COMMISSION STAFF WORKING DOCUMENT Subsidiarity Grid Accompanying the document Proposal for a Regulation of the European Parliament and of the Council on standards of quality and safety for substances of human origin intended for human application and repealing Directives 2002/98/EC and 2004/23/EC
Date: 2022-07-14
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: artificial reproduction, blood transfusion, cytology, health control, quality standard, safety standard, stem cell, substance of human origin, therapeutics

EN 

  EN 

   EUROPEAN COMMISSION  Brussels, 14.7.2022  SWD(2022) 189 final  COMMISSION STAFF WORKING DOCUMENT Subsidiarity Grid Accompanying the document Proposal for a Regulation of the European Parliament and of the Council  on standards of quality and safety for substances of human origin intended for human application and repealing Directives 2002/98/EC and 2004/23/EC {COM(2022) 338 final} - {SEC(2022) 304 final} - {SWD(2022) 190 final} - {SWD(2022) 191 final}  
 
 
Subsidiarity Grid  

1.  Can the Union act? What is the legal basis and competence of the Unions’ intended action? 

1.1 Which article(s) of the Treaty are used to support the legislative proposal or policy initiative? 

The  legislation  on  blood,  tissues  and  cells  (BTC)  is  based  on  Article  168  of  the  TFEU.  This  Treaty 
Article gives the EU a mandate to set out measures establishing high standards of quality and safety 
for BTC while allowing Member States to maintain or introduce more stringent protective measures.  

1.2 Is the Union competence represented by this Treaty article exclusive, shared or supporting in 
nature? 

In the case of common safety concerns in public health, the Union’s competence is shared with 
Member States.  

2.  Subsidiarity Principle: Why should the EU act? 

2.1 Does the proposal fulfil the procedural requirements of Protocol No. 21: 

-  Has there been a wide consultation before proposing the act? 
- 

Is there a detailed statement with qualitative and, where possible, quantitative indicators 
allowing an appraisal of whether the action can best be achieved at Union level? 

- 

To collect all relevant views and engage with stakeholders as much as possible, different 
consultation methods were combined. DG SANTE consulted with stakeholders via (i) the 
publication of the inception impact assessment for feedback, (ii) two online consultations 
(one for all interested stakeholders/citizen, the other one targeted at organisations directly 
impacted by the BTC legislation), (iii) hearings with Member States competent authorities 
and stakeholders and (iv) bilateral meetings with stakeholder organisations. Because of the 
COVID-19 pandemic, all meetings were held in virtual format. In addition, a series of 11 
three-hour online participatory workshops was conducted, involving competent authorities 
and invited stakeholders with experience relevant to the topics to be discussed. Some 
stakeholders were also engaged via semi-structured interviews. Finally, online questionnaires 
addressed to competent authorities, and representatives of all impacted stakeholders 
categories were used to fill remaining gaps in the evidence base. A summary of all these 
activities and their outcomes is provided in the Annex 2 – Synopsis report, of the Impact 
Assessment SWD.  

- 

The explanatory memorandum and the impact assessment SWD (chapter 3) contain a section 
on the principle of subsidiarity (see also question 2.2 below).  

2.2 Does the explanatory memorandum (and any impact assessment) accompanying the 

Commission’s proposal contain an adequate justification regarding the conformity with the 
principle of subsidiarity? 

Ever-evolving disease threats, such as Zika, Human Immunodeficiency Virus (HIV) or Viral Hepatitis B, 
C and D, which can be transmitted through BTC, or more recently COVID-19, constitute cross-border 
threats  to  public  health.  The  exchange  of  BTC  between  Member  States  and  with  third  countries  is 
necessary  for  ensuring  patient  access  and  sufficiency  of  supply.  The  extent  of  exchange  is 

1 https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:12016E/PRO/02&from=EN  

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considerable, although it varies highly from substance to substance.  

