Cytotherapy 25 (2023) 1259 1264 Contents lists available at ScienceDirect CYTOTHERAPY journal homepage: www.isct-cytotherapy.org Review Article A management model in blood, tissue and cell establishments to ensure rapid and sustainable patient access to advanced therapy medicinal products in Europe €3, Allison Waters4, Emile van den Akker5, Joaquín Delgadillo1,2,*, Erja Kerkela Chantal Lechanteur6, Etienne Baudoux6, Nicola Gardiner7, John De Vos8, Joaquim Vives1,9,10,** 1 Banc de Sang i Teixits (BST), Edifici Dr. Frederic Duran i Jorda , Barcelona, Spain 2 Transfusion Medicine Group, Vall d’Hebron Research Institute (VHIR), Universitat Auto noma de Barcelona, Barcelona, Spain 3 Finnish Red Cross Blood Service, Vantaa, Finland 4 Irish Blood Transfusion Service, National Blood Centre, Dublin, Ireland 5 Department of Hematopoiesis and Sanquin Research, Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands 6 University of Liege, Laboratory of Cell and Gene Therapy LTCG, Liege, Belgium 7 Cryobiology Laboratory Stem Cell Facility, St. James’s Hospital, Dublin, Ireland 8 Departement d’ingenierie Cellulaire et Tissulaire, Unite de Therapie Cellulaire, Ho ^pital Saint-Eloi, Montpellier, France 9 Musculoskeletal Tissue Engineering Group, Vall d’Hebron Research Institute (VHIR), Universitat Auto noma de Barcelona, Barcelona, Spain 10 Departament de Medicina, Universitat Auto noma de Barcelona, Barcelona, Spain A R T I C L E I N F O A B S T R A C T Article History: Blood, tissue and cell establishments (BTCs) stand out in the management of donor selection, procurement Received 17 May 2023 and processing of all types of substances of human origin (SoHO). In the last decades, the framework created Accepted 2 August 2023 around BTCs, including hospitals and national health system networks, and their links to research, develop- ment and innovation organizations and agencies have spurred their involvement in the study of ground- Key Words: advanced therapy medicinal product breaking advanced therapy medicinal products (ATMP). To further improve strategic synergies in the blood establishment development of ATMPs, it will be required to promote intra- and inter-European collaborations by creating business model an international network involving BTCs and major stakeholders (i.e., research organizations, hospitals, uni- cell processing versities, patient associations, public agencies). This vision is already shared with the European Blood Alli- clinical translation ance, the association of non-profit blood establishments, with 26 member states throughout the European donation Union and European Free Trade Association states. Herein we present and analyze the “BTC for ATMP Devel- donor opment And Manufacture” (BADAM) model, an ethically responsible business model based on the values and regulatory development missions of BTCs and their commitment to health equity, patient access and education (based on voluntary substances of human origin tissue bank donation of SoHO to address unmet clinical needs, while contributing to training professionals and scientific literacy of our Society). © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Blood, Tissue and Cell Establishments in Context (BTCs), and (ii) biological drug and vaccine development, largely con- ducted by the biotechnology and pharmaceutical industry. Although Cell, gene and tissue (CGT)-based therapies emerged out of revo- BTCs were primarily established to provide high-quality blood and its lutionizing (i) traditional cell therapies (namely, blood transfusion components for clinical use in therapy and diagnostics, they have and hematopoietic stem cell transplantation), typically conducted in gradually expanded operations to processing and banking all types hospitals and elaborated in blood, tissue and cell establishments of substances of human origin (SoHO) as well as complex prod- ucts resulting from their manipulation (e.g., hematopoietic stem cells; advanced therapy medicinal products [ATMPs]) [1]. In all * Correspondence: Joaquín Delgadillo, Banc de Sang i Teixits (BST), Edifici Dr. Fred- cases, voluntary donors are on the foundation of BTCs, providing eric Duran i Jorda, Barcelona, Spain. SoHO as starting materials for clinical purposes and also offering ** Correspondence: Joaquim Vives, Banc de Sang i Teixits (BST), Edifici Dr. Frederic Duran i Jorda, Barcelona, Spain. human biological reagents for high-quality research & develop- E-mail addresses: jadelgadillo@bst.cat (J. Delgadillo), jvives@bst.cat (J. Vives). ment & innovation (RDI) activities in cell biology, process https://doi.org/10.1016/j.jcyt.2023.08.001 1465-3249/© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) 1260 J. Delgadillo et al. / Cytotherapy 25 (2023) 1259 1264 engineering, diagnostics, pharmaceutical manufacturing and med- unmet medical need, where no authorized ATMP is available. Addi- ical practice [2,3]. Due to the nature of their services, BTCs hold a