Overcoming the challenges of future medicine

The article, written by Núria Nieto, Advanced Therapies Specialist at Klinea; Jordi Gibert, Head of the Biotechnology Unit at Klinea; and Ander Izeta, Head of the Advanced Therapies Unit at Donostia University Hospital, addresses the technical, regulatory and organisational challenges that condition the integration of ATMPs as a standard of care.

Advanced therapy medicinal products (ATMPs) are revolutionising medicine, moving from experimental to actual clinical treatments, such as CAR-T therapies and bioengineered corneal implants. In Europe, some hospitals already produce and apply these therapies under hospital exemption schemes, expanding their access.

However, their development and scaling up present significant challenges throughout the value chain: GMP production, logistics, regulation, specialised training and high costs. At the same time, emerging technologies such as artificial intelligence, advanced cultivation systems and biobanks offer new opportunities, but also introduce regulatory uncertainties.

Technical and manufacturing challenges

ATMPs present significant technical and manufacturing challenges, especially in the transition from preclinical research to industrial production under GMP standards. Their living, personalized and heterogeneous nature, especially in autologous therapies, hinders standardization, quality control and scalability. ​Added to this are obstacles in obtaining biological material, the costly production of viral vectors, logistical complexities and the need for cryogenic transport, specialized infrastructures and complete traceability. ​Quality controls are highly demanding and, in the case of pluripotent cells, must also mitigate risks such as tumorigenicity, representing technical and regulatory vulnerability.

Regulatory challenges

In the regulatory sphere, there remains a lack of international harmonisation, which hinders the approval and global expansion of these therapies. Although frameworks such as European Regulation 1394/2007 exist, the uneven application of hospital exemptions between countries creates legal uncertainty and inequality in access. Finally, the high cost of therapies such as CAR-T poses a challenge to the sustainability of public health systems. Although pay-for-performance models have been introduced, their impact is limited, while public-academic initiatives demonstrate that it is possible to develop more accessible alternatives with greater public control. 

Evidence, predictability and safety

The responsible development of ATMPs requires strengthening the generation of clinical evidence, predictability and safety, but there is currently no comprehensive pan-European system for collecting longitudinal data on real-world efficacy and safety. Initiatives such as the EBMT registry are a notable exception, providing long-term clinical evidence on CAR-T therapies. The low predictive capacity of traditional preclinical models increases clinical trial failures and development costs, driving the use of organoids, organ-on-chip systems and artificial intelligence-based in silico models. 

At the same time, the proliferation of unregulated therapies poses a serious risk to patients and calls for international coordination and greater biomedical literacy. Added to this is the shortage of professionals with specialised interdisciplinary training in ATMPs.

Emerging solutions and future prospects

In response, technological, organisational and regulatory solutions are emerging. Automation and semi-closed systems improve the scalability and reproducibility of manufacturing, while decentralised production in hospitals has been shown to reduce costs and time without compromising safety. Digital tools and artificial intelligence are transforming quality control through real-time monitoring and process optimisation, in line with the Bioprocessing 4.0 approach. In the regulatory sphere, accelerated programmes and European collaborative networks facilitate the development, evaluation and public production of ATMPs. Finally, the creation of interoperable registries and the promotion of specialised training programmes will be key to consolidating a sustainable ecosystem based on real evidence.

ATMPs are already a clinical reality, but their impact will depend on ensuring safe, timely and equitable access. In order to integrate them as a standard of care, it is essential to adapt regulatory and organisational frameworks, promoting decentralised models, flexible regulations and value- and results-based financing.