(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.

(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 quality and safety 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. In accordance with Article 3 of the Charter of Fundamental Rights of the European Union, those safety standards should be based on the fundamental principle that the human body or its parts cannot be a source of financial gain.

(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.

(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 and the cross-border sharing of these substances . 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.

(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 , taking into consideration the special characteristics of each type of substance, as recognised by the technical guidelines referred to in this Regulation .

(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.

(9)

All SoHOs that are intended to be applied to humans fall within the scope of this Regulation. Articles 53, 54, 55 and 56 of this Regulation should apply also to SoHO donations intended for research. 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.

(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. Furthermore, this Regulation should not apply where the handling of SoHOs occurs during a surgical intervention within a sterile field or within a closed-system medical device. 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, contamination of medical personnel or environmental contamination, loss of traceability or damage to the biological properties inherent to the substance, and necessary for efficacy or functionality 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.

(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 and Regulation (EU) No 536/2014 of the European Parliament and of the Council  (1a), this Regulation should at least apply to the recruitment and selection of donors, donation, collection and donor testing as well as to release, distribution , issuing , 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.

(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.

(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 for them as a result of the donation. This Regulation should therefore include principles and technical rules to monitor and protect donors. This is particularly important where the donation involves significant risk to the donor’s health such as where there is a need for pre-treatment with medicinal products, for example in the case of oocytes, a medical intervention to collect the substance, for example in the case of bone marrow or peripheral blood stem cells, or a possibility for donors to donate frequently, for example in the case of plasma . As different types of donation entail different risks for donors, with varying levels of significance, the monitoring of donor health should be proportionate to those levels of risk.

(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.

(15)

This Regulation does not prevent Member States from maintaining or introducing more stringent protective measures that are compatible with Union law and founded on the principle of voluntary and unpaid donation . Member States should notify the Commission as soon as possible after their introduction so that the other Member States can be informed accordingly, via the EU SoHO Platform, 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 based on scientific evidence and the means of achieving that aim are appropriate and necessary. In order to prevent any discrimination, it is appropriate to require that Member States report to the Commission any such measures that could constitute discrimination, in particular as several Member States have implemented restrictions against men who have sex with men in blood donation procedures. Member States should therefore replace donor eligibility criteria based on sexual orientation or gender identity with individual risk-based screening criteria for all donors, regardless of their gender or sexual orientation.

(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.

(16)

This Regulation should not interfere with national legislation in the health area with objectives other than quality and safety of SoHOs , where such legislation 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 . However, decisions should adhere to the Charter of Fundamental Rights of the European Union . 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.

(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 , except provisions regarding donor protection . 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 .

(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. Such solidarity should be built from the local and regional levels up to the national and Union levels, ensuring autonomy, spreading the responsibility of donation evenly across the Union population and ensuring that recipients receive appropriate treatments. Voluntary and unpaid SoHO donation is also a factor which contributes to high safety standards for SoHOs and therefore to the protection of human health , and increases public trust in donation systems . 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 acceptable to ensure that donors are not financially disadvantaged by their donation. Thus, financially neutral compensation to remove any such risk is acceptable but should never produce a financial gain for the donor or constitute an incentive that would cause a donor to be dishonest when giving their medical or behavioural history or to donate in any way that could pose risks, in particular donating more frequently than is allowed, to their own health and to that of prospective recipients. Compensation and reimbursement should under no circumstances serve an incentive to recruit donors, should not expose vulnerable persons in society to exploitation and should not lead to competition among SoHO entities for the recruitment of donors. Such compensation should, therefore, be based on quantifiable criteria, for example. time given for the donation or proven expenses, and transparent criteria set by national authorities, at a level justified and appropriate in their Member State to respect the principle of financial neutrality . Recruitment campaigns and advertisements should not refer to any compensation, in order to avoid risks to the health of donors or to that of prospective donors.