The BTC legislation has been in place for more than 15 years now. Its evaluation concluded that, in 
general,  the  Blood  and  Tissues  and  Cells  Directives  improved  the  quality  and  safety  of  BTC  in  a 
manner  that  would  not  have  happened,  or  would  have  happened  more  slowly,  without  EU 
legislation; indeed, intensive activity to raise safety and quality to a common level were seen across 
the  EU  following  the  adoption of  the  legislation.  The  outdating of  technical  requirements  over  the 
years  has  led  to  a  diversification  of  standards  with  more  stringent  national  requirements 
compensating for shortcomings of the legislation. Although this is permitted by the Treaty, it limits 
exchanges between Member States. EU action is required to reinforce the framework, increase trust 
and  facilitate  that  patients  in  all  Member  States  can  benefit  equally  from  safe  and  effective  BTC. 
Increasing cross-border exchanges of BTC necessitate ever-closer cooperation between a number of 
health  professional  groups  and  authorities  to ensure  that  BTC  remain traceable  from the  donor  to 
the  recipient  and  vice  versa.  The  evaluation  confirmed  the  benefits  of  setting  quality  and  safety 
standards for BTC at EU level although pointed to a need for a more responsive approach to changing 
risks. 

2.3 Based on the answers to the questions below, can the objectives of the proposed action be 

achieved sufficiently by the Member States acting alone (necessity for EU action)? 

The evaluation of the BTC legislation has shown that there are barriers to the exchange of BTC 
among Member States, due to more stringent requirements currently in place in some of them, and 
lack of trust. The problem affects all Member States, and it is more prominent in those Member 
States having more stringent protective measures in place. In the absence of EU level action, the 
problems highlighted in the evaluation of the BTC legislation are expected to further deteriorate. 
While Member States can take actions at national level, only EU action will allow for more 
harmonised standards for safety and quality of BTC in the whole EU, and more trust among Member 
States thanks to strengthened oversight practices. This will facilitate the exchange of BTC, hence 
access to patients to safe and effective therapies across all EU. 

(a)  Are there significant/appreciable transnational/cross-border aspects to the problems being 

tackled? Have these been quantified? 

As stated above, the extent of exchange of BTC is significant, within the EU and with third countries. 
There is significant import of bone preparations, particularly from the United States, and corneas are 
regularly  exchanged  between  Member  States  and  imported  to  the  EU.  There  is  a  continuous  and 
significant  exchange  and  import  of  plasma  for  PDMP  manufacture  (25%  of  the  plasma  needed  for 
manufacturing  PDMP  to  treat  EU  patients  is  imported  from  the  USA).  Almost  half  of  all 
haematopoietic  stem  cell  transplants  (around  17.500  units)  involve  a  donation  made  in  another 
country to improve the genetic match. There are substantial cross-border shipments from some EU 
hubs  where  gamete  collection  is  organised  (leading  sperm  banks  in  Denmark  supply  to  many 
countries, Spanish IVF clinics collect and supply egg-cells to many patients from other countries).  

However, the evaluation of the legislation has shown that there are barriers to the exchange of BTC 
so it is difficult to assess  the  full potential for exchange  of those  therapies  among Member States, 
due to more stringent requirements currently in place in some of them, and lack of trust. 

(b)  Would national action or the absence of the EU level action conflict with core objectives of 

the Treaty2 or significantly damage the interests of other Member States? 

2 https://europa.eu/european-union/about-eu/eu-in-brief_en  

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To better protect the health of EU citizens, the Commission is building a strong European Health 
Union. In the absence of EU level action, the problems highlighted in the evaluation of the BTC 
legislation are expected to further deteriorate, as new epidemiological threats can emerge, scientific 
developments will continue, together with innovative practices in processing BTC. Such deterioration 
will have a negative impact on the timely access for patients to therapies that can save their life, and 
overall on the protection of patients, BTC donors and children born from medically assisted 
reproduction. 

(c)  To what extent do Member States have the ability or possibility to enact appropriate 

measures? 

