EUROPEAN COMMISSION

Brussels, 14.7.2022

COM(2022) 338 final

2022/0216(COD)

Proposal for a

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on standards of quality and safety for substances of human origin intended for human application and repealing Directives 2002/98/EC and 2004/23/EC

(Text with EEA relevance)

{SEC(2022) 304 final} - {SWD(2022) 189 final} - {SWD(2022) 190 final} - {SWD(2022) 191 final}

EXPLANATORY MEMORANDUM

1.CONTEXT OF THE PROPOSAL

•Reasons for and objectives of the proposal

The Blood Directive - 2002/98/EC 1 and the Tissues and Cells Directive - 2004/23/EC 2 (the BTC legislation) have helped ensure the safety of millions of patients undergoing blood transfusion, transplantation and medically assisted reproduction. The legislation sets out quality and safety requirements for all activities from donation to human application (unless the donations are used to manufacture medicinal products or medical devices, in which case the legislation only applies to donation, collection and testing).

Every year, EU patients are treated with 25 million blood transfusions (during surgery emergency, cancer or other care), a million cycles of medically assisted reproduction, over 35,000 transplants of stem cells (mainly for blood cancers) and hundred thousands of replacement tissues (e.g., for orthopaedic, skin, cardiac or eye problems). These therapies are only available thanks to the willingness of fellow citizens to make altruistic donations.

In the European Union, the collection, processing and supply of each individual unit is typically organised on a local small-scale by public services, (academic) hospitals and non-profit actors.

After almost 20 years in place, the legislation no longer addresses the scientific and technical state of the art and needs to be updated to take into account developments that have taken place in the sector. While an evaluation of the BTC legislation 3  confirmed that it has brought very good levels of overall safety and quality in these sectors (less than one serious patient reaction for every 12,000 applications), shortcomings of the legislation were identified as follows:

•Patients are not fully protected from avoidable risks due to out-of-date technical rules;

•Blood, tissues and cells (BTC) donors and children born from donated eggs, sperm or embryos (offspring) are exposed to avoidable risks;

•Member States have divergent approaches to oversight that hampers cross-border exchanges of BTC;

•Full potential of BTC processed or used in new ways is not reached for patients;

•Patients are vulnerable to interruptions in EU supply of BTC.

The COVID-19 pandemic highlighted some of these shortcomings, in particular, those impacting on rules for preventing the risk of disease transmission by BTC and the lack of measures to ensure sufficiency of supply. The proposal aims to address these shortcomings, by revising the current legislation. The overall objective is to ensure a high level of health protection for EU citizens and ensure they have access to safe and effective BTC. As new technologies or risks will continue to emerge, it is desirable that the future framework is more effectively implemented, future proof, crisis resistant and agile enough to accommodate new risks and trends while continuing to provide appropriate safety and quality requirements. Being a REFIT initiative, areas for improving the efficiency of the legislation and simplifying its implementation by all stakeholders were also explored.

•Consistency with existing provisions in the policy area

The EU framework for safety and quality of substances of human origin (SoHOs) has currently three main Directives, respectively for Blood, Tissues and Cells, and Organs, together with implementing legislation. Each Directive sets safety and quality standards for all the steps from donation and collection from a donor body, over testing, processing, storage and distribution, to eventual application in the patients’ body. The current proposal covers blood, tissues and cells, and has links with the Organs Directive 4 , in particular regarding closer collaboration between Member States’ competent authorities for blood, tissues and cells, and those for organs, and regarding vigilance requirements.

Where BTC can be used in the manufacture of health products that are regulated by other Union legislation, or as the starting and raw material thereof, the SoHO framework applies on the first activities in the chain (donation, collection, testing) while these later activities (manufacturing, storage, distribution etc.) are regulated under these other appropriate legislative frameworks (e.g. medicinal products, including advanced therapy medicinal products, or medical devices) 5 . There are in place some mechanisms to ensure coherence between the BTC legislation and those adjacent frameworks. This proposal will reinforce the cooperation among those adjacent frameworks.

As part of the Pharmaceutical Strategy for Europe , there is an ongoing evaluation and revision of the pharmaceutical legal framework 6 . This proposal will feed into that work, in particular regarding the regulatory delineation between the BTC sector and the pharmaceutical sector. The delineating criteria are set by definitions in the pharmaceutical framework and are not altered by this proposal.

•Consistency with other Union policies

This initiative is part of the EU’s ambition to build a stronger European Health Union, so as to: (1) better protect the health of our citizens (including patients, donors and offspring); (2) equip the EU and its Member States to better prevent and address future pandemics (surveillance, data analysis, risk assessment, early warning and response) and (3) improve the resilience of EU health systems (sufficient supply of SoHOs).

The proposal further establishes links with the European Centre for Disease Prevention and Control (ECDC), for which the mandate has been proposed to be strengthened 7 , also in this field of SoHOs.

2.LEGAL BASIS, SUBSIDIARITY AND PROPORTIONALITY

•Legal basis

The SoHO legislation is based on Article 168(4)(a) of the Treaty on the Functioning of the European Union (TFEU). As a shared competence with the Member States, and in line with the principle of subsidiarity, this Treaty Article gives the EU a mandate to set out measures establishing high standards of quality and safety for SoHOs while allowing Member States to maintain or introduce more stringent protective measures. Member States remain responsible for decisions of an ethical and organisational nature, such as allowing the donation of certain SoHOs or deciding allocation of certain SoHOs or who may access certain SoHO therapies (e.g., access to in vitro fertilisation therapies). While the EU Charter on Fundamental Rights requires non-commercialisation of the human body which translates into a principle of voluntary unpaid donation in the EU legislation, it is for the Member States to define the detailed implementation of this principle within the context of each country. When a Member State chooses to allow a particular new practice that can bring ethical questions (such as testing or storage of embryos), the safety and quality of this practice are then regulated by the EU SoHO legislation.

•Subsidiarity (for non-exclusive competence)

Ever-evolving disease threats, such as Zika, Human Immunodeficiency Virus (HIV) or viral hepatitis B, C and D, which can be transmitted through SoHOs, constitute cross-border threats to public health. In addition, the exchange of SoHOs between Member States and with third countries is necessary for ensuring optimal patient access and sufficiency of supply. This is in particular the case for SoHOs that are used as personalised therapies where it is essential that a recipient is specifically matched with a donor. Increasing cross-border exchanges of SoHOs necessitate ever-closer cooperation between a number of health professional groups and authorities to ensure that SoHOs remain traceable from the donor to the recipient and vice versa.

Certain types of sector-specific expertise may also not be easily available in every Member State.

By providing a framework for cross-border cooperation, based on a common set of rules, and connected to sector-specific expertise, EU-level measures are best placed to address such issues effectively. Establishing high standards of quality and safety for SoHOs at EU level facilitates equal access to safe therapies for all EU citizens, and encourages circulation of SoHO materials and products between Member States. Providing for a common framework that supports joint practices will promote simplification and efficiency.

•Proportionality

The overall initiative is limited to aspects that Member States cannot achieve satisfactorily on their own, and where there is clear EU added value. Many of the pursued objectives can only be met through highly technical rules and guidance that require specific expertise for their regular updating. From the three policy options considered (see the impact assessment staff working document, section 5.2), the preferred option requires that blood and tissue establishments meet safety and quality standards by following guidelines developed and updated by nominated expert bodies such as the ECDC and the European Directorate for the Quality of Medicines & HealthCare (EDQM, a Directorate of the Council of Europe). This option provides the highest effectiveness and efficiency, avoids the need for re-developing guidelines, and can ensure a high level of harmonisation as well as rapid updating of standards.

The key added value of the EU approach in this proposal is to ensure, where appropriate, that common standards and guidelines make full use of the high level of latest scientific and technical expertise, as already available in expert bodies such as the ECDC and the EDQM, and therewith facilitate cross-border exchange of and access to safe SoHOs. In addition, the sharing of data through a common platform, and following common guidance, will enable policy making based on significantly more robust data.

As stated in the impact assessment staff working document (section 7.5), the proposal does not interfere with the right for Member States to maintain and introduce more stringent measures when they consider them necessary (Article 168(4) of the TFEU) but does increase the level of safety and quality to be achieved in all Member States, thus reducing the need in most cases for more stringent measures that can create barriers to cross-border exchange and to patient access. In addition, the proposal will ensure the adoption of more stringent measures is made more visible so that exchanges can be more easily organised in full respect of those measures. Given that rules relating to ethical aspects of this field, or to healthcare organisation, are not included in the proposal, no special circumstances in individual Member States were identified that required a particular territorial variation in the measures to be applied.

•Choice of the instrument

The proposal takes the form of a new Regulation repealing two existing basic Acts, both Directives. A key element of the proposal is to establish more harmonised measures for Member States and organisations involved in collection, testing, processing, distribution, application of SoHOs, from donors to patients. Insufficient minimum harmonisation was identified as a key reason for reduced trust between Member States, resulting in reduced cross-border exchange and sub-optimal access for patients to SoHOs. A Regulation is considered the most suitable instrument since it does not require transposition and is directly applicable. 

3.RESULTS OF EX-POST EVALUATIONS, STAKEHOLDER CONSULTATIONS AND IMPACT ASSESSMENTS

•Ex-post evaluations/fitness checks of existing legislation

The evaluation of the BTC legislation, published in 2019, identified the following gaps and shortcomings:

1.Patients are not fully protected from avoidable risks: the EU safety and quality requirements have not kept up to date with frequently changing scientific and epidemiological developments thus potentially exposing patients treated with BTC to avoidable risks. The ECDC provides up-to-date but non-binding guidance on safety measures, e.g. to address COVID-19 risks. The EDQM provides guidance on quality of BTC and many Member States put more stringent requirements in place. This situation can create legal confusion and unequal levels of safety and quality for patients. In addition, while new therapies have emerged since the BTC legislation was adopted, it is not always clear whether, and if so which, of the BTC Directives apply, leaving these substances unregulated or regulated in divergent ways (e.g., breast milk and faecal microbiota transplants). Some of these SoHOs do not meet the definitions of blood, tissues and cells included in the current legislation.

2.Divergent approaches to oversight cause unequal levels of safety and quality and barriers to the exchange of BTC across the EU: divergent national interpretations and implementations of the legislation lead to unequal protection and a lack of mutual trust between national authorities. This in turn creates barriers to cross-border exchange and to availability of BTC. These differences reflect the lack of common provisions for verification of effective implementation of inspection, authorisation and vigilance, and inconsistency in the levels of capacities, skills and independence required of inspectors supervising BTC establishments.

3.BTC donors and offspring (including children born from donated eggs, sperm or embryos) are exposed to avoidable risks: the current BTC legislation contains only very limited measures to protect and monitor BTC donors and offspring from donated sperm, eggs or embryos. In particular, the requirements to report donor adverse reactions are too limited and provisions for testing egg and sperm donors for genetic conditions are out of date with the technology available. Growing demand by commercial companies (e.g. egg banks for in vitro fertilisation, plasma collectors for medicinal product manufacture) increases the pressure to donate and consequently the need for robust donor protection measures.

4.The BTC legislation lags behind innovation: new ways of processing donations in BTC establishments may bring significant benefits. However, these new therapies can also put patients at risk, as current authorisation procedures for new BTC processes do not require evidence that risk is justified by benefits. Moreover, this lack of adequate procedures does not inspire trust and prevent healthcare actors from developing and adopting innovative processes. Besides risks and benefits, safety and quality measures also need to take account of the typical economic (public/non-profit) settings where BTC are developed and prepared, and of the often incremental and open-access nature of these innovations. In addition, there are sometimes difficulties in defining the borderlines for novel BTC with other regulatory frameworks, in particular where medicinal products and medical devices are concerned. This creates administrative burdens and implicit disincentives for BTC establishments, healthcare professionals and academia to innovate. This legal uncertainty issue requires further evidence gathering to allow its extent and consequences to be fully assessed.

5.The EU is vulnerable to interruptions in supply of some BTC: for some essential BTC, the EU is highly dependent on imports to ensure sufficiency. In particular, the EU relies on the United States for an adequate supply of plasma used to manufacture plasma-derived medicines. In the current legislation, sufficiency of supply through voluntary unpaid donation is encouraged, though without concrete measures to protect or increase supply. This approach has not proven adequate to protect EU patients from the risk of shortages or sudden supply disruption. The lack of EU and national monitoring provisions for the supply of BTC makes it difficult to predict EU supply interruptions and to take action to mitigate the risks to patients.

The proposal therefore provides measures to:

1.Ensure safety and quality for patients treated with SoHO therapies and fully protect them from avoidable risks linked to SoHOs.

2.Ensure safety and quality for SoHO donors and for children born from donated eggs, sperm or embryos.

3.Strengthen and allow for harmonisation of oversight practices among Member States.

4.Facilitate the development of safe and effective innovative SoHO therapies.

5.Improve the resilience of the sector, mitigating risk of shortages.

Objectives 1 and 2 are closely linked, as they both involve setting technical requirements for safety and quality to better protect EU citizens. While the EU has no mandate to intervene directly in supply management, reliable monitoring and notification of shortages would help Member States detect sudden drops in supply of SoHOs, trends towards shortages or dependencies on other Member States or on third countries, and would help them to take appropriate mitigation actions.

•Stakeholder consultations

Stakeholder consultations were a key step in the impact assessment phase for the revision of the legislative framework on blood, tissues, and cells. Consultation activities aimed to assess stakeholders’ views and opinions on (i) the validity of the findings of the evaluation (2019) 8 , (ii) the three proposed policy options described in an Inception Impact Assessment (IIA) 9 and (iii) the extent to which they would address the shortcomings identified in the evaluation, and their likely impacts.

Stakeholders were consulted via (i) the IIA publication for feedback, (ii) online surveys and questionnaires, (iii) hearings and participatory workshops with national competent authorities and stakeholders, (iv) bilateral meetings with stakeholder organisations and (v) interviews with specific stakeholders.

Overall, there is support among all stakeholders for the common measures proposed (revised legislation that allows for up-to-date technical guidance and fills existing legal gaps; strengthened oversight practices,; mechanism for legal advice whether and what SoHO requirements apply to a substance, if needed in coordination with other EU legal frameworks; tailored authorisation of SoHOs used or processed in new ways; and crisis preparedness and management). Stakeholders also expressed broad support for option 2 (technical rules set by expert bodies), which is seen as the most effective approach. Analysis of quantitative data from the public consultations confirmed that the degree of conflict among stakeholders was low, as this preference was widely agreed between all stakeholder categories. However, sector experts and national authorities also highlighted conditions that must be met for the option 2 approach to be a success, including the need for transparent drafting procedures that ensure that professionals as well as Member States can provide inputs, the need to allow for more stringent national requirements and the need to accommodate for geographic differences between the EU and the Council of Europe.

In addition, the analysis of respondents to the consultations highlighted once again the strong links between the blood sector on the one hand and the tissue and cell sector on the other, thus supporting the decision to combine both Directives into a single legal act on SoHOs (Organs being excluded).

Donors and patients as well as ethics bodies raised important points to be taken into consideration during the implementation phase of the new legal framework, regarding for example donor protection, voluntary unpaid donation principles or the use of new training opportunities for inspectors about fundamental rights (to further enable them to ensure that those are respected by establishments, and in particular non-discrimination of donors).

Many stakeholders also underlined the lack of legal clarity on the delineation with other EU legal frameworks (in particular medicinal products, including advanced therapy medicinal products, and medical devices) and indicated many cases where they believe SoHO-based therapies are not appropriately regulated, including some cases with a negative impact on feasibility to supply and eventual patient access. Stakeholders considered that the eventual choice for the most appropriate legal framework should aim in first place to ensure safety and quality, but also take account of the setting of, the costs for and the feasibility of providing access to safe and effective therapies. There was broad support for a dedicated SoHO legal advisory mechanism and for efficient coordination with advisory mechanisms in other sectors. It was largely considered that this will allow to strengthen legal clarity as well as improve interplay where SoHOs become starting materials for therapies manufactured under these other legal frameworks.

Also, while supportive, stakeholders pointed out that EU-level supply monitoring and crisis preparedness measures will demand significant efforts, without having any direct impact on the risk of shortages of critical SoHO. Finally, National Competent Authorities (NCAs) and blood and tissue establishments expressed concerns regarding some specific measures that would increase their costs or administrative burden. Consideration of EU level measures to provide support was taken into account when preparing the legal proposal.

An overview of the activities carried out and the results is available in Annexes 2 and 18 of the impact assessment staff working document.

•Collection and use of expertise

The Commission used the findings from the evaluation of the BTC legislation (2019). The impact assessment has been based on research and analyses done by the Commission. The Commission also contracted two external, independent consultant teams, to perform:

–A study, carried out by ICF S.A. supporting the impact assessment of the policy options, which gathered information on impacts and costs for stakeholders of the proposed measures and options, and further documented borderline case studies. The study also organised participatory workshops bringing stakeholders together to discuss various topics. The study was guided by a steering group composed of three senior experts in the field of blood, tissues and cells, who supervised the process and validated the study findings. The external support study will be published alongside this proposal.

–A feasibility study, carried out by Deloitte, focusing specifically on the costs, benefits and optimal approaches to the digitalisation of the sector. The preliminary report from that study is published as Annex 19 of the impact assessment staff working document.

Many of the 448 references in the BTC legislation evaluation were articles published in scientific journals and included data and evidence that was still relevant for the impact assessment of the policy options. In addition, a number of further scientific articles were published more recently and were also used as evidence sources for the impact assessment. These represent high quality evidence, due to the peer review process used by the publishers.

