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# Participation in SoHO and ATMP public consultations: a fragmented institutional landscape

Michael Morrison, Valentin Brunel, Aurélie Mahalatchimy

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Michael Morrison, Valentin Brunel, Aurélie Mahalatchimy. Participation in SoHO and ATMP public consultations: a fragmented institutional landscape. Humanities and Social Sciences Communications, 2025, 12, 10.1057/s41599-025-04552-1. hal-04990054

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https://doi.org/10.1057/s41599-025-04552-1

**To cite this article:** Morrison, M., Brunel, V. & Mahalatchimy, A. Participation in SoHO and ATMP public consultations: a fragmented institutional landscape. Humanit Soc Sci Commun 12, 262 (2025). https://doi.org/10.1057/s41599-025-04552-1

**Title:** Participation in SoHO and ATMP public consultations: a fragmented institutional landscape.

**Abstract**

This paper looks at the recent EU public consultations on the proposed Substances of Human Origin (SoHO) Regulation and compares them with the prior consultations on the ATMP Regulation. Information on each contributor to the three most recent consultations on SoHO and the two available consultations on the ATMP was collected, analysed, and used to develop a novel typology of entities participating in the consultations. This data set included the country of origin of each entity making a contribution and the type of entity involved (academic/research Institutions, National Bodies, companies, business organizations, patient and consumer organizations, learned societies, individual citizens, networks/Innovation organizations, and other Non-Governmental Organizations). The results show that the SoHO consultations attracted a far greater total volume of participants and displayed a greater variety of organizations from more distinct countries compared to the ATMP consultations. The most significant finding is the very low overlap in organisations making a contribution to both a SoHO and an ATMP consultations. This strongly suggests that there is significant institutional fragmentation between organisations collecting human biomaterials and organisations developing ATMP for market. Given that collection of biomaterials is a necessary first step in the development of most ATMP, European policy makers wishing to support 'homegrown' innovation with ATMP should give greater consideration to building better links between organisations collecting biomaterials and ATMP developers.

# 1 Introduction

Biomedical innovation (BI), in areas such as gene therapy, tissue engineering and regenerative medicine, offer great clinical and economic promise, but also pose considerable risks to human and environmental wellbeing. BI can be defined as a set of (evolving) processes and products based on biological elements of human or animal origin intended to generate improvements in human health and economic competitiveness (Mahalatchimy 2019). For the purposes of this paper, we are exclusively concerned with BI employing human biological materials. Regulation of BI is essential to ensure quality and safety, but the relationship between BI and the law is complex. Biomedical innovations challenge the scope and relevance of existing legal frameworks and concepts (Pottage, 2007), but they also elicit novel and creative regulatory responses (Faulkner, 2009). In this regard, the law does not merely respond to technological change, but rather law and BI are co-produced. Law and regulation actively shape the meaning, social organization, conduct, and dissemination of BI as much as technical and medical innovations provoke legal adaptations (Jasanoff 2004).

The regulation of BI is also, and not unrelatedly, a site of political contestation (Faulkner,
2012b). This is especially the case within the European Union (EU) where the aim of legislation
on BI is not only to harmonise conditions for market access across Member States and to
guarantee a high level of protection of human health, but to create a shared space of
definitions, standards and practices of BI that can be considered ‘European’. The creation of
EU regulations on BI are a site at which visions of ‘Europe’ itself as a political entity are
articulated, contested and ultimately enacted (Callon, 2004; Mahalatchimy et al 2021). Under
the tripartite ‘co-decision’ ordinary system of the EU, the European Commission proposes new
legislation, the European Parliament (representing EU citizens), and the Council of the
European Union (representing the political positions of Member States) debate and finally vote
on it. Most of the time, proposals of the Commission are based on previous works including a
process of public consultation. As Faulkner (2012a) has observed the ‘public’ in EU public
consultations on BI is primarily constituted in terms of ‘stakeholders’ such as national and
European regulators, biotechnology, pharmaceutical and medical device companies,
scientists engaged in research and development, clinicians, hospital managers, industry
bodies, patient organisations, tissue and blood banks, and business consultants offering
advice to smaller companies. As such the consultation is a process where “a great deal of
lobbying by interest groups occurs” (Faulkner 2012a, p393). This makes the EU public
consultations on regulations an important, but largely under-explored, site for studying the co-
production of law and BI in Europe.

The aim of this paper is to scrutinise the public consultations on two prominent examples of EU legislation on BI: the Advanced Therapy Medicinal Products (ATMP) Regulation (EP & Council 2007) and the proposed new Regulation covering Substances of Human Origin (SoHO) (EC P 2022). The ATMP Regulation has been the subject of considerable legal (Rial-Sebbag et al., 2019) and critical (Faulkner 2012a; 2012b) scrutiny, while the SoHO Regulation has already attracted commentary and critique even at the proposal stage (Cuende et al., 2023; Martens & Arifagic, 2023). It will almost certainly attract further commentary since the SoHO Regulation has been adopted on 13 June 2024 and will be applicable from 7 August 2027 (EP & Council 2024). However, very little scholarly attention has been given to the public consultations themselves, which represents a notable gap in the academic literature, and in our understanding of the shaping of these regulatory frameworks.

The ATMP Regulation governs medicinal products that utilise genes, cells or tissue
engineering as their basis for medicinal action. Its establishment represents a seminal
development in shaping the “sociotechnical regime” (Berkhout et al 2003) of regenerative
medicine in Europe; it creates and governs the pathway for commercialisation and market
access for cell and gene-based medicines and impacts the trajectories of scientific research
and clinical practice in this domain. The SoHO Regulation is a recent development and will
replace and repeal the existing Blood Directive and the Tissues and Cells Directive, while also
aiming to cover biomaterials that were not covered in the previous legislation, such as breast
milk and faecal or intestinal microbiota. This choice of cases provides for a comparison
between the participants in a foundational moment in the EU regulatory landscape for BI (the
formation of the ATMP regulation) and a contemporary window into the present stakeholder
landscape through the consultations on the new SoHO Regulation.