tionally, it facilitates RDI in advanced therapies by non-profit organi- key position connecting donors and patients, understanding per- zations, such as academia, BTCs and hospitals. fectly the entire value chain from donor selection and SoHO pro- There is a broad consensus in the field on both the necessity and curement up to product release and patient treatment. Given the limitations of HE; however, the harmonization of criteria and more variety of SoHO, the spectrum and capacity of BTCs for conducting guidance for its use across the EU are much needed [16]. Divergent RDI and manufacturing activities are vast. Initially, CGT-based interpretation and implementation of Article 28(2) could have a neg- therapies were predominantly developed in academic hospital ative impact on patient access to treatments and ATMP develop- environments, in the autologous setting, with high production ment, and it also hampers transnational collaboration in HE- costs, poor clinical trial design and concerns regarding serious ATMPs [17]. Therefore, easily accessible, public EU-wide registries side effects, which largely discouraged the biopharmaceutical or databases, of the HE applications and approvals in the EU would industry from entering the ATMP development field in its early help distinguishing between ATMPs that are or are not commer- stages [4 6]. Remarkably, a gradually greater understanding of cially viable, reduce patient risks, facilitate industry awareness of the biology of these living drugs, the implementation of quality business opportunities and boost progressive entry of ATMPs into standards (European Directorate for the Quality of Medicines and the therapeutic repertoire of health systems in a complementary HealthCare; good pharmaceutical practices [GxP]) and a growing fashion to commercial development [14,15,18]. In this context, body of evidence of efficacy and safety at longer follow-up times developers need more practical assistance with regulatory, of patients receiving the first ATMPs have persuaded all the stake- manufacturing and pharmacovigilance activities, which are indeed holders involved (including regulators, clinicians, patients and the areas of expertise of BTCs that could be further realized with funders) of the actual benefits of these developments, although at the creation of centralized platforms for training and guidance via the cost of tremendous upheaval in bioprocessing and quality pan-European BTCs networks [16,19]. management [7,8]. Due to the lack of clear registries, it is difficult to estimate the The expertise of BTCs in mapping donor-to-donor variability, magnitude of the use of HE [20]. Available information points out processing SoHO in compliance with strict quality standards and that these ATMPs have close proximity to clinical practice, and their active participation in the research, development and clinical- manufacturing is primarily motivated by clinical needs and clinical grade manufacturing of the first generation of ATMPs are key to offer- experience. Regulatory aspects motivated or limited HE utilization, ing revolutionary treatments targeting rare diseases and conditions whereas financial resources generally limited HE use [14]. Most coun- lacking effective treatment [9,10]. As an illustrative example, chime- tries apply the definition of “non-routine” on a case-by-case basis per ric antigen receptor (CAR) T-cell based immune therapy (in whose product, and there are differences in the individual details required development, manufacturing and/or distribution BTCs have been for HE approval [21]. Some countries require extensive documenta- actively involved) has achieved unprecedented success as a life-sav- tion and authorize specific products whereas others authorize estab- ing technology for hematologic malignancies [11]. lishments based on manufacturing licenses for ATMP product types. Therefore, BTCs are strategically positioned to bring innovative Interestingly, Spain seems to be the only EU country having approval therapies to patients while adapting the existing framework in blood, for a CAR-T granted under HE. In February 2021, the CAR-T product cell and tissue procurement and processing, therefore adding value ARI-0001, developed at Hospital Clínic de Barcelona, received autho- to voluntary SoHO donation. We are marching toward an age in rization under the HE approval pathway for the treatment of patients which blood will be the safest it has ever been. Similarly, BTCs are relapsed/refractory acute lymphoblastic leukemia. This was an committed to deliver advanced CGT-based therapies with same accu- important landmark, given that it is the first CAR developed from racy, efficiency and reliability. bench to bedside in the EU and the first to receive the authorization of a governmental drug agency outside the centralized MA pathway Role of BTCs in ATMP Development and Manufacturing [22]. The centralized procedure for the authorization of