(18a)

As indicated by the Council of Europe Committee on Bioethics  (24a) , it should be possible to compensate donors for any quantifiable expenses and losses, financial or non-financial, that they incur as a result of a donation. When calculating such compensation, SoHO entities should be able to take into account non-financial variables to determine the appropriate level and form of compensation to be given to donors, as long as such compensation complies with the principle of voluntary and unpaid donation laid down in this Regulation.

(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.

(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 and under no circumstances attribute or imply levels of safety or efficacy that are not supported by scientific methods . This should ensure that donors, or their families, are not coerced to donate by exaggerated descriptions of benefits and prospective recipients 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.

(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 independent 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. The list of all SoHO national competent authorities should be made publicly available.

(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.

(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 interference by industry or other actors that might affect their operational impartiality.

(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.

(24)

When there is doubt about the regulatory status of a particular substance, product or activity under this Regulation, competent authorities should consult the relevant authorities responsible for other relevant regulatory frameworks, namely medicinal products, advanced therapies, medical devices, organs or food , and the SoHO Coordination Board (SCB) , with the aim of ensuring coherent procedures for the application of this Regulation and other relevant Union legislation . Competent authorities should inform the SCB of the outcome of their consultations and submit a request to it for its opinion on the regulatory status of the substance . 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. Member States should respect the SCB’s opinion on the regulatory status of substances . 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 or the SCB , decide on the regulatory status of a particular substance, product or activity under this Regulation.

(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.

(26)

Commission experts should have the necessary experience and knowledge to 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.

(27)

Since SoHO preparations are subjected to a series of SoHO activities prior to their release, distribution and issuing , 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.

(28)

Applicants requesting authorisation for a SoHO preparation should use the Euro GTP II methodologies or equivalent tools to assess the risk level of their SoHO preparation. Applicants should share the results of the risk assessments with competent authorities when requesting authorisation. 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 , pursuant to Regulation (EU) No 536/2014. Where the standard treatment or control group is based on medicinal products, the studies should be considered to be clinical trials as defined in and regulated by Regulation (EU) No 536/2014 . The competent authority should approve the plans before they are implemented and should assess the outcome data as part of a SoHO preparation authorisation.

(28a)

SoHO entities should request approval for SoHO clinical studies from the competent authorities, both in the context of the authorisation process of a new SoHO treatment or when comparing previously authorised treatments. In SoHO clinical studies, patients’ rights, safety, dignity and well-being should always be the priority and the clinical study should be designed in a way that leads to reliable and robust data and conclusions.

(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.

(29)

In the interests of efficiency, it should be permitted to conduct clinical 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 . The commitment to publish the clinical results obtained should be a requirement for SoHO clinical studies . Whilst applicants can choose to record the clinical data generated during the clinical studies 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.  The existence of a registry of SoHO clinical studies at Union level is critical to facilitate patient participation in clinical studies, to boost multi-centre studies and to foster collaboration to generate more robust results and conclusions, and to make such generated knowledge available to other researchers, healthcare professionals, participants themselves and the general public.

(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.

(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 , through the EU SoHO Platform , 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. Competent authorities should also share with each other information on SoHO clinical studies, via the EU SoHO Platform.

(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.

(32)

Competent authorities should periodically 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.

(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 based on scientific evidence 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 . Member States should be able to decide that SoHO entities should be permitted to follow other recognised guidelines, provided that such guidelines are based on the most up-to-date scientific evidence and achieve the same level of quality, safety and efficacy . Member States should be involved in both the drafting of and voting on those guidelines and should follow a transparent process of consultation with other relevant Union authorities and stakeholders . SoHO entities should be permitted to follow other guidelines, provided that it has been demonstrated that those other guidelines are based on the most up-to-date scientific evidence and 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. When assessing scientific guidelines, it is important that the Commission, the ECDC, and the EDQM involve existing scientific, donor and patient representative groups.

(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.

(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 also 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 , without prejudice to the Union’s legal autonomy . 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. The Commission should also establish a memorandum of understanding with the EDQM related to transparency of membership and of outputs, and conflict of interest rules for experts and stakeholders involved in drafting EDQM guidelines. Such cooperation should be without prejudice to the autonomy of Union law and should take into account Union principles on transparency and stakeholder participation.