The relationship between SoHO and ATMP regulations also affects the boundary between
transplants and transfusions that, in the EU, are considered non-commercial activities
primarily provided through public healthcare systems, and cell or tissue based medicinal
products, which are mainly developed on a for-profit basis by commercial entities (Cuende et
al 2023). With human cells and tissues, the boundary between surgery-like processes and
medicine-like products has always been blurry and contested (Webster et al., 2011). Under
the prior framework there were a number of borderline cases where it was unclear whether
treatments should fall under the Tissues and Cells Directive or the ATMP Regulation (Cuende
et al., 2023; Izeta et al., 2016; Martens & Arifagic, 2023), and some cases where services
previously provided by public hospitals under the Tissues and Cells Directive were reclassified
as ATMPs (Dimitropoulos et al., 2016; Pirnay et al., 2013).
Falling into one category or the other has significant consequences in terms of the associated administrative burden and costs for parties working with human cell and tissue-based treatments, meaning that the final outcomes of both ATMP, and now SoHO, have direct implications for commercial developers, hospitals and clinicians, as well as for public and private tissue and blood banks (Chabannon et al 2014). The cost of processing cells and tissues under one framework compared to the other also directly affects access and availability of treatments, so there are stakes for patient groups, especially with regards to rare diseases (Callon & Rabeharisoa, 2008) and for healthcare payers too. Under the EU model of 'subsidiarity,' responsibility for implementing the regulatory provisions set out in EU law is devolved to Member States and their national regulatory bodies ('competent authorities'), so these organisations also have a stake in shaping the law on BI. Given this mix of (potentially conflicting) interests it is important to understand which groups and sectors are actually represented in the public consultations on the ATMP and SoHO regulations. Specifically, it is useful to know not only who was or was not represented, but to consider the weight of representation, as evidenced by volume of submissions from different sectors. Greater representation is likely to equate to greater influence on the Commission and on the final wording of legislation. Comparing participants in the ATMP and SoHO public consultations also allows for a comparison over two points in time and two dimensions of BI in Europe.

There are several reasons to expect the same stakeholders to be represented in both sets of consultations. Collection of biomaterials is a critical first step in developing ATMP (Bisson 2014; Crookes et al 2020) and the way in which collection of human biomaterials is regulated under SoHO will have a direct effect on how the later steps of advanced therapy development are conducted. The aforementioned existence of 'borderline cases' where the applicability of the ATMP Regulation is unclear, and the increasing deployment of mechanisms for early-interaction with regulators to improve clarity about regulatory pathways all suggest a blurry boundary and shared set of interests between stakeholders developing SoHO and ATMP treatments. Further, many clinical sites administer both treatments that fall under the remit of the ATMP regulation and those that would be covered by SoHO provisions. This is especially the case with the recent launch of the EMA's "ATMP pilot for Academia and non-profit organizations" which aims to provide enhanced support to academic and non-profit organizations developing ATMPs and to identify and address potential gaps in the existing regulatory tools and guidance for these groups.

Using the public consultations on the processes of adoption of the two Regulations to interrogate the structure of the European BI space will provide valuable insights into the shaping of EU legislation on BI. For policy makers and lawyers this study offers an improved typology of actors in BI policy engagement as well as insights into the practical functioning of EU public consultation policy in BI and the institutional politics of regulatory reform. For developers of human cell, tissue or gene-based therapies, this analysis sheds light on stakeholders' strategies in addressing fields with overlapping legislative regimes. The governance of human biological material for medical and biotechnological ends is also a longstanding topic of interest to scholars of Science, Technology and Innovation Studies (Pavone and Govan 2017; Mourby et al 2022), for whom all of the issues covered here are likely to be of interest.

## 2 Methods

Our research identified all consultations relating to legislative acts pertaining to both Substances of Human Origin (SoHO) and Advanced Therapy Medicinal Products (ATMP). This was achieved by i) searching the European Commission website (EC, N.D.) for Consultations using the subject filter 'advanced therapy' and selecting only responses relating to the legislative level (i.e. not guidelines), and ii) visiting the European Commission website
for revised EU rules for the Blood, tissues and cells for human application to identify the last three (i.e. most recent) consultations on the SoHO legislation. This led to the establishment of a list of 5 documents: The ATMP public consultations of 2008 and 2012, and the SoHO public consultations of 2020, 2021 and 2022¹.

<table><caption>Table 1: ATMP Public consultations studied.</caption><thead><tr><th>Titles of consultations</th><th>Dates of consultations</th><th>Number of replies</th></tr></thead><tbody><tr><td>ATMP Public consultation 2008: Proposals to amend Annex I to Directive 2001/83/EC as regards advanced therapy medicinal products</td><td>8 May 2008 - 10 June 2008</td><td>44</td></tr><tr><td>ATMP Public consultation 2012: Regulation on Advanced Therapy Medicinal Products</td><td>20 December 2012 - 31 March 2013</td><td>63</td></tr><tr><td></td><td>Total</td><td>107</td></tr></tbody></table>

<table><caption>Table 2: SoHO Public consultations studied.</caption><thead><tr><th>Titles of consultations</th><th>Dates of consultations</th><th>Number of replies</th></tr></thead><tbody><tr><td>SoHO Public consultation 2020: Revision of the Union legislation on blood, tissues and cells, European Commission Inception Impact assessment, Roadmap</td><td>17 November 2020 - 14 December 2020</td><td>82</td></tr><tr><td>SoHO Public consultation 2021: Questionnaire Blood, tissues and cells for medical treatments & therapies - revised EU rules</td><td>21 January 2021 - 15 April 2021</td><td>214</td></tr><tr><td>SoHO Public consultation 2022: Commission Adoption, Blood, tissues and cells for medical treatments & therapies - revised EU rules</td><td>14 July 2022 - 08 September 2022</td><td>113</td></tr><tr><td></td><td>Total</td><td>409</td></tr></tbody></table>

Once all consultations were collected, we identified all the actors involved in the consultation process. In several cases, multiple actors answered together in a single response. However, we counted these organisations individually to have a more complete and realistic idea of which organisations have been involved. This led us to a larger total of contributions: 544 contributions from 387 organisations and individuals corresponding to the five public consultations. This number of 387 organisations was obtained by adding all the unique organisations participating in consultations, plus all “anonymous” contributions individually. We thus presupposed that all “anonymous” contributions came from different individuals.

For every public consultation, we collected its title, date of publication, as well as the topic to which it referred, i.e. either ATMP or SoHO. Then, for each consultation, all organizations participating in the public consultation process were indexed and sorted in a table. Additional information was collected on the organisations' websites, such as country of registration and specific activity, to enable us to characterise them according to our typology.