medicines The “Academic Niche” for Manufacturing ATMPs applies to ATMP and involves a single application, a single evaluation and a single authorization throughout the EU. Three additional regu- The availability of ATMPs is greatly influenced by the huge costs latory pathways exempt ATMPs from the centralized authorization associated with both their development and production, which pathway, namely (i) hospital exemption (HE), (ii) named patient use makes the return on investment challenging for pharmaceutical com- and (iii) compassionate use, which are all authorized on a national panies, especially when considering the often-small patient popula- level. Named patient use and compassionate use pathways facilitate tion sizes, even under “orphan designation” incentives [23,24]. early access to investigational medicinal products for individual Nonetheless, industry has (i) succeeded in conducting clinical trials patients in life-threatening unmet medical need who are not enrolled with ATMPs; (ii) brought the first products to marketing authoriza- in a clinical trial [12 15], in accordance with the specifications and tion (MA) and (iii) defined novel modes of interaction with academia. under the direct responsibility of the medical practitioner (Directive However, some of the ATMPs with granted MAs have been, not sur- 2001/83/EC, Article 5). prisingly, withdrawn from the market for “commercial reasons,” in HE is described in Article 28(2) of the Regulation (EU) 1394/2007 some cases due to lack of reimbursement [20,25], therefore limiting and applies only to custom-made ATMPs, prepared locally on a “non- patient access to potentially beneficial treatments. routine basis,” used in a hospital setting, under the responsibility of a Clearly, non-profit institutions are major contributors to the treating physician, for a specific patient. In addition, a competent development of ATMPs but typically lack either the capacity or the authority must authorize HE for use limited to the same Member interest to pursue the full developmental pathway to MA and are State where it was developed, and the product must comply with the somehow risk-averse. They respond to clinical needs and foster ther- same national requirements concerning quality, traceability and apeutic innovation in an environment that is not industrial. European pharmacovigilance that apply to authorized medicinal products. As a investigator-initiated multicenter trials of ATMPs critically depend general rule, a risk benefit approach and safety reporting are strictly on academic Good Manufacturing Practice (GMP) facilities, as will the required regardless of how the HE has been implemented [15]. The future delivery of many of the new medicines even after commercial- obvious advantage of the exemption is that patients can receive ization [25]. Initiatives such as the pre-GMP facility created in the ATMP treatments under controlled conditions, particularly in areas of Karolinska Institute University Hospital (Stockholm, Sweden) J. Delgadillo et al. / Cytotherapy 25 (2023) 1259 1264 1261 contribute to support process development and accelerate the trans- “competence centers,” therefore filling the gap between industry, fer of cell product manufacturing from research to clinical GMP-grade regulatory authorities, and health care providers by the provision of and, ultimately, to the clinic [26]. Similarly, a cooperation between technical, personnel, and infrastructure resources. Helsinki University Central Hospital (HUCH), the Finnish Red Cross Blood Service (FRCBS) and the University of Helsinki was signed to promote experimental treatments and clinical trials using cell ther- apy products as part of the treatment of patients in HUCH. In this con- BTCs, Facilitators of Patient Access to ATMPs text, the manufacturing capacity and regulatory expertise of FRCBS, in particular (or BTCs in general), can be effectively employed to Considering that major reasons for ATMP failure are likely related advance in new developments. Moreover, HE has provided the regu- to high cost of development, quality control, regulatory require- latory niche for local manufacturing of ATMPs within an academic ments, starting material and donor-related aspects, qualified person- institution, including public facilities and non-profit organizations nel, infrastructure and logistic limitations, we propose that BTCs such as hospitals and BTCs. According to Priesner and Hildebrandt would fit perfectly into the idea of sustainable regional GxP/ATMP [25], the position of academia has changed substantially, being now “competence centers” and act as local manufacturers for ATMPs. BTCs at the front and at the end of the path of clinical development. are non-profit but can typically invest to a reasonable extent in RDI Indeed, BTCs provide the appropriate environment needed for 360° activities and collaborate closely with clinicians and the industry. product development and