The new legal framework applicable to substances of human origin

The recently adopted Regulation (EU) 2024/1938 on standards of quality and safety for substances of human origin (SoHO) sets new rules which significantly strengthen the quality and safety standards applicable to donations and transplants of blood, tissues and cells (BTC).

The new rules cover a wide range of activities, including registration and testing of donors, collection and processing of blood, tissues and cells for human use and monitoring the clinical outcome of substances of human origin.

The Regulation reaffirms the principles of voluntary and free donation, as well as therapeutic approaches based on the most up-to-date and consolidated scientific evidence that will be the subject of common guidelines and recommendations.

It also broadens the scope of SoHO by including human breast milk and intestinal microbiota.

How the SoHO affect the lives of citizens

Every year, millions of EU citizens need blood transfusions during an operation or following an accident, bone marrow transplants to treat leukaemia, and in vitro fertilization cycles to become parents.

A note from the EU Council specifies that among the purposes of the common standards is to facilitate cross-border trade and access to substances of human origin.

According to the figures released by the European Commission and the Council, each year the European Union counts 25 million units of blood transfused, e.g. for surgery or trauma care, 15 million of blood and plasma donors, 4,6 million of patients transfused, over 200,000 babies born from medically assisted reproduction, 36,000 stem cells transplants for blood cancers and other conditions, over 10,000 cornea transplants for restoring sight, 2,000 skin transplants for burn wounds and other injuries and 650 heart valves implanted.

The priority goals of the new legislation

The revised legal framework aims at ensuring a better protection for donors and recipients of SoHO by increasing the quality and safety of collection, donation, transfusion, transplantation and use processes, and establishing platforms for follow-up data and reporting of adverse events.

The European Union is committed trough a Regulation, harmonizing the rules applicable across the board, to overcome the divergent approaches of oversight as over the years they have generated unequal levels of quality and safety in addition to barriers to the exchange of BTC across the EU.

Another crucial issue addressed by the new legislation is to mitigate the risk of shortage of BTC, especially as far as plasma is concerned, if you consider that the EU depends on the United States for about 40 percent of its plasma needs for the production of plasma-derived medicinal products (PDMPs).

The Regulation also aims at introducing a common procedure for assessing and authorising the preparation of SoHO, proportionate to the risks they entail. It also requires all entities conducting activities that affect the safety and quality of SoHO to register with their competent authorities.

A SoHO Coordination Board (SCB) will also be established, with and for EU member States to support the implementation of the new regulation and provide legal clarifications.

Finally, the EU SoHO digital platform will be created, to collect all the necessary information, simplify reporting and increase visibility for citizens.

The supply of blood and blood products

To improve strategic autonomy and prepare for future health emergencies, much more plasma needs to be collected. It has to be considered that in the EU, 62 % of plasma is collected by public/NGOs collection services, while the private sector collects 38 %, sourced from only four countries (Austria, Czechia, Germany and Hungary). High dependence from third country makes blood and blood products supply at risk.

Therefore, ensuring self-sufficiency and quality on all blood products (red blood cells, white blood cells, platelets and plasma) remains essential.

The new legislation facilitates the achievement of this objective by encouraging donations be obtained on a voluntary basis and promoting the exchange of SoHO between member States.

The increasing use of medically assisted reproduction (MAR)

Late motherhood and the increasing number of LGBT couples have dramatically increased the demand for gametes over the past two decades.

The number of cross-border travel for access to treatments for medically assisted reproduction has also significantly grown.

Consequently, children born from donated eggs, sperm or embryos are exposed to avoidable risks which the rules set by the new legislation try to mitigate.

The potential benefit of intestinal microbiota on viral infections

As the human microbiome includes all microorganisms contained in or on the human body, the use of targeted microbiome therapeutics has great potential for disease management.

The use of repurposed bacteria could provide a new therapeutic solution for treating persistent or resistant diseases.

However, monitoring the safety of such products for several issues including the presence of resistance genes and assessments for toxin production will be paramount.

The challenges ahead

Many activities that are carried out, from the moment of the registration of a potential SoHO donor to the use of SoHO in a recipient, or from the moment of collection of SoHO from a person for human application to themselves or from persons as part of their own current or future medically assisted reproduction treatment or as part of such treatment in the context of within-relationship use, have an impact on the safety, quality or effectiveness of SoHO or the safety of SoHO donors.

SoHO entities and establishments shall be subject to supervisory activities and inspections performed by SoHO competent authorities at regular intervals to ensure compliance with the new rules.

Both SoHO entities and establishments shall then ensure to meet all the requirements set by the new legislation by the time it will be applicable (three years after its entry into force, i.e.: by summer 2027).

The above implies that they will have to put in place an updated system of tracking their activities; to adopt, review or update their standard operating procedures, to upgrade their quality management systems and reporting data mechanism.

SoHO entities and establishments will have to seek advice, take action and possibly schedule a preliminary audit without delay to mitigate the risk of being non-compliant with the provisions set by the new Regulation.