Member States make national decisions on the organisation of healthcare, on ethical rules regarding 
permission for certain BTC practices such as third party egg donation or surrogacy, consent rules for 
donation after death or for the implementation of the voluntary unpaid donation (VUD) principle. In 
accordance with Article 168(4)(a) of the TFEU, they can also put more stringent protective measures 
in place for BTC. 
It should be noted that for the objective of “improving the resilience of the sector, mitigating risk of 
shortages”,  the  Commission  has  no  legal  mandate  to  put  in  place  direct  measures  affecting  the 
demand for BTC. The organisation of collection and exchanges of BTC is a competence of Member 
States. However, from the evaluation, and even more with the pandemic, it  became clear that not 
having  monitoring  measures  and  measures  for  crisis  preparedness  nor  crisis  management  was  an 
issue,  and  this  is  where  the  EU  could  act.  Such  tools  would  be  crucial  for  Member  States  to  take 
mitigation measures in case of drops in supply. 

(d)  How does the problem and its causes (e.g. negative externalities, spill-over effects) vary 

across the national, regional and local levels of the EU? 

The problem varies according to Member States, being more prominent in those Member States 
having more stringent protective measures in place. Indeed, the outdating of technical rules for 
safety and quality, together with the incomplete scope, has caused some Member States to put 
increasing numbers of more stringent measures in place. However, in some other Member States or 
regions, where more stringent measures have not been put in place, the application of the outdated, 
or overly generic, requirements in the current legislation, mean that some patients treated with BTC 
therapies, BTC donors and offspring born from medically assisted reproduction are exposed to 
avoidable risks. Access to innovative therapies is also unequal for all EU citizens or innovative 
therapies are used with widely varying levels of supportive evidence of efficacy.  

(e)  Is the problem widespread across the EU or limited to a few Member States? 

The problem is affecting all Member States, to diverse degrees. 

(f)  Are Member States overstretched in achieving the objectives of the planned measure? 

Some sector-specific expertise might not be easily available in all Member States, and it 
brings simplification and efficiency to provide for a framework allowing and supporting joint 
practices, such as joint inspections of establishments (those providing BTC to many Member 
States, or those having a specific technology/process in place), joint assessment of new 
processes etc. 

(g)  How do the views/preferred courses of action of national, regional and local authorities 

differ across the EU? 

It should be noted that in the BTC sector, only three Member States (Germany, Italy and 

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Spain) have, in addition to the national authority, also regional authorities, which oversee the 
establishments. From the consultation activities carried out, a small number of specific 
comments were received from regional authorities (the Spanish ones, in the targeted 
consultation). Their views are in general similar to the consensus that emerged from all the 
consultation activities. They however prefer a stronger role of EU legislation for setting 
technical rules than the average of respondents, including the national authorities. They 
mention that also regional competent authorities should be able to access advice from the 
borderline classification mechanism, if it is set up, and they report complexities (it is also 
time-consuming) from their own experience on getting responses from national/EU level on 
borderline cases. They have more limited concerns than the national authorities on the cost 
and administrative burden of implementing requirements for reporting and monitoring of 
activity data (e.g. donations, supply, shortages) nationally and at an EU level. 

2.4 Based on the answer to the questions below, can the objectives of the proposed action be 

better achieved at Union level by reason of scale or effects of that action (EU added value)? 

The key added value of the EU approach in this proposal is to ensure, where appropriate, that 
common standards and guidance make full use of the high level of latest scientific and technical 
expertise, as already available in expert bodies such as the ECDC and the EDQM, and therewith 
facilitate cross-border exchange of and access to safe BTC.  
EU action will enable simplification and efficiency, by providing for a framework allowing and 
supporting joint practices, and building on and sharing Member States’ expertise. In addition, the 
sharing of data through a common platform, and following common guidance, will enable policy 
making based on significantly more robust data. 

(a)  Are there clear benefits from EU level action?  

The COVID-19 pandemic highlighted the risks for supply interruptions, the need for adequate 
donor and recipient protection, and the need for rapid and adequate authorisations of health 
innovations in the BTC sector. By providing a framework for cross-border cooperation, based 
on a common set of rules, EU-level measures are best placed to address such issues 
effectively. Establishing minimum standards of quality and safety for BTC at an EU level 
brings significant efficiencies for Member States, avoiding the need for multiple exercises in 
risk, benefit and cost analysis. Such minimum standards can also allow more stringent rules 
on national level if it is considered necessary by the Member State. 

(b)  Are there economies of scale? Can the objectives be met more efficiently at EU level (larger 

benefits per unit cost)? Will the functioning of the internal market be improved? 

