Spain’s Hospital-Based CAR-T Goes Global: A Therapy, a System, or a New Paradigm?
When I posted recently about Spain’s public hospital-led CAR-T programs, the feedback was immense, ranging from supportive insights to challenging questions. Since then, I’ve dedicated more time to understanding the inner workings of Spain’s model by reviewing peer-reviewed articles, speaking with experts in Europe, and evaluating what sets this model apart. What I’ve learned suggests that this story is still unfolding.
I’m based in the U.S. and work at Cytoart — a company that supports CAR-T trials and diagnostics, though we are not developers ourselves. I don’t represent a hospital or a pharmaceutical company, but I work closely with stakeholders across both. What drew me to Spain’s model is how it challenges conventional assumptions: a publicly funded, hospital-manufactured, regulator-approved CAR-T therapy delivered at a fraction of commercial cost. This analysis reflects an external, cross-border perspective shaped by field conversations, peer-reviewed literature, and operational experience.
1. The Foundation: Hospital Exemption and EU Policy
Spain’s model operates under Hospital Exemption (HE), a provision in EU Regulation (EC) No 1394/2007 on advanced therapy medicinal products (ATMPs). This allows hospitals to manufacture and administer ATMPs, such as CAR-T therapies, without full EMA marketing authorization, provided that the product is:
Prepared on a non-routine basis,
Used in a hospital setting,
Administered under the exclusive responsibility of a medical practitioner,
For an individual patient.
What sets Spain apart is its commitment to scaling this exemption into a nationally coordinated program. The first CAR-T therapy developed under this framework was ARI-0001, targeting CD19 in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) (Nature BMT 2021). Since then, additional products have followed under the same framework, including therapies for myeloma and lymphoma.
2. From UPenn to Barcelona
Per Nature 2021, Dr. Carlos Fernández de Larrea (profile) helped lead the development of academic CAR-T therapy at Hospital Clínic de Barcelona. He trained with CAR-T pioneers at the University of Pennsylvania and initially used a construct similar to Novartis’s CTL019. Novartis authorized the hospital to treat patients using their design under HE.
As the program expanded, six hospitals joined. Patient numbers increased. What began as a local initiative evolved into a national network.
The shift raised an important question: was it still a hospital-scale compassionate use program, or had it become a parallel path to commercial CAR-T?
Ultimately, the program formally designated its product as ARI-0001, which later received conditional approval from the Spanish Medicines Agency (AEMPS) under the HE framework for adults with relapsed or refractory ALL.
3. Expanding the Pipeline
Spain’s hospital-based CAR-T program, Project ARI, is named in honor of Ariana Benedé, a young patient who, despite battling leukemia, helped lead a fundraising campaign to bring CAR-T therapy to Spain. Though she passed away in 2016 before receiving the treatment herself, her advocacy was instrumental in launching the program, and her legacy lives on through the development of ARI-0001 and the broader impact of the ARI Project.
ARI-0002h is a BCMA-targeting CAR-T developed for multiple myeloma. It was approved for use in 2023 by the Spanish Medicines Agency (AEMPS) under the hospital exemption pathway. The therapy continues to be manufactured and administered at Hospital Clínic and IDIBAPS.
ARI-0003 is a dual-targeting CAR-T against CD19 and BCMA, aiming to reduce relapse risk in non-Hodgkin lymphoma. Detailed preclinical and early translational data were recently published in Molecular Therapy (2025), supporting its ongoing clinical development.
4. Why Their Costs Are Lower
Spain’s hospital CAR-T therapies reportedly cost under €100,000, compared to over $400,000 in commercial settings. This cost difference is not merely a factor of scale; it reflects a fundamentally different operational model, one that is integrated and tailored to the hospital environment.
According to the INSPIRE project, which mapped Europe’s academic CAR-T ecosystem, these programs emphasize research-driven, patient-focused care. Manufacturing, clinical development, and patient treatment often happen within the same institution. This integration brings several structural cost efficiencies:
Manufacturing and infusion occur at the same site, eliminating the need for complex logistics or warehousing.
Automated, closed platforms like Miltenyi Biotec's CliniMACS Prodigy® Instrument reduce contamination risks, lower labor costs, and minimize the space required for cleanroom facilities. Sometimes, this only requires a quarter of the footprint needed for traditional systems.
