Introduction The path from academic development of Advanced Therapy Medicinal Products (ATMPs) to marketing authorization remains complex, with challenges across upscaling, manufacturing, regulatory approval, and clinical integration. Europe continues to lag behind the U.S. and China in the number and scope of clinical trials. To help address this gap, it is essential to assess whether overall production capacity is a limiting factor in ATMP development and implementation. In this context, we aimed to map current practices, technologies, organizational structures, and challenges within ATMP facilities across Europe, to support innovation and process optimization.

Methods A 371-question conditional SurveyMonkey questionnaire was developed to assess activities from 1 January 2021 to 31 December 2023 across domains including organization type, ATMPs developed, infrastructure, personnel, cell culture technologies, procedures, and process control. The survey was distributed between 13 June and 15 September 2024 via DARE-NL, NXTGEN Hightech, T2Evolve, GoCART, and EBMT CTIWP, targeting academic, non-profit, and commercial facilities involved in (pre-)GMP-grade ATMP production. Descriptive analysis was performed. The study adhered to EBMT guidelines, GDPR (2016/679).

Results Responses (n=92) were collected from 33 countries (Europe n=75), with most from the Netherlands (n=18), Spain (n=13), Italy (n=7), and Germany (n=7). Most respondents (84%) were hospital-linked, with 81% treating patients with ATMPs—38% adults, 10% pediatric, 33% both. Nearly half (48%) of facilities handled, developed, or produced ATMPs between 2021 and 2023. Most were embedded within hospitals (n=14/33) or universities (n=11/33) and operated as standalone (n=14/33) or integrated units (e.g., hematology n=8/33). In around 50% of facilities, equipment and personnel were shared with the hosting department; in one-third, neither were shared. Leukapheresis was the most common cell source (n=35/44), followed by bone marrow (n=13) and umbilical cord tissue (n=9). Frequently used cell types included stem cells (n=20), αβ T cells (n=18), MSCs (n=14), and NK cells (n=13). Most centers (n=42) developed CTMPs; GTMPs and TEPs were reported by 29 and 9 centers, respectively. Genetic modification approaches included viral vectors, transposons, CRISPR/Cas KO (n=6), and KI (n=5). Gene delivery was mainly via viral vectors (n=22) and electroporation (n=14). The CliniMACS Prodigy (Miltenyi Biotec) was the most used cell culture system, reported by 44% (n=19/43) of ATMP-producing centers, with another 12 (of 24) planning future adoption. Its closed system, ease of use, compatibility with culture processes, minimal labor needs, and availability were cited as key drivers of adoption. Major disadvantages included consumables exclusivity, high running costs, and limited system interoperability. Closed systems are widely adopted in Europe (e.g., Netherlands, Germany, Spain, Austria, Belgium, Switzerland, Denmark). Most centers operate 1–2 units; a few use ≥7. Typical production scale was 100 mL, with a few scaling to 1–2 L. Closed systems are primarily used for autologous batch production or personalized therapies, sometimes in combination with other systems (e.g., HYPER flasks). Six centers reported successfully transitioning from open/semi-closed to closed systems. Fifteen centers in total had made such transitions. Top challenges included cost, process adaptation and scale-up, regulatory compliance, and compatibility with existing workflows. Expertise and staff training requirements were also reported as barriers.

Conclusions We mapped the landscape of ATMP development infrastructure, highlighting common challenges and needs in Europe. The CliniMACS Prodigy has become a leading platform for closed-system ATMP manufacturing. However, significant barriers remain, particularly around cost, process flexibility, and equipment interoperability. Assessing and strengthening production capacity is a critical first step toward closing the clinical trial gap between Europe and global frontrunners. Greater cross-institutional collaboration and harmonization are needed to enable scalable, cost-effective, and compliant ATMP production.

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2025
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