Although some typological information about contributors is provided by the European Commission, categories are not used in a consistent or harmonised way across consultations. Moreover, contributors are free to declare their own status and country of origin, which has led to several gaps in the information or failure to publish relevant information. As a result, the publicly available typologies are not suitable for our purposes, and it was necessary to undertake more detailed classification work to support our analysis. The typology used below was constructed to account for the diversity and complexity of organisations encountered.
Two levels of classifications were established. The first level is general and includes the following categories: Academics/Research institutions, National Bodies/Public Authorities, National Bodies/Services, Business Associations, Companies/Business organisations, Individuals, Learned Societies, Patient & Consumer Organisations, Networks/Innovation organisations & movements, Other Non-Governmental Organisations (see Supplementary Material).

The second level of typology was used to gather specific data on the covered organisations (such as memberships, key elements of the organisations self-description, et cetera) to ensure the relevance of the entire typology of the first level classification. For instance, one cannot expect to find all cell and tissue banks within one category as we have chosen to distinguish between Not for Profit/public bank (as National Bodies/Services), Private banks (as Companies/Business organisations) and Associations of banks or of tissue establishments (as Learned Societies). These second level data could be used in the future to provide more in-depth analysis of each type of first level categorisation. However, it is not yet suitable for dissemination as further work remains to be done to harmonise and clean that part of the dataset.

It should be highlighted that no classification exercise is neutral. It implies at least two consequences. First, our choices of classification are necessarily influenced both by our knowledge (here expertise and intellectual commitments arising from Social and Human Sciences in the field of biomedical innovations) and the objectives of this study. For instance, the distinction between private and public organisations (Companies/Business organisations vs. National Bodies/Public Authorities and National Bodies/Services) or the wish to identify various forms of collaborations (such as Business Associations and Networks/Innovation organisations & movements). Second, our choices of classification may be challenged as researchers with other knowledge or objectives or other actors, could have chosen other categories for classification or may have distributed the organisations differently among our categories. Two examples illustrate this second aspect. On the one hand, the classification available on the European Commission website for SoHO has not been retained as it is declarative, clearly contains some mistakes, and did not align with our preferred approach to classification. On the other hand, organisations aiming to promote donation (of blood, bone marrow, or cord blood) whatever their names (association, federation, foundation) as well as the Romanian organisation named “SOS Infertility Association” have not been classified as “Patient and Consumer organisation”. They have been classified as “Other non-governmental organisations” as they are not necessarily and unambiguously established by patients or representing patients’ interests (in particular, tissue donors are not necessarily patients or, in the case of altruistic donation, consumers, meaning organisations acting in support of donation or of donors can fall under this category of Other NGOs).

First, we will report how we devised the sets of organisational categories and allocated each organisation to a category. Next, we will explain how we allocated each organisation to a country of origin and consider the consequences of our approach to the data set.

## 2.1 Detailed description of organisational typology

Through the detailed description of our typology, we are also highlighting where choosing a category for a specific organisation or type of organisations has required more extensive discussions.

**Academic/Research Institutions:** All organizations belonging to the academic world such as academics, Universities and University hospitals, as well as partnerships of academics, including research projects, and groups of academics or of academic research units (e. g. Groupe de Travail des Unités de Thérapie Cellulaire et Géniques Hospitalières, Academic
ATMP working group Netherlands & Belgium), and foundations based on academia (such as Genethon, The Veneto Eye Bank Foundation) have been included in this category. Research projects, including those based on public-private partnerships (such as Clinigene) have also been included in this category.

**National Bodies** include all organizations related to States' powers, or publicly-owned such as administrations, hospitals, public services (excepting academic and research organizations). They have been separated into National Bodies/Public Authorities (including in particular National Medicines Agencies; HTA Bodies; Transplantation Authorities; Ministries; Standards Authorities; Policy bodies; Policy & regulation bodies; Tissue & Cell Banking Authorities; Cancer Authorities; Advice bodies) and National Bodies/Services (including Not-for profit/Public banks; Networks of hospitals such as AP-HP, and Healthcare services opened to the public). It should be highlighted that UK NHS Services (which are also public hospitals) as well as Red Cross Services which have answered these consultations (as they are the only or dominant services for blood collection in particular, in some countries, i.e. Austria, Belgium and Finland) have been included in this category. Moreover "National" has been understood very broadly in order to include European levels authorities such as the European Directorate for the Quality of Medicines & HealthCare (EDQM) at the Council of Europe level, or the European Medicines Agency or the EU innovation network at the European Union level.

For business, a distinction has been made between **Business Associations** covering Associations or partnerships of private companies and **Companies/Business organisations** including all privately owned companies or business such as pharma, consulting and regulatory companies, but also private clinics, private banks.

**Patient & Consumer Organisations** cover organisations created for patients and/or by patients or consumers, aiming at a better protection and understanding of the field or illness involved.

For the purposes of this project, the category of **Learned societies** is understood in a broad sense to encompass groups of experts on a specific topic. This includes professional organisations and organisations grouping experts on a specific topic to promote an academic discipline or a group of related academic disciplines. In that context, it should be underlined that Associations of Tissue banks such as AATB (American), AEBT (Spanish), EATB (European) have been categorized as Learned Societies, while Hospitals Federations have been classified as National bodies/Services.

**Individuals** covered contributions made with no apparent or claimed¹ organisational background. We have distinguished between Individuals/EU citizens, Individuals/Non-EU citizens, and Individuals/NA (as a good number of individuals have also remained anonymous). It should be noted that individuals from the UK have been considered either EU citizens or non-EU citizens, depending on the time of their answers (before or after Brexit, dated on 1st February 2020).

Finally, the two last categories are more heterogeneous. On the one hand, **Networks/Innovation organisations & movements** cover organisations aiming at creating interest groups on certain topics and issues, often merging public and private partners with academics. On the other hand, **Other Non-Governmental Organisations** include NGOs that are not covered in other categories, such as wider Citizen Organisations.

## 2.2 Allocation of country of origin

In addition, we searched the websites of every participating organisation in order to identify their country of origin because the countries mentioned in the public consultations were almost never provided, and not always relevant. The methodological choice made was to focus first
on the country of registration of each organisation. While the process was obvious for most of
the organisations (e.g. national bodies), it still raised some issues and required a few
explanations as they have an impact on the results.