(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.

(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, quality and sustainability 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 transparent 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, including those exacerbated by climate change, 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.

(37)

It is necessary and beneficial to all parties to promote information and awareness campaigns at national and Union level on the importance of SoHOs. The aim of these campaigns should be to ensure the broadest possible donor base, with a view to ensuring a more resilient supply system, and 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 and equal access to SoHOs for medical treatments, Member States and the Union should support the establishment of public donation facilities and promote the voluntary and unpaid donation of SoHOs of high quality and safety with a view to increasing the collection capacity and autonomy in the Union. Member States are also urged to take steps to encourage a strong involvement of all relevant sectors, in particular the public and non-profit sector, in the provision of SoHO services, in particular for critical SoHOs and the related research and development.

(37a)

The COVID-19 pandemic can be considered one of the biggest health crises to affect Europe. It had adverse effects on the resilience of the donor base in some countries whose collection systems rely on a small number of donors donating more frequently than elsewhere. This crisis highlighted the vulnerabilities of the Union in very different aspects, ranging from the lack of coordination between Member States, which is essential to addressing such situations, to the Union’s strong dependence on third countries for the production and supply of raw materials and active substances needed for the elaboration of medical treatments. In the case of SoHOs, the pandemic drastically reduced the number of donors and exports from third countries, putting the Union in a situation of shortages of some SoHOs and patients at serious risk due to a lack of adequate treatments. In this context, the initiatives for a strong European Health Union should work in favour of European autonomy, in particular as regards the supply of SoHOs and the ability to minimise the risk of shortages, especially of SoHOs for therapeutic use. The lessons learned and the resulting measures taken at Union level should serve as a reference for the prevention, detection and resolution of future health crises. Regulation (EU) 2022/2371 of the European Parliament and of the Council  (1a) lays down the guidelines to be followed for that purpose. To increase European autonomy in terms of SoHOs, Member States should be urged to increase their collection capacity and donor base for critical SoHOs, in particular plasma, by developing non-profit and public plasmapheresis programmes.

(37b)

In order to ensure autonomy and sustainability of supply of SoHOs, Member States should establish national SoHO emergency and continuity of supply plans setting out measures for cases where the supply situation for critical SoHOs presents or is likely to present a serious risk to human health. Such plans should include measures, including optimisation of use, that impact demand for critical SoHOs, targets to ensure autonomy of supply of critical SoHOs, donor recruitment and retainment strategies and arrangements for cooperation between competent authorities, experts and relevant stakeholders. National SoHO emergency and continuity of supply plans should be further supplemented by the strategy for the promotion of European autonomy in terms of SoHO supply and the SoHO entity emergency and continuity of supply plans, primarily focusing on supply monitoring, reporting obligations and sharing of best practices within the Union. Moreover, Member States should be encouraged to establish certain areas, such as transfusion medicine, as an independent medical subject with structured training, including medical specialisation schools and programmes for continuous medical education for all medical staff. Providing training and better information for the prescribers would reduce the risk of unnecessary application of SoHOs. Furthermore, as recommended by the World Health Organization, Member States should additionally support optimal clinical use of SoHOs, in particular where there are alternatives which can reduce the demand for SoHOs. Member States would thus ensure efficient implementation of the Patient Blood Management (PBM) approach, which improves patients’ safety by minimising the risks associated with transfusion, and improve patient outcomes, while at the same time ensuring sufficiency of blood supplies and reducing financial pressure on health systems.

(37c)

In cases where the availability of SoHO preparations or SoHO-derived products depends on potential commercial interests, such as some plasma-derived products, there is a risk of not having the interests of patients and research at the forefront. There could even be situations in which some products with low profitability are no longer produced, thereby hampering their accessibility for patients. Similarly, investment in research and innovation for this type of products could be very small or non-existent. Prices of SoHO-derived products, which are obtained from voluntary and unpaid donations, should be fair and transparent. For certain products with low profitability, Member States should encourage research and innovation and should ensure that such products continue to be manufactured.