More collaboration and support among the national competent authorities (NCAs) would help to 
address the issues highlighted in the evaluation, bringing simplification and improving the 
effectiveness of the legislation and the efficiency of its implementation. Sharing information across 
Member States at NCAs level, e.g. on the supply of critical BTC, authorisations of preparation 
processes, or results of the inspection of an establishment, will help other Member States. Surpluses 
for a certain BTC will be transparent and authorities may re-use an authorisation already given (by 
assessing that the procedure is equivalent, without re-assessing a complete risk assessment or 
clinical evidence provided). The burden associated with this data sharing will be significantly reduced 
by the provision of an EU digital platform where data can be entered directly by operators and 
accessed by authorities. Also, collaboration among Member States (e.g. joint inspections and joint 
preparation process assessments) will lead to building more trust among the NCAs, which ultimately 
should facilitate exchange of BTC, hence access for patients. All this will be more efficient at EU level, 
rather than compared to actions taken individual by all Member States.  Commission audits of 

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national competent authorities will increase mutual trust and avoid the need for the administrative 
burden associated with treating inter-Member State distribution of BTC as import. 

While  substances  of  human  origins  are  not  considered  tradeable  commodities  as  such,  there  are 
significant cross-border exchanges taking place, in particular for substances where exact matching is 
required (e.g. bone marrow). Improving harmonisation of technical and safety rules, and increasing 
transparency  where  national  differences  in  requirements  remain  in  place,  will  reduce  variations  in 
national rules that create barriers to the exchange of BTC among Member States. 

(c)  What are the benefits in replacing different national policies and rules with a more 

homogenous policy approach? 

There is already a BTC legislation in place at EU level. However, shortcomings were 
highlighted and this proposal aims at addressing them, to make the BTC legal framework 
more effective, future proof and crisis resistant.   

(d)  Do the benefits of EU-level action outweigh the loss of competence of the Member States 
and the local and regional authorities (beyond the costs and benefits of acting at national, 
regional and local levels)? 

The proposed EU action will bring simplification and more harmonisation among Member 
States, to better protect all EU citizens and facilitate their access to safe, effective and 
innovative BTC therapies. Member States will not lose competences, and they will be able to 
maintain or introduce more stringent protective measures. 

(e)  Will there be improved legal clarity for those having to implement the legislation? 

The evaluation of the BTC legislation showed that there are sometimes difficulties in defining the 
borderlines for novel BTC with other regulatory frameworks, in particular where medicinal products 
and medical devices are concerned. This creates administrative burdens and implicit disincentives for 
BTC establishments, healthcare professionals and academia to innovate. The proposal plans for an 
EU-level advisory mechanism to clarify the applicability of BTC requirements. A coherence 
mechanism with equivalent advisory mechanisms in other legal frameworks (pharma, devices) is 
planned to allow for common advice to public and commercial developers of borderline 
technologies.  

The current co-existence of outdated technical rules in EU legislation with regularly updated 
guidance on the same topics from the European Centre for Disease Prevention and Control and the 
European Directorate for the Quality of Medicines will be replaced by a clear hierarchy of norms with 
cross-references to the source of technical standards to be followed. An EU digital platform funded 
and supported by the Commission will enable sharing openly information on the quality and safety 
requirements and will also allow timely updates in case of emergency (e.g new epidemiological 
threat that could be transmitted via BTC). This increased transparency, and the publication of 
national more stringent rules put in place in the same EU digital platform, will further bring clarity for 
all stakeholders implementing the legislation. 

3.  Proportionality: How the EU should act 

3.1  Does the explanatory memorandum (and any impact assessment) accompanying the 

Commission’s proposal contain an adequate justification regarding the proportionality of the 
proposal and a statement allowing appraisal of the compliance of the proposal with the 
principle of proportionality? 