Evidence on costs is particularly difficult to gather in the SoHO sector, due to the predominant role of public sector organisations (public administrations, hospitals), where real costs related to SoHO activities are sometimes absorbed in overall hospital or institutional budgets. This explains the high variety of costs reported through the survey performed by the external study supporting the impact assessment, with NCAs and professionals. Sector experts, both from NCAs and from public establishments, were therefore brought together to identify and agree on reasonable average values and validate key assumptions that have been used to calculate costs.

The identified impacts of the proposed policy measures were subjected to a multi-criteria decision analysis to compare the effectiveness and efficiency of the options. To that end, the impact assessment piloted the tool developed by the Joint Research Centre of the European Commission, SOCRATES (SOcial multi-CRiteria AssessmenT of European policieS), using it to compare the different options based on previously established criteria.

•Impact assessments

The impact assessment analysed three policy options for the setting of safety and quality standards:

–Option 1 - Decentralised regulation: it provides blood and tissue establishments with the freedom to make reference to a variety of national and international guidance when conducting risk assessments of their own activities, with a view to setting their internal technical methods.

–Option 2 - Joint regulation: it requires blood and tissue establishments to follow the technical guideline developed and updated by nominated expert bodies.

–Option 3 - Central Regulation: it requires blood and tissue establishments to follow the safety and quality standards, all provided for in EU legislation.

The preferred option is Option 2. Joint regulation brings the highest effectiveness and efficiency as it builds on established expertise in the field of SoHOs to ensure that up-to-date standards are applied across the EU. Option 1 would allow changes to standards to be implemented more quickly, but with a high level of variation across the EU and a high workload on small blood and tissue establishments. Option 3 would allow for the highest level of harmonisation, but would require more time to adapt standards and bring additional costs for EU institutions.

This proposal therefore introduces high level standards in the legislative text for patient, donor and offspring protection and empowers the Commission to adopt implementing acts on the implementation of those standards if needed. Where there are no such implementing acts, professionals should, to meet these standards, apply safety and quality guidelines developed by the EDQM and the ECDC, in line with option 2. However, in line with option 1, it can also be acceptable to apply other, equivalent, guidelines accepted by national authorities and demonstrated as achieving equivalent standards of safety and quality. In the absence of a technical guideline from expert bodies, establishments can set their own technical method taking into account internationally recognised standards, scientific evidence and a documented risk assessment. This approach will facilitate an efficient and responsive implementation of safety and quality standards whenever risks and technologies change. It is proportionate in that it ensures EU legislation would be adopted for the implementation of a particular standard only when necessary and when it adds EU value (option 3).

In addition, a series of common measures was assessed, in particular to fill some legal gaps in the BTC framework, strengthen oversight, facilitate innovation, through advice on when the SoHO legislation is applicable and a (risk-) proportionate authorisation pathway for new processes, and manage SoHOs supply (crisis). The implementation of some of these common measures will be supported by guidelines from expert bodies (option 2).

Regarding the measure on establishing a SoHO advisory mechanism, this proposal does not propose any changes in the delineation of the borderline with the legal frameworks for pharmaceuticals or medical devices. The delineating criteria are defined in those other frameworks, in particular in Article 1 of Regulation (EU) 2017/745 (‘devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable’), in Article 2 of Directive 2001/83/EC on medicinal products (‘intended to be placed on the market’ and ‘prepared industrially’), and consequently in Article 2 of Regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products (‘substantial manipulation’ and ‘not intended to be used for the same essential function’). This measure will rather facilitate coordination with established (or future) advisory mechanisms in those other frameworks.

The preferred option would ensure that citizens are better protected when donating, or being treated with a substance of human origin, with more harmonised and up-to-date safety and quality rules across the EU. In addition, offspring from medically assisted reproduction will be better protected, as will patients treated with currently unregulated SoHOs (e.g. therapeutic use of donated breast milk or bedside preparations of SoHOs).

The preferred option would bring a positive impact for professionals, in particular in blood and tissue establishments, when working with SoHO. Outdated, and sometimes costly, technical rules for safety and quality will be removed and replaced with standards based on the best scientific evidence and expertise available that will be updated in a timely manner (bringing efficiencies for establishments). The preferred option also allows for guidance to make common measures more efficient: a clear and (risk-) proportionate pathway will facilitate access to SoHOs prepared or used in new ways and supply-crisis management will be better aligned and coordinated.

The common measures will also strengthen oversight by competent authorities, by bringing in principles and new or more-efficient practices (e.g., joint inspections). Authorities will also benefit from more proportionate measures (e.g., risk based inspections) and EU level support (e.g. a digital platform, EU auditing of oversight systems, EU training courses for authority personnel). These measures will increase mutual trust and facilitate the collaboration between Member States, which should ultimately facilitate the cross-border exchanges of SoHOs, hence patient access.

Digitalisation will allow for further efficiencies in administrative processes, and the possibility for sharing of information will limit duplication of work across Member States.

The main costs relate to monitoring measures (donor, offspring, supply), to registration of bedside preparations of SoHOs and to the risk-proportionate pathway to authorise SoHOs processed or used in new ways. Those costs mostly fall on professionals in blood and tissue establishments, hospitals and clinics and, to a lesser degree, on competent authorities. EU measures can be considered to offset these costs for professionals and authorities, in particular in the adjustment phase and in particular through supporting digitalisation.

For EU institutions, the set-up of a common IT platform (the EU SoHO Platform) brings a significant cost, but will allow for a lightening of the (administrative) burden for national authorities and professionals. Further EU costs relate to coordination and co-funding of expert bodies.

•Regulatory fitness and simplification

This initiative is part of the Commission Work Programme 2021 under Annex II (REFIT initiatives).

The revision of the BTC legislation, with an approach proportionate to risks in different areas (authorisation or registration of establishments/entities, authorisation of new preparation processes, health monitoring of certain SoHO donors and offspring), brings opportunities for savings in the sector, and for carrying out some activities more efficiently with the same resources (e.g. risk-based inspections), though these opportunities have not always been fully quantified. The table below gives an overview of the main opportunities under the preferred option.

Digital impacts are also expected, as data in the SoHO sector can become valuable digital assets in the areas of public health and innovation. A single IT system will bring important benefits as it can host flexible solutions, allowing Member States and establishments to maintain and connect with their own system or re-use existing components. It could become an important node in the EU digital ecosystem, and in particular in the future European Health Data Space (EHDS), which aims at opening opportunities and removing barriers to the use and reuse of health data, for the provision of healthcare, personalised medicine, research and innovation, policy making and regulatory activities. To benefit from the EHDS in the future, competent authorities in the field of SoHOs could consider the collaboration with competent bodies under the EHDS at national and EU level, including for aspects related to technical and semantic interoperability.

•Fundamental rights

The proposal would bring positive impacts on some fundamental rights of citizens (health protection, non-discrimination, privacy, informed consent), in particular by strengthening the provisions relating to donor protection and vigilance and the reporting of genetic conditions in children born from medically assisted reproduction with third party donation, and by ensuring that requirements for safety and quality are based on scientific evidence. However, for most of the ethical aspects, in particular the rights of children born from medically assisted reproduction, decisions are taken by Member States at national level.

The proposal maintains the current principle of voluntary and unpaid donation (VUD) in line with Article 3 of the EU Charter of Fundamental Rights that prohibits the commercialisation of the human body. However, the proposal harmonises the differing versions in the blood and the tissue and cell Directives and adapts them to the principle of ‘financial neutrality’ recently recommended by the Council of Europe Committee on Bioethics 12 .

4.BUDGETARY IMPLICATIONS

The legislative financial statement attached to this proposal sets out the budgetary, human and administrative resource implications. Appropriations will be reallocated within the financial envelope of the EU4Health Programme 13 in the Multiannual Financial Framework (MFF) 2021-2027. That Programme was established to respond to the need for further action at Union level to support cooperation and coordination among the Member States. That Programme should be a means to promote strengthened exchange of best practices between Member States, to support networks for the sharing of knowledge or for mutual learning, to address cross-border threats to health so as to reduce the risks of such threats and to mitigate their consequences, and to improve efficiency by avoiding the duplication of activities and optimising the use of financial resources. In that context, some activities organised jointly among Member States, such as inspections or SoHO preparations assessments, could be eligible for Union financial support.

5.OTHER ELEMENTS

•Implementation plans and monitoring, evaluation and reporting arrangements

The Commission will review the monitoring indicators periodically and evaluate the impacts of the legislative act after five years. The monitoring will be possible thanks to the data from reporting obligations on Member States and SoHO entities. The EU SoHO Platform will enable the collection of all elements of the continuous monitoring plan as it automates the extraction of relevant indicators without additional input from stakeholders. For the evaluation, additional data will be collected, in particular on the costs, the usability and the integration across systems. The data platform will be used to transparently publish aggregated indicators of general interest, such as serious adverse occurrences related to SoHOs, insufficiencies of supply or authorised SoHO preparations.

•Detailed explanation of the specific provisions of the proposal

The new Regulation, repealing the Blood Directive 2002/98/EC and the Tissues and Cells Directive 2004/23/EC, and their implementing legislation, is structured around obligations for the different stakeholders: the national competent authorities, the entities handling SoHOs, and the Commission. It includes specific requirements for all organisations that carry out activities that can affect the safety, quality or efficacy of SoHOs used for human application and describes obligations for designated authorities that will verify the proper implementation of the provisions. It will consist of the following main chapters:

Chapter I: General provisions

Chapter I contains general provisions of this Regulation. It defines the subject matter and the scope of application of the Regulation. In recognition of the importance of ensuring safety and quality of SoHOs that are not defined by the terms ‘blood’, ‘tissue’ or ‘cell’, such as breast milk and intestinal microbiota, and to future-proof the legislation in this regard, the scope is defined by the broader term SoHOs. Solid organs continue to be regulated by Directive 2010/53/EU and are excluded from the definition of this term. This chapter contains the definitions of the different elements of the Regulation and of the terminology used throughout the text. Furthermore, it introduces the description of SoHO activities and describes the possible more stringent measures set by Member States, in line with Article 168(4)(a) of the TFEU. Certain exclusions are described, along with the partial applicability of this Regulation when SoHOs are used to manufacture products regulated by other Union legislation, or as the starting and raw material thereof.

Chapter II: Competent Authorities

Chapter II contains the provisions regarding competent authorities for SoHOs, which are responsible for the SoHO supervisory activities. It covers the designation of competent authorities, the possibility to delegate certain SoHO supervisory activities, and general principles for their functioning (independence and impartiality, transparency). It also defines their general responsibilities and obligations. It covers the communication between competent authorities (within the SoHO sector) and consultation and cooperation with authorities of other regulated sectors. It lays down general obligations for authority personnel and provides for competent authorities obligations regarding Commission controls.

Chapter III: SoHO Supervisory Activities

Chapter III covers all activities competent authorities undertake vis-à-vis SoHO entities or processes, with the obligation to maintain a register of SoHO entities and a procedure for their registration; the obligation to have a system for the authorisation of SoHO preparations, and a procedure for these authorisations, with provisions for conducting the assessment of SoHO preparations, possibly in a joint process with one or more competent authorities, and further specific obligations for SoHO preparation assessors. This Chapter also covers the obligation to have an authorisation system for SoHO establishments (specific in case of importing SoHO entities) and a procedure for their authorisation (SoHO establishments/importing SoHO entities). It stipulates the obligations for inspections of SoHO establishments and other SoHO entities, possibly via joint inspections, and the specific obligations for inspectors. It provides for the obligations for competent authorities regarding data publication, traceability, vigilance and, SoHO Rapid Alerts.

Chapter IV: General Obligations on SoHO Entities 

Chapter IV outlines all the general obligations on SoHO entities, namely their registration, the nomination of a Responsible Person if they release SoHOs for clinical use, the obligations regarding export of SoHOs. It also lays down the obligation for authorisation of SoHO preparations, and the procedure for application for such authorisation. It also covers the obligations for importing SoHO entities regarding their authorisation, and the application for such authorisation. It provides for the obligations for SoHO entities regarding activity data collection and reporting, traceability and coding, the obligation to apply the Single European Code to SoHOs distributed for human application (except for some specific SoHOs), and vigilance notifications.

Chapter V: General Obligations on SoHO Establishments 

Chapter V lays down the general obligations on SoHO establishments, a sub-set of SoHO entities that process and store SoHOs. It provides for their authorisation and the application procedure for such authorisation, the obligation to have a Quality Management system in place, and the obligation to designate a physician responsible for specific tasks.

Chapter VI: SoHO Donor Protection

Chapter VI contains the provisions related to the protection of SoHO donors, with standards, and how to implement these standards concerning donor protection.

Chapter VII: Recipient and Offspring Protection 

Chapter VII contains the provisions related to the protection of patients treated with SoHO (recipients) and offspring from medically assisted reproduction, with standards, and how to implement these standards concerning recipient and offspring protection. It also stipulates conditions for the release of SoHOs for human application, and conditions for exceptional release.

Chapter VIII: Supply Continuity

Chapter VIII lays down provisions to ensure the continuity of supply of SoHOs. It covers the obligation for Member States to have national SoHO emergency plans (for SoHOs that are critically important for patients) and the responsibilities of competent authorities and entities regarding supply alerts for critical SoHOs. It also stipulates the conditions for derogation from the obligations to authorise SoHO preparations in emergencies, provides for additional emergency measures taken by Member States and finally lays down the obligation for SoHO entities carrying out activities with critical SoHOs to have an emergency plan in place.

Chapter IX: SoHO Coordination Board

Chapter IX establishes the SoHO Coordination Board (SCB) to support Member States in the coordination of implementation of this Regulation and the delegated and implementing acts adopted pursuant to it. This chapter also provides for the composition of the Board and how its functioning is organised.

Chapter X: Union Activities 

Chapter X outlines the activities organised at Union level, regarding training and exchange of competent authorities’ personnel, the Commission controls in Member States, and the support provided by the Commission to support the implementation of the Regulation. It also refers to the cooperation with the EDQM, which should address procedures for the development and revision of technical guidelines, including evidence gathering, guideline drafting and public consultation.

Chapter XI: EU SoHO Platform

Chapter XI describes the EU SoHO Platform that will support information sharing between authorities and with SoHO entities, and outlines its general functionalities.

Chapter XII: Procedural Provisions 

Chapter XII contains the procedural provisions of the Regulation with regard to confidentiality and data protection obligations. It furthermore contains provisions regarding the exercise of delegation, the urgency procedure and the committee procedure. Finally, it lays down the penalties applicable to infringements of the provisions of this Regulation to be set by Member States.

As regards delegated acts, following the adoption of the proposal, the Commission intends to create an expert group in line with decision C (2016) 3301 in order to advise and assist it in the preparation of delegated acts, as well as on issues related to implementation of the Regulation as regards:

(a)preparing opinions at the request of the Commission on the regulatory status of a substance, product or activity (and consulting equivalent advisory bodies established in other relevant Union legislation);

(b)providing expertise relevant for the development of technical guidelines, other guidelines and technical methods to the Commission;

(c)reviewing reports on activity data and on vigilance data prior to publication by the Commission;

(d)contributing to the continuous monitoring of technical progress and assessment of whether the safety and quality requirements set out in this Regulation are adequate to ensure safety and quality of SoHOs and SoHO preparations and the safety of SoHO donors;

(e)supporting the Commission to exchange views with Union or international level professional associations working in the field of SoHOs on issues of general interest in relation to the applicability of the provisions of this Regulation;

(f)providing expertise to the Commission for the development of guidelines, standards or similar on an international level for SoHOs and their quality and safety, when appropriate;

(g)advising the Commission on the appropriate content and format of Union training programmes for competent authority personnel and supporting the performance of training activities;

(h)providing advice and expertise on the preparation of delegated acts.

The expert group should also provide technical advice to the Commission when it considers that the EDQM guidelines are not sufficient to meet a standard for donor protection or a standard for recipient and offspring protection as provided for in this Regulation.

Chapter XIII: Transitional Provisions 

This Chapter sets the transitional provisions applicable to establishments and SoHO preparations authorised under the former BTC legislation. It stipulates the status of SoHO stored before the application of this Regulation. Finally, it contains the transitional measures related to the date of adoption of certain delegated and implementing acts.

Chapter XIV: Final Provisions 

The final chapter stipulates the repeal of Directives 2002/98/EC and 2004/23/EC. It also sets the provision for the evaluation of the Regulation, and its dates of entry into force and application.

2022/0216 (COD)

Proposal for a

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on standards of quality and safety for substances of human origin intended for human application and repealing Directives 2002/98/EC and 2004/23/EC

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the Functioning of the European Union, and in particular Article 168(4), point (a), thereof,

Having regard to the proposal from the European Commission,

After transmission of the draft legislative act to the national parliaments,

Having regard to the opinion of the European Economic and Social Committee 14 ,

Having regard to the opinion of the Committee of the Regions 15 ,

Acting in accordance with the ordinary legislative procedure,

Whereas:

(1)In accordance with Article 168(1), first subparagraph, of the Treaty on the Functioning of the European Union (TFEU) and Article 35 of the Charter of Fundamental Rights of the European Union, a high level of human health protection is to be ensured in the definition and implementation of all Union policies and activities.