manufacturing: procurement of starting BTCs hold a central position between donors and patients and man- materials, patient recruitment, storage or final-stage preparation of age the entire value chain from donor selection, testing and donation products tested in late-phase, industry-sponsored trials and for to pharmaceutical quality-assured manufacturing and logistics to authorized products [24,27]. BTCs also have extensive experience hospitals. Novel cell therapies fit perfectly in the product portfolio of with donor recruitment, apheresis collection and timely issue of cells. BTCs, and ATMPs are nowadays a central part of strategic plans of This requires knowledge of trans-national and trans-continental European BTCs, with investments in infrastructure, such as clean SoHO import and export regulations and requirements. Specifically, rooms and adequately trained personnel, which most academic the collaboration of BTC with experienced hospital and clinical research institutes cannot do. Besides infrastructure and logistics, research facilities is required for the provision of on-site point-of- BTCs have the capacity to understand the regulatory aspects and care ATMP treatment. In contrasts, Iancu et al. [28] pointed out that implement GxP in the work routines, as demonstrated by their active hospital-based GMP facilities have supported primarily investigator- participation in the developments, such as the illustrative examples initiated clinical trials but are increasingly involved in interactions listed in Table 1 [30 34]. with industry. Several academic hospitals have built their own per- Commercial ATMP, especially autologous gene and cell therapy sonalized patient treatment programs and within those their own in- products such as CAR-T cells but also modified hematopoietic stem house manufacturing capacity (i.e., tumor-infiltrating lymphocyte cells, require formidable logistics, including long air transports cou- therapy) [28,29]. pled with dedicated vans [35]. With the foreseen extension of ATMP As suggested by Priesner and Hildebrandt [25], regional ATMP to other, more frequent, indications, such logistic arrangements will “competence centers” could manufacture and provide for ATMPs not be viable. This is because of unbearable costs and incompatibility locally, in a highly skilled environment and in the structural and reg- with the transition to a climate-neutral economy. It is possible that a ulatory framework needed, as an alternative to centralized decentralized system will become necessary, where the private sec- manufacturing. In this context, BTCs could play a major role to pro- tor provide the reagents and marketing authorization whereas BTCs vide broader access to innovative therapies as regional ATMP handle the SoHO to produce the ATMPs. Table 1 Illustrative examples of developments by BTCs. BTC ATMP Stage Role of BTC Model Ref BST TEP composed of MSC,WJ Phase 1/2 Regulatory development and GMP Public co-development (IGTP:BST) [30] loaded into third-party production funded by the PERIS Program pericardial matrix (BST (Health Department, Government +IGTP) of Catalonia, Spain) Sanquin TIL therapy melanoma Phase 3 Local production at different public finance by the European Com- [31] partners mission within Horizon2020 Framework Programme BST Transfer of Adenovirus, Phase 3 Local production for partner clinical Public/private consortium funded by ClinicalTrials.gov Id. Cytomegalovirus and groups, therefore expanding the European Commission within NCT04832607 Epstein-Barr virus-specific capacity to reach larger population Horizon2020 Framework T cells (TRACE) of patients to successfully com- Programme plete Phase III studies CHUL MSCs CU Local production for own hospital Public funding within the NHS [32] and other partners in Belgium FRCBS BM-MSC, autologous HE Local production under HE to Finnish Public co-development [33] keratinocytes hospitals BST, CHUL, CHUM Commercial CAR-T Marketed Procurement of starting material Public/private agreement between [34] products (apheresis), QC, logistics and BTCs and Pharma companies administration into patients. Different types of ATMP (somatic, gene and tissue engineering products) are considered in this list of representative initiatives developed by BTCs, which comprise different stages of development (phase 1/2/3I, compassionate, HE, commercial) from public and/or private collaborations. BTCs listed include BST (Banc de Sang i Teixits, Spain); CHUL (Centre Hospitalier Universitaire Liege, Belgium); CHUM (University Hospital of Montpellier); and FRCBS (Finnish Red Cross Blood Service, Finland). ATMP, advanced therapy medicinal product; BM, bone marrow; BTC, blood, tissue and cell establishment; CAR-T, chimeric antigen receptor-T cell; CU, compassionate use; HE, hospital exemption; IGTP, Institut de Recerca Germans Trias i Pujol; MSC, mesenchymal stromal cells; NHS, national health system; TEP, tissue-engineered product; TIL, tumor-infiltrating lymphocyte; WJ, Wharton’s jelly. 