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The measures proposed are limited to actions that need to be taken at an EU level in order to be 
effective and efficient.  
For effectiveness, the newly defined scope, the new measures for donor protection and the 
clarification on the technical safety and quality rules to be applied, all ensure that citizens, whether 
donors, patients or children born from medically assisted reproduction, are guaranteed an equal 
level of protection across the EU, including when they are treated in Member States other than their 
own or when they donate BTC or are treated with BTC, including novel BTC, originating in another 
Member State.  
For efficiency, the newly defined measures on joint inspections and joint preparation process 
authorisations, the provision of an EU digital platform with supply data from across the EU and the 
sharing of authorised process information will facilitate common use of single authorisations or 
inspections for multiple purposes in multiple Member States and will support the efficient sharing of 
BTC for patient benefit on a routine basis and in emergency situations. 

3.2 Based on the answers to the questions below and information available from any impact 
assessment, the explanatory memorandum or other sources, is the proposed action an 
appropriate way to achieve the intended objectives? 

The proposal takes the form of a new Regulation repealing two existing Directives. This type of 
instrument is considered most suitable, considering that a key element of the proposal is to establish 
more harmonised measures for Member States and organisations involved in collection, testing, 
processing, distribution, application of substances of human origin, from donors to patients. 
Insufficient harmonisation was identified as a key reason for reduced trust between Member States, 
resulting in reduced cross-border exchange and sub-optimal access for patients to BTC. The measures 
do not require the implementation of national measures and can be directly applicable. 

(a)  Is the initiative limited to those aspects that Member States cannot achieve satisfactorily on 

their own, and where the Union can do better? 

Significant and wide-ranging expertise is needed to set technical standards for operators 
working with BTC and to keep them up to date with continuously evolving epidemiological 
risks and new technologies in this field. Very few Member States can harness this level of 
expertise for every technical aspect of ensuring the safety and quality of BTC for donors and 
patients in their own Member State. The added value of the EU approach in this proposal is 
to ensure full utilisation of the high level of scientific and technical expertise already 
concentrated in the European Centre for Disease Prevention and Control and the European 
Directorate for the Quality of Medicines.  
The expertise and resources required by competent authorities to oversee these activities, 
particularly to authorise and monitor them, is available to varying degrees across Member 
States. The evaluation highlighted the need for strengthened oversight to improve inter-
Member State trust and exchange of BTC but this strengthening brings increased workload 
and expertise requirements for authorities. In this context, the proposal includes measures 
to promote sharing of expertise at the authority level and provides for the use of EU level 
digital tools for monitoring and sharing, without the need for duplicating these at national 
level. 

(b)  Is the form of Union action (choice of instrument) justified, as simple as possible, and 

coherent with the satisfactory achievement of, and ensuring compliance with the objectives 
pursued (e.g. choice between regulation, (framework) directive, recommendation, or 
alternative regulatory methods such as co-legislation, etc.)? 

The current legislation for the BTC field includes two basic Acts, both Directives, and 7 implementing 

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Acts. The transposition of these Directives into national legislation in different ways has contributed 
to  the  variations  in  practice  and  oversight  across  the  Union.    This  has  been  highlighted  in  the 
evaluation  and  stakeholders  clearly  support  a  more  harmonised  approach  to  ensuring  safety  and 
quality  with  clearer  common  rules.    The  main  aim  of  this  greater  harmonisation  is  to  increase  the 
exchange of BTC and to ensure that all citizens have equal protection from the risks of donating or 
being treated with these substances, while ensuring that Member State competences for healthcare 
organisation  are  not  compromised.  To  achieve  this  aim,  the  two  basic  Acts  will  be  replaced  by  a 
Regulation  and  the  existing  implementing  legislation  will  also  be  repealed.    This  instrument  will 
provide a significantly higher level of clarity and conformity to common safety and quality principles. 
In  the  legal  proposal,  an  efficient  implementation,  adding  flexibility  and  proportionality,  will  be 
followed.  With  regards  to  technical  safety  and  quality  rules,  however,  the  proposed  Regulation 
provides for a clear hierarchy of norms to be followed. As part of that hierarchy, co-regulation, based 
on legal references to the standards of expert bodies such as the ECDC and the EDQM, will become 
the most used approach for technical rules.  The approach will facilitate an efficient and responsive 
updating of technical standards whenever risks and technologies change and is proportionate in that 
it ensures EU legislation would be adopted for technical rules only when necessary and when it adds 
value. At the lowest level of the hierarchy, when no technical standard is defined in the EU legislation 
or  by  referenced  expert  bodies,  operators  will  apply  a  locally  defined  rule  that  is  in  line  with 
internationally  recognised  standards,  scientific  evidence  and/or  a  documented  risk  assessment. 
Finally, it needs to be recalled that Member States have the right in the TFEU to set more stringent 
standards. This proposal will respect  this, but will bring more transparency on such more stringent 
national standards and facilitate cross-border exchange and optimal access to BTC for patients across 
the EU. 
Some technical topics, such as coding and importing rules, will require implementing legislation but 
the  number  of  implementing  or  delegated  Acts  will  be  significantly  reduced,  with  this  greater 
reliance  on  up-to-date  expert  standards.  The  harmonisation  of  oversight  activities  will  be  greatly 
increased by the adoption of guidance for authorities, in consultation with  a representative ad-hoc 
co-ordination group of experts and Member State representatives. 
Of  the  policy  options  considered  in  the  Impact  Assessment,  this  approach  emerged  as  the  most 
effective and simplest one to achieve the key objective of improved and common levels of donor and 
patient protection. 