(2)Article 168(4), point (a), TFEU provides that the European Parliament and the Council should adopt measures setting high standards of quality and safety for organs and substances of human origin (SoHOs), blood and blood derivatives. At the same time, Member States cannot be prevented from maintaining or introducing more stringent protective measures. Pursuant to Article 193 TFEU, Member States are to notify the Commission of any such measures. According to Article 168(7) TFEU, the measures adopted pursuant to Article 168(4), point (a) should not affect national provisions on the donation or medical use of organs and blood.

(3)As regards Article 168(4), point (a), TFEU, standards for the safety and quality of organs and SoHOs, blood and blood derivatives should ensure a high level of human health protection. Therefore, this Regulation aims at setting high standards by ensuring, amongst others, the protection of SoHO donors, taking into consideration their fundamental role in the provision of SoHOs and for recipients, as well as measures to monitor and support the sufficiency of the supply of SoHOs that are critical for the health of patients.

(4)Directives 2002/98/EC 16  and 2004/23/EC 17  of the European Parliament and of the Council constitute the Union’s regulatory framework for blood and for tissues and cells, respectively. Although these Directives have harmonised to a certain degree the rules of Member States in the area of safety and quality of blood, tissues and cells, they include a significant number of options and possibilities for Member States to implement the rules they laid down. This results in divergences between national rules, which can create obstacles to cross-border sharing of these substances. A fundamental revision of those Directives is needed for a robust, transparent, up-to-date and sustainable regulatory framework for these substances, which achieves safety and quality for all parties involved, enhances legal certainty and supports continuous supply, whilst facilitating innovation for the benefit of public health. In order to achieve a coherent application of the legal framework, it is appropriate to repeal Directives 2002/98/EC and 2004/23/EC and to replace them by a Regulation.

(5)Directives 2002/98/EC and 2004/23/EC are highly interconnected and contain very similar provisions for oversight and equivalent principles for safety and quality in the two sectors they regulate. In addition, many authorities and operators work across these sectors. As this Regulation aims to define high level principles that will be common to both the blood and of tissues and cells sectors, it would be appropriate that it replaces these Directives and merges the revised provisions into one legal act. 

(6)This Regulation should apply to blood and blood components, as regulated by Directive 2002/98/EC, as well as to tissues and cells, including haematopoietic peripheral blood, umbilical-cord blood and bone-marrow stem cells, reproductive cells and tissues, foetal tissues and cells and adult and embryonic stem cells, as regulated by Directive 2004/23/EC. Since donation and human application of SoHOs other than blood, tissues and cells are increasingly common, it is necessary to extend the scope of this Regulation to any SoHO, regardless of whether it meets the definition of ‘blood’, ‘tissue’ or ‘cell’, to avoid that certain groups of donors or recipients are not protected by an appropriate Union level quality and safety framework. This will, for example, ensure the protection of donors and recipients of human breast milk, intestinal microbiota, blood preparations that are not used for transfusion, and any other SoHO that may be applied to humans in the future.

(7)Solid organs are excluded from the definition of SoHOs for the purposes of this Regulation and, thus, from its scope. Their donation and transplantation are significantly different and are regulated in a dedicated legal framework, set out in Directive 2010/53/EU 18 of the European Parliament and of the Council. Shortcomings have not been raised regarding the existing quality and safety provisions for organs. Nonetheless, when organs are removed from a donor for the purposes of separating tissues or cells for human application, for example heart valves from a heart or pancreatic islets from a pancreas, this Regulation should apply.

(8)Ensuring the quality and safety of SoHOs is crucial, especially where such substances interact with the body of the recipient. Hence, this Regulation should not cover the placing of a substance on the body when it does not have any biological or physiological interaction with that body, such as in the case of wigs made from human hair.

(9)All SoHOs that are intended to be applied to humans fall within the scope of this Regulation. SoHOs can be prepared and stored in a variety of ways, becoming SoHO preparations, which can be applied to recipients. In these circumstances, this Regulation should apply to all activities from donor recruitment to human application and outcome monitoring. SoHOs or SoHO preparations can also be used to manufacture products regulated by other Union legislation, or as the starting and raw material thereof, in particular on medical devices, regulated by Regulation (EU) 2017/745 of the European Parliament and of the Council 19 , on medicinal products, regulated by Directive 2001/83/EC of the European Parliament and of the Council 20 and by Regulation (EC) No 726/2004 of the European Parliament and of the Council 21 , including on advanced therapy medicinal products, regulated by Regulation (EC) No 1394/2007 of the European Parliament and of the Council 22 , or on food, regulated by Regulation (EC) No 1925/2006 of the European Parliament and of the Council 23 . The criteria that define when SoHOs or SOHO preparations become products regulated under other Union legislation are not defined in this Regulation but are defined in those other acts. In addition, this Regulation should apply without prejudice to Union legislation on genetically modified organisms.

(10)When SoHOs are used in the autologous setting without any manipulation, processing or storage, the application of this Regulation would not be proportionate to the limited quality and safety risks arising in such a setting. When autologous SoHOs are collected and processed before being re-used in the same person, risks appear that should be mitigated. Thus, there needs to be an assessment and authorisation of the processes applied to ensure that they are demonstrated to be safe and effective for the recipient. When autologous SoHOs are collected to be processed and also stored, risks of cross-contamination, loss of traceability or damage to the biological properties inherent to the substance, and necessary for efficacy in the recipient, also appear. Thus, the requirements for SoHO establishment authorisation should apply. 

(11)When SoHOs are used to manufacture products regulated by other Union legislation, or as the starting and raw material thereof, in order to ensure a high level of protection and contribute to legal clarity and certainty, this Regulation should apply to the extent that the activities to which they are subjected are not regulated by the other Union legislative framework. Without prejudice to other Union legislation, and in particular to Directive 2001/83/EC, Regulations (EC) No 726/2004, (EC) No 1925/2006, (EC) No 1394/2007 and (EU) 2017/745, this Regulation should at least apply to the recruitment and selection of donors, donation, collection and donor testing as well as to release, distribution, import and export when those activities concern SoHOs up to the point of their transfer to operators regulated by other Union legislation. This means that close interaction between this regulatory framework and other related frameworks is essential to ensure interplay and coherence between relevant legal frameworks, without gaps or overlaps. 

(12)SoHOs can also be combined with other regulated products before human application. In these circumstances, close interaction between this regulatory framework and other related frameworks is also necessary to ensure a high level of human health protection for all cases where these substances are used.

(13)Given the special nature of SoHOs, resulting from their human origin, and the increasing demands for these substances for human application or for the manufacture of products regulated by other Union legislation, or as the starting and raw material thereof, it is necessary to ensure a high level of health protection for donors as well as for recipients. SoHOs should be obtained from individuals whose health status is such that no detrimental effects will ensue as a result of the donation. This Regulation should therefore include principles and technical rules to monitor and protect donors. As different types of donation imply different risks for donors, with varying levels of significance, the monitoring of donor health should be proportionate to those levels of risk. This is particularly important when donation involves some risk to the donor’s health due to a need for pre-treatment with medicinal products, a medical intervention to collect the substance or a need for donors to donate repeatedly. Donations of oocytes, bone marrow, peripheral blood stem cells and plasma should be considered to imply a significant risk.

(14)When a harmful genetic condition is detected in the offspring resulting from medically assisted reproduction with third party donation, the transmission of that information enables the prevention of further use of donations affected by that genetic risk. It is thus important that relevant information in such cases is effectively communicated between SoHO entities and acted upon appropriately.

(15)This Regulation does not prevent Member States from maintaining or introducing more stringent protective measures that are compatible with Union law. Member States should notify the Commission of any such measures. More stringent protective measures put in place by Member States should be evidence-based and proportionate to the risk to human health, for example based on overall safety concerns and corresponding risks in a Member State or specific local risks. They should not discriminate against persons on grounds of sex, racial or ethnic origin, religion or belief, disability, age or sexual orientation, unless that measure or its application is objectively justified by a legitimate aim, and the means of achieving that aim are appropriate and necessary. 

(16)This Regulation should not interfere with national legislation in the health area with objectives other than quality and safety of SoHOs that is compatible with Union law, in particular legislation concerning ethical aspects. Such aspects arise due to the human origin of the substances, which touches upon various sensitive and ethical concerns for Member States and citizens, such as access to particular services that use SoHOs. This Regulation should also not interfere with decisions of an ethical nature made by Member States. Such ethical decisions might concern the use, or limitation of the use, of specific types of SoHOs or specific uses of SoHOs, including reproductive cells and embryonic stem cells. When a Member State allows the use of such cells, this Regulation should apply in full with a view to ensuring safety and quality and to protecting human health.

(17)This Regulation is not meant to cover research using SoHOs when that research does not involve application to the human body, for example in vitro research or research in animals. However, human substances used in research involving studies where they are applied to the human body should comply with the rules laid down in this Regulation. 

(18)As a matter of principle, programmes promoting the donation of SoHOs should be founded on the principle of voluntary and unpaid donation, altruism of the donor and solidarity between donor and recipient. Voluntary and unpaid SoHO donation is also a factor which can contribute to high safety standards for SoHOs and therefore to the protection of human health. It is also recognised, including by the Council of Europe  Committee on Bioethics 24 , that while financial gain should be avoided, it may also be necessary to ensure that donors are not financially disadvantaged by their donation. Thus, compensation to remove any such risk is acceptable but should never constitute an incentive that would cause a donor to be dishonest when giving their medical or behavioural history or to donate more frequently than is allowed, posing risks to their own health and to that of prospective recipients. Such compensation should, therefore, be set by national authorities, at a level appropriate in their Member State to reach such objectives. 

(19)In order to maintain public trust in SoHO donation and use programmes, information that is given to prospective donors, recipients or physicians regarding the likely use and benefits of particular SoHOs or SoHO preparations when applied to recipients should accurately reflect reliable scientific evidence. This should ensure that donors, or their families, are not coerced to donate by exaggerated descriptions of benefits and prospective patients are not given false hopes when making decisions on their options for treatment. The verification of compliance with this Regulation through supervisory activities is of fundamental importance to ensure that, across the Union, the objectives of the Regulation are effectively achieved. The responsibility to enforce this Regulation lies with the Member States, whose competent authorities should monitor and verify, through the organisation of supervisory activities, that relevant Union requirements are effectively complied with and enforced. 

(20)Competent authorities should be designated by the Member States for all the areas that fall within the scope of this Regulation. While Member States are best placed to identify the competent authority or authorities for each area, for example by geography, topic or substance, they should also be required to designate a single national authority that ensures appropriately coordinated communication with other Member States’ competent authorities and with the Commission. The SoHO National Authority should be considered the same as the designated competent authority in Member States where only one competent authority is designated.

(21)For the performance of supervisory activities aimed at verifying the correct application of SoHO legislation, Member States should designate competent authorities that act independently and impartially. It is therefore important that their function of oversight is separate and independent from the performance of SoHO activities. In particular, competent authorities should be free from undue political influence and from industry interference that might affect their operational impartiality.

(22)For the performance of supervisory activities aimed at verifying the correct application of SoHO legislation, Member States should designate competent authorities that act in the public interest, are appropriately resourced and equipped, and offer guarantees of impartiality, professionalism and transparency. When infringements relate to direct health risks, and the publication of information regarding those infringements can contribute to risk mitigation and the protection of donors, recipients or offspring from medically assisted reproduction, competent authorities should, where necessary, be able to prioritise transparency of their enforcement activities over the protection of confidentiality of the party that has infringed the Regulation. 

(23)The correct application and enforcement of the rules falling within the scope of this Regulation require an appropriate knowledge of those rules. It is therefore important that the staff performing supervisory activities have an appropriate professional background and are regularly trained, in accordance with their area of competence, on the obligations resulting from this Regulation. 

(24)When there is doubt about the regulatory status of a particular substance, product or activity under this Regulation, competent authorities should consult with the relevant authorities responsible for other relevant regulatory frameworks, namely medicinal products, medical devices, organs or food, with the aim of ensuring coherent procedures for the application of this Regulation. Competent authorities should inform the SoHO Coordination Board of the outcome of their consultations. When SoHOs or SoHO preparations are used to manufacture products regulated under other Union legislation, or as the starting and raw material thereof, competent authorities should cooperate with the relevant authorities on their territory. This cooperation should aim to reach an agreed approach for any subsequent communications between the authorities responsible for SoHO and for the other relevant sectors, as needed, regarding authorisation and monitoring of the SoHOs or the product manufactured from SoHOs. It should in principle be the responsibility of the Member States to decide on a case-by-case basis on the regulatory status of a substance, product or activity. However, in order to ensure consistent decisions across all Member States with regard to borderline cases, the Commission should be empowered to, on its own initiative or at the duly substantiated request of a Member State, decide on the regulatory status of a particular substance, product or activity under this Regulation. 

(25)Competent authorities should perform supervisory activities regularly, on the basis of a risk assessment and with appropriate frequency, on entities and activities governed by this Regulation. The frequency of supervisory activities and the mode, whether on-site or by remote document review, should be established by the competent authorities, having regard to the need to adjust the control effort to the risk and to the level of compliance expected in the different situations, including the possible violations of this Regulation perpetrated through fraudulent or other illegal practices and previous compliance history. Accordingly, the likelihood of non-compliance with all the areas of this Regulation should be taken into account when scheduling supervisory activities.

(26)Commission experts should be able to perform controls, including audits, in Member States to verify the effective application of the relevant requirements of competent authorities and of the supervisory activity systems. Commission controls should also serve to investigate and collect information on enforcement practices or problems, emergencies and new developments in Member States. Official controls should be performed by personnel who are independent, free from any conflict of interest and in particular who are not in a situation which, directly or indirectly, could affect their ability to carry out their professional duties in an impartial manner.

(27)Since SoHO preparations are subjected to a series of SoHO activities prior to their release and distribution, competent authorities should assess and authorise SoHO preparations to verify that a high level of safety, quality and efficacy is achieved consistently by the application of that specific series of activities, performed in that specific manner. When SoHOs are prepared with newly developed and validated collection, testing or processing methods, consideration should be given to the demonstration of safety and efficacy in recipients by means of requirements for clinical outcome data collection and review. The extent of such required clinical outcome data should correlate with the level of risk associated with the activities performed for that SoHO preparation and use. Where a new or modified SoHO preparation poses negligible risks for recipients (or offspring in the case of medically assisted reproduction), the vigilance reporting requirements provided for in this Regulation should be adequate to demonstrate safety and quality. This should apply for well-established SoHO preparations that are introduced in a new SoHO entity but have been robustly demonstrated as safe and effective by their use in other entities.

(28)With regard to SoHO preparations that pose a certain level of risk (low, moderate or high), the applicant should propose a plan for clinical outcome monitoring that should fulfil different requirements appropriate to the risk indicated. The most up-to-date guidance of the European Directorate for the Quality of Medicines & HealthCare (EDQM, a Directorate of the Council of Europe) should be considered relevant in the design of clinical follow-up studies proportionate in extent and complexity to the identified level of risk of the SoHO preparation. In the case of low risk, in addition to the mandatory continuous vigilance reporting, the applicant should organise proactive clinical follow-up for a defined number of patients. For moderate and high risk, in addition to the mandatory vigilance reporting and the clinical follow-up, the applicant should propose clinical investigation studies with monitoring of pre-defined clinical end-points. In case of high risk, these should include a comparison with standard treatments, ideally in a study with subjects allocated to test and control groups in a randomised manner. The competent authority should approve the plans before they are implemented and should assess the outcome data as part of a SoHO preparation authorisation. 

(29)In the interests of efficiency, it should be permitted to conduct clinical outcome studies using the established framework in the pharmaceutical sector for clinical trials, as set out in Regulation (EU) No 536/2014 of the European Parliament and of the Council 25 , when operators wish to do so. Whilst applicants can choose to record the clinical data generated during the clinical outcome monitoring themselves, they should also be permitted to use existing clinical data registries as a means of such recording when those registries have been verified by the competent authority, or are certified by an external institution, in terms of the reliability of their data management procedures.

(30)In order to facilitate innovation and reduce administrative burden, competent authorities should share with each other information on the authorisation of new SoHO preparations and the evidence used for such authorisations, including for the validation of certified medical devices used for SoHO collection, processing, storage or application to patients. Such sharing could allow authorities to accept previous authorisations granted to other entities, including in other Member States and to thus significantly reduce the requirements to generate evidence.

(31)A broad range of public and private organisations influence the safety, quality and efficacy of SoHOs, even if they do not maintain banks of those SoHOs. Many organisations carry out a single SoHO activity, such as collection or donor testing on behalf of one or many organisations that maintain banks of SoHOs. The SoHO entity concept includes this broad range of organisations, from donor registries to physicians that apply SoHOs to recipients or use SoHO processing devices at the recipient’s bedside. The registration of all such SoHO entities should ensure that competent authorities have a clear overview of the field and its scale and can take enforcement action when deemed necessary. A SoHO entity registration should refer to the legal entity, regardless of the number of physical sites associated with the entity.

(32)Competent authorities should review the SoHO entities registered in their territory and ensure that those entities that carry out both processing and storage of SoHOs are inspected and authorised as SoHO establishments before starting those activities. A SoHO establishment authorisation should refer to the legal entity, even when one SoHO establishment has many physical sites. Competent authorities should consider the impact on safety, quality and efficacy of the SoHO activities carried out at SoHO entities that do not meet the definition of a SoHO establishment and decide whether particular entities should be subject to establishment authorisations due to the risk or scale associated with their activities. Similarly, SoHO entities that have a poor record in terms of compliance with reporting or other obligations might be suitable candidates for authorisation as SoHO establishments.

