Our study describes the market availability of authorised ATMPs across 23 EU MS, addressing a regional gap in previous research in which Central and Eastern EU MS were underrepresented. The main difference in our methodology lies in the definition of ATMP availability. Previous studies analysed the situation based on reimbursement status [8,9,10, 14, 21]. That reflects affordability but may underestimate availability, as these products may reach patients even in the absence of a formal reimbursement decision.

This discrepancy is highlighted when comparing our results with a recent report published by the Danish Association of the Pharmaceutical Industry (Lif). Lif mapped ATMP access in 11 European countries based on the information provided by local industry associations [14]. The report aligns with our findings only in Germany, where statutory health insurance funds automatically cover newly marketed products. In all other countries, the Lif report identified lower availability than in our study. A significant difference was observed in Italy (five available ATMPs compared to eleven in our study). Italian regulatory framework provides immediate availability of innovative medicinal products to patients through inclusion in class C(nn), even without formal inclusion in the regional hospital therapeutic schedules [22].

ATMPs can also be accessed on a case-by-case basis following the special requests [21]. For instance, in Bulgaria, patients can access two ATMPs after a request by a medical specialist, followed by an eligibility check by the Ministry of Health and Bulgarian Drug Agency. Additionally, discrepancies may arise from differing reimbursement processes for inpatient and outpatient settings. In the Czech Republic, only two of the six marketed ATMPs underwent the formal reimbursement procedure, which applies only to medicinal products in outpatient settings, a criterion that most ATMPs do not meet.

Sales data may serve as another source for evaluating market availability [23, 24]. However, such data are typically not fully accessible to the public. Our study relies on open or requestable data, although their inconsistency presents a primary limitation complicating the accurate determination of market availability. While both sales data and our study data reflect only one aspect of patient access – availability – they should not be neglected. Standardising data collection and reporting practices by NCAs would enhance future research accuracy and offer a more comprehensive understanding of how ATMPs reach patients.

We observed significant variation in the ATMP availability among EU MS, ranging from 0 to 89%. Factors leading to unequal availability may parallel those observed for orphan medicinal products: national health strategies for rare diseases, diverse national P&R policies, and economic aspects, such as public health resources and market size [16, 23,24,25].

Germany exhibited the highest ratio of ATMPs marketed, which aligns with previous studies confirming its leadership in the availability of centrally authorised products, orphan medicinal products, and fast patient access [16, 23, 26]. This position derives from Germany’s policy allowing reimbursement and free price setting for all new treatments during the first six months [13] and its inclusion in the reference pricing systems of other countries. Similarly, legislative measures in Italy, through the “innovative product” designation, and in France, through the “Temporary Authorisation for Use” (ATU) program, foster patient access to innovative therapies addressing unmet medical needs [27]. Germany, France, and Italy, as MS with the highest ATMP availability in this study, emphasise how market size, innovation-supporting policies, and reimbursement outcomes of previously launched ATMPs shape commercial strategies by MAHs.

In contrast, no ATMPs have been marketed in Estonia and Latvia to date of research, which is consistent with EFPIA (European Federation of Pharmaceutical Industries and Associations) surveys (based on the reimbursement status) reporting low availability rates of centrally authorised products and orphan medicinal products in the Baltic States. These surveys also identified Malta as the EU MS with the lowest availability rate; however, this MS was not included in our study as NCA did not confirm that no ATMP is available [26, 28]. Smaller markets usually encounter delays in the launch of new medicines [29]. Securing timely access to these treatments often necessitates implementing cross-border healthcare solutions.

However, market size alone does not guarantee the availability. In Spain, despite being included in the main EU4 markets, the availability of ATMPs is 33% (six ATMPs), slightly above the average of analysed EU MS. While MAHs express the intention to commercialise 83% of ATMPs (15/18) in Spain, no agreements on P&R conditions have been reached for four ATMPs, and the discussions for the remaining are ongoing [30]. The willingness of national health systems to pay for ATMPs is affected by the high short-term cost of ATMPs combined with limited efficacy data and uncertainty in long-term benefits [31]. The decision-making in this field is complex and shaped by various clinical and economic considerations and price agreements, as addressed comprehensively in recent literature [10, 12, 13, 32, 33]. An important step in this context is the recent EU Health Technology Assessment Regulation (Regulation (EU) 2021/2282), which mandates Joint Clinical Assessments (JCA) for newly authorised oncology medicinal products and ATMPs from January 2025 [34]. The single scientific basis for national decisions is expected to facilitate patient access to innovative treatments across the EU. However, challenges in adapting national HTA processes to integrate the JCA findings effectively may paradoxically delay market access in the initial phase.