(c)  Does the Union action leave as much scope for national decision as possible while achieving 
satisfactorily the objectives set? (e.g. is it possible to limit the European action to minimum 
standards or use a less stringent policy instrument or approach?) 

The proposal balances the need for clear and high standards to protect donors and patients equally 
while ensuring that Member State competences for health care organisation are not compromised. 
The  legal  basis  allows  Member  States  to  adopt  more  stringent  measures  when  they  consider  it 
necessary.  The proposal does not interfere with that right but does increase the level of safety and 
quality to be achieved in all Member States, thus reducing the need for more stringent measures that 
can  create  hurdles  to  exchange  and  to  patient  access.  In  addition,  the  proposal  will  ensure  the 
adoption  of  more  stringent  measures  is  made  more  visible  so  that  exchanges  can  be  more  easily 
organised despite those measures. 
The  principle  of  proportionality  is  strongly  reflected  also  in  the  new  provisions  for  oversight  of 
operators working on BTC. Although the scope of the proposal will affect operators and activities not 
previously within the scope of the BTC framework, a graded approach to oversight has been defined, 
with lighter requirements for registration only or for preparation process authorisation only for those 
entities  carrying  out  BTC  activities  with  lower  risk  levels.  Some  entities  previously  inspected  and 
authorised  as  BTC  establishments  will  change  to  a  simpler  registration  with  limited  reporting 

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requirements.  Furthermore,  planning  of  inspections  will  be  adapted  to  the  inherent  risk  of  the 
establishments,  allowing  for  more  frequent  inspections  for  those  with  high  volumes,  complex 
activities  or with  a  poor  safety-record.  Similarly,  although  the  proposal  includes  new  requirements 
for demonstrating efficacy for novel ways of processing or using BTC, these requirements are graded 
according to the degree of risk or novelty and the most demanding clinical studies will be required 
only for those novel processes that imply higher risk for patients. 

(d)  Does the initiative create financial or administrative cost for the Union, national 

governments, regional or local authorities, economic operators or citizens? Are these costs 
commensurate with the objective to be achieved? 

The administrative  costs  relative  to the  baseline  have  been estimated in the impact  assessment  as 
comprising  a  EUR  22  million  one-off  investment  between  2023/4  and  2027,  and  EUR  12  million 
recurrent  annual  costs.  Of  these  recurrent  administrative  costs  for  the  public  authorities,  EUR  9 
million  are  for  the  European  Commission  and  EUR  3  million  are  for  Member  States  public 
authorities).  The  largest  part  of  the  one-off  investments  would  amount  to  EUR  12  million  for  the 
Commission and EUR 10 million for the Member States public authorities. These costs are relative to 
the baseline, expressed as present value over 2022-2031. 

(e)  While respecting the Union law, have special circumstances applying in individual Member 

States been taken into account? 

Given that rules relating to ethical aspects of this field, or to healthcare organisation, are not 
included in this proposal, no special circumstances in individual Member States were identified that 
required a particular territorial variation in the measures to be applied. 

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