(33)With regards to standards concerning donor, recipient and offspring protection, this Regulation should provide for a hierarchy of rules for their implementation. As risks and technologies change, this hierarchy of rules should facilitate an efficient and responsive uptake of the most up-to-date guidelines for implementing the standards set out in this Regulation. As part of that hierarchy, in the absence of Union legislation describing particular procedures to be applied and followed to meet the standards set out in this Regulation, following the guidelines of the European Centre for Disease Prevention and Control (ECDC) and the EDQM should be considered as a means to demonstrate compliance with the standards laid down in this Regulation to ensure high level of quality, safety and efficacy. SoHO entities should be permitted to follow other guidelines, provided that it has been demonstrated that those other guidelines achieve the same level of quality, safety and efficacy. In cases of detailed technical issues for which neither Union legislation nor the ECDC and the EDQM have defined a technical guideline or rule, operators should apply a locally defined rule that is in line with relevant internationally recognised guidelines and scientific evidence and is appropriate to mitigate any risk identified. 

(34)Where evidence demonstrates that specific processing steps reduce or eliminate the risk of transmission of specific infectious or non-infectious disease agents, the quality and safety standards for the verification of donor eligibility by means of donor health evaluations, including testing, and the related guidelines for their implementation, should take this evidence into account. Thus, in the case of, for example, plasma for fractionation, that in a subsequent step in the manufacturing process of medicinal products undergoes sterilisation steps, certain donor eligibility criteria used for donation of plasma for transfusion might not be necessary nor appropriate.

(35)The EDQM is a structural part of the Council of Europe working under the European Pharmacopoeia Partial Agreement. The text of the Convention on the elaboration of a European Pharmacopoeia (ETS No. 050), accepted by Council Decision 94/358/EC 26 , is considered to be the text of the European Pharmacopoeia Partial Agreement. Member States of the Council of Europe that have signed and ratified the European Pharmacopoeia Convention are the member States of the European Pharmacopoeia Partial Agreement and are therefore the members of the intergovernmental bodies functioning within the framework of this partial agreement, including among others: the European Pharmacopoeia Commission, the European Committee on Organ Transplantation (CD-P-TO), the European Committee on Blood Transfusion (CD-P-TS) and the European Committee on Pharmaceuticals and Pharmaceutical Care (CD-P-PH). The European Pharmacopoeia Convention has been signed and ratified by the European Union and all its Member States, all of whom are represented in their intergovernmental bodies. In this context, the work of the EDQM on developing and updating guidelines on safety and quality of blood, tissues and cells, should be considered an important contribution to the field of SoHOs in the Union and should be reflected in this Regulation. The guidelines address issues of quality and safety beyond the risks of communicable disease transmission, such as donor eligibility criteria for the prevention of the transmission of cancer and other non-communicable diseases and the assurance of safety and quality during collection, processing, storage and distribution.  It should therefore be possible to use those guidelines as one of the means to implement the technical standards provided for in this Regulation.

(36)The ECDC, established by Regulation (EC) No 851/2004 of the European Parliament and of the Council 27 , is a Union agency with the mission of strengthening Europe's defences against communicable diseases. The work of the ECDC on developing and updating guidelines on safety and quality of SoHOs from a communicable disease threat perspective, should be considered an important contribution in the field of SoHOs in the Union and should be reflected in this Regulation. In addition, the ECDC established an expert network for the Microbial Safety of SoHOs, which ensures the implementation of the requirements on the ECDC’s relations with the Union Member States and EEA Member States stated in Regulation (EC) No 851/2004, regarding strategic and operational collaboration on technical and scientific issues, surveillance, responses to health threats, scientific opinions, scientific and technical assistance, collection of data, identification of emerging health threats, and public information campaigns related to the safety of SoHOs. This SoHO expert network should provide information or advice in relation to relevant outbreaks of communicable diseases, in particular regarding the eligibility and testing of donors and the investigation of serious adverse occurrences involving suspected transmission of a communicable disease. 

(37)It is necessary to promote information and awareness campaigns at national and Union level on the importance of SoHOs. The aim of these campaigns should be to help European citizens to decide whether to become donors during their lifetime and let their families or legal representatives know their wishes regarding donation after death. As there is a need to ensure the availability of SoHOs for medical treatments, Member States should promote the donation of SoHOs, including plasma, of high quality and safety, thereby also increasing self-sufficiency in the Union. Member States are also urged to take steps to encourage a strong public and non-profit sector involvement in the provision of SoHO services, in particular for critical SoHOs and the related research and development.

(38)In order to promote a coordinated application of this Regulation, a SoHO Coordination Board (SCB) should be set up. The Commission should participate in its activities and chair it. The SCB should contribute to a coordinating the application of this Regulation throughout the Union, including by helping Member States to conduct SoHO supervisory activities. The SCB should be composed of persons designated by the Member States based on their role and expertise in their competent authorities, and should also involve experts that are not working for competent authorities, for specific tasks where access to necessary in-depth technical expertise in the field of SoHOs is required. In the latter case, appropriate consideration should be given to the possibility of involving European expert bodies such as the ECDC and the EDQM and existing professional, scientific and donor and patient representative groups at Union level in the field of SoHOs.

(39)Some substances, products or activities have been subject to different legal frameworks with different requirements in the Member States. This causes confusion among operators in the field, and the consequent legal uncertainty is a disincentive to professionals to develop new ways to prepare and use SoHOs. The SCB should receive relevant information on national decisions made on cases where questions were raised on the regulatory status of SoHOs. The SCB should keep a compendium of the opinions issued by the SCB or the competent authorities and of decisions made at Member State level, so that competent authorities considering the regulatory status under this Regulation of a particular substance, product or activity may inform their decision-making process by referring to that compendium. The SCB should also document agreed best practices to support a common Union approach. It should also cooperate with similar Union level bodies established in other Union legislation with a view to facilitating coordinated and coherent application of this Regulation between Member States and across bordering legislative frameworks. These measures should promote a coherent cross-sectoral approach and facilitate SoHO innovation.

(40)The concept of a plasma master file (PMF) was established in Commission Directive 2003/63/EC 28 . Since that Directive provided for a specific regulatory role for the European Medicines Agency (EMA) in relation to authorisation of plasma for fractionation, the SCB should also collaborate with the relevant EMA expert working groups to exchange experience and good practices so that criteria for the eligibility of donors of plasma for fractionation and of donors of blood for transfusion are implemented by Member States in a consistent and coherent way.

(41)In order to limit administrative burden on competent authorities and the Commission, the latter should establish an online platform (the ‘EU SoHO Platform’) to facilitate timely submission of data and reports as well as improved transparency of national reporting and supervisory activities.

(42)The processing of personal data under this Regulation should be subject to strict guarantees of confidentiality and should comply with the rules on the protection of personal data laid down in Regulation (EU) 2016/679 of the European Parliament and of the Council and in Regulation (EU) 2018/1725 of the European Parliament and of the Council .

(43)As the EU SoHO Platform requires the processing of personal data, it will be designed respecting the principles of data protection. Any processing of personal data should be limited to achieving the objectives and obligations of this Regulation. Access to the EU SoHO Platform should be limited to the extent necessary to carry out supervisory activities provided for in this Regulation.

(44)This Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter of Fundamental Rights of the European Union and in particular human dignity, the integrity of the person, the protection of personal data, the freedom of art and science and to conduct business, non-discrimination, the right to health protection and access to health care, and the rights of the child. To achieve these aims, all supervisory and SoHO activities should always be carried out in a manner that fully respects those rights and principles. The right for dignity and integrity of donors, recipients and of offspring born from medically assisted reproduction should always be taken into account, amongst others, by ensuring that consent for donation is freely given and donors or their representatives are informed with regards to the intended use of the donated material, that donor eligibility criteria are based on scientific evidence, that the use of SoHOs in humans is not promoted for commercial purposes or with false or misleading information regarding efficacy so that the donors and recipients can make well-informed and deliberate choices, that activities are conducted in a transparent manner that prioritises the safety of donors and recipients, and that allocation and equitable access to SoHOs are defined in a transparent manner, on the basis of an objective evaluation of medical needs. This Regulation should therefore be applied accordingly. 

(45)SoHOs, by definition, relate to persons, and there are circumstances where the processing of personal data relating to donors and recipients may be necessary to achieve the objectives and requirements of this Regulation, especially provisions relating to vigilance and communication between competent authorities. This Regulation should provide a legal basis under Article 6 and, where relevant, fulfil the conditions under Article 9(2), point (i), of Regulation (EU) 2016/679 for processing of such personal data. With respect to personal data processed by the Commission, this Regulation should provide a legal basis under Article 5 and, where relevant, fulfil the conditions under Article 10(2), point (i), of Regulation (EU) 2018/1725. Data on safety and efficacy of new SoHO preparations in recipients should also be shared, with appropriate protective measures, to allow aggregation at Union level for more robust evidence gathering on the clinical efficacy of SoHO preparations. For all data processing, such processing should be necessary and appropriate with a view to ensuring compliance with this Regulation in order to protect human health. Data on donors, recipients and offspring should hence be limited to the minimum necessary and pseudonymised. donors, recipients and offspring should be informed of the processing of their personal data in line with the requirements of Regulations (EU) 2016/679 and (EU) 2018/1725, and in particular as provided for under this Regulation, including the possibility of exceptional cases where circumstances require such processing.

(46)In order to enable better access to health data in the interests of public health, Member States should entrust competent authorities as data controllers within the meaning of Regulation (EU) 2016/679 with powers to take decisions on the access to and re-use of such data. 

(47)The exchange of SoHOs between Member States is necessary for ensuring optimal patient access and sufficiency of supply, particularly in the case of local crises or shortages. For certain SoHOs that need to be matched between the donor and the recipient, such exchanges are essential to allow patients to receive the treatment they need. In this context, the objective of this Regulation, namely to ensure quality and safety of SoHOs and a high level of protection of donors, needs to be achieved at Union level, by establishing high standards of quality and safety for SoHOs, based on a common set of requirements that are implemented in a consistent manner across the Union. Thus, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve that objective. 

(48)In order to be able to supplement this Regulation where necessary with additional standards concerning the protection of donors, recipients and offspring from medically assisted reproduction to take into account technical and scientific developments in the field of SoHOs, and with additional rules on the authorisation of importing SoHO entities, on obligations and procedures for importing SoHO entities, on the organisation of Union training and exchange programmes, on technical specifications concerning the EU SoHO Platform, and on data protection, the power to adopt acts in accordance with Article 290 TFEU should be delegated to the Commission. It is of particular importance that the Commission carries out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making 29 . In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member States' experts, and their experts systematically have access to meetings of Commission expert groups dealing with the preparation of delegated acts.

(49)In order to ensure uniform conditions for the implementation of this Regulation regarding the authorisation system for importing SoHO entities, the application for importing SoHO entity authorisations, the activity data collection and reporting by SoHO entities, the European coding system, the establishment, management and functioning of the SCB, and the general functionalities of the EU SoHO Platform, implementing powers should be conferred on the Commission. 

(50)In order to ensure uniform conditions for the implementation of this Regulation, including the determination of the regulatory status of a substance, product or activity, rules and practical arrangements in respect of the consultation and cooperation with competent authorities of other regulatory sectors, the national registers of SoHO entities, the registration process of SoHO entities, the SoHO preparation authorisation system and the authorisation of SoHO preparations, the SoHO establishment authorisation system, the inspections of SoHO establishments, the consultation and coordination related to vigilance, the quality management system for SoHO establishments, the implementation of the standards concerning the protection of donors, recipients and offspring from medically assisted reproduction, the national SoHO emergency plans, the tasks of the SoHO Coordination Board, and the transitional provisions concerning SoHO preparations, implementing powers should be conferred on the Commission. Those powers should be exercised in accordance with Regulation (EU) No 182/2011 of the European Parliament and of the Council 30 .  

(51)Transitional provisions should be laid down in order to ensure a smooth transition from the former regimes for tissues and cells and for blood and blood components to this new Regulation, in particular in order to adapt practices to the new requirements, the changes in SoHO entities, SoHO establishments and SoHO preparations, and to avoid that donated SoHOs are discarded unnecessarily. A transitional regime for establishments already designated, authorised, accredited or licensed before the date of application of this Regulation should be introduced to ensure legal certainty and clarity. In particular, there should be clarity for the establishments concerned as regards their registration and authorisation status as well as their tasks and responsibilities under this Regulation, whilst allowing competent authorities additional time to transfer the relevant information to the systems introduced by this Regulation. To allow for a smooth transition, it is also appropriate that those preparation processes already authorised and lawfully used under the former regimes are still valid, and that SoHOs already collected and stored before the date of application of this Regulation may be used for a certain period of time. The European Data Protection Supervisor was consulted in accordance with Article 42(1) of Regulation (EU) 2018/1725 and delivered an opinion on … [date of the opinion] 31 , 

HAVE ADOPTED THIS REGULATION:

CHAPTER I

GENERAL PROVISIONS

Article 1

Subject matter

This Regulation establishes measures setting high standards of quality and safety for all substances of human origin (‘SoHOs’) intended for human application and for activities related to those substances in order to ensure a high level of human health protection, in particular for SoHO donors, SoHO recipients and offspring from medically assisted reproduction. This Regulation is without prejudice to national legislation which establishes rules relating to aspects of SoHOs other than their quality and safety and the safety of SoHO donors.

Article 2

Scope

1.This Regulation shall apply to SoHOs intended for human application, to SoHO preparations, to products manufactured from SoHOs and intended for human application, to SoHO donors and recipients, and to the following SoHO activities:

(a)SoHO donor recruitment;

(b)SoHO donor history review and eligibility assessment;

(c)SoHO testing of donors for eligibility or matching purposes;

(d)collection of SoHOs from donors or patients;

(e)processing of SoHOs;

(f)quality control testing of SoHOs;

(g)storage of SoHOs;

(h)SoHO release;

(i)distribution of SoHOs;

(j)import of SoHOs;

(k)export of SoHOs;

(l)human application of SoHOs;

(m)SoHO clinical outcome monitoring. 

2.In cases of autologous use of SoHOs where:

(a)SoHOs are processed and stored before application, this Regulation shall apply in full;

(b)SoHOs are processed and not stored before application, only the provisions on vigilance referred to in Article 35, on SoHO rapid alerts referred to in Article 36, on SoHO entity registration referred to in Article 37, on SoHO preparation authorisation referred to in Article 40,  and on activity data collection and reporting referred to in Article 44 shall apply; 

(c)SoHOs are not processed and not stored before application, this Regulation shall not apply.

3.For SoHOs that are used to manufacture products in accordance with Union legislation on medical devices, regulated by Regulation (EU) 2017/745, on medicinal products, regulated by Regulation (EC) No 726/2004 and Directive 2001/83/EC, including on advanced therapy medicinal products, regulated by Regulation (EC) No 1394/2007, or on food, regulated by Regulation (EC) No 1925/2006, or as the starting and raw material thereof, the provisions of this Regulation applicable to the activities of 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 shall apply. Insofar as the activities of SoHO release, distribution, import and export relate to SoHOs prior to their distribution to an operator regulated by the other Union legislation referred to in this subparagraph, the provisions of this Regulation shall also apply.

By way of derogation from the first subparagraph, in cases where SoHOs, SoHO preparations, or products manufactured from SoHO, as referred to in that subparagraph, are exclusively for autologous use, only those provisions of this Regulation that concern the collection of SoHOs from patients shall apply.

4.Where non-viable SoHOs or their derivatives, as defined in Article 2, point (17), of Regulation (EU) 2017/745, incorporate, as an integral part, a medical device, and where the action of the non-viable SoHOs or their derivatives is principal and not ancillary to that of the device, the non-viable SoHOs or their derivatives shall be governed by this Regulation. If the action of the non-viable SoHOs or their derivatives is ancillary to that of the device and not principal, the provisions of this Regulation, insofar as they concern donor recruitment, donor history review and eligibility assessment, testing of donors for eligibility or matching purposes, collection of SoHOs from donors or patients, shall apply.

