SoHO Regulation further apply to substances used in manufactured products (e.g. medical devices or medicinal products). However, solid organs for transplantation are explicitly excluded from the definition of SoHO and remain regulated in Directive 2010/53/EU.
The SoHO Regulation further covers a wide range of activities having direct impact on the quality, safety or effectiveness of SoHO, including registration and testing of donors, collection and processing, quality control, distribution, import, export, human application and clinical-outcome registration of SoHO (“SoHO activities”).
3. Key objectives
3.1 Safety above all?
A highly emphasised topic in connection with, and in the SoHO Regulation itself, is the high standard of quality, safety and effectiveness of SoHO and the protection of SoHO donors, recipients and children born from medically assisted reproduction. While safety in general is undoubtedly of great importance, it must be considered that more blood and plasma are currently needed for medical care and pharmaceutical production than is available in the EU. Therefore, the requirements for guaranteeing the aspired safety standard must be well balanced with the requirement to maintain a sufficient number of donors.
3.1.1 Securing high standards
As to high quality, safety and effectiveness standards for SoHO, the SoHO Regulation provides a variety of rules for entities carrying out SoHO activities (“SoHO entities”) with the aim of mitigating transmission risks of communicable and non-communicable diseases as well as pathogens, toxins and genetic conditions. If none of these rules apply to particular (e.g. new) procedures, guidelines established by the European Centre for Disease Prevention and Control and the European Directorate for the Quality of Medicines & HealthCare of the Council of Europe should be considered instead. The aim is to keep technical rules and reinforced expertise up to date and to open the doors to new developments. In any case, Member States may still decide to introduce more stringent requirements through their national laws.
3.1.2 Principle of voluntary and unpaid SoHO donations
The SoHO Regulation creates specific rules for protecting donors. To avoid donor exploitation and donor health risks, financial incentives or inducements to SoHO donors or any persons granting consent on a donor’s behalf are prohibited.
On the other hand, considering the increasing need for SoHO, the willingness to donate must be encouraged. In practice, calls for donation and related advertising alone have not had enough impact, but four Member States (Austria, Germany, Hungary and the Czech Republic) have achieved a significantly higher number of donations than others – due to offering (limited) compensation for donations. The Austrian Supreme Court ruled in 2020 that a lump-sum compensation for plasma donors and additional bonuses for repeated donations are permissible (OGH, 26 November 2020, 4 Ob 183/20w). The new SoHO Regulation follows this basic idea. Therefore, all forms of compensation (including flat-rate compensation) or reimbursement are acceptable, subject to national law. The donor should be placed in a financially neutral position, meaning they should neither have to bear a loss nor make a profit from her/his willingness to donate.
3.2 EU-wide authorisation and assessment procedures for innovative SoHO preparations
Another key aspect to facilitate innovation and to simplify requirements for companies using SoHO is the possibility of EU-wide authorisation for SoHO preparations. Such authorisations will be granted by independent and impartial SoHO competent authorities, designated by the Member States, to applicant SoHO entities located in their territory. They carry out risk-based assessments and authorise SoHO preparations, prior to their release and distribution, to ensure that a high level of quality, safety and effectiveness is achieved consistently throughout all intended SoHO activities.
For new collecting, testing or processing methods, the safety and efficacy or functionality for SoHO recipients shall be demonstrated by collecting and reviewing additional data on clinical outcomes to an extent appropriate to the risks identified. In case of negligible risk or a high certainty of positive benefit-risk-assessment, meeting the SoHO Regulation’s requirements for vigilance should be sufficient. This particularly applies to well-established and used SoHO preparations being introduced in a new SoHO entity. If scientific evidence and clinical data provided for the benefit-risk assessment are not sufficient or the risk associated with SoHO preparations is considered more than negligible, further requirements must be met. Depending on the risk identified, additionally to the mandatory continuous vigilance reporting, proactive clinical follow-ups, clinical studies with monitoring of pre-defined clinical end-points or even SoHO clinical studies including a comparison to a standard therapy may be required.
Authorisations granted are valid throughout the European Union. Where a Member State has adopted a more stringent requirement related to a specific SoHO preparation, that Member State may decline to recognise the validity of the SoHO preparation authorisation of another Member State until compliance with its more stringent requirement has been demonstrated.