Big pharma typically manufactures in Grade B cleanroom environments, which require significant infrastructure and operational costs. In contrast, hospital-based programs often use Grade C, and sometimes even Grade D, cleanrooms depending on the therapy and production volume. Moving from Grade B to C—or C to D—can reduce facility-related costs by 60% to 80%. This cleanroom flexibility is just one example of how regulatory adaptation contributes to cost efficiency in decentralized models.
Although hospital financial models vary, with some programs still exploring licensing, the overall approach remains distinct from commercial biotech companies. The focus is on delivering effective, safe therapy within a public healthcare setting, not on building products for global market launch.
Lower costs are not the result of shortcuts; they stem from careful, context-specific design choices that maximize both functional efficiency and accessibility.
5. Global Reach and the Challenge of Exporting a System
Spain is not alone. A broader academic CAR-T movement is gaining momentum across Europe.
According to INSPIRE (2023):
21 academic CAR-T programs are under development at 14 institutions
5 centers have each treated more than 40 patients
Leading hubs include Barcelona, Paris, Milan, and Amsterdam
These programs show that academic institutions can meet Good Manufacturing Practice (GMP) standards, ensure quality control, and deliver clinical efficacy, even with limited resources.
India also provides an important case study outside Europe. A peer-reviewed study showed that decentralized CAR-T manufacturing using a closed, automated system was feasible in a developing country setting, with an estimated production cost of $35,107 per dose (PubMed, 2022). However, more recent data suggests that sustaining these low costs is difficult in practice. For example, Var-CEL, India’s second approved CAR-T product, is now projected to cost approximately $60,000 per dose (AABB, 2025).
Although this remains more economical than U.S.-based pricing, it highlights a broader truth: exporting hospital-based models is not straightforward. Cell therapy depends on more than the product itself. It requires:
coordinated cell collection and processing
compliant GMP production
conditioning protocols
infusion logistics and follow-up
institutional pharmacovigilance
As BMJ Open (2023) points out, ensuring consistent care standards across different countries is challenging, particularly in settings with variable infrastructure, staffing, or regulatory frameworks.
Final Thought: Centralized vs. Decentralized
This is not about replacing commercial CAR-T. Centralized models led by industry have been essential in reaching thousands of patients worldwide, enabling scalable production, global regulatory approval, and robust clinical development.
But decentralized, hospital-integrated models like Spain’s offer something different: localized manufacturing, faster deployment, and potentially lower costs. These models may be particularly valuable in public health systems seeking cost-effective, adaptable, and self-sufficient solutions.
We’re entering a multipolar CAR-T era where centralized and decentralized models coexist. One offers reach and uniformity; the other, proximity and flexibility.
It's not a competition but rather an evolution.
And it’s a model worth watching.
References
C-Level Executive & Entrepreneur in Biopharma - Immunology & Oncology | Advisor in Formulation Development/CMC & Drug Delivery
4moVery interesting article. Do you know how many patients were treated with ARI-0001 and how big pharma reacted, as it is a direct competitor in Spain?
Sr. Director of Regulatory Affairs at Tiger BioSciences
5mo💡 Great insight
Regulatory Mentor for Biotech & CGT Start-ups and Professionals 😎 Helping you attract funding to begin your development pathway to commercialisation with confidence, clarity and credibility 😎
5moSuper interesting post and discussion comments. I can see more countries including the UK being interested in this approach given the frustration of patient organisations, physicians and academics. It would be helpful having a summary comparing decentralised vs hospital exemption. What's the reimbursement approach for these hospital models Frank Li? With regards to India - the issue with sustaining low costs might also be the cost of equipment and materials especially if some of these are imported. Also what's the situation in China?
Executive Managing Partner | Redefining How Life Sciences Professionals Connect and Collaborate
5moThe ultimate manufacturing evolution would be a Point of Care manufacturing. Very insightful Frank Li
C-Suite Ready (Succession or Board-Level Readiness) Biotech & Pharma Quality Leader | Global GMP & Regulatory Strategist | Cell/Gene Therapy QA Expert | Start-Up to Commercial Scale
5moThanks for sharing, Frank