1262 J. Delgadillo et al. / Cytotherapy 25 (2023) 1259 1264 Educational and Training Initiatives significant development of this sector of activity and at the request of manufacturers who are already facing recruitment difficulties, both The fast-growing field of ATMPs may potentially offer novel thera- quantitatively and qualitatively. peutic approaches for a variety of pathologies; therefore, basic and However, despite the emergence of new educational courses, as advanced education (from regulatory to scientific and technical well as multiple national and international ATMP collaborations, the aspects) is a must for all professionals involved [36]. However, the role of the BTCs is rarely discussed and often omitted completely new and emerging nature of the ATMP sector means that those cur- [39 41]. It is not possible to successfully address tailor-made ATMP rently working in BTCs may not have had the opportunity to profes- educational needs of the new CGT workforce if the role of BTCs is not sionally train in ATMP bioprocessing during their initial yet fully acknowledged, defined or understood. Although universities undergraduate and postgraduate education. Technicians and phar- already play an important role in ATMP development, it could be macists trained for ATMP development and production are particu- made more prominent by improving interactions with support larly needed, including in the private sector. Consequently, evolving organizations [19,40], such as the European Blood Alliance (EBA). The the current ATMP educational opportunities to align with established EBA supports members to invest in new therapeutic fields by leverag- strengths of BTCs will be a key component to expanding the capabili- ing its members’ experience with donors and blood product ties within these establishments as well as adapting other profes- manufacturing. EBA is currently supporting ATMP development sional profiles to the characteristics of the CGT field, given that the through facilitating collaborative networks and through the provision manufacturing and management of ATMP developments is inter-dis- of information on new technologies and best practices pertaining to ciplinary and complex. Compliance with tissue and cells, blood and quality and safety of SoHOs [42]. Consultation with BTC on future ATMP legislation is crucial throughout the coordination of the multi- ATMP educational strategies is crucial for ATMP experts, alongside ple facilities required to ensure these therapies are available to a BTC specialists, to provide guidance on the requirements for future broad number of patients [37,38]. undergraduate and postgraduate educational modules. An effort is needed to understand the educational requirements surrounding the various ways in which BTCs may support ATMPs, A Business Model for BTCs in ATMP including everything related to SoHO donation and processing of starting materials, their storage, distribution, quality assessment, BTCs are a unique type of institution that emerged in the inter- safety and regulatory requirements. At present, there are several phase of transfusion medicine, immunology, transplantation, stem postgraduate opportunities in Advanced Therapies across Europe. cell biology and therapy [43]. The fact that CGT-based therapies are Universities have evolved their courses to offering to include ATMP composed of living entities, rather than small molecules or biologi- postgraduate education (e.g., Universidad de Granada, in Spain; Uni- cals, adds complexity to all segments of the value chain, from SoHO versities of Manchester and Sheffield, in the UK; University of Gal- procurement to logistics of final product administration into patients. way, in Ireland; Katholieke Universiteit Leuven, in Belgium). Training Typically, activities in BTCs comprise diverse clinical and laboratory- professionals on the particular needs of the CGT field is key to main- based services and are overseen by multiple regulatory agencies for tain a specialized workforce in the numbers required, albeit the mandatory and voluntary quality management systems geared global shortage of labor force. Such precise combination of concepts toward patient safety Figure 1 shows the assets of BTCs (including and skills is best understood and taught by BTCs and, consequently, it their own organizational model, specialized workforce, dedicated makes sense their involvement in educational and training initiatives. equipment and facilities, core services, integration with national In this context, leading BTCs (namely, Sanquin in the Netherlands and health networks and expertise in the management of ethics, regula- Banc de Sang i Teixits in Spain) support a joint Master’s Degree in tory and quality aspects of SoHo) required to address medical needs Transfusion Medicine and Cellular and Tissue Therapies co-ordinated and deliver personalized treatments by testing and