3.3 National supervision
Each SoHO entity must be registered with their competent national authority, either in a national register or on the EU SoHO Platform, prior to commencing SoHO activities. SoHO entities are obligated to establish, maintain and keep up to date a quality management system as well as a traceability system and a system for detecting, investigating and recording information concerning adverse reactions and adverse events. Emergency plans including respective notification procedures to the SoHO competent authorities of, for example, adverse events related to SoHO or sudden shortages of critical SoHO, must be implemented. Further, SoHO entities must collect and report annually respective SoHO activity data to the EU IT platform.
SoHO entities carrying out both processing and storage as well as release, import or export of SoHO are SoHO establishments and must obtain a specific authorisation of their SoHO competent authority. Even if a SoHO entity does not fall within the definition of SoHO establishments, SoHO competent authorities may decide that, due to the significant influence on SoHO safety and quality or involvement with multiple SoHO establishments, this SoHO entity requires such an authorisation, nonetheless. Being qualified as a SoHO establishment brings along additional obligations related to the specific SoHO activity carried out.
Thus, SoHO competent authorities not only assess and authorise SoHO preparations, but verify the effective compliance by SoHO entities with the SoHO Regulation’s requirements (also through inspections) and, by doing so, ensure independent and transparent supervision of SoHO-related activities, while ensuring a more efficient use of resources, on a national basis.
3.4 SoHO coordination board
At the EU level, a new SoHO coordination board (“SCB”) has been established. It is hosted by the European Commission and consists of Member States’ representatives. The SCB facilitates coordination between Member States, in particular with regards to the implementation of the regulation, by assisting competent national authorities. This includes the liaison for the exchange of experiences and best practices, support of joint inspections of SoHO entities and clarification of the regulatory status of certain existing substances, products or activities upon request, also consulting experts if needed. Additionally, the SCB plays an important role regarding supply continuity. Member States are obliged to establish emergency plans if the supply situation of critical SoHO may cause serious risk to human health. A summary of these plans and related major reviews shall be presented within the SCB. In case of cross-border issues, the SCB is responsible for supporting a coordinated approach to ensure the implementation of the national SoHO emergency plans, communicating and collaborating with relevant international organisations and authorities.
3.5 Digital central communication hub: the EU SoHO Platform
To limit administrative burden and to promote communication and transparency, an online platform, the so-called EU SoHO Platform, has been established. On the one hand, it serves a secure and time-efficient communication channel, for SoHO competent authorities to launch SoHO rapid alerts and for communication with SoHO entities regarding documents related to the authorisation procedure and reports on their SoHO activity data. SoHO competent authorities are then provided with an annual aggregated report. Thus, administrative processes are streamlined, communication is accelerated and resources are conserved.
Furthermore, the platform enables public access to information regarding, for example, registries of SoHO entities, approved clinical studies and authorised SoHO preparations (in compliance with data protection), list of the regulatory status of substances, products and activities requiring an opinion on their regulatory status, best practices by SCB and the work of SCB and national authorities.
4. Summary
The new SoHO Regulation strives to meet the aspiration and requirement for a high-quality, safe and efficient health care system in the European Union. Therefore, rules have been established to ensure a high level of safety and quality for the benefit of donors, recipients and children born from medically assisted reproduction, including up-to-date technical guidelines, extended protective measures and a harmonised supervisory system for SoHO entities. At the same time, however, companies operating as SoHO entities are given certain simplifications to carry out their SoHO activities, including EU-wide authorisation of SoHO preparations and the establishment of coordination and communications platforms like the SCB and the EU SoHO platform. This will significantly facilitate cross-border exchange and access to SoHO, improve patient access to therapies they need and ensure reliable supply of critical SoHO within the European Union. In addition, scientific and technical innovation is promoted, and the SoHO Regulation can be considered future-proof in many aspects due to its legal flexibility. As a result, it contributes to the EU’s strategic autonomy and independence from third countries regarding the supply of SoHO in the future. However, whether the SoHO Regulation can fulfil its significant potential depends very much on the willingness of the Member States to comply and cooperate
By Sarah Rosenthaler, Associate, Schoenherr