Article 3

Definitions 

For the purpose of this Regulation the following definitions shall apply:

(1)‘blood’ means the liquid that circulates in arteries and veins carrying oxygen to and carbon dioxide from the tissues of the body;

(2)‘blood component’ means a constituent of blood such as red cells, white cells, platelets and plasma, that can be separated from it; 

(3)‘cell’ means a mass of cytoplasm with or without a nucleus, that is bound externally by a cell membrane. Usually microscopic in size, cells are the smallest structural and functional unit of an organism;

(4)‘tissue’ means a group of cells that function together as a unit;

(5)‘substance of human origin’ (SoHO) means any substance collected from the human body in whatever manner, whether it contains cells or not and whether those cells are living or not. For the purposes of this Regulation, SoHO does not include organs in the sense of Article 3, point (h), of Directive 2010/53/EU;

(6)‘human application’ means inserted, implanted, injected, infused, transfused, transplanted, ingested, transferred (as in transfer to the uterus or fallopian tube of a woman), inseminated or otherwise added to the human body in order to create a biological, mechanical or physiological interaction with that body;

(7)‘SoHO activity’ means an action, or series of actions, that has a direct impact on the safety, quality or efficacy of SoHOs, as listed in Article 2(1);

(8)‘SoHO donor’ means any person who has presented themselves to a SoHO entity with a view to making a donation of SoHOs, whether that donation is successful or not;

(9)‘SoHO recipient’ means the person to whom SoHOs are applied;

(10)‘medically assisted reproduction’ means the facilitation of conception by intra-uterine insemination of sperm, in vitro fertilisation or any other laboratory or medical intervention that promotes conception;

(11)‘offspring from medically assisted reproduction’ means fetuses and children that are born following medically assisted reproduction; 

(12)‘SoHO preparation’ means a particular type of SoHO that:

(a)has been subjected to one or more SoHO activities, including processing, in accordance with defined quality and safety parameters;

(b)meets a pre-defined specification; and

(c)is intended for application to a recipient for a specific clinical indication or is intended for distribution for manufacture of a product regulated by other Union legislation, or as the starting and raw material thereof;

(13)‘donor recruitment’ means any activity aimed at encouraging persons to become SoHO donors;

(14)‘collection’ means a process by which SoHOs are removed, procured, excreted, secreted or obtained by any other manner, including any preparatory steps, such as hormone treatment, needed to facilitate the process;

(15)‘processing’ means any operation involved in the handling of SoHOs, including washing, shaping, separation, fertilisation, decontamination, sterilisation, preservation and packaging;

(16)‘quality control’ means several tests or checks to confirm that a SoHO activity or SoHO preparation meets pre-defined quality criteria; 

(17)‘storage’ means the maintenance of SoHOs under appropriate controlled conditions until distribution;

(18)‘release’ means a process through which it is verified that a SoHO or a SoHO preparation meets defined safety and quality criteria and the conditions of any applicable authorisation before distribution;

(19)‘distribution’ means transportation and delivery, within the Union, of released SoHOs or SoHO preparations intended for human application or for the manufacture of products regulated under other Union legislation, or as the starting and raw material thereof, including within the same organisation when SoHOs are delivered from a SoHO entity to a unit responsible for human application;

(20)‘import’ means activities carried out to bring SoHOs or SoHO preparations into the Union from a third country, including the organisation of such activities and physical verification of coherence with associated documentation, the appropriateness of transport conditions, the integrity of packaging and the adequacy of labelling before release;

(21)‘export’ means distribution of SoHOs or SoHO preparations to third countries;

(22)‘clinical outcome monitoring’ means evaluation of the health of a SoHO recipient for the purpose of monitoring the results of a SoHO preparation application, maintaining care and demonstrating safety and efficacy;

(23)‘autologous use’ means collection of SoHO from one individual for subequent application to the same individual, with or without further SoHO activities between collection and application;

(24)‘SoHO entity’ means an organisation legally established in the Union that carries out one or more of the SoHO activities set out in Article 2(1);

(25)‘SoHO preparation authorisation’ means the formal approval by a competent authority of a SoHO preparation, including the approval of the chain of activities carried out to obtain the SoHO preparation;

(26)‘vigilance’ means a set of organised surveillance and reporting procedures relating to adverse occurrences;

(27)‘adverse occurrence’ means any incident that caused harm to a living SoHO donor, harm to a SoHO recipient or to offspring from medically assisted reproduction or that implied a risk of such harm; 

(28)‘serious adverse occurrence’ (SAO) means an adverse occurrence that resulted in, or implied a risk of, any of the following:

(a)death;

(b)life-threatening, disabling or incapacitating condition, including transmission of a pathogen that might cause such condition;

(c)transmission of a genetic condition to offspring from medically assisted reproduction with third party donation; 

(d)hospitalisation or prolongation of hospitalisation;

(e)the need for a clinical intervention to prevent any of the above;

(f)loss of a quantity of SoHOs that causes human applications to be postponed or cancelled;

(g)loss of highly matched or autologous SoHOs;

(h)a mix-up of reproductive cells in such a way that an oocyte is fertilised with sperm from an individual other than the intended individual or reproductive cells are inseminated or transferred to the uterus or fallopian tube of a woman other than the intended recipient;

(i)prolonged sub-optimal health of a SoHO donor following single or multiple donations;

(29)‘SoHO rapid alert’ means a communication regarding a SAO, a communicable disease outbreak or other information that might be of relevance to the safety and quality of SoHOs in more than one Member State and is to be transmitted rapidly between competent authorities and the Commission to facilitate the implementation of mitigating measures;

(30)‘non-viable’ means having no potential for metabolism or multiplication;

(31)‘EU SoHO Platform’ means the digital platform established by the Commission to exchange information concerning SoHO activities;

(32)‘SoHO supervisory activity’ means any activity as provided for in Chapter III performed by a competent authority or by a delegated body in order to verify and enforce compliance with this Regulation;

(33)‘the compendium’ means a list kept up-to-date by the SoHO Coordination Board of decisions, taken at Member State level, and opinions, issued by competent authorities and by the SCB, on the regulatory status of specific substances, products or activities and published on the EU SoHO platform;

(34)‘quality management system’ means a formalised system that documents processes, procedures, and responsibilities to support achieving defined quality standards in a consistent manner;

(35)‘delegated body’ means a legal body to which the competent authority has delegated certain SoHO supervisory activities in accordance with Article 6;

(36)‘audit’ means a systematic and independent examination to determine whether activities and the related results of such activities comply with legislation and planned arrangements and whether these arrangements are applied effectively and are suitable to achieve the objectives;

(37)‘inspection’ means a formal and objective control by a competent authority or delegated body to assess compliance with this Regulation and other relevant Union or national legislation and to identify the need for corrective or preventive action to achieve compliance;

(38)‘Union training’ means activities for the personnel of competent authorities and, where appropriate, for personnel of delegated bodies performing SoHO supervisory activities;

(39)‘assessors’ means personnel performing the assessment of SoHO preparations as referred to in Article 22;

(40)‘SoHO establishment’ means a SoHO entity that carries out both processing and storage of SoHOs;

(41)‘critical SoHO’ means a SoHO for which an insufficient supply will result in serious harm or risk of harm to patients;

(42)‘critical SoHO entity’ means a SoHO entity that carries out activities contributing to the supply of critical SoHOs and the scale of those activities is such that a failure to carry them out cannot be compensated by activities of other entities or alternative substances or products for patients; 

(43)‘conditional authorisation’ means the granting of permission by a competent authority to a SoHO entity to perform certain SoHO activities under specific conditions defined by that competent authority;

(44)‘on-site inspection’ means an inspection carried out at the premises of the SoHO establishment, or other SoHO entity, concerned;

(45)‘technical guidelines’ means a description of a series of methodological procedures and parameters that, if followed, achieve a level of quality and safety of a SoHO activity or a SoHO preparation that is considered to be acceptable as a means to comply with regulatory standards;

(46)‘joint inspection’ means an inspection carried out by inspectors from more than one Member State;

(47)‘traceability’ means the ability to locate and identify SoHOs during any step from collection through processing and storage to distribution or disposal, including the ability to:

(a)identify the SoHO donor and the SoHO entity processing or storing the SoHOs;

(b)identify the recipient at the SoHO entity applying the SoHOs to the recipient;

(c)locate and identify all relevant data relating to the safety and quality of the SoHOs and any materials coming into contact with those SoHOs; 

(48)‘Single European Code’ (SEC) means the unique identifier applied to certain SoHOs distributed in the Union;

(49)‘SAO notification’ means the communication from a SoHO entity, a SoHO establishment or a SoHO donor or recipient to a competent authority, of a serious adverse occurrence or a suspected serious adverse occurrence associated with a SoHO donation or human application;

(50)‘SAO investigation report’ means the report from a SoHO entity or a SoHO establishment to a competent authority on a specific SAO, describing the outcome and including an assessment of the seriousness and the level of imputability, the likely cause and any corrective action taken;

(51)‘imputability’ means the likelihood that a serious adverse occurrence, in a SoHO donor, is related to the donation process or, in a recipient, to the application of the SoHOs;

(52)‘seriousness’ means the degree of severity of an adverse occurrence, involving harm to a SoHO donor, recipient or offspring from medically assisted reproduction, at and above which the occurrence shall be notified to a competent authority;

(53)‘self-reporting’ means the notification of a SAO by a SoHO recipient or a SoHO donor directly to the competent authorities;

(54)‘Annual SoHO Vigilance Report’ means the annual report published by the Commission aggregating the summaries from the SoHO National Authorities on SAO notifications and SAO investigation reports received;

(55)‘deferral’ means temporary or permanent suspension of the eligibility of an individual to donate SoHO;

(56)‘responsible person’ means the nominated individual in a SoHO entity that has responsibility for SoHO release;

(57)‘process validation’ means establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce results meeting predetermined specifications and quality attributes;

(58)‘equipment qualification’ means establishing documented evidence that provides a high degree of assurance that a specific piece of equipment will consistently perform to predetermined specifications;

(59)‘EDQM SoHO monograph’ means a specification of the critical quality parameters of a particular SoHO preparation defined by the European Directorate for the Quality of Medicines and HealthCare of the Council of Europe;

(60)‘Annual SoHO Activity Report’ means the annual report published by the Commission aggregating the data reports from SoHO entities carrying out the following activities: donor recruitment, collection, distribution, import, export and human application of SoHOs;

(61)‘reproductive cells’ means all cells intended to be used for the purpose of medically assisted reproduction;

(62)‘third party donation’ means a donation of reproductive cells by a person to a person or a couple with whom the donor does not have an intimate physical relationship;

(63)‘within couple use’ means use of reproductive cells for medically assisted reproduction from two persons with an intimate physical relationship, where one person supplies their own oocytes and the other person supplies their own sperm;

(64)‘compensation’ means making good of any losses associated with donation;

(65)‘allogeneic use’ means collection of SoHO from one individual for subsequent application to another individual;

(66)‘SoHO supply alert’ means a communication regarding a significant interruption to the supply of critical SoHOs that is to be transmitted to a competent authority, and when necessary, by a SoHO National Authority to the competent authorities of other Member States;

(67)‘plasma master file’ (PMF) means a compilation of the required scientific data, covering all aspects of the use of plasma, from collection to the creation of a plasma pool, on the quality and safety of human plasma relevant to the medicinal products, medical devices and investigational products that use human plasma in their manufacture;

(68)‘plasma for transfusion’ means plasma separated from whole blood or collected by apheresis for the purpose of transfusion to a recipient;

(69)‘plasma for fractionation’ means plasma separated from whole blood or collected by apheresis and used as the starting material for manufacturing of plasma-derived medicinal products;

(70)‘apheresis’ means a process by which a specific blood component or type of stem cell is separated from whole blood during the donation, allowing the remaining blood components to be returned immediately to the donor.

Article 4

More stringent Member State measures

1.Member States may maintain or introduce within their territories measures that are more stringent than the ones provided for in this Regulation on condition that those national measures are compatible with Union law, and are proportionate to the risk to human health.

2.Member States shall make available to the public details of measures put in place in accordance with paragraph 1 without undue delay, including on the internet. The SoHO National Authority shall submit the details of any more stringent measure to the EU SoHO Platform referred to in Chapter XI.

CHAPTER II

COMPETENT AUTHORITIES

Article 5

Designation of competent authorities

1.Member States shall designate the competent authority or authorities to which they confer responsibility for the SoHO supervisory activities provided for in Chapter III. The organisation or organisations designated shall be independent from any SoHO entity.

2.For the same territory, a Member State may confer responsibilities for SoHO supervisory activities to more than one competent authority, at national, regional or local level.

3.Member States shall ensure that competent authorities:

(a)have the autonomy to act and make decisions independently and impartially while respecting the internal administrative organisational requirements determined by the Constitutions of the Member States;

(b)have the necessary powers:

(i)to properly perform their supervisory activities, including access to the premises of, and documents and samples kept by, SoHO entities and any third parties contracted by a SoHO entity;

(ii)to order the immediate suspension or cessation of a SoHO activity that poses immediate risk to SoHO donors, SoHO recipients or the general public;

(iii)to take decisions on the access and re-use of personal data;

(c)have sufficient resources, operational capacity, and expertise to achieve the aims of, and fulfil their obligations under, this Regulation;

(d)are governed by appropriate confidentiality obligations in accordance with Article 75.

4.Each Member State shall designate a single SoHO National Authority, in conformity with Member States’ constitutional requirements, responsible for coordinating exchanges with the Commission and with other Member States’ SoHO National Authorities.

5.Member States shall submit to the EU SoHO Platform referred to in Chapter XI:

(a)the names and contact details of the competent authorities designated pursuant to paragraph 1;  

(b)the names and contact details of their SoHO National Authority referred to in paragraph 4.

6.Member States shall update the EU SoHO Platform without undue delay with any changes to the information referred to in paragraph 5.

Article 6

Delegation by competent authorities of certain SoHO supervisory activities

1.Member States or competent authorities may delegate certain SoHO supervisory activities to one or more delegated bodies in accordance with the conditions provided for in Article 10. Member States or competent authorities shall ensure that delegated bodies have the powers needed to effectively perform any activities delegated to them. 

2.Where Member States or competent authorities decide to delegate certain SoHO supervisory activities to one or more delegated bodies, they shall submit information regarding such delegations to the EU SoHO Platform referred to in Chapter XI with details of the delegated supervisory tasks.

Article 7

Independence and impartiality

1.Competent authorities shall act independently, in the public interest and free from any external influence. 

2.Competent authorities shall ensure that their personnel have no direct or indirect economic, financial or personal interest that might be considered prejudicial to their independence and, in particular, that they are not in a situation that may, directly or indirectly, affect the impartiality of their professional conduct.

3.Paragraphs 1 and 2 shall also apply to delegated bodies.

Article 8

Transparency

1.Without prejudice to Article 75, competent authorities shall carry out their supervisory activities in a transparent manner and they shall make accessible and clear to the public decisions taken in cases where a SoHO entity has failed to comply with an obligation under this Regulation and where such failure causes or may cause a serious risk to human health.

2.Paragraph 1 shall not affect national legislation on access to information.

3.Competent authorities shall lay down practical arrangements for implementing the transparency rules referred to in paragraph 1 in their internal rules.

4.Paragraphs 1, 2 and 3 shall also apply to delegated bodies.

Article 9

General responsibilities and obligations

1.Competent authorities shall be responsible for the SoHO supervisory activities referred to in Chapter III in order to verify the effective compliance of SoHO entities in their territory with the requirements set out in this Regulation.

2.Competent authorities shall have in place:

(a)a sufficient number of suitably qualified personnel to carry out the supervisory functions provided for in this Regulation;

(b)procedures to ensure the independence, impartiality, effectiveness, quality, suitability for purpose and consistency of their SoHO supervisory activities;

(c)appropriate and properly maintained facilities and equipment to ensure that personnel can perform their SoHO supervisory activities efficiently and effectively;

(d)a quality management system for their SoHO supervisory activities that includes a plan for continuity of their activities in case of exceptional circumstances.

3.Paragraphs 1 and 2 shall also apply to delegated bodies.

Article 10

Conditions for delegating certain SoHO supervisory activities to delegated bodies

1.Member States and competent authorities that delegate certain SoHO supervisory activities to a delegated body referred to in Article 6 shall conclude a written agreement on the delegation.

2.Competent authorities shall ensure that the agreement referred to in paragraph 1 includes the following:

(a)a precise description of the SoHO supervisory activities that the delegated body is expected to perform, and the conditions under which those activities are expected to be performed;

(b)the conditions to be met by the delegated body, including that the delegated body:

(i)has the expertise, equipment and infrastructure required to perform those SoHO supervisory activities delegated to it;

(ii)has a sufficient number of suitably qualified and experienced staff;

(iii)participates in certification or other schemes at Union level, when available, to ensure the uniform application of principles of good practices required for their relevant sector;

(iv)has sufficient powers to perform the SoHO supervisory activities delegated to it;

(c)a precise description of arrangements ensuring an efficient and effective coordination between the delegating competent authorities and the delegated body;

(d)provisions for the fulfilment of the obligations of the delegated body as set out in Articles 11 and 12.

Article 11

Obligations of the delegated bodies

Delegated bodies to which certain SoHO supervisory activities have been delegated in accordance with Article 6 shall:

(a)communicate to the delegating competent authorities, on a regular basis and whenever those competent authorities so request, the outcome of the SoHO supervisory activities performed by them;

(b)immediately inform the delegating competent authorities whenever the outcome of the delegated SoHO supervisory activities indicates non-compliance or points to the likelihood of non-compliance, unless specific arrangements established between those competent authorities and the delegated bodies provide otherwise; and

(c)cooperate with the delegating competent authorities, including by providing access to their premises and facilities.

Article 12

Obligations of the delegating competent authorities

Competent authorities that have delegated certain SoHO supervisory activities to delegated bodies in accordance with Article 6 shall:

(a)organise audits or inspections of such bodies, as necessary and taking into account participation of such bodies in certification or other schemes referred to in Article 10(2), point (b)(iii); 

(b)fully or partly withdraw the delegation without delay in particular in cases where:

(i)there is evidence that such delegated bodies are failing to properly perform the activities delegated to them;

(ii)the delegated bodies fail to take appropriate and timely action to remedy the shortcomings identified; or

(iii)the independence or impartiality of the delegated bodies has been shown to be compromised.

Article 13

Communication and coordination between SoHO competent authorities

1.Where more than one authority is competent to perform SoHO supervisory activities in a Member State pursuant to Article 5(2), the Member State shall ensure efficient and effective coordination between all SoHO competent authorities involved, to ensure consistency and effectiveness of SoHO supervisory activities as set by this Regulation across its territory.

2.Competent authorities shall cooperate with each other and with the Commission. They shall communicate information to each other and, in particular, to the SoHO National Authority as necessary for the effective implementation of the supervisory functions provided for in this Regulation.