For partnerships of academics or research projects, the country of the leader or coordinator was chosen. Second, if certain organisations participated as subsidiary companies, we chose to consider the country of origin of the 'mother' company. This classification was however not always perfectly applicable since company ownership often follows intricate paths. For the most part, the country of registration when indicated on companies' websites was considered as the country of origin of the organisation. In case of a doubt or of unknown origin or registration, the country of activity or where the head office was located was considered to be the country of origin. If even that remained unclear, the country declared in the consultation document was considered to be the country of origin. Third, it should be highlighted that organisations of European governance such as the committees or groups from the European Medicines Agency or the Council of Europe have been classified as National bodies and their country of location was chosen although they are clearly more European than National. While this is unsatisfactory from a legal perspective, it is preferable not to have a 'European' geographic classifier, in order to consistently account for other entities such as Learned Societies which often have a 'European' character but may be based in an EU or non-EU country. When considering Networks or Learned Societies for instance, it should be emphasized that the country declared as country of origin does not necessarily mean the country of major activity nor the country where most members come from. Finally, for individuals who are not "organisations" per se, we chose to consider the country declared in the consultation if applicable. Otherwise, the individuals were considered anonymous.

3 Results

3.1 Profile of Organisations participating in SoHO and ATMP respectively

The first point to note is the large discrepancy in the number of responses to the SoHO consultations compared with the number of contributions to the ATMP consultations. Figure 1 shows the comparison of types of organisations that have participated in the SoHO and ATMP consultations according to our typology, and on the basis of the number of contributions.

<caption>Figure 1: Types of participating organisations in SoHO and ATMP consultations</caption>

Figure 1 shows three main similarities between the SoHO and ATMP consultation participants respectively based on counting the number of contributions. Firstly, Companies/Business organisations have provided most contributions in both SoHO (22%) and ATMP (27%) consultations. Secondly, National Bodies were the second most participating organisations in both SoHO and ATMP consultations, with an equal proportion participating in each consultation (21%). The third similarity lies in the finding that Patients & Consumer Organisations have almost equally contributed to SoHO consultations (5%) and ATMP consultations (4%), and they are in sixth position in both cases.

There are several differences between the two sets of consultations. The major points of
difference are: Academic/Research institutions have strongly (third position with almost 20%)
participated in ATMP consultations, almost equivalent to National Bodies in contrast to what
was seen in the SoHO consultations where the participation of academic/research institutions
falls to only 6% of participants. Business Associations have participated more in ATMP
consultations (fourth position with 13%) than in SoHO consultations (shared sixth position with
5%). Individuals have participated considerably more in SoHO consultations (fourth position
with 9%) compared to ATMP consultations (last position with just 2%). Learned societies
demonstrated the third highest participation in SoHO consultations (18%) but were less influential in terms of ATMP consultations where they appear in fifth position (10%). Academic/Research institutions and Networks/Innovation Organisations & movements (joint fifth position with 6%), as well as Business Associations, Patients & Consumer Organisations, and Other Non-Governmental Organisations (joint sixth position with 5%) all participated to a similar degree in SoHO consultations. Networks/Innovation Organisations & movements have participated twice as much in SoHO consultations (shared fifth position with 6%) as in ATMP consultations (seventh position with 3%). Organisations classified as "Other Non-Governmental organisations" and "NA" for "Not Available" information have participated in SoHO consultations (respectively 5% and 3%) and not in ATMP consultations. Thus, there are more points of difference than similarities.

Figure 2: Countries of participating organisations in SoHO and ATMP consultations.

Figure 2 shows the countries of origin of each organisation that participated in the SoHO and ATMP consultations respectively based on counting the number of contributions. Figure 2 shows only one key similarity between the SoHO and ATMP consultation participants. With the exception of the UK, Spain and the USA, the countries that contributed the most to both SoHO and ATMP consultations respectively are the same: Belgium, France, Germany, the Netherlands, and Italy.

Again, there are more differences than similarities between participation in the two sets of consultations. The UK and USA were part of the countries contributing most to ATMP consultations (respectively 16% and 12%), but not to SoHO consultations (3% and 4%). More EU countries have contributed to SoHO consultations. Spain (with 7%) as well as Denmark (5%), Portugal and Austria (3% in both cases), and Romania (2%) appear clearly as contributing countries, in addition to Other EU countries (14%), to the SoHO consultations. However, these countries do not appear significantly regarding ATMP consultations, where they are embedded within 'Other EU' countries that count for 9% in total. Canada has clearly appeared as a country participating in ATMP consultations (2%) and not in SoHO consultations. France, Germany, and the Netherlands which were among the countries contributing most to SoHO consultations (with Belgium) participating slightly more to ATMP consultations.

## 3.2 Contribution of National Bodies

Figure 3 shows the countries of origin of the public authorities which contributed to SoHO and ATMP consultations among the 'National bodies' based on counting the number of contributions. Figure 3 highlights strong differences within the public authorities participating in SoHO and ATMP consultations.

Figure 3: Public authorities participating in SoHO and ATMP consultations.

In the following results, the percentages are derived from the total number of unique participating countries (23). Apart from the Czech Republic and an unknown country ('NA'), all represented countries (21 out of 23, i.e. 91,3%) contributed to at least one SoHO consultation. The only information we have regarding the 'NA' (Not available) country is that it comes from an agency outside the European Economic Area. By descending order, these 21 contributions came from public authorities based in: France (8 contributions), the Netherlands (6 contributions), Spain and Germany (5 contributions each), Sweden, Norway, and Italy (4 contributions each), Denmark, Bulgaria, Belgium, and Austria (3 contributions each), Portugal, Finland, and Estonia (2 contributions each), the UK, Switzerland, Slovenia, Latvia, Ireland, Hungary, and Croatia (each providing a single contribution). 10 countries out of 23 (43,5%) contributed to at least one ATMP consultation. In descending order, these are: the UK, the Netherlands, Germany, then Spain, Italy, France, Finland, Czech Republic, Belgium, and 'NA'.
8 countries out of 23 (34,8%) contributed to at least one ATMP consultation and one SoHO consultation: the UK, Spain, the Netherlands, Italy, Germany, France, Finland, and Belgium. 2 countries out of 23 (8,7%), the Czech Republic and an unknown country ('NA') contributed to one ATMP consultation and not to any SoHO consultation.