(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.

(38)

In order to promote a coordinated and coherent 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 agencies and bodies such as the ECDC and  the European Medicines Agency (EMA). The European Parliament, the EDQM and existing professional, scientific experts and donor and recipient patient representative groups and stakeholders at Union level in the field of SoHOs could also be invited . Other Union institutions, including the European Parliament, expert bodies, offices and agencies such as the EMA, ECDC and the EDQM, should have an observer role. All members of the SCB should provide declarations of interest, adhering to a high degree of transparency concerning its outputs. Members of the SCB, observers and experts should act independently, in the public interest and be free from any external influence that might affect the impartiality of their professional conduct.

(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.

(39)

Some substances, products or activities have been subject to different legal frameworks with different requirements in the Member States. This can sometimes cause confusion among operators in the field, and the consequent legal uncertainty can be a disincentive to professionals to develop new ways to prepare and use SoHOs. The SCB should receive on an ongoing basis relevant information on national decisions made on cases where questions were raised on the regulatory status of SoHOs. The SCB should monitor those opinions in order to react quickly and in an informed manner to further requests for opinions from other Member States, 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 , ensure a high level of protection of public health, and facilitate SoHO innovation.

(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.

(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 , to make it possible to share the elements used to determine the regulatory status of a substance, to improve the transparency of national reporting and supervisory activities and ensure better communication, collaboration and coordination in relation to, and exchange of, SoHOs between Member States . The national competent authorities should be encouraged to use the EU SoHO Platform instead of maintaining national registers, in particular to limit the administrative burden. Member States should also be able to utilize the EU SoHO Platform as a channel for national initiatives and campaigns to encourage the exchange of best practices. Such national initiatives and campaigns should be established in close cooperation with patient organisations, and aim to promote the need to maintain sustainable supplies of SoHO products. The EU SoHO Platform should also serve as a reliable source of information for the general public regarding the work of the SCB, national competent authorities and other expert bodies, including the EDQM, and SoHO entities and establishments. The online platform could be further used for the sharing of best practices between Member States with regard to initiatives, such as campaigns, to support the supply of SoHOs.

(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.

(43)

As the EU SoHO Platform requires the processing of personal data, it will be designed respecting the principles of data protection laid down in Article 5 of Regulation (EU) 2016/679 . 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.

(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 and the prohibition of making the human body and its parts a source of financial gain, the protection of natural persons with regard to the processing of their 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 and criteria of compatibility between donors and recipients , 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 and non-discriminatory 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.

(44a)

Due to the high sensitivity of donor anonymity and taking into account the rights of offspring from medically assisted reproduction following third party donation, SoHO entities should ensure donors and recipients of reproductive cells are duly informed about the possibility of ID release and the implications thereof, pursuant to provisions laid down in national legislation.

(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.

(45)

SoHOs, by definition, relate to natural 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 processed in pseudonymised or anonymised form, as appropriate in each case . 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.

(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. Furthermore, access to secondary data for research purposes should be provided via the European Health Data Space, once it is established.

(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 .

(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 the optimal timeframe . This Regulation should serve to increase coordination between Member States and facilitate the cross-border exchange of SoHOs .

(47a)

The objectives of this Regulation, namely to ensure that SoHOs are of high quality and safe and to provide a high level of protection for donors, need 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 those objectives. Member States in turn should enhance education and provide appropriate training for medical personnel regarding SoHO collection, processing, storage, application, transfusion and procurement.

(47b)

In some cases, such as bone marrow or haematopoietic stem cell transplants, the level of donor/recipient compatibility has to be extremely high. Therefore, coordination is needed at a global level, so that each patient has as many options as possible as regards finding a compatible donor.

(a)

SoHO donor recruitment;

(a)

SoHO donor recruitment , except if that is the sole SoHO activity of the entity in which case only Article 54(3b) shall apply ;

(ha)

issuing of SoHOs;

(ma)

SoHO clinical studies.