3.In cases where competent authorities provide an opinion to a SoHO entity on the applicability of this Regulation to a particular substance or activity within their territory, those competent authorities shall notify the SoHO National Authority, which, in turn, shall notify the SoHO Coordination Board (‘SCB’) of the opinion given to the SoHO entity.

4.Following a reasoned request from a competent authority of another Member State, the competent authority shall without undue delay inform the requesting competent authority of the outcome of supervisory activities concerning a SoHO entity on its territory, and, as necessary and proportionate, provide the records referred to in Articles 29 and 30.

Article 14

Obligations to consult and cooperate with authorities of other regulatory sectors

1.In all cases where questions arise as to the regulatory status of a substance, product or activity, competent authorities shall consult with authorities established in other relevant Union legislation referred to in Article 2(3), as relevant. In such cases, competent authorities shall also consult the compendium referred to Article 3 point (33). 

2.In the course of the consultation referred to in paragraph 1, the competent authorities may also submit a request to the SCB for its opinion on the regulatory status of the substance, product or activity under this Regulation and shall do so in all cases where the competent authorities, after the consultations referred to in paragraph 1, are not in a position to take a decision in that respect.

The competent authorities may also indicate that they consider there is a need that the SCB consults, in accordance with Article 68(1), point (b), with the equivalent advisory bodies established in other relevant Union legislation referred to in Article 2(3).

3.The competent authorities shall inform the SCB of the subsequent decision taken in their Member State, following the consultations referred to in paragraph 1 of this Article, regarding the regulatory status of the substance, product or activity concerned under this Regulation and on any consensus reached as a result of those consultations for publication in the compendium by the SCB.

4.The Commission may, upon a duly substantiated request of a Member State following the consultation referred to in paragraph 1, or on its own initiative, by means of implementing acts, determine the regulatory status of a substance, product or activity under this Regulation, in case questions arise in that respect, notably when these questions cannot be resolved at the Member State level, or in discussions between the SCB and the advisory bodies established in other relevant Union legislation, in accordance with Article 68(1), point (b).

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

5.For SoHOs that are intended to be subsequently used to manufacture products under other Union legislation, or as the starting and raw material thereof, as referred to in Article 2(3), or SoHOs that are intended to be combined with medical devices, as referred to in Article 2(4), the competent authority shall cooperate with the authorities responsible for the supervisory activities under the relevant Union legislation, with a view to ensuring coherent oversight. During the process, the competent authorities may seek the assistance of the SCB.

6.The consultation and cooperation referred to in paragraphs 1, 2 and 5 may also be initiated on the basis of a request for advice from a SoHO entity, as referred to in Article 40.

7.The Commission may, by means of implementing acts, lay down rules concerning procedures for consultation referred to in paragraph 1 and cooperation referred to in paragraph 5 by the competent authorities when they consult the authorities established in other relevant Union legislation referred to in Article 2(3).

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 15

Right of appeal

1.Where decisions are taken by competent authorities concerning natural or legal persons, those decisions shall be subject to such persons’ right of appeal in accordance with national legislation.

2.The right of appeal shall not affect the obligation of competent authorities to take prompt action to eliminate or contain the risks to human health in accordance with this Regulation.

3.Paragraphs 1 and 2 shall also apply to delegated bodies.

Article 16

General obligations concerning the personnel of competent authorities

1.Competent authorities shall:

(a)have, or have access to, a sufficient number of personnel so that SoHO supervisory activities can be performed efficiently and effectively;

(b)ensure that the personnel performing SoHO supervisory activities are suitably qualified and experienced;

(c)have procedures or arrangements in place to ensure that personnel performing SoHO supervisory activities are free from any conflict of interest;

(d)have procedures in place to ensure confidentiality and maintain professional secrecy.

2.Personnel performing SoHO supervisory activities shall:

(a)declare in writing any direct or indirect interests referred to in Article 7(2) and update that declaration yearly and whenever the declared information changes or any new interest arises;

(b)receive, for their area of competence, appropriate training enabling them to undertake their duties competently and in a consistent manner;

(c)keep up-to-date in their area of competence and receive regular additional training as necessary;

(d)participate in training in the subject matter and on the obligations of competent authorities resulting from this Regulation, as referred to in paragraph 3. 

3.Competent authorities, in cooperation with delegated bodies as necessary, shall develop and implement training programmes for the purpose of ensuring that personnel performing SoHO supervisory activities receive the training referred to in paragraph 2, points (b), (c) and (d). Competent authorities shall maintain records of the training undertaken by their personnel. Competent authorities shall provide opportunities for their personnel to participate in the Union training referred to in Article 69 where such Union training is available and appropriate.

4.Paragraphs 1, 2 and 3 shall also apply to delegated bodies.

Article 17

Obligations as regards Commission controls

Competent authorities and delegated bodies shall cooperate with the Commission for the performance of Commission controls referred to in Article 70. In particular, they shall:

(a)take appropriate follow-up measures to remedy the shortcomings identified through the controls provided for in Article 70;

(b)give the necessary technical assistance and provide the available documentation, upon justified request, and other technical support that Commission experts request to enable them to perform controls efficiently and effectively; and

(c)give the necessary assistance to ensure that the Commission experts have access to all premises or part of premises, and to information, including IT systems, relevant for the execution of their duties.

CHAPTER III

SoHO SUPERVISORY ACTIVITIES

Article 18

Register of SoHO entities

1.SoHO National Authorities shall establish and maintain a register of SoHO entities on their territory.

2.Instead of establishing a register of SoHO entities, as referred to in paragraph 1, a SoHO National Authority may use the EU SoHO Platform as referred to in Chapter XI. In this case, the SoHO National Authority shall instruct competent authorities, where necessary, and SoHO entities to register directly on the EU SoHO Platform.

3.Competent authorities shall verify that each registered SoHO entity has provided the following information:

(a)name or business name and address of the SoHO entity, and name and contact details of a contact person;

(b)a declaration that the SoHO entity complies with the obligations and requirements on SoHO entities set out in this Regulation, in particular Articles 44, 47, 56 and 59, as relevant;

(c)a statement from the SoHO entity that it accepts to be inspected as provided for in this Regulation;

(d)a list of the SoHO activities that the SoHO entity is carrying out;

(e)the name and curriculum vitae of the responsible person for release of SoHOs as referred to in Article 38, if the SoHO entity releases SoHOs or SoHO preparations.

4.In cases where SoHO National Authorities establish their own registries of SoHO entities as referred to in paragraph 1, they shall submit the information included in the registries to the EU SoHO Platform as referred to in Chapter XI. Competent authorities shall be responsible for ensuring that the information regarding the SoHO entities on their territory pursuant to this Article and to Article 19 is congruent in the register of SoHO entities and in the EU SoHO Platform, and shall submit any changes to the EU SoHO Platform without undue delay. 

5.The Commission may adopt implementing acts concerning the compatibility and comparability of the registers of SoHO entities for facilitating the submission to the EU SoHO Platform.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 19

Registration of SoHO entities

1.Competent authorities shall have procedures in place for the registration of SoHO entities in accordance with Article 37.

2.Competent authorities shall:

(a)acknowledge receipt of the registration within 14 working days of its submission;

(b)request the SoHO entity to provide supplementary information, if needed;

(c)inform the SoHO entity in cases where the registration indicates that an authorisation pursuant to Articles 21, 27 or 28 is required;

(d)identify whether the entity is a critical SoHO entity, and inform the entity in cases where it is considered a critical SoHO entity;

(e)submit any additional information on the registration as necessary, including the requirement for an authorisation pursuant to point (c), and whether the SoHO entity is a critical SoHO entity to the EU SoHO Platform referred to in Chapter XI.

3.The Commission may adopt implementing acts concerning the registration process to facilitate the compatibility of the registers of SoHO entities with the EU SoHO Platform.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 20

SoHO preparation authorisation system

1.Competent authorities shall establish and maintain a system for receiving and processing requests for the authorisation of SoHO preparations. The system shall allow for the suspension or withdrawal of authorisations.

2.Competent authorities shall authorise SoHO preparations pursuant to Articles 21, 22 and, where applicable, Article 23.

3.SoHO preparation authorisations shall be valid throughout the Union for the period defined in the terms of the authorisation, when such a time period has been defined, or until a competent authority has suspended or withdrawn the authorisation. Where a Member State has adopted a more stringent measure, in accordance with Article 4, which relates to a specific SoHO preparation, that Member State may decline to recognise the validity of the SoHO preparation authorisation of another Member State pending verification that the more stringent measure has been met.

4.The Commission may adopt implementing acts concerning the compatibility and comparability of the SoHO preparation authorisation system.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 21

Authorisation of SoHO preparations

1.Competent authorities shall have procedures in place to allow that applications for the authorisation of SoHO preparations are submitted in accordance with Article 41. They shall provide guidelines and templates for the submission of applications for SoHO preparation authorisation. When developing these guidelines and templates, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c). Competent authorities may establish simplified procedures for applications concerning modifications to previously authorised SoHO preparations.

2.Upon receipt of an application for the authorisation of a SoHO preparation, competent authorities shall:

(a)acknowledge receipt of the application within 14 working days;

(b)assess the SoHO preparation pursuant to Article 22 and examine agreements between the applicant SoHO entity and any third parties contracted by that SoHO entity concerning SoHO activities, where applicable; 

(c)grant a conditional authorisation for the use of the SoHO preparation in all cases where clinical outcome data is required for authorisation, pursuant to Article 22(4), points (d) and (e); 

(d)grant or refuse the authorisation for the SoHO preparation, as appropriate.

3.Competent authorities shall submit information regarding SoHO preparation authorisations, including a summary of the evidence used to authorise each SoHO preparation, to the EU SoHO Platform referred to in Chapter XI, and, for each SoHO preparation, amend accordingly the authorisation status of the SoHO entity to which the SoHO preparation is linked to in the EU SoHO Platform, including the name and contact details of the SoHO preparation authorisation holder.

4.Competent authorities shall conclude the SoHO preparation authorisation steps, referred to in paragraph 2 of this Article, within 3 months from receipt of the application, excluding the time needed for clinical outcome monitoring or studies. They may suspend this time limit for the duration of the consultation processes referred to in Article 14(1) and (2).

5.Upon receipt of a request for an opinion in course of the conformity assessment procedure pursuant to Article 52 of Regulation (EU) 2017/745, the competent authorities receiving the request shall follow the relevant procedure of that Regulation, and inform the SCB of the opinion provided. 

6.Competent authorities may, in accordance with national legislation, suspend the authorisation of a SoHO preparation if SoHO supervisory activities demonstrate or give reasonable ground for suspecting that: 

(a)such preparation, or any of the activities performed for that preparation, do not comply with the conditions of its authorisation or the requirements of this Regulation; and

(b)that non-compliance implies a risk to the safety of SoHO donors, recipients or offspring from medically assisted reproduction.

Competent authorities shall specify a period of time for the investigation of the suspected non-compliance and for SoHO entities to rectify a confirmed non-compliance, during which the suspension will remain in place.

7.In cases where SoHO entities are not able to rectify confirmed non-compliances referred to in paragraph 6 in the specified time period, competent authorities shall, in accordance with national legislation, withdraw the authorisation of the SoHO preparation concerned. 

8.Competent authorities may, in accordance with national legislation, withdraw the authorisation of a SoHO preparation if the competent authorities have confirmed that the SoHO preparation in question does not comply with subsequently updated criteria for authorisation or the SoHO entity has repeatedly failed to comply with the conditions of its authorisation. 

9.In cases of authorisation suspension or withdrawal, as referred to in paragraphs 6, 7 and 8, competent authorities shall, without undue delay, amend accordingly the authorisation status of the SoHO entity concerned in the EU SoHO Platform as referred to in Chapter XI.

10.Competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

11.The Commission may adopt implementing acts concerning the procedures to authorise SoHO preparations pursuant to this Article. 

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 22

Assessment of SoHO preparations

1.The assessment of a SoHO preparation, shall include a review of all SoHO activities that are performed for that SoHO preparation and that might influence the safety, quality and efficacy of the SoHO preparation. 

2.The assessment of SoHO preparations shall be carried out by assessors meeting the requirements set out in Article 24.

3.In cases where the SoHO preparation subject to the application for authorisation pursuant to Article 21 has been duly authorised in another SoHO entity in the same or in another Member State, competent authorities may authorise that SoHO preparation in the applicant SoHO entity, provided that the competent authorities have verified that the SoHO activities performed for the SoHO preparation are carried out by the applicant SoHO entity in a manner such that the safety, quality and efficacy results will be equivalent to those demonstrated in the SoHO entity where the SoHO preparation was first authorised.

4.In cases where the SoHO preparation, subject to the application for authorisation pursuant to Article 21, has not been duly authorised in another SoHO entity, competent authorities: 

(a)shall assess all the information provided by the applicant pursuant to Article 41;

(b)shall review the SoHO preparation dossier referred to in Article 41(2), point (a);

(c)shall initiate the consultation described in Article 14(1), if during the review of the SoHO preparation dossier referred to in point (b), questions arise as to whether the SoHO preparation falls, in part or fully, within the scope of this Regulation or other Union legislation, taking into account the activities performed for the SoHO preparation and the intended human application;

(d)shall review and evaluate the risk assessment performed by the applicant as pursuant to Article 41(2), point (b);

(e)shall evaluate the plan for clinical outcome monitoring and its proportionality to the level of risk of the SoHO preparation as referred to in Article 41(3), points (a), (b) and (c), as applicable;

(f)may consult the SCB, pursuant to Article 68(1) on the evidence necessary and sufficient for the authorisation of a particular SoHO preparation;

(g)shall assess, in the case of a conditional authorisation pursuant to Article 21(2), point (c), the results of the clinical outcome monitoring.

5.When assessing the SoHO preparation pursuant to paragraph 4, points (e) and (g), competent authorities shall consider, in the cases where the applicant has proposed to record, and recorded, the results of the clinical outcome monitoring in an existing clinical registry, that this is an acceptable method, provided that those competent authorities have verified that the registry has data quality management procedures in place that ensure accuracy and completeness of data.

6.Competent authorities shall conduct the assessment steps referred to in paragraphs 3 and 4 of this Article by means of a remote document review. Competent authorities may also, as part of the SoHO preparation assessment, carry out inspections pursuant to Articles 29, 30 and 31.

7.When conducting the assessment steps referred to in paragraph 4 of this Article, competent authorities shall consult the best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

Article 23

Joint SoHO preparation assessments

1.At the request of one or more competent authorities, SoHO preparation assessments as referred to in Article 22 may be carried out by competent authorities from more than one Member State, as a joint SoHO preparation assessment. 

2.The competent authority receiving a request for a joint SoHO preparation assessment may accept such a request, and coordinate and support that assessment, where that competent authority agrees that there are reasonable grounds for conducting a joint assessment.

3.Competent authorities participating in a joint assessment shall conclude a prior written agreement on the joint assessment. The agreement shall at least defines the following:

(a)the scope of the joint assessment;

(b)the roles of the participating assessors during and following the assessment, including the designation of an authority leading the assessment;

(c)the powers and responsibilities of each of the authorities.

4.Member States may set up joint assessment programmes to facilitate frequent or routine joint assessments. In such cases, competent authorities may sign a single written agreement provided that agreement meets the requirements in paragraph 3.

5.On completion of a joint SoHO preparation authorisation, the competent authority in the territory where the SoHO preparation authorisation holder is based shall submit the information, as pursuant to Article 21(3), regarding the new authorised SoHO preparation in the EU SoHO Platform. 

Article 24

Specific obligations concerning SoHO preparation assessors

1.Assessors shall:

(a)possess a diploma, certificate or other evidence of formal qualifications in the field of medical or biological sciences, awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned;

(b)have expertise in the processes being assessed and the human applications for which the SoHO preparations will be used.

2.The assessment of SoHO preparations as referred to in Article 22 may be done jointly by a team of persons which collectively have the qualifications and experience set out in paragraph 1.

3.In exceptional cases, competent authorities may consider that a person’s considerable and relevant experience may exempt this person from the requirements set out in paragraph 1.

4.Before assessors take up their duties, competent authorities shall provide assessors with a specific induction training on the procedures to be followed for the assessment of SoHO preparations in accordance with Article 22.

5.Competent authorities shall ensure that the specific induction training is complemented by specialised training for assessment of processing methods and technologies used for specific types of SoHO preparations and by continuous training, as appropriate, throughout the career of the assessors. Competent authorities shall make all reasonable efforts to ensure that assessors that participate in joint assessments have completed the relevant Union training referred to in Article 69(1) and are included in the list referred to in Article 69(5).

6.Assessors may be assisted by technical experts provided that competent authorities ensure that those experts comply with the requirements of this Regulation, in particular with the obligations set out in Articles 7 and 76.

Article 25

SoHO establishment authorisation system

1.Competent authorities shall establish and maintain a system for receiving and processing requests for the authorisation of SoHO establishments.

2.Competent authorities shall authorise as SoHO establishments the SoHO entities that both process and store SoHOs in accordance with Article 27.

3.Competent authorities may decide that certain SoHO entities that do not process and store SoHO also need to be authorised as SoHO establishments, in particular SoHO entities that: 

(a)have significant influence on the safety and quality of SoHOs due to the scale, criticality or complexity of the SoHO activities they perform; or

(b)carry out SoHO activities in connection with multiple SoHO establishments.

4.Paragraph 3 shall not apply to SoHO entities that import SoHO.