Figure 4 shows the countries of origin of the National services which contributed to SoHO and ATMP consultations among the 'National bodies' based on counting the number of contributions. Figure 4 highlights strong differences within the National services participating in SoHO and ATMP consultations.

<caption>Figure 4: National services participating in SoHO and ATMP consultations.</caption>

In the following results, the percentages are derived from the total number of unique participating countries (13). Apart from the UK, all represented countries (12 out of 13, i.e. 92,3%) contributed to at least one SoHO consultation. In descending order, these are: the Netherlands (5 contributions), Spain and Italy (4 contributions each), France and Finland (3 contributions each), Latvia, Hungary and Austria (2 contributions each), Norway, Greece, Croatia, and Belgium (1 contribution each). 3 countries out of 13 (23,1%) contributed to at least one ATMP consultation. In descending order, these are: the UK and France (3 contributions each), and Finland (1 contribution). 2 countries out of 13 (15,4%) contributed to at least one ATMP consultation and one SoHO consultation: France with an equal contribution to ATMP and SoHO consultations (3 on each topic), and Finland (one contribution to an ATMP consultation and 3 to SoHO consultations. 1 country out of 13 (7,7%), the UK contributed to ATMP consultations and not to any SoHO consultation.

<table><thead><tr><th>Organisation</th><th>ATMP</th><th>SoHO</th><th>Both</th><th>Type</th><th>Country</th></tr></thead><tbody><tr><td>European Association for Bioindustries (EuropaBio)</td><td>2</td><td>3</td><td>5</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>Etablissement Français du Sang</td><td>2</td><td>2</td><td>4</td><td>National Bodies/Services</td><td>France</td></tr><tr><td>EUCOPE - European Confederation of Pharmaceutical Entrepreneurs</td><td>1</td><td>3</td><td>4</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>European Association of Hospital Pharmacists (EAHP)</td><td>1</td><td>3</td><td>4</td><td>Learned Societies</td><td>Belgium</td></tr><tr><td>European Federation of Pharmaceutical Industries and Associations (EFPIA)</td><td>1</td><td>3</td><td>4</td><td>Business Associations</td><td>Belgium</td></tr><tr><td>Finnish Red Cross Blood Service</td><td>1</td><td>3</td><td>4</td><td>National Bodies/Services</td><td>Finland</td></tr><tr><td>International Plasma Fractionation Association (IPFA)</td><td>1</td><td>3</td><td>4</td><td>Learned Societies</td><td>Netherlands</td></tr><tr><td>Centro Nazionale Trapianti</td><td>1</td><td>2</td><td>3</td><td>National Bodies/Public Authorities</td><td>Italy</td></tr><tr><td>European Association of Tissue Banks (EATB)</td><td>1</td><td>2</td><td>3</td><td>Learned Societies</td><td>Germany</td></tr><tr><td>European Eye Bank Association (EEAB)</td><td>1</td><td>2</td><td>3</td><td>Learned Societies</td><td>Italy</td></tr><tr><td>European Society for Blood and Bone Marrow Transplantation (EBMT)</td><td>1</td><td>2</td><td>3</td><td>Learned Societies</td><td>Netherlands</td></tr><tr><td>EURORDIS - European Organisation for Rare Diseases</td><td>1</td><td>2</td><td>3</td><td>Patient & Consumer Organisations</td><td>Belgium</td></tr><tr><td>Finnish Medicines Agency (Fimea)</td><td>1</td><td>2</td><td>3</td><td>National Bodies/Public Authorities</td><td>Finland</td></tr><tr><td>German Pharmaceutical Industry Association (BPI eV)</td><td>2</td><td>1</td><td>3</td><td>Business Associations</td><td>Germany</td></tr><tr><td>Leids Universitair Medisch Centrum</td><td>2</td><td>1</td><td>3</td><td>Academic/Research Institutions</td><td>Netherlands</td></tr><tr><td>University Hospital Leuven</td><td>2</td><td>1</td><td>3</td><td>Academic/Research Institutions</td><td>Belgium</td></tr><tr><td>Belgian Superior Health Council</td><td>1</td><td>1</td><td>2</td><td>National Bodies/Public Authorities</td><td>Belgium</td></tr><tr><td>European Medicines Agency (EMA)</td><td>1</td><td>1</td><td>2</td><td>National Bodies/Public Authorities</td><td>UK</td></tr><tr><td>Paul-Ehrlich-Institut Germany</td><td>1</td><td>1</td><td>2</td><td>National Bodies/Public Authorities</td><td>Germany</td></tr><tr><td>The Veneto Eye Bank Foundation (Fondazione Banca degli Occhi del Veneto Onlus)</td><td>1</td><td>1</td><td>2</td><td>Academic/Research Institutions</td><td>Italy</td></tr><tr><td>Tissue Bank of France (TBF)</td><td>1</td><td>1</td><td>2</td><td>Companies/Business organisations</td><td>France</td></tr></tbody></table>
Table 3: Types and origins of organisations participating in both a SoHO and an ATMP consultation.

Table 3 shows the types of organisations and their countries of origin that participated to at least one consultation on both SoHO and ATMP legislations based on the list of unique organisations participating to these consultations (387). Only one organisation, Europabio which is a Business Association, contributed to all consultations on ATMP and SoHO. Only 21 organisations out of a total of 387 identified organisations participated in both a SoHO and an ATMP consultations (5,4%). Among them, regarding their typology:

* National bodies (7/21, 33,3%) and Learned Societies (5/21, 23.8%) have been the most represented.

* Business associations (4/21, 19%) and Academic/Research Institutions (3/21, 14,3%) holds the middle ground.

* Companies/Business Organisations and Patient and Consumer Organisations, have been the least represented (1/21, 4,8% each).

Among them, regarding their countries: Belgium has been the most represented (7/21, 33,3%), followed by Italy, Germany and Netherlands (3/21, 14,3% each), then France and Finland (2/21, 9,5% each), and finally the UK (1, 4,8% each). However, although the EMA counted for the UK for country's attribution purpose (as it was based there before Brexit), it is a European Union agency. No Networks/Innovation organisations & movements, Individuals, Other Non-Governmental organisations participated in both a SoHO and an ATMP consultations.

# 4 Discussion

These findings suggest three main areas for discussion.