(a)

exchange of information on availability and stocks of SoHOs, and promotion of actions relating to the security of SoHO supply;

(b)

coordination between competent authorities and the Commission and Union agencies in the event of SoHO-related health emergencies.

(1)

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

(1)

‘blood’ means the liquid that circulates in arteries and veins carrying oxygen to and carbon dioxide from the tissues of the body and its constituent parts ;

(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;

(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 , but includes substances which can be extracted from them ;

(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);

(7)

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

(7a)

(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 ;

(8)

‘SoHO donor’ means a living or deceased SoHO donor ;

(8a)

(8b)

(9)

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

(9)

‘SoHO recipient’ means the person to whom SoHOs are applied or for whom such an application is envisaged ;

(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;

(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 and involves the use of SoHOs ;

(11)

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

(11)

‘offspring from medically assisted reproduction’ means children that are born following medically assisted reproduction;

(11a)

(a)

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

(a)

has been subjected to processing and, where relevant, one or more other SoHO activities in accordance with defined quality and safety parameters;

(b)

meets a pre-defined specification; and

(b)

meets a pre-defined specification;

(13)

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

(13)

‘donor recruitment’ means any activity aimed at informing persons about activities related to SoHO donation or at encouraging them to donate SoHOs ;

(15)

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

(15)

‘processing’ means any operation involved in the handling of SoHOs, including washing, shaping, separation, fertilisation, decontamination, sterilisation, preservation and packaging; it does not include the handling of SoHOs within the same sterile field during a surgical intervention or within a closed-system medical device, where those SoHOs are either released or for autologous application;

(17)

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

(17)

‘storage’ means the maintenance of SoHOs under appropriate controlled conditions until distribution , issuing, export or human application ;

(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;

(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 or until issuing ;

(18a)

(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 ;

(23)

‘autologous use’ means collection of SoHO from one individual for subsequent application to the same individual;

(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;

(27)

‘adverse occurrence’ means any incident associated with the donation or human application of SoHOs, which caused harm to a living SoHO donor, harm to a SoHO recipient , to offspring from medically assisted reproduction or to unborn offspring from medically assisted reproduction or that implied a risk of such harm;

(ha)

the transfer of embryos to a person other than the person intended;

(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;

(29)

‘SoHO rapid alert’ means a communication regarding an adverse occurrence , 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 preventing or mitigating measures;

(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;

(33)

‘the compendium of SoHOs ’ 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;

(38)

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

(38)

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

(40)

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

(40)

‘SoHO establishment’ means a SoHO entity that carries out processing and storage or processing and release or storage and release of SoHOs;

(41)

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

(41)

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

(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 ;

(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 SoHO recipients ;

(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:

(47)

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

(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;

(51)

‘imputability’ means the likelihood that an adverse occurrence, in a SoHO donor, is related to the collection process or, in a SoHO recipient or offspring from medically assisted reproduction , to the application of the SoHOs;

(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;

(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, storage, 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;

(61)

‘ SoHO for reproduction ’ means all cells intended to be used for the purpose of medically assisted reproduction , and embryos resulting from fertilisation ;

(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;

(62)

‘third party donation’ means a donation of a SoHO for reproduction by a person to a recipient or a couple with whom the donor does not have an intimate physical relationship;

(62a)

(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;

(63)

‘within relationship use’ means use of reproductive cells for medically assisted reproduction between persons with an intimate physical relationship, where a person provides their own oocytes and another person supplies their own sperm for the human application to a person within the relationship;

(64)

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

(64)

‘compensation’ means making good of any quantifiable losses and reimbursement of expenses associated with donation;

(64a)

(70a)

(70b)

(70c)

(70d)

(a)

shall not directly or indirectly constitute discrimination between SoHO donors based on any of the grounds recognised by Article 21 of the Charter of Fundamental Rights of the European Union, in particular discrimination based on sexual orientation. Member States shall report to the Commission any restrictions that they or SoHO entities in their territory impose that can reasonably be considered to constitute such discrimination and provide a summary of the scientific evidence used to justify these measures to protect SoHO donors, SoHO recipients or offspring from medically assisted reproduction;

(b)

may contribute to setting up a European supply chain and to achieving the objective of European autonomy and coordination between Member States; they may also be aimed at reinforcing the principle of voluntary and unpaid donation.