5.SoHO establishment authorisations shall be valid throughout the Union for the period defined in the terms of the authorisation, when such a time period has been defined, or until a competent authority has suspended or withdrawn the authorisation or the establishment has ceased to conduct SoHO activities. Where a Member State has adopted a more stringent measure, in accordance with Article 4, which relates to a specific SoHO establishment authorisation, that Member State may decline to recognise the validity of the SoHO establishment authorisation of another Member State pending verification that the more stringent measure has been met.

6.The Commission may adopt implementing acts to specify uniform procedures and working methods for establishing and maintaining a SoHO establishment authorisation system.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 26

Importing SoHO entity authorisation system

1.Competent authorities shall establish and maintain a system for receiving and processing requests for the authorisation of importing SoHO entities.

2.Competent authorities shall authorise as importing SoHO entities the SoHO entities that import SoHOs pursuant to Article 28.

3.Importing SoHO entity authorisations shall be valid throughout the Union for the period defined in the terms of the authorisation, when such a time period has been defined, or until a competent authority has suspended or withdrawn the authorisation or the entity has ceased to conduct SoHO activities. Where a Member State has adopted a more stringent measure, in accordance with Article 4, which relates to a specific importing SoHO entity authorisation, that Member State may decline to recognise the validity of the importing SoHO entity authorisation of another Member State pending verification that the more stringent measure has been met.

4.The Commission shall adopt implementing acts to specify uniform procedures and working methods for establishing and maintaining an importing SoHO entity authorisation system.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 27

Authorisation of SoHO establishments

1.Competent authorities shall provide guidelines and templates to allow that applications from SoHO entities for their authorisation as SoHO establishments are submitted in accordance with Article 49. When developing these guidelines and templates, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c). 

2.Upon receipt of an application for the authorisation of a SoHO establishment, competent authorities shall:

(a)acknowledge receipt of the application within 14 working days;

(b)assess the application;

(c)examine agreements between the applicant SoHO establishment and any third parties contracted by that SoHO establishment to perform SoHO activities;

(d)request that the applicant SoHO establishment provides supplementary information, if needed;

(e)carry out an on-site system inspection of the applicant SoHO establishment and, where applicable, of third parties contracted by the SoHO establishment to perform SoHO activities, pursuant to Article 29;

(f)inform the applicant, without undue delay, of the outcome of the assessment and inspections referred to in points (b), (c), (d) when relevant and (e) and of the decision on the authorisation; 

(g)grant or refuse the authorisation of the applicant SoHO establishment as a SoHO establishment, as appropriate, and indicate which SoHO activities are covered by the authorisation and which conditions apply, if any;

(h)assess and, as appropriate, approve subsequent changes made by the SoHO establishment to the information provided in the application and communicated to them according to Article 49(2);

(i)submit information regarding the authorisation by amending accordingly the status of the SoHO entity concerned, and including the name and contact details of the SoHO establishment authorisation holder, in the EU SoHO Platform as referred to in Chapter XI without undue delay.

3.Competent authorities may suspend the authorisation of a SoHO establishment, or of certain SoHO activities the establishment is authorised to perform, if SoHO supervisory activities demonstrate or give reasonable grounds for suspecting, that the SoHO establishment in question: 

(a)does not comply with the conditions of its authorisation or the provisions of this Regulation; and

(b)that non-compliance, or suspected non-compliance, implies a risk to the safety of SoHO donors or recipients or offspring from medically assisted reproduction. 

Competent authorities shall specify a period of time for the investigation of a suspected non-compliance and for the SoHO establishment to rectify a confirmed non-compliance, during which the suspension will remain in place.

4.In cases where competent authorities have confirmed non-compliances referred to in paragraph 3 and SoHO establishments are not able to rectify them in the specified time period, competent authorities shall, in accordance with national legislation, withdraw the authorisation of a SoHO establishment. 

5.Competent authorities may, in accordance with national legislation, withdraw the authorisation of a SoHO establishment if the competent authorities have confirmed that the SoHO establishment no longer complies with updated criteria for authorisation or the SoHO establishment has repeatedly failed to comply with the conditions of its authorisation. 

6.In cases of authorisation suspension or withdrawal, as referred to in paragraphs 3, 4 and 5, competent authorities shall amend accordingly the authorisation status of the SoHO establishment concerned in the EU SoHO Platform as referred to in Chapter XI without undue delay.

Article 28

Authorisation of importing SoHO entities

1.Competent authorities shall provide guidelines and templates to allow that applications from SoHO entities for their authorisation as importing SoHO entities are submitted in accordance with Article 43. In developing these guidelines and templates, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

2.Upon receipt of an application for the authorisation of an importing SoHO entity, competent authorities shall:

(a)acknowledge receipt of the application within 14 working days;

(b)assess the application;

(c)examine agreements between the applicant SoHO entity and any third parties contracted by that SoHO entity to perform SoHO activities;

(d)request that the applicant provides supplementary information, if needed;

(e)inform the applicant, without undue delay, of the outcome of the assessment and examinations referred to in points (b), (c) and (d) where relevant, and of the decision on the authorisation;

(f)grant or refuse the authorisation of the applicant as an importing SoHO entity, as appropriate, and indicate which SoHOs are covered by the authorisation and which conditions apply, if any;

(g)assess and, as appropriate, approve subsequent changes made by the SoHO importing entity and communicated to them as referred to in Article 43(3);

(h)submit information regarding the authorisation, by amending accordingly the status of the SoHO entity concerned, and including the name and contact details of the importing SoHO entity authorisation holder, in the EU SoHO Platform as referred to in Chapter XI, without undue delay.

3.In cases where the applicant intends to distribute the imported SoHOs to other Member States, competent authorities may perform the actions set out in paragraph 2, points (b), (c) and (d), in consultation with the SoHO National Authorities of the Member States concerned.

4.Competent authorities may require to inspect any party in a third country supplying SoHOs to the applicant prior to granting or refusing the importing SoHO entity authorisation, in particular in cases where the application concerns regular and repeated import of SoHOs from the same party.

5.Competent authorities may suspend the authorisation of an importing SoHO entity if SoHO supervisory activities demonstrate or give reasonable grounds to suspect: 

(a)that the SoHO entity in question does not comply with the conditions of the authorisation or the provisions of this Regulation; and

(b)that this non-compliance, or suspected non-compliance, implies a risk to the safety of recipients or offspring from medically assisted reproduction. 

6.Competent authorities shall specify a period of time for the investigation of a suspected non-compliance and for the importing SoHO entity to rectify a confirmed non-compliance, during which the suspension shall remain in place. In cases where competent authorities have confirmed non-compliances referred to in paragraph 5 and the importing SoHO entity is not able to rectify them in the specified time period, competent authorities shall withdraw the authorisation of the importing SoHO entity.

7.Competent authorities may, in accordance with national legislation, withdraw the authorisation of an importing SoHO entity if the competent authorities have confirmed that the importing SoHO entity no longer complies with updated criteria for authorisation or the importing SoHO entity has repeatedly failed to comply with the conditions of its authorisation.

8.In cases of authorisation suspension or withdrawal, as referred to in paragraphs 5, 6 and 7, competent authorities shall amend accordingly the authorisation status of the SoHO entity concerned in the EU SoHO Platform as referred to in Chapter XI without undue delay.

9.By derogation from paragraph 1, in case of emergency competent authorities may authorise imports of SoHOs for immediate application to a specific recipient when justified by the clinical circumstances on a case-by-case basis.

10.The Commission is empowered to adopt delegated acts in accordance with Article 77 in order to be able to supplement this Regulation by laying down specific criteria for the assessments, examinations and inspections in the course of the authorisation.

11.Where, in the case of risk to quality and safety of imported SoHOs, imperative grounds of urgency so require, the procedure provided for in Article 78 shall apply to delegated acts adopted pursuant to this Article.

Article 29

Inspections of SoHO establishments

1.Competent authorities shall carry out the following inspections on SoHO establishments, as appropriate:

(a)announced routine system inspections;

(b)announced or unannounced inspections, in particular in the case of investigations of fraudulent or other illegal activities, or on the basis of information that might indicate non-compliance with the rules of this Regulation;

(c)inspections as provided for in Article 22(6), Article 27(2), point (d), Article 28(4), Article 31 and Article 35(5).

2.Competent authorities that during inspections identify non-compliances with the rules of this Regulation may include follow-up inspections, where necessary and proportionate, to verify that SoHO establishments have undertaken effective corrective and preventive actions.

3.Competent authorities of the Member State in which the SoHO establishment is located shall carry out the inspections.

4.Competent authorities shall carry out on-site inspections of SoHO establishments and, where applicable, of any third parties contracted by the SoHO establishment to perform SoHO activities.

5.By derogation from paragraph 4, competent authorities may conduct inspections, in full or in part, by means of a remote document review, provided that:

(a)such inspection mode does not pose a risk to the safety and quality of SoHOs;

(b)such inspection does not prejudice the effectiveness of inspections; and

(c)the maximum interval between two on-site inspections pursuant to paragraph 11 is not exceeded.

6.Competent authorities shall ensure that inspections are carried out by inspectors meeting the requirements set out in Article 32.

7.Inspectors shall verify that SoHO establishments meet the general standards concerning SoHO donor protection laid down in Article 53, the standards concerning the voluntary and unpaid nature of SoHO donations laid down in Article 54, the standards concerning information to be provided prior to consent or authorisation laid down in Article 55 and the general standards concerning recipient and offspring protection laid down in Article 58, as applicable.

In cases where the SoHO establishments follow:

(a)the technical guidelines published by the ECDC and by the EDQM referred to in Articles 56(4), point (a), and 59(4), point (a), as applicable, the inspectors shall consider the standards or elements thereof, to be met, insofar as they are addressed by the guidelines;

(b)other guidelines as referred to in Articles 56(4), point (b), and 59(4), point (b), the inspectors shall assess on a case-by-case basis such guidelines in terms of level of safety, quality and efficacy achieved, as applicable, and accept or decline whether that level is equivalent to the level set by the technical guidelines referred to in Articles 56(4), point (a), and 59(4), point (a);

(c)other technical methods as referred to in Articles 56(4), point (c), and 59(4), point (c), the inspectors shall evaluate the risk assessment and record provided, assess the adequacy of the technical methods applied.

8.In cases of paragraph 7, second subparagraph, point (b) where competent authorities, prior to the inspection, have accepted the level safety, quality and efficacy achieved by those other guidelines, as equivalent to the level set by the technical guidelines referred to in paragraph 7, second subparagraph, point (a), the inspectors shall consider the standards or elements thereof, to be met, insofar as they are addressed by the guidelines.

9.Inspectors may carry out one or more of the following activities: 

(a)inspect SoHO establishment facilities and, where applicable, the facilities of any third parties contracted by the SoHO establishment concerning SoHO activities;

(b)evaluate and verify the procedures and the SoHO activities performed in SoHO establishments and, where applicable, in facilities of third parties that are relevant to the requirements of this Regulation;

(c)examine any documents or other records kept by SoHO establishments and, where applicable, third parties relating to the requirements of this Regulation and in particular Chapter V thereof;

(d)evaluate the design and implementation of the quality management system in place pursuant to Article 50;

(e)take samples for analysis and copies of documents if required;

(f)evaluate the emergency plan in place in accordance with Article 66, where applicable;

(g)order the suspension or cessation of any procedure or activity where necessary and proportionate to the risk detected.

10.Competent authorities shall carry out inspections pursuant to paragraph 1, point (a), regularly, on a risk basis and with appropriate frequency, taking account of:

(a)identified risks associated with:

(i)the SoHOs processed and stored;

(ii)the activities of the SoHO establishments, in particular the processes carried out;

(b)the establishments’ past record as regards the outcome of previous inspections carried out on them and their compliance with the rules of this Regulation;

(c)results from certification or accreditation by international bodies, where those bodies verify provisions that are equivalent to those in this Regulation; and

(d)the reliability and effectiveness of the quality management systems referred to in Article 50.

11.The interval between two on-site inspections shall not exceed 4 years.

12.Competent authorities shall consider on-site inspections carried out in the course of the authorisation of an establishment in accordance with Article 27(2), point (d), as the first on-site inspection in the sense of this Article.

13.Competent authorities shall provide immediate preliminary feedback on their findings at the request of the SoHO establishment concerned.

14.Following each inspection, the competent authorities shall draw up a report on the findings of the inspection that concern compliance with the legal and technical requirements applicable under this Regulation and provide it to the SoHO establishment concerned. In the report, the competent authorities may set out any corrective or preventive action needed or may request the SoHO establishment to respond with a proposal for such actions, with associated dates for completion.

15.Where more than one authority is competent to perform SoHO supervisory activities in a Member State pursuant to Article 5(2), on a reasoned request from another competent authority in their Member State, the competent authority shall forthwith communicate the report referred to in paragraph 14 of this Article to the requesting competent authority.

16.For the purpose of standardised inspections referred to in paragraph 1 of this Article, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

17.The Commission may adopt implementing acts concerning the procedures to be followed for inspections of SoHO establishments.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 30

Inspections of other SoHO entities

1.Competent authorities may carry out inspections pursuant to Article 29(1) on SoHO entities other than SoHO establishments as necessary and proportionate to the risks associated with the SoHOs and the SoHO activities registered for that SoHO entity, and the SoHO entity’s past record, in particular as regards the outcome of previous inspections carried out on it and its compliance with the rules of this Regulation. 

2.In the cases referred to in paragraph 1, Article 29 shall apply, mutatis mutandis, to the inspection of SoHO entities other than SoHO establishments.

3.For the purpose of a standardised approach to the inspection of SoHO entities other than SoHO establishments, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

Article 31

Joint inspections

1.At a request of one or more competent authorities, inspections pursuant to Articles 29(1) and 30(1) may be carried out by inspectors from more than one Member State as a joint inspection.

2.The competent authority receiving a request for a joint inspection, shall make all reasonable efforts to accept such request, and coordinate and support that inspection, in cases where:

(a)it is demonstrated, or there is reasonable ground for suspecting, that the activities carried out on the territory of another Member State pose a risk to the safety and quality of SoHOs distributed in the requesting Member State;

(b)competent authorities of the requesting Member State require specialist technical expertise of another Member State for that inspection;

(c)the competent authority of the Member State receiving the request agrees that there are other reasonable grounds for conducting a joint inspection.

3.The authorities participating in a joint inspection shall conclude an agreement prior to the inspection that defines at least the following:

(a)the scope and objective of the joint inspection;

(b)the roles of the participating inspectors during and following the inspection, including the designation of an authority leading the inspection;

(c)the powers and responsibilities of each of the authorities.

The authorities participating shall commit themselves in that agreement to jointly accept the results of the inspection.

4.The authority leading the joint inspection shall ensure that joint inspections are carried out in accordance with the national legislation of the Member State in which the joint inspection takes place.

The competent authority for the SoHO entity or SoHO establishment concerned shall, prior to the inspection, inform that SoHO entity or SoHO establishment about the joint inspection, unless the competent authorities concerned have reasonable grounds to suspect illegal or fraudulent activity.

5.Articles 7, 8 and 76 shall apply to all competent authorities involved in joint inspections.

6.Member States may set up joint inspection programmes to facilitate routine joint inspections. Member States may operate such programmes under a single agreement as referred to in paragraph 3.

Article 32

Specific obligations concerning inspectors

1.Inspectors shall possess a diploma, certificate or other evidence of formal qualifications in a relevant field, awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned.

In exceptional cases, competent authorities may consider that a person’s considerable and relevant experience may exempt this person from the requirement set out in the first subparagraph.

2.Competent authorities shall provide inspectors with a specific induction training before inspectors take up their duties. For the specific induction training, competent authorities shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

3.Competent authorities shall ensure that the specific induction training includes at least the following:

(a)the inspection techniques and procedures to be followed, including practical exercises;

(b)an overview of relevant Union and national inspection guidance, and the best practices agreed and documented by the SCB as referred to in Article 68(1), point (c);

(c)on overview of the authorisation systems in the Member State concerned;

(d)the applicable legal framework for the performance of SoHO supervisory activities;

(e)technical aspects concerning SoHO activities;

(f)SoHO technical guidelines as referred to in Articles 56 and 59;

(g)an overview of the organisation and functioning of national regulatory authorities in the field of SoHOs and related fields;

(h)an overview of the national health system and SoHO organisational structures in the Member State concerned.

4.Competent authorities shall ensure that the specific induction training is complemented by specialised training for inspection of specific types of establishments and by continuous training, as appropriate, throughout the career of the inspectors. Competent authorities shall make all reasonable efforts to ensure that inspectors that participate in joint inspections have completed the relevant Union training referred to in Article 69(1) and are included in the list referred to in Article 69(5).

5.Inspectors may be assisted by technical experts provided that the competent authorities ensure that those experts comply with the requirements of this Regulation, in particular with the obligations set out in Articles 7 and 76.

6.Paragraphs 1 to 5 shall also apply to delegated bodies.

Article 33

Activity data extraction and publication

1.Competent authorities shall verify that SoHO entities that have activity data collection and reporting obligations pursuant to Article 44 submit complete and accurate annual reports of those activities to the EU SoHO Platform referred to in Chapter XI.

2.Competent authorities shall extract an aggregated annual report of SoHO activity data for their SoHO entities from the EU SoHO Platform. They shall make that report available to the public, including on the internet.

Article 34

Traceability

1.Competent authorities shall verify that SoHO entities have appropriate procedures in place to ensure traceability and coding of SoHOs as referred to in Article 45.

