Introduction
In access terms, ATMPs concentrate clinical risk, operational complexity, and financial exposure into a small number of high-consequence treatment episodes. This combination increases the importance of governance arrangements that protect patients, support decision accountability, and reduce unwarranted variation in who receives treatment, where, and under what conditions.
Governance and equity safeguards span several levels. At the system level, they include the legal basis for authorisation and any exceptional routes, minimum expectations for quality and traceability, and oversight of long-term follow-up. At the delivery level, they include centre designation, accreditation, workforce competencies, and rules that determine whether treatment can proceed when capacity is constrained. At the population level, they include prioritisation, transparency, and protections against inequitable access driven by geography, funding fragmentation, or informal pathways.
Regulatory architecture and exceptional routes
In many jurisdictions, ATMP governance starts with a central authorisation model and common baseline requirements for quality, safety, and efficacy. In the European Union, Regulation (EC) No 1394/2007 establishes the specific framework for ATMPs, including the dedicated classification and scientific oversight structures that distinguish these products from conventional biologics.
Alongside standard authorisation, exceptional routes can influence equity and system confidence. The European “hospital exemption” provides a legal mechanism for certain non-routine ATMPs prepared and used within a Member State under a physician’s responsibility, subject to national controls. In practice, hospital exemption can function as an access bridge in high unmet need scenarios, but it also creates governance challenges because national interpretations, quality expectations, and transparency practices can vary. This may lead to inconsistent patient protections and uneven availability across regions.
Quality, traceability, and chain of responsibility
ATMP delivery often requires complex custody chains across procurement, manufacturing, transport, storage, and administration. Governance therefore depends on clear allocation of responsibilities between manufacturers, treatment centres, logistics partners, and laboratories, with controls that remain robust under time pressure.
Traceability is not only a safety requirement, but also an equity issue. When traceability and handling requirements restrict treatment to a small number of capable sites, access can become geographically concentrated. Conversely, relaxed controls risk increasing variability in product quality and patient outcomes. For access teams, this makes it necessary to understand where minimum standards are fixed by regulation and where they are operationally defined through national implementation, accreditation expectations, and contractual quality agreements.
Oversight of real-world follow-up and outcome data
ATMP value and risk profiles are often resolved after launch through structured follow-up rather than solely at initial authorisation. Governance arrangements for registries, data linkage, and outcome definitions therefore affect both reimbursement credibility and clinical safety surveillance.
A recurring issue is that long-term follow-up creates dependencies on data access, patient mobility, and provider incentives. If outcome capture is incomplete or inconsistent, performance-linked arrangements become difficult to administer, and comparative assessments across centres or regions become unreliable. Governance choices, such as who owns the dataset, how outcome definitions are locked, and how data are audited, can therefore influence both affordability solutions and public trust.
Transparency, accountability, and public confidence
ATMP access decisions often involve confidential commercial terms and selective commissioning. While confidentiality can be necessary for negotiation, it can also reduce external scrutiny and limit shared learning about what works operationally and clinically.
Transparency issues arise in several places: clarity on which pathway was used (standard authorisation versus exceptional routes), what minimum evidence or quality conditions were applied, and what post-launch monitoring is required. Governance models that specify decision rationales, publish high-level outcome expectations, and implement audit-ready data processes tend to reduce reputational risk and strengthen payer confidence, even where detailed pricing terms remain confidential.
Equity, prioritisation, and geographical variation
Equity concerns in ATMPs are commonly driven by differences in system capacity, fiscal headroom, and centre distribution. Even where a product is formally reimbursed, practical access may depend on whether patients can reach a qualified centre, whether referral pathways are consistent, and whether local budgets can absorb near-term costs.
Prioritisation becomes relevant when supply is constrained, when centres have limited slots, or when eligibility criteria are clinically nuanced. Governance safeguards in this setting typically include explicit referral criteria, transparent waiting list rules, and mechanisms to review decisions when patient circumstances change. Without these controls, equity can be undermined by informal prioritisation, variation in clinician risk tolerance, or differential ability to navigate specialist networks. Evidence from analyses of gene therapy access highlights persistent disparities linked to geography and national system fragmentation, even under a central authorisation framework.
Safeguards against unproven offerings and boundary management
ATMP-related innovation has been accompanied by a market of unproven cell-based interventions offered outside established regulatory controls. These offerings create patient safety risks and can also distort perceptions of legitimate therapies, particularly in areas with high unmet need.
Safeguards include clear enforcement policies, public warnings, and professional standards that define acceptable evidence thresholds and oversight expectations for clinical use. The European Medicines Agency has issued specific warnings regarding unproven cell-based therapies, and professional guidance such as the International Society for Stem Cell Research standards addresses ethical oversight and responsible translation.
A practical governance challenge is boundary management: distinguishing legitimate early access, hospital-based development, and carefully overseen investigator-led use from activity that bypasses evidence generation and oversight. Access planning is affected because boundary disputes can influence payer confidence, commissioning requirements, and willingness to support registries or performance-linked arrangements.
Summary
ATMP governance combines legal frameworks, delivery controls, and monitoring expectations to manage high-consequence treatment episodes and long-term uncertainty. Exceptional routes such as hospital exemption can improve availability in specific contexts but introduce variability that can affect quality and equity. Traceability and chain-of-responsibility controls protect patients but may concentrate access in a limited number of centres, amplifying geographical variation. Long-term follow-up governance underpins both safety surveillance and the credibility of outcomes-linked reimbursement, but depends on workable data infrastructure and auditability. Transparency and safeguards against unproven offerings influence public confidence and can indirectly affect payer and provider risk tolerance in adopting ATMPs.
Links
Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA): Monitoring registers.
Scientific publications
Brinsfield TN, Pinson NR, Levine AD. The evolution and ongoing challenge of unproven cell-based interventions. Stem Cells Transl Med. 2024. doi: 10.1093/stcltm/szae050.
Desmet T, Michelsen S, Van den Brande E, Van Dyck W, Simoens S, Huys I. Towards implementing new payment models for the reimbursement of high-cost, curative therapies in Europe: insights from semi-structured interviews. Front Pharmacol. 2025;15:1397531. doi: 10.3389/fphar.2024.1397531.
Domanović D, et al. ATMPs prepared under hospital exemption: European Blood Alliance position paper. HemaSphere. 2025. doi: 10.1002/hem3.70215.
Lovell-Badge R, et al. ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update. Stem Cell Reports. 2021;16(6):1398-1408. doi: 10.1016/j.stemcr.2021.05.012.
Reckelbus M, Mohan R, Locquet P, Van Steijvoort E, Huys I, Borry P. Disparities in access to gene therapy in the European Union: ethical and regulatory challenges. J Law Biosci. 2025. doi: 10.1093/jlb/lsaf018.