## 4.1 Few organisations participated in both SoHO & ATMP consultations.

Firstly, only a tiny proportion (5,4%) of organisations contributed to both at least one SoHO and at least one ATMP consultation. This strongly suggests that different actors are responsible for the initial stage of collection of biological materials, from those responsible for the manufacturing and commercialisation stages of advanced therapies as medicinal products. There is another dimension of fragmentation of BI evident. This relates to the type of therapies, between ATMP and other human biological material- based therapies which are not ATMP, such as blood transfusion, and tissues and cells transplants. This implies a range of constituencies with a stake in how the SoHO and ATMP regulations are formulated. On the one hand, ATMPs have a high profile in the policy frameworks of certain European governments, especially those countries with high income, strong investment in healthcare and robust biomedical innovation sectors. This is reflected in polices, and sometimes new agencies, intended to support innovation in BI and promote commercialisation of ATMP (Ministre de l'Économie, des Finances et de la Souveraineté industrielle et numérique, 2022; BIH N.D.; Mahler and Besser 2020; Lauter and Wirsching 2011; Guijo et al 2020; Gardner and Webster 2017; RegMed-XB, N.D.). On the other hand, SoHO is much broader in scope than the ATMP legislation and covers domains such as assisted human reproduction, tissue transplants and transfusions, blood and tissue banking, plasma-derived products and others which typically span both public and private sectors. These aspects of fragmentation are reflected in the low overall number of organisations which submitted at least one contribution to each of the SoHo and ATMP consultations, and the much greater volume of overall contributions to the SoHO consultations than the ATMP consultations.
National Bodies are something of an exception to this finding. They have highly and equally participated in both SoHO and ATMP consultations; they appeared in second position (21%). The strong participation of National bodies to both a SoHO and an ATMP consultations can be explained by their functions. National bodies are the organisations that bear delegated responsibilities for EU Member States implementation of EU legislations on SoHO and ATMP. Indeed, among the National bodies, a greater variety of countries have been represented regarding public authorities than services. There are also a significant number of national services included in National bodies, although their legal and operational activities vary according not only to the nation states considered but also to the SoHO subtopics that fall under their remit (e.g. blood transfusion services are generally distinct from services of transplants of tissues and cells). In that context, it can be highlighted that organisations involved with the procurement, donation, or storage of blood feature strongly as contributors to both SoHO and the ATMP consultations. For the older ATMP consultation this likely reflects a core of national services in high income western European countries such as the UK National Blood Service, with experience in routinely processing human cells and tissues, which was in scarce supply at the time. For SoHO, there is a wider variety of national service organisations associated with other types of biomaterials that are routinely collected for medical use other than medicines development (e.g. corneas, breast milk, etc- see Bahadur, Morrison and Machin 2011 p870) included in the category of 'national bodies'.

## 4.2 Discrepancies in the countries of organisations participating in SoHO & ATMP consultations respectively.

There is considerable discrepancy in the geographical locations of organisations making one or more contributions to the consultations on the ATMP regulation compared to those taking part in the SoHO consultations. The countries that contributed the most to both SoHO and ATMP consultations respectively are the same; in descending order: Belgium, France, Germany, the Netherlands, and Italy. The UK and US each make a significant contribution to the ATMP consultations but less so to SoHO consultations. In the case of the ATMP Regulation, the geographic distribution of contributing organisations reflects the concentration of interest in advanced therapies in high income countries with high investment in healthcare and innovation. Surveys from the time of the ATMP Regulation show that the USA had more cell and gene therapy products on the market and in clinical trials (the latter by a very large margin) than any other country globally (P. Martin et al., 2009). The important involvement of the USA (12%) and the visible involvement of Canada (2%) in ATMP consultations can be surprising given that the public consultations relate to European Union legislation. However, it reveals how much the ATMP field is international and how much the European Market was targeted by external countries, especially the USA.

After the USA, Germany was the next largest national player in terms of approved advanced therapies, and while few other European countries had cell or gene therapies on the market in the 2009 survey, the UK, Spain, France, and Denmark were all reported to have products in various stages of clinical development, while most other European countries had none (Martin, Hawksley and Turner 2009, P35). Another survey from the time found that “cellular therapies were performed in a limited number of countries and with different intensity [...] High cellular therapy rates were reported in Belgium, the Netherlands, Slovenia, Switzerland, and Turkey” (I. Martin et al., 2010, p6). While the findings of these surveys do not map exactly onto the list of main contributors to the ATMP regulation, they illuminate a pattern of mainly western European and US dominance of the advanced therapy development landscape. Some anomalies are likely due to the reporting criteria used by different surveys. For example, Martin et al (2010) included non-expanded autologous cell treatments, some of which would not count as ATMPs in their definition of ‘cell therapy,’ which might explain the presence of Slovenia and Turkey in their data. Neither survey identified Italy as a prominent ATMP developer, but Italian companies and scientists clearly had an interest in ATMPs, as evidenced, for example, by the
development of Holoclar, the first stem cell product to actually be approved under the ATMP framework in 2015, which was manufactured by Holostem Terapie Avanzate in Modena, Italy and would have been in development at the time of the consultations. The important involvement of Belgium to both ATMP and SoHO consultations should be put in perspective with the European institutions being mainly established in Brussels, which leads to an important number of organisations having their headquarters there.

The countries represented in the 21 organisations that participated in both a SoHO and an ATMP consultations can be considered the European countries that are most active across the two fields, as confirmed by the involvement of the public authorities of these countries. Ultimately, the continuity of contributors from these countries into the SoHO consultations can be interpreted as evidence of a continued interest in ATMP development, extending to a concern with how SoHO provisions will impact the collection of starting materials for advanced therapies, by organisations based in western Europe and the USA.

However, the SoHO consultations involved more EU countries and a greater diversity of participating countries overall than the ATMP consultations. For certain countries, notably the US and the UK, the proportion of the contribution is distinct between the consultations on SoHO and ATMP. The absence of the UK from the SoHO consultations can be explained by the fact that the UK was part of the EU during ATMP consultations whereas by the time of the SoHO consultations, the UK had left the EU. When the SoHO covers biomaterial-based therapies which are not ATMP (or medicines more widely), these are often not intended to be circulated internationally as medicinal products; rather they tend to be locally-applied medical interventions. The aim of SoHO is to secure the safe circulation of tissues and cells for human application within the EU; this includes import and export of tissues and cells across the borders of the EU. Previous work has demonstrated that the main countries from which EU Member States import human cells and tissues include the US, Canada, Israel, and Switzerland, all of which exhibit a relatively small number of contributing organisations to the SoHO consultations (EC 2016). Therefore, we can explain the more limited interest of these countries in SoHO compared to ATMP as reflecting the respectively smaller scale of their role as exporters as compared to the extent of their interest as commercial therapy developers.