(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 ;

(a)

have the autonomy to act and make decisions independently and impartially while respecting the internal administrative organisational requirements determined in national legislation ;

(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;

(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 or that does not comply with the conditions of its authorisation or with this Regulation ;

(c)

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

(c)

have sufficient human and financial resources, operational capacity, and expertise , including technical expertise, to achieve the aims of, and fulfil their obligations under, this Regulation;

(a)

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

(a)

human and financial resources, operational capacity, and expertise, including technical expertise, 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;

(b)

procedures to ensure the independence, impartiality , transparency , 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;

(c)

appropriate and properly maintained facilities and equipment to ensure that personnel can perform their SoHO supervisory activities efficiently , safely and effectively;

(aa)

make the declarations of interest referred to in Article 7(2) publicly available on their website;

(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

(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; or

(a)

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

(a)

does not comply with the conditions of its authorisation or the provisions of this Regulation; or

(aa)

does not take corrective or preventive action following an inspection by national authorities pursuant to Article 29(14); and

(a)

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

(a)

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

(b)

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

(b)

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

(a)

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

(a)

the inspection techniques and procedures to be followed, including practical exercises and conflict of interest rules ;

(a)

the name or business name and address of the SoHO entity or entities carrying out the clinical study, and the name and contact details of the researchers and a contact person;

(b)

where necessary, a positive recommendation by a relevant ethics committee;

(c)

a summary of the study design;

(d)

date of commencement and completion of the various stages of the clinical study;

(e)

not more than one year after the end of the clinical study, a summary of the results and conclusions;

(f)

a summary intended for the general public of the clinical study and the results obtained.

(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:

(b)

the results of a risk assessment conducted in accordance with Article 41a(4);

(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;

(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 , and as set out in Article 41a(5) ;

(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.

(a)

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

(b)

whether the SoHO preparations meet the defined quality criteria in the EDQM SoHO monograph referred to in point (a) and are 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;

(c)

information regarding previous use and authorisation of the SoHO preparations in other SoHO entities, as available on the EU SoHO Platform;

(d)

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 preparations, where available;

(e)

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 preparations.

(a)

in the context of clinical outcome monitoring for the authorisation of a new SoHO preparation as referred to in Article 41(2), point (c):

(b)

in the context of a comparative clinical study with previously authorised SoHO treatments.

(b)

investigation of suspected adverse occurrences in SoHO donors and recipients;

(b)

investigation of suspected adverse occurrences in SoHO donors , SoHO recipients and, where relevant, offspring from medically assisted reproduction ;

(a)

meet all applicable consent or authorisation requirements in force in the Member State concerned;

(a)

meet all applicable informed consent or authorisation requirements in force in the Member State concerned;

(b)

provide donors or their relatives or any persons granting authorisation on their behalf, in accordance with national legislation, with the information referred to in Article 55 and in a way that is adequate in view of their capacity to understand it ;

(b)

provide donors or their relatives or any persons granting authorisation on their behalf, in accordance with national legislation, with the information referred to in Article 55 and in a way that enables them to give informed consent and request further information if needed ;

(j)

verify, by means of a registry , that donors are not donating more frequently than indicated as safe in technical guidelines as referred to in Article 56 and demonstrate that their health is not compromised;

(j)

verify, by means of national registries , that donors are not donating more frequently than indicated as safe in technical guidelines as referred to in Article 56 and demonstrate that their health is not compromised;

(ja)

verify, by means of national registries, that donors meet donor eligibility criteria, if required in the case of specific types of donation, on the basis of the latest available scientific evidence and medical expertise;

(la)

inform the SoHO recipients of donor anonymity requirements and the possibility of ID release and the implications thereof for medically assisted reproduction with third party donation of reproductive cells, pursuant to national legislation.