processing SoHOs by Universitat Auto  noma de Barcelona (UAB) and Leiden University extracted either from third-party donors or from the same patient. Medical Centre (LUMC), which is a clear example of higher educa- Herein, we considered current models in European BTCs to increase tional initiatives to train a new generation of professionals in the con- competitiveness by their active participation in the value chain to text of SoHO donation and processing, including ATMP development help transform their national health systems and make them more and manufacturing. Moreover, short courses and workshops are also sustainable while ensuring an ethically responsible use of SoHO. To organized by universities, scientific and professional societies and define BADAM (BTC for ATMP Development And Manufacture), we consultants covering key areas of the entire ATMP value chain, from borrowed concepts from Banda et al. [44] in their description of early discovery to post-marketing monitoring. emerging business models in regenerative medicine, who identified The UK-based “Advanced Therapy Manufacturing Industry Con- six models: (i) materials and service provision business model; (ii) sortium” (AToMIC) is working with academic institutions to improve early-exit phase 1/2 business model; (iii) manufacturing and scale-up student preparedness for the ATMP industry [39]. Catapult provides business model; (iv) translational services business model; (v) virtual educational platforms for translational facilities to progress research business model and (vi) the integrated business model. BADAM is in products to the commercial market and regulatory advice for market- fact a variant of the integrated business model in which co-operation ing authorizations. Furthermore, the United Kingdom’s National with partner institutions from both public and private sectors is Health Service (NHS) Blood and Transplant (NHSBT) in collaboration mutually reinforced according to the different requirements of each with the Advanced Therapy Treatment Centre (ATTC) have created partner at given stages of ATMP development (e.g., SoHO procure- modules for staff in cell and gene therapy, procurement of starting ment, regulatory non-clinical development, clinical development or materials, distribution, handling practices and traceability. In Ireland, support to marketed ATMPs), also considering the UK point-of-care the Cell and Gene Therapy and Vaccine Manufacturing Forum aims to model [45]. Two illustrative examples of the application of BADAM address key barriers to ATMPs, including those in education and are (i) the co-development of PeriCord [30] and (ii) the hub-and- training. In October 2022, an ATMP-focused website called “ATMP spoke model for CAR-T cell therapies [34] (Table 1). For the first Ireland” was launched to connect parties working in the sector. example, PeriCord is a bioimplant composed of decellularized peri- Launched in June 2023, the initiative “Bio’Occ” involves the Universi- cardium loaded with multipotent mesenchymal stromal cells derived ties of Montpellier and Toulouse, and the Blood bank of Toulouse and from the Wharton’s jelly of the umbilical cord [46]. The pharmaceuti- the Cell Processing Facility of the University Hospital of Montpellier cal formulation of PeriCord was adapted to current GMP from previ- BTC, aim at attract and train the talents and actors of tomorrow in ous research and existing know-how in the consortium. We the field of bioproductions including ATMPs in response to the performed two parallel developments: (i) the establishment of a J. Delgadillo et al. / Cytotherapy 25 (2023) 1259 1264 1263 Ideally, a BTC network should be backed by stakeholders involved in the CGT field, including scientific societies and professional net- works. Existing initiatives at the national level include ATMP Ireland, ATMP Sweden, Red Espan ~ ola de Terapias Avanzadas (TERAV/TerCel) in Spain [47] or the Advanced Therapy Manufacturing Industry Con- sortium (AToMIC) in the United Kingdom. Moreover, the EBA has taken a strategic stand for supporting members’ efforts to invest in new therapeutic fields, leveraging on the members’ experience with donors and blood product manufacturing and facilitating the creation of a network for ATMP development and production. Final Remarks Figure 1. A management model in BTC establishments to ensure rapid and sustainable patient access to advanced therapy medicinal products in Europe. The management The synergistic goal between all the stakeholders in the field, model of BTCs for emerging uses of SoHO is characterized by its central role in the whether academic, non-profit, industrial, clinical, regulatory, patient value chain. BTCs are strategically positioned between SoHO procurement (used as advocacy or policy making representative, should be to develop a starting materials in the manufacture of advanced therapy medicinal products) and landscape toward effective clinical