### 4.3 Discrepancy in the types of organisations participating in SoHO & ATMP consultations

Companies/Business Organisations and National Bodies are the two types of organisations most participating in both SoHO and ATMP consultations respectively. For the ATMP Regulation, Companies/Business Organisations are the largest single group (representing 27% of contributions) with business associations representing the fourth largest set of contributors (13% of contributions). National Bodies (including both services and public authorities) are the next largest contributors, with Academic/research institutions in third position amounting to almost 20% of contributions. These figures represent the strong commercial interest in the ATMP sector, but also the prominent role of academic institutions in developing ATMPs both in terms of basic research on cell and gene therapies undertaken in university laboratories and in clinical experimentation and clinical trials conducted by academic clinicians (Pearce et al., 2014).

Beyond this, the high proportion of private sector interest in the ATMP consultation reflects the origins of the Regulation as a proposed 'tissue engineering directive' which was originally envisaged as a response to the perceived failure of commercial tissue engineering products in Europe (Faulkner, 2012a; Faulkner et al., 2006). The eventual formulation of the ATMP regulation imposed a largely product-orientated framework on cell and tissue-based products, that are 'substantially manipulated' as distinct from transplants and 'minimally manipulated' cell-based therapies, which were at that time regulated under the Tissues and Cells Directive. As Faulkner (2012a, p396) notes this represented "a clear attempt to define a borderline between capitalist commodity market and non-market forms of the technical practice of tissue
and cell therapy, typically, although not straightforwardly, institutionalized in the distinction
between hospitals and commercial enterprises". Clinical innovation, which does not use or
require market authorisation, was permitted under the ATMP regulation, but restricted to a set
of 'hospital exemption' (HE) provisions (Cuende et al., 2014). From the existing form of the
legislation, it can be seen that the greater contributions of the private sector to the consultation
paid off, as the final ATMP regulation adopts a largely commercially-orientated model of
regulation, based on the existing framework for small molecule pharmaceuticals (Faulkner
2012a; 2012b) which added new bureaucratic and procedural burdens for (largely public
sector) hospitals and other clinical services providing existing cell and tissue based therapies
such that were reclassified as ATMPs (Dimitropoulos et al., 2016; Pirnay et al., 2013).
Moreover, since its inception, the application of the hospital exemption has been subject to
critical scrutiny from industry who have argued that "lack of transparency around HE use (e.g.,
which organizations are licensed to use it, for which indication(s) and for how many patients)
has raised concern within the ATMP community around its possible exploitation and the
potential impact of such on technological innovation, economic environments and, most
importantly, public health" (Hills et al., 2020, p773).

For the SoHO consultations we again see that Companies/business organisations and National Bodies are the largest contributors. In SoHO this strong private participation is represented mainly by companies (22%, first position). As noted, human tissues and cells form the starting material for many ATMPs so there is some continuity of commercial interest across the ATMP and SoHO regulations as evidenced by the presence of industry lobby groups such as EFPIA, EuropaBio and EUCOPE as participants in both consultations (Table 3). Business associations have been more active than single Companies/Business Organisations when contributing to both a SoHO and an ATMP consultations. This can be linked to the role of these organisation types as it is one of their key goals to represent the sectoral interests of their collective membership, which here are private companies. A clear part of their interest is to secure the high evidentiary and reporting standards for procurement of human biological materials being used to develop advanced therapies, as this extract from one of the EuropaBio contributions shows:

"[blood, tissues and cells] regulation must not be used to provide for medicinal products for which no marketing authorisation is sought. As national legislation is not clear or has not addressed this issue, developers face uncertainty. The Tissues and Cells Directive should clarify the minimum requirements (for collection, labelling, testing, and storage/transport) in cases where human tissues and cells are used as a starting material for ATMPs" (EuropaBio contribution to the 2020 SoHO consultation).

This type of argument, as with industry's critique of the HE, is usually couched in terms of
protecting public health, although it must also be noted that the high evidentiary bar and
associated bureaucratic requirements (e.g. Good Manufacturing Practice accreditation) also
serve to reduce competition by making it harder for both lower-resourced commercial firms
and public sector organisations to develop ATMPs. The EMA's "ATMP pilot for Academia and
non-profit organisations" may signal a change of tack from the EU in this regard, but it is a too
recent development to have had much demonstrable effect yet. However, ATMP development
is expensive and difficult, and ATMP developers are only a subset of the commercial tissues
and cells sector. The low number of entities contributing to at least one ATMP and at least one
SoHO consultation means there are likely to be firms with an interest in SoHO that are not
developing ATMPs but commercialise other blood, cell or tissue related services or 'borderline'
products.

Although there are roughly equal volumes of Academic/research institutions contributing to both the SoHO and the ATMP consultations, there are more learned societies (and professional organisations) contributing to SoHO compared to ATMP, and also several learned societies in the data set contributed multiple times across the three SoHO consultations. This partly reflects the greater variety of uses for human biological materials besides producing
ATMPs. However, the issues of 'borderline products' and access to cell and tissue based treatments has become more politicized and more contested in the years since the introduction of the ATMP legislation (Collis, 2023; Cuende et al., 2023; Izeta et al., 2016; Pirnay et al., 2013) and addressing borderline products was flagged as a specific issue to be addressed by the proposed SoHO regulation (Martens And Arifagic, 2023). Several groups that we classed as 'Learned societies' such as the European Haematology Association and the Association of European Cancer Leagues have issued public calls for regulatory reform to support clinical development of cell treatments (EHA/AECL 2024). Public hospitals in Spain have used the hospital exemption to develop and deliver a small number of 'public sector' ATMPs (Trias et al., 2022), and these developments are set in wider backdrop of rising interest in 'social pharmaceutical innovation': "novel forms of collaborative processes, programs, policies, procedures and/or designs involving diverse sets of actors that break with conventional pharmaceutical innovation practices for the production of safe, effective, and accessible interventions that address unmet societal needs of rare disease patients and that are not primarily market driven" (Douglas et al., 2022, p4).