Beyond market dynamics and regulatory environment, ATMP availability is further influenced by product-specific limitations in manufacture, distribution, and administration, which MAH has to deal with. The manufacturing complexity is not comparable to other biological medicinal products and may strain the manufacturing capacity. “Fresh products” with limited shelf-life require specialised handling, temperature chain maintenance, and fast administration by trained healthcare professionals in specialised facilities certified by MAHs [35]. Additionally, some countries may face organisational and technical issues in establishing centres suitable for administering ATMPs [36]. Countries involved in ATMP clinical trials may be preferred for initial product launches. Their prior experience with product administration and established supply chains may provide a strategic advantage in facilitating early access. This aligns with our findings, as most ATMP clinical trials in the EU are conducted in France, Germany, Italy and Spain, followed by Belgium and the Netherlands [37].

All these regulatory or product-specific limitations may lead to difficulties in commercialisation, prioritisation of MS and unequal availability. Larger, more established companies can generally expand across a wide range of markets more quickly than small-medium enterprises [38].

Our study further explores the potential influence of three factors on ATMP availability across EU MS, covering the practical, commercial and economic dimensions relevant to the market access: time since granting marketing authorisation, target patient population size, and cost. We found no significant correlation between the number of MS where an ATMP is available and the analysed factors when evaluating all ATMPs. These factors do not relate to overall ATMP availability linearly, suggesting a more complex decision process by all involved stakeholders and emphasising the specific nature of each ATMP. The correlation analysis is further complicated by a limited number of authorised ATMPs and a short period since marketing authorisations.

When analysing ATMP subgroups, time dependency can be observed for CAR T-cell therapies. This finding suggests that recently authorised products may require more time to build a sufficient infrastructure, leading to delayed launches in multiple countries. Time is crucial for manufacturing scale-up and establishing distribution networks and certified facilities across MS. CAR T-cell therapies and other autologous products may require a more robust network, as the treatment process involves the collection of patients’ cells and their transport for product manufacturing. This time dependency does not apply to all ATMPs. Although four of the six most available ATMPs were authorised for over five years at the time of research, there are ATMPs authorised for a longer time with lower availability. That points to the interconnection of various factors influencing the ATMP expansion to multiple MS.

We also observed a correlation between the availability of CAR T-cell therapies and cost; however, this finding requires cautious interpretation. Given the data source, Germany, with its unique market position, and the existing price differences across EU MS, this study should provide rather an exploratory insight than definitive conclusions applicable to all EU MS. Additionally, the final cost of medicines is shaped by managed entry agreements (MEA) and confidential pricing agreements, which facilitate negotiations between MAHs and healthcare payers and determine patient access. The list prices of CAR T-cell therapies are remarkably similar, making cost comparisons within this category irrelevant. Rather than focus on the exact costs of individual products, we can consider the cost range from €71,400 to over €2,3 mil for the six most available products to illustrate the lack of cost impact. Notably, the costliest product is also the most available (present in 83% of analysed EU MS), highlighting that although the cost and P&R negotiations influence the final patient access, it is not the only factor that drives ATMP availability.

Our study did not confirm any relationship between ATMP availability and the size of the target population. Two opposing mechanisms may contribute to this finding. On the one hand, greater demand from patients and healthcare professionals is expected to facilitate ATMP availability but simultaneously creates challenges for manufacturing capacity. This constraint might be expected for autologous products, such as CAR T-cell therapies, but it is also documented for an allogenic product, Alofisel. The Danish Nordic Institute of Health Economics reported that the number of eligible patients for Alofisel treatment was between 540 and 555 at the time of application submission for HTA evaluation. Nevertheless, the manufacturing capacity allows for treating only 20 to 45 patients annually [39].

On the other hand, extremely small patient populations present a distinct challenge, especially when combined with distribution and administration requirements, as illustrated by Strimvelis and Upstaza. Strimvelis has been administered exclusively in one facility since 2016, as only 15 patients per year are estimated to be eligible in Europe. The administration and manufacturing sites are co-located, ensuring fast administration due to the limited shelf-life of several hours. Instead of expanding into additional MS markets, the MAH promotes cross-border access to treatment by establishing a patient support program [40, 41]. Upstaza requires administration in centres specialised in stereotactic neurosurgery by qualified neurosurgeons [42]. This requirement, combined with a small target population (only units of patients), concentrates the product in a few treatment centres across Europe.