translation to produce better (that patients in partner hospitals through synergies with their respective national health is, improved safety and efficacy) and affordable medicines that will systems. The schematic shows the assets of BTCs and the three main lines of activity, namely SoHO donation and processing, development of innovative therapies and diag- eventually support health equity and facilitate patient access to nostic and safety testing. (Color version of figure is available online.) ATMPs, compatible with sustainable development goals. The HE could provide a regulatory framework for the local manufacturing of ATMPs but needs better harmonization between Member State and procedure for decellularization of human cadaveric pericardium, guidance in its use. Transparency is an important part to be devel- which is acting as a cell supportive material (scaffold) for surgical oped from of public EU-wide databases, also to promote transna- implantation and (ii) the design and validation of methods for a com- tional collaboration. The expertise of BTCs in processing ATMPs in bined “matrix:cell” bioimplant in compliance with GMP. Data result- compliance with quality standards as well as having infrastructure, ing from validations of methods for manufacture and logistics and close collaboration to clinics in place, makes them logi- characterization of PeriCord allowed us the authorization for its pro- cal candidates for acting as regional “ATMP competence centers” and duction for a first-in-human clinical trial (ClinicalTrials.gov Id. providers of these new treatments, qualified for a decentralized pri- NCT03798353) [30]. vate sector ATMP use. Examples like PeriCord highlights the practical To fully realize BADAM in an international level, synergistic col- value of (i) access to voluntary donated SoHO from all sorts; (ii) com- laborations among BTCs are needed in almost all, if not all, segments pliance with strict regulations and pharmaceutical quality standards; of the value chain. In Figure 2, we show the impact of SoHO testing (iii) strengthening collaboration between BTCs and (iv) active and processing and the different roles played by BTCs in two dimen- involvement in RDI consortia with national and international labora- sions, namely “treatment dimension” (focused on patients) and tories and societies, qualify cell and tissue banks like ours to become “product dimensions” (focused on bioprocessing), which are defined key players in the design, production and testing of the new genera- based on the steps required in the development of ATMP from non- tion of living medicines. clinical to clinical and post-approval follow-up. Funding No funding was received. Author Contributions Conception and design of the study: JD and JV. Acquisition of data: JD, AW, EvdA, EK, CL, EB, JDV and JV. Analysis and interpretation of data: JD, AW, EvdA, EK, CL, EB, JDV and JV. Drafting or revising the manuscript: JD, AW, EvdA, EK, CL, EB, NG, JDV and JV. All authors have approved the final article. Declaration of Competing Interest All authors are employees of either non-profit Blood, Tissue and Cell Establishments or academic hospitals, whose role in the develop- ment, manufacturing and distribution of advanced therapies are the main topic of this manuscript. AW is member of the European Blood Alliance Donor Studies working group. Acknowledgments Figure 2. Value added by BTCs in the development of innovative therapies. Potential The position stated in this manuscript by the Authors has received participation of BTCs at the different stages of product development are highlighted in the independent support of the European Blood Alliance (EBA). The red. Impact on either the treatment or the product dimensions have also been consid- ered by placing the different contributions above or under the diagonal of the graph, authors would also like to acknowledge Drs. Margarida Serra, Erik respectively. PD, pharmacodynamics; PK, pharmacokinetics; PoC, proof of concept; Kremer and Ioannis Papantoniou for critically reviewing the final Tox, toxicology. (Color version of figure is available online.) draft of the manuscript and providing helpful comments. 1264 J. Delgadillo et al. / Cytotherapy 25 (2023) 1259 1264 References [24] de Wilde S, Guchelaar HJ, Herberts C, Lowdell M, Hildebrandt M, Zandvliet M, et al. Development of cell therapy medicinal products by academic institutes. [1] Querol S, Rubinstein P, Madrigal A. The wider perspective: cord blood banks and Drug Discov Today 2016;21(8):1206–12. their future prospects. Br J Haematol 2021;195(4):507–17. [25] Priesner C, Hildebrandt M. Advanced therapy medicinal products and the chang- [2] Silberstein LE, Toy P. Research opportunities in transfusion medicine. JAMA ing role of academia. Transfus Med Hemother 2022;49(3):158–62. 2001;285(5):577–80. [26] Silva DN, Chrobok M, Ahlen G, Blomberg P, Sallberg M, Pasetto A. 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