This concern with the impact of SoHO provisions on the cost and bureaucratic burden of providing medical care is reflected in the contributions of public sector tissue organisations to the SoHO public consultations:

> "Registration as a SoHo entity brings certain obligations and requirements for these organizations. This registration requirement is new compared to the existing legislation [...] The registration of these organizations as SoHo entities would increase costs and most likely reduce the number of organizations offering these services, while the contribution of this requirement to the safety and quality of SoHOs remains unclear" (Tampere University Regea Tissue Center contribution to Soho 2022 consultation).

> "we believe it is imminent for Europe to reflect more (1) how the very low number of cord blood samples currently being preserved can be substantially increased when revising the legislation and (2) how European patients can benefit more from advanced therapies based on cell and tissue material. [...] Any further policy option should strike a more fair balance by ensuring these types of medical innovation and basic material for ATMPs is promoted equally across all EU Member States" (Polski Bank Komórek Macierzystych S.A contribution to SoHO 2020 consultation).

Taken in concert, this suggests that the greater number of contributors to SoHO compared to the ATMP consultations and the greater geographic diversity of contributors to SoHO compared to the ATMP consultations is partly a result of the wider scope of biomaterials and purposes (such as human gametes for assisted reproductive services) covered by SoHO, but also reflects SoHO as a site for contesting different visions of the future of European cell and tissue-based therapies. The stakes in SoHO concern which types of organisations can afford to undertake procurement, storage and processing of human biological materials, especially regarding treatments on the 'borderline' between product and process, and as a result who can provide such treatments and with what effects on access and availability of treatments across all European countries.

## 5 Conclusion

The proposal for the SoHO Regulation attempts a degree of legal defragmentation. By this we mean gathering together, connecting or 'harmonising' entities or concepts within one legislative framework. This is evident in the aim to replace the prior Tissues and Cells Directive and the Blood directive, and regulate the collection (donation, procurement and testing) of blood, cells and tissues (as well as other biological substances of human origin) through a single instrument. It is also clear in the Commission's decision to replace the former Directives with a Regulation to be implemented directly instead of being transposed, with interpretation
and adaptation, into the existing national legislation of different Member States. The aim is to
reduce variability in standards pertaining to the quality and safety of donated human
biomaterials across the Union, although as Martens and Arifagic noted (2023) the proposed
Regulation does retain some derogations such as allowing Member States to set more
stringent criteria for access to certain SoHO (for example, via assisted reproductive
treatments). However, this attempt at legal defragmentation takes place against a background
of a highly fragmented institutional landscape. The most significant finding of this research is
the very low overlap in organisations making a contribution to both a SoHO and an ATMP
consultation, which strongly suggests a fragmented landscape of stakeholders in the two
domains. The fact that the ATMP consultations preceded the SoHO consultations by several
years, and yet we see only a small 'core' of the actors who contributed to the ATMP
consultations contributing to the later SoHO consultations indicates that the landscape has
remained fragmented over time with limited overlap between ATMP developers and institutions
involved in tissues and cells collection.

Our findings strongly suggest low institutional cohesion across the wider BI sector, although further research would help to clarify what actually happens in practice between ATMP and SoHO organisations. For example, it is possible biobanks and innovation networks play a role in mediating communication, and the flow of biological materials, across organisations working under the two frameworks. Policy makers wishing to support ATMP development should take into account this apparent fragmentation and find ways to help these two sets of actors to communicate with one another. There is some evidence that this is already happening in dedicated areas, such as CAR-T cell development, and through initiatives such as the EuroGCT (gene and cell therapies) project where both SoHO and ATMPs therapies are covered and content is dedicated to all actors. However, it does also suggest a potential future role for the SoHO coordination board, which was scheduled to be established by 7 August 2024 "to promote coordination between Member States (...), and to support them in that coordination, as well as to facilitate cooperation with stakeholders in that regard" (Regulation (EU) 2024/1938). Indeed, one of the assigned task of the SoHO coordination board is to provide "assistance and advice for the cooperation between SoHO competent authorities and other competent authorities, with a view to ensuring coherent oversight where the regulatory status of SoHO changes (...)" (Ibid).

Ultimately, the regulation of BI within the European Union must consider the needs of different stakeholders, to find a balance that enables smooth interactions between organisations collecting substances of human origin and those using them to develop ATMPs without inhibiting the activities of other actors in the sector especially public sector hospitals and tissue banks. This necessarily also involves a balancing of the Commissions' responsibilities in the areas of the common market and public health. It is a balance with direct implications for healthcare provision and affordability, and illustrates how these regulatory consultations, despite limited involvement of anything resembling a European citizenry (Faulkner 2012b), are important sites at which the political shape of Europe is negotiated and enacted, and as such are worthy of further study.

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Figures legends

Figure 1: Types of participating organisations in SoHO and ATMP consultations

Figure 2: Countries of participating organisations in SoHO and ATMP consultations.

Figure 3: Public authorities participating in SoHO and ATMP consultations.

Figure 4: National services participating in SoHO and ATMP consultations.

Competing Interest Statement

[Author 1] and [Author 2] have been funded by ANR-funded I-BioLex project (ANR-20-CE26-0007-01) and by the European Union's Horizon 2020 EuroGCT project (GA: No 965241).

[Author 3] was funded by the European Union as part of the HLA-homozygous iPSC-cardiomyocyteE Aggregate manufacturing technologies for allogenic cell therapy to the heart (HEAL) consortium (project no 101056712). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the
European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them.

[Author 3] is a current member of the editorial board of Social Sciences and Humanities Communications.

### Data Availability Statement

The dataset generated for this study can be found in the Supplementary materials accompanying this paper.

### Ethical Approval and Informed Consent

This article does not contain any studies with human participants performed by any of the authors.

### Author Contributions

[redacted] formulated the research question and coordinated the work. [redacted] and [redacted] designed and executed the data collection and data cleaning. [redacted] produced the figures and tables. [redacted] and [redacted] interpreted the findings and all authors contributed to drafting the manuscript text.

### Acknowledgments

The authors would like to thank Alex Faulkner and John Gardner for useful discussions on refining and applying the typology of contributors participating in public consultations used in this paper.

<footnote n="1">¹We did not include prior consultations on the evaluation of the Blood, tissues and cells legislation.</footnote>

<footnote n="2">²For example, some ‘individual’ responses came from staff at the US Food and Drug Administration, but where they have chosen to respond under their own name and not officially on behalf of their organization.</footnote>