2.Competent authorities shall establish procedures for the unique identification of SoHO establishments that are subject to the provisions on the Single European Code in Article 46. Competent authorities shall ensure that such identification complies with the technical standards defined for that coding system. For this purpose, competent authorities may use a SoHO establishment identification code generated by the EU SoHO Platform.

Article 35

Vigilance

1.Competent authorities shall be responsible for the management of vigilance associated with SoHO activities. They shall provide guidance and templates for the submission of SAO notifications and of SAO investigation reports as referred to in Article 47.

2.Upon receipt of a SAO notification, competent authorities shall:

(a)acknowledge receipt of the SAO notification;

(b)verify that the SAO notification includes the information referred to in Article 47(3); 

(c)assess the adequacy of the investigation planned to establish imputability and root cause;

(d)respond to the submitting SoHO entity without undue delay.

3.Competent authorities may provide advice on the investigation planned by the SoHO entity. In preparing such advice, competent authorities may request contributing advice from the SCB pursuant to Article 68(1). In case the SAO concerns a suspected transmission of a communicable disease, competent authorities shall inform the ECDC and take into account any advice or information provided by the ECDC or its SoHO expert network.

4.Upon receipt of a SAO investigation report, competent authorities shall:

(a)acknowledge receipt of the SAO investigation report;

(b)verify that the SAO investigation report includes the information pursuant to Article 47(5); 

(c)assess the results of the investigation and of the corrective and preventive actions described;

(d)inform the submitting SoHO entity of the conclusion of the SAO assessment.

5.Competent authorities may carry out inspections, pursuant to Articles 29 or 30, as appropriate, when the SAO notification or SAO investigation report received indicates, or gives reasonable grounds for suspecting, that requirements of this Regulation have not been complied with, or to verify an accurate implementation of corrective and preventive actions planned.

6.Upon receipt of a SAO notification with implications for safety, quality or supply of a product manufactured under other Union legislation from that SoHO or SoHO preparation, competent authorities shall inform, without undue delay, the relevant authorities competent for that product, pursuant to Article 14(5).

7.Upon receipt of information regarding a serious incident and field safety corrective action according to Regulation (EU) 2017/745, the competent authorities receiving such information shall inform the SoHO entities concerned. The competent authorities shall submit that information to their National SoHO Authority, provided that the incident meets the definition of a SAO.

8.Competent authorities shall provide a channel for self-reporting of SAOs by SoHO recipients and donors. Upon receipt of such notifications, competent authorities shall inform, as appropriate, the relevant SoHO entities or SoHO establishments thereof, and ensure that an adequate investigation of the occurrence is initiated by the SoHO entities or establishments concerned and that adequate corrective and preventive action have been taken by the SoHO entities or establishments concerned when necessary, and respond to the recipient or donor concerned.

9.Competent authorities shall ensure that the procedures referred to in paragraphs 1 to 5 provide for an adequate interconnection between the SAO notifications pursuant to this Article and the reporting system established in accordance with Article 11 of Directive 2010/53/EU, for instances where SAO notifications relate to SoHO donations after death, by donors that also donated organs.

10.Competent authorities shall submit to their SoHO National Authorities an annual summary of the SAO notifications and SAO investigation reports received. The SoHO National Authorities shall submit an annual summary of those SAO notifications and investigation reports to the EU SoHO Platform referred to in Chapter XI before 31 May of the subsequent year and shall make an aggregated version of that summary available to the public in their Member State, including on the internet. They shall include in the annual summary the numbers and types of those SAO reported to them that meet thresholds of seriousness and imputability that are agreed at Union level within the SCB.  

11.The Commission shall aggregate the annual summaries of the SoHO National Authorities, prepare and publish an annual SoHO vigilance report after having shared the report with the SoHO National Authorities for review and approval.

12.For the development of the guidance and templates referred to in paragraph 1 of this Article, and for the submission of the annual summaries referred to in paragraph 10 of this Article, competent authorities shall consult the best practices agreed and documented by the SCB as referred to in Article 68(1), point (c).

13.The Commission may adopt implementing acts concerning the procedures to be followed for consultation and coordination between competent authorities and the ECDC concerning relevant SAO notifications and investigations.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 36

SoHO rapid alerts

1.Competent authorities shall, upon receipt of a notification of a SAO or other information with implications for safety or quality or supply of SoHOs in one or more Member States, launch a SoHO rapid alert on the EU SoHO Platform referred to in Chapter XI.

2.Competent authorities shall launch a SoHO rapid alert in particular in the following circumstances:

(a)a risk to the quality or safety of SoHOs has been identified concerning SoHOs that have been distributed from their Member State to at least one other Member State;

(b)an outbreak of a communicable disease has occurred in their Member State and they have put in place donor deferral or testing measures to mitigate the risks of transmission by SoHOs;

(c)a defect or serious supply interruption has occurred concerning equipment, devices, materials or reagents that are critical for the collection, processing, storage or distribution of SoHOs and that might be used in other Member States;

(d)other information is available to the competent authorities that could reasonably be considered useful in other Member States to reduce risks to the safety or quality of SoHOs and where the launch of a SoHO rapid alert would be proportionate and necessary.

3.The ECDC, with the support of its SoHO expert network, may also launch an alert in the EU SoHO Platform when surveillance of communicable diseases indicates a new risk to the safety of SoHOs. The ECDC may indicate in such an alert that it has provided guidelines on the mitigation of risks associated with communicable disease outbreaks, in particular concerning the eligibility and testing of SoHO donors.

4.Competent authorities that receive a SoHO rapid alert shall communicate information to the relevant organisations representing groups of SoHO entities or professionals without undue delay with a view to ensuring that risk mitigating actions can be taken promptly and that relevant information available at the SoHO professional level can be shared with the competent authorities. Competent authorities may also supplement the information provided in the alert with further information such as details of relevant mitigating actions taken in their Member State.

5.Competent authorities and the ECDC shall consult the relevant best practices agreed and documented by the SCB as referred to in Article 68(1), point (c), when launching and handling a SoHO rapid alert.

CHAPTER IV

GENERAL OBLIGATIONS ON SOHO ENTITIES

Article 37

SoHO entity registration

1.Entities shall register as a SoHO entity before commencing any SoHO activity. To register, they shall provide the information as referred to in Article 18. SoHO entities may request from their competent authorities an opinion on the applicability of the registration requirements in this Chapter to the SoHO activities concerned prior to the registration.

2.In Member States where the EU SoHO Platform is used for registration of SoHO entities, as referred to in Article 18(2), organisations meeting the definition of a SoHO entity shall register directly in the EU SoHO Platform in accordance with their competent authorities’ instructions.

3.SoHO entities that implement changes to their SoHO activities or contact details shall register those changes without undue delay. Where such changes imply SoHO activities including both processing and storage of SoHOs, those SoHO entities shall comply with the requirements of Articles 48 and 49.

Article 38

Responsible person for release of SoHOs

1.In cases where a SoHO entity releases SoHOs or SoHO preparations for distribution for human application, or for the manufacture of products regulated by other Union legislation, or as the starting and raw material thereof, as referred to in Article 60, that entity shall designate a person responsible for release.

2.The responsible person for release of SoHOs shall be in possession of a diploma, certificate or other evidence of formal qualifications in the field of medical or biological sciences awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned and shall have at least 2 years of experience in the relevant field.

3.The responsible person for release of SoHOs may delegate the tasks specified in paragraph 1 to other persons who shall be qualified by training and experience to perform such tasks. In such cases, that person shall perform those tasks under the responsibility of the responsible person for release of SoHOs.

Article 39

Export

SoHO entities shall ensure that SoHOs or SoHO preparations exported or re-exported from the Union comply with the relevant requirements of this Regulation unless the SoHO entity can demonstrate that the authorities of the importing country or the laws, regulations, standards, codes of practice or other legal and administrative procedures as may be in force in the importing country indicate that a deviation from the requirements of this Regulation is acceptable. SoHO entities shall not deviate from the standards referred to in Chapter VI.

Article 40

SoHO preparation authorisation

1.SoHO entities shall not release or, in an autologous context, prepare and apply immediately to a recipient, SoHO preparations without prior SoHO preparation authorisation. In cases where a SoHO entity modifies an activity carried out for an authorised SoHO preparation, it shall obtain an authorisation for that modified SoHO preparation.

2.SoHO entities may request advice from their competent authorities on the applicability of the authorisation requirements in this Regulation to their SoHO activities prior to submitting an application for a preparation authorisation.

3.SoHO entities may request to their competent authorities a derogation from the requirement for a SoHO preparation authorisation in the exceptional circumstances referred to in Article 64.

Article 41

Application for the authorisation of SoHO preparations

1.SoHO entities shall send applications for the authorisation of a SoHO preparation to their competent authorities. The applicant shall provide the name and contact details of the prospective SoHO preparation authorisation holder responsible for the application. This paragraph shall be without prejudice to Article 38(1). 

2.The applicant shall provide the following:

(a)a SoHO preparation dossier describing the details of the SoHO activities performed for that SoHO preparation and including at least:

(i)any specific SoHO donor eligibility or SoHO donor testing procedures;

(ii)any specific SoHO collection procedures;

(iii)a description of the processing applied including details of the air quality standards maintained in the processing facilities and the rationale for the air quality standard applied;

(iv)a description of equipment, reagents and materials used and their certification status in accordance with Regulation (EU) 2017/745; 

(v)any specific storage conditions and storage time limits;

(vi)any quality control and release parameters;

(vii)data concerning procedures performed for process validation and equipment qualification;

(viii)details of any third parties contracted by the SoHO entity to perform activities for the SoHO preparation; 

(ix)the clinical indications for which the SoHO preparation is to be applied;

(b)the results of a risk assessment conducted on the combination of SoHO activities performed for the SoHO preparation, together with the intended clinical indication for which it is intended to be applied, taking into account:

(i)whether the SoHO preparation is described in, and aligned with, an EDQM SoHO monograph included in the technical guidelines referred to in Article 59(4), point (a);

(ii)whether the SoHO preparation meets the defined quality criteria in the EDQM SoHO monograph referred to in point (i) and is intended to be used for the indication and with the mode of application to which that monograph refers, where such details are provided in that monograph;

(iii)information regarding previous use and authorisation of the SoHO preparation in other SoHO entities, as available in the EU SoHO Platform;

(iv)evidence generated as part of the process of certification, in accordance with Regulation (EU) 2017/745, of any certified medical device used for the SoHO preparation, where available;

(v)documentation of a systematic process of identification, quantification and evaluation of any risks to the donor or the recipient arising from the chain of activities performed for the SoHO preparation;

(c)in cases where the indicated risk is other than negligible, a proposal for clinical outcome monitoring to demonstrate safety, quality and efficacy of the SoHO preparation, in line with the results of the risk assessment;

(d)an indication of the data which should be regarded as proprietary accompanied by verifiable justification, where appropriate.

3.In the proposal referred to in paragraph 2, point (c), the applicant shall propose a clinical outcome monitoring plan as follows:  

(a)in cases of low risk, clinical follow-up of a defined number of patients;

(b)in cases of moderate risk, in addition to point (a), a clinical investigation study of a statistically significant number of patients assessing pre-defined clinical endpoints;

(c)in cases of high risk, in addition to point (a), a clinical investigation study of a statistically significant number of patients assessing pre-defined clinical endpoints with a comparison to standard therapy.

4.SoHO entities shall perform the clinical outcome monitoring once a conditional authorisation has been granted pursuant to Article 21(2), point (c), and submit the results to their competent authorities. In conducting the clinical investigation study as referred to in paragraph 3, points (b) and (c), for the SoHO preparation concerned, the applicant may use an existing clinical registry to record its results provided that their competent authorities have verified that the registry has data quality management procedures in place that ensure accuracy and completeness of data.

5.SoHO entities shall not make any change to the chain of activities performed for an authorised SoHO preparation, without the prior written approval of their competent authorities. SoHO entities shall also inform their competent authorities of changes in the SoHO preparation authorisation holder’s details.

6.The SoHO preparation authorisation holder shall be based in the Union. In cases where other SoHO entities carry out one or more of the processing steps for the SoHO preparation, the SoHO entity that holds the SoHO preparation authorisation shall be responsible for the release and shall supervise it, even if the release physically takes place at the site of the other SoHO entities.

Article 42

Importing SoHO entity authorisation

1.SoHO entities shall not import SoHOs without a prior importing SoHO entity authorisation.

2.In the case of importing SoHO entities that only import human plasma that is intended to be used for the manufacture of medicinal products regulated by other Union legislation and is included in a plasma master file (PMF) as referred to in Directive 2003/63/EC, paragraph 1 of this Article shall not apply.

3.The Commission shall adopt delegated acts in accordance with Article 77 supplementing this Regulation by laying down obligations and procedures for importing SoHO entities regarding the import of SoHOs in order to verify equivalent standards of quality and safety of such imports.

Article 43

Application for importing SoHO entity authorisations

1.SoHO entities shall send applications for authorisation as importing SoHO entities to their competent authorities.

2.The applicant SOHO entity shall provide the name and contact details of the prospective importing SoHO entity authorisation holder. This paragraph shall be without prejudice to Article 38(1).

3.The importing SoHO entity shall not make any substantial changes to the importing SoHO activities subject to the authorisation without the prior written approval of its competent authority. The same shall apply in case of changes in the importing SoHO entity authorisation holder’s details.

4.The importing SoHO entity authorisation holder shall be based in the Union, and be responsible for the physical reception and visual examination and verification of imported SoHOs prior to their release. The importing SoHO entity shall verify coherence between the SoHO received and the associated documentation and conduct an examination of the integrity of packaging and the compliance of labelling and transport conditions with the relevant standards and technical guidelines as referred to in Articles 57, 58 and 59. 

5.An authorised importing entity may delegate the physical reception, visual examination and verification referred to in paragraph 4 to the entity that will apply the SoHO to the recipient in cases where imports are organised for individual named recipients.

6.The Commission shall adopt implementing acts specifying the information to be provided in an application for an authorisation for importing SoHOs or SoHO preparations to ensure compatibility and comparability of such data.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 44

Activity data collection and reporting

1.SoHO entities shall collect data relating to their activities in cases where those activities include:

(a)SoHO donor recruitment;

(b)collection;

(c)distribution;

(d)import;

(e)export;

(f)human application.

2.The data collected pursuant to paragraph 1 shall comprise the elements set out in the EU SoHO Platform as referred to in Chapter XI.

3.The Commission shall adopt implementing acts laying down technical procedures to ensure uniformity and compatibility and comparability for the implementation of this Article. 

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

4.SoHO entities shall submit to the EU SoHO Platform an annual summary of the data collected pursuant to this Article. In cases where national or international registries collect activity data meeting the criteria defined in the SoHO platform and such registries have been verified by competent authorities as having in place data quality management procedures that ensure accuracy and completeness of data, SoHO entities may delegate the submission of the activity data referred to in this Article to such registries. The Commission shall aggregate the annual summaries of the SoHO entities, prepare and publish an Annual SoHO Activity Report. 

Article 45

Traceability and coding

1.SoHO entities shall implement a traceability system in order to unmistakably link each SoHO donor to their SoHO donation and to all documents, samples, SoHO preparations and SoHO entities that are associated with that SoHO from the point of collection to human application and outcome monitoring. With regard to imported SoHOs, importing SoHO entities shall ensure an equivalent level of traceability.

2.SoHO entities distributing SoHOs shall generate a code that contains the information included in the traceability system referred to in paragraph 1. They shall ensure that the code:

(a)is unique within the Union;

(b)is machine-readable, unless the size or storage conditions mean that a machine-readable code cannot be applied;

(c)does not reveal the identity of the donor;

(d)complies with technical rules for the Single European Code (SEC) for SoHOs, referred to in Article 46, where applicable as indicated in that Article.

3.SoHO entities shall include the codes referred to in paragraph 2 on the labels to be applied to the SoHO or SoHO preparations prior to distribution, or on the documents accompanying the distributed SoHO or SoHO preparations where it can be guaranteed that such documents will not be separated from the SoHO or SoHO preparation concerned. 

4.SoHO entities shall use a labelling system that meets the labelling requirements set out in the relevant technical guidelines referred to in Articles 56(4) and 59(4). SoHO entities shall keep the data necessary to ensure traceability for a minimum of 30 years. They may store the data in electronic form.

Article 46

European coding system

1.SoHO entities shall apply a Single European Code (‘SEC’) to SoHO preparations distributed for human application. In cases where SoHOs or SoHO preparations are transferred for further processing in another SoHO entity or released for manufacture of products regulated by other Union legislation, or as the starting and raw material thereof, SoHO entities shall, at least, apply the part of the SEC that allows identification of the donation. The SEC shall appear on the packaging or on a label attached thereto, or on the documents referring to the SoHO where it can be guaranteed that such documents accompany the SoHO concerned.

2.Paragraph 1 shall not apply to:

(a)reproductive cells for within couple use;

(b)blood or blood components for transfusion or for the manufacture of medicinal products;

(c)SoHOs applied to a recipient without being stored;

(d)SoHOs imported into the Union in case of emergency authorised directly by competent authorities pursuant to Article 28(9); 

(e)SoHOs that are imported to or donated in the same SoHO entity where they are applied.

3.The Commission shall adopt implementing acts concerning the format of the Single European Code and the requirements related to its application to SoHO establishments and to SoHOs at the point of distribution or point of transport and delivery for further processing.

Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).

Article 47