Introduction
Advanced therapy medicinal products (ATMPs) are medicinal products based on genes, cells, or tissue engineering, with delivery models that often differ materially from conventional hospital medicines. The operational pathway can include patient identification and referral, centre qualification, collection of starting material, manufacturing and release, time-critical transport, administration in specialist settings, and prolonged follow-up. Each step introduces capacity constraints that can translate into waiting times, centre-level variation, and uneven access between regions or countries.
Operational delivery is also shaped by quality system requirements. For many ATMPs, manufacturing is performed under good manufacturing practice (GMP), and the boundary between clinical and manufacturing responsibilities is operationally important, particularly where hospital-based steps interact with external manufacturers and logistics providers.
Service delivery models and centre eligibility
Many autologous cell therapies require defined treatment networks, where referral centres and authorised treatment centres have differentiated roles, and where patient throughput depends on staffing, bed capacity, and coordination infrastructure. Where accreditation or standards are used to formalise requirements for collection, processing, and administration, these can function as proxies for readiness, specifying expectations for governance, training, quality management systems, and auditability.
Service models also determine how responsibilities are distributed across the pathway. The balance between centralised manufacturing and decentralised (hospital-based) activities affects the number of handovers, the feasibility of standard operating procedures across sites, and the ability to scale capacity without compromising consistency.
Capacity planning across the patient pathway
Capacity limitations do not arise only at manufacturing. Constraints can appear at referral and work-up, in apheresis or tissue procurement scheduling, in bridging therapy management during manufacturing lead time, and in the availability of appropriately trained clinical teams for administration and toxicity monitoring. Evidence from real-world delivery of complex cell therapies indicates that delays and bottlenecks may occur at multiple points and can interact, for example when manufacturing slots and bed capacity are misaligned.
For access teams, the operational implication is that “eligible population” and “treatable population” can diverge in practice. Capacity mapping therefore often needs to consider end-to-end throughput, not only the availability of the product.
Manufacturing throughput and release readiness
Manufacturing capacity is influenced by process complexity, the degree of automation, facility classification and environmental controls, availability of skilled operators, and the time required for quality control testing and batch release. Reviews of CAR T-cell manufacturing highlight that process parameters, comparability expectations, and release testing strategies are not purely technical choices; they drive cycle time, failure risk, and the number of parallel manufacturing runs required to achieve a target volume.
Operationally, the release step is frequently a pacing item because it depends on validated assays, data review, and formal release roles that vary by jurisdiction. In the European Union, the qualified person (QP) concept is often relevant for cross-border distribution and batch certification activities, and it can become a practical constraint if release responsibilities are concentrated in limited organisations or geographies.
Logistics and chain of identity controls
ATMP logistics frequently combine time sensitivity with stringent requirements for traceability. Chain of identity (COI) links material and data to a specific patient, while chain of custody (COC) records each handover across clinical sites, couriers, and manufacturers. These controls are operational necessities for personalised therapies and become more complex as networks expand internationally.
Cold chain requirements vary by modality (for example, fresh versus cryopreserved starting material; cryogenic finished product), and operational risk management must address transport lane qualification, contingency planning, deviation handling, and documentation suitable for inspection. ISO 21973:2020 provides an internationally recognised standard describing general requirements and considerations for transportation of cells for therapeutic use, including planning, verification and validation, communication, and documentation.
Clinical delivery, monitoring, and follow-up infrastructure
Delivery readiness also depends on clinical capability. Some ATMPs require inpatient administration, intensive monitoring, and rapid escalation pathways for recognised toxicities. In cellular immunotherapies, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are examples of adverse events that require defined protocols, trained multidisciplinary teams, and access to supportive treatments and critical care.
Follow-up requirements can extend for years, particularly for gene therapies where long-term safety monitoring is expected. Operationally, long follow-up periods create requirements for data continuity, patient tracking across care settings, and mechanisms to manage loss to follow-up, all of which affect the feasibility of outcomes-based agreements and post-authorisation evidence generation.
Operational data, registries, and audit readiness
Operational delivery generates multiple data streams: scheduling and chain-of-custody logs, manufacturing batch records, clinical outcomes, and safety follow-up. The ability to integrate these data is often limited by fragmented systems across hospitals, manufacturers, and couriers. Stakeholder-focused analyses of the CAR T supply chain emphasise that handovers are recurrent points of failure risk, and that partial solutions targeted at single stakeholders may not address cross-system dependencies.
From an access perspective, these operational data constraints matter because payers and health technology assessment (HTA) stakeholders may require credible evidence of outcomes in routine practice, sometimes linked to centre eligibility, registry participation, or minimum data sets that are only feasible if data capture is designed into the delivery pathway.
Summary
ATMP delivery relies on an end-to-end operational pathway that often differs from conventional medicines, with capacity constraints that can arise in referral, collection, manufacturing, logistics, administration, and long-term follow-up. Standards and guidance relating to GMP, accreditation expectations, and transport planning influence how reliably these pathways can be implemented at scale. Manufacturing throughput is shaped by process design, quality control and release requirements, and the availability of qualified roles and validated assays. Logistics introduces additional dependencies through COI and COC controls and time-critical cold chain management, particularly for international networks. Clinical delivery capability, toxicity management, and long-term follow-up infrastructure contribute materially to real-world treatable capacity and to the feasibility of routine outcomes evidence generation.
Links
European Medicines Agency (EMA): Advanced therapy medicinal products: Overview.
US Food and Drug Administration (FDA): Cellular & Gene Therapy Guidances. (24 September 2025).
Key scientific publications
Ceja MA, Khericha M, Harris CM, Puig-Saus C, Chen YY. CAR-T cell manufacturing: Major process parameters and next-generation strategies. J Exp Med. 2024;221(2):e20230903. doi: 10.1084/jem.20230903.
Dias J, Garcia J, Agliardi G, et al. CAR-T cell manufacturing landscape – Lessons from the past decade and considerations for early clinical development. Mol Ther Methods Clin Dev. 2024;32:101250. doi: 10.1016/j.omtm.2024.101250.
Gavan SP, Thompson AJ, Payne K. Capturing the impact of constraints on the cost-effectiveness of cell and gene therapies: a systematic review. PharmacoEconomics. 2023;41:675-692. doi: 10.1007/s40273-022-01234-7.
Holland SM, Sohal A, Nand AA, Hutmacher DW. A quest for stakeholder synchronization in the CAR T-cell therapy supply chain. Front Bioeng Biotechnol. 2024;12:1413688. doi: 10.3389/fbioe.2024.1413688.
Sureda A, El Adam S, Yang S, et al. Logistical challenges of CAR T-cell therapy in non-Hodgkin lymphoma: a survey of healthcare professionals. Future Oncol. 2024;20(36):2855-2868. doi: 10.1080/14796694.2024.2393566.