Advanced therapies have ground-breaking therapeutic potential for patients, including in currently underserved areas, bringing the possibility of a cure to life-threatening conditions with a one-off treatment. Despite its head start with the adoption of the ATMP Regulation in 2007, today Europe has a lower number of ATMP clinical trials, less ATMP developers, and less investments flow than other regions.

The revision of the EU pharmaceutical legislation, expected in the coming weeks, is an opportunity to turn these trends by strengthening the EU framework to enable companies to grow in Europe and accelerate patient access to biotechnology-based therapies. The wrong policy choices will lead large companies to disinvest from Europe, disrupting the fragile ecosystem and decreasing the ability of European companies to attract investments and ultimately push them outside Europe.

It is important to acknowledge that the revision will not be enough to turn the tide. Improving access and retaining a globally competitive biopharmaceutical industry will require balanced policy interventions at EU and national level that can support the growth of the entire innovation ecosystem.

Stable and predictable incentives are key to successful therapeutic development

The journey to bring a medicine from bench to patients is not straightforward. It is lengthy and fraught with setbacks. It took thirty years and many setbacks from the initial publication of the concept by academia and to the authorisation of the first CAR-T therapies.[1] During that time, scientists from academia and industry collaborated to develop the chimeric antigen receptor construct, establish the manufacturing process, develop clinical trial protocols, and secure regulatory approval.

Strong, stable, and predictable regulatory incentives and intellectual property protections helped ensure development continued and failures became a treatment capable of curing cancer.

If the revision of the EU pharmaceutical legislation weakens incentives and undermines their predictability, investments to support such projects in Europe will further decrease as developers focus on regions that continue to reward innovation.

Growing Europe’s biomanufacturing capacities is key to improving access to ATMPs

Manufacturing is an essential step in moving medicines from bench to patients and producing ATMPs is expensive and complex. It requires significant investments, specific infrastructures, and a skilled workforce. Despite significant investments and technological progress, many technology platforms have not yet reached the maturity to support scale up. Developers also continue to face labour shortages as biomanufacturing processes require advanced degrees and additional qualifications.

Scaling up manufacturing processes remains a challenge for developers. Autologous therapies rely on the patient’s own cells as the therapeutic vehicle that currently must be produced in labs. Gene therapies are highly sensitive to changes in manufacturing process that may affect efficacy and safety. Developers also continue to face challenges with outdated good manufacturing practices and limited mutual recognition agreements between countries.

Europe should accelerate investments in biomanufacturing to bolster its strategic autonomy and enable scale up of manufacturing through technology maturity and enable Europe’s transition to a resilient and sustainable economy.

A single, efficient, and future-proof regulatory system for ATMPs

The EU created the first regulatory framework to support the development and access to advanced therapies but ATMPs continues to face significant hurdles for regulatory approval. At the same time, Europe seems to be inching closer to a two-tier regulatory system for ATMPs

Coordination and harmonisation between regulators are key to enable efficient regulatory processes. In the EU, different regulatory requirements are creating duplication of data and delays that impact the financial viability of smaller companies and patient access. Europe’s regulatory framework is also ill-adapted to the use of novel clinical trial designs and real-world data which are key to assess ATMPs.

Europe has also been inching closer to a two-tier system under which different standards would apply to different categories of developers. The misuse of hospital exemption, which allows Member States to authorise the clinical use of advanced therapies without marketing authorisation, is having unintended consequences on the ATMP sector from reducing the clinical trial population to weakening Europe’s attractiveness and competitiveness as centrally authorised ATMPs must comply with stringent regulatory requirements.

Hospital exemption is but one example of a two-tier regulatory system hindering the growth of Europe’s ATMP industry. It has an important role to play to enable patients access to advanced therapies where no alternative exists. However, its use should remain an exemption and limited to where there is no authorised ATMPs or investigational ATMPs.

The revision of the EU pharmaceutical legislation is an opportunity to address the existing shortcomings of the EU’s regulatory system for ATMPs and create a single, efficient, and future-proof framework that can support the authorisation and access to the growing number of ATMPs in the pipeline.

Using the right tools to improve access to ATMPs

ATMPs may be authorised at EU level, but access decisions are at national level. Healthcare systems are different across the EU as Member States have distinct regulatory practices and experiences that condition how they perceive and assess value.

­­­Health Technology Assessment and Pricing & Reimbursement are fragmented and often ill-adapted to assess the value ATMPs. Developers face lengthy reimbursement decisions which can have a significant impact on company resources and further delay access. This is particularly critical for smaller developers who may decide to focus on easier markets outside Europe.

Weakening and conditioning incentives and intellectual property on launching a product in all EU markets will not improve access but only decrease the attractiveness of Europe. It also fails to consider that many ATMPs have a tailored manufacturing process, almost produced for individual patients, upon demand and delivered just in time.

Improving access to ATMPs at patient level, where it matters most, requires a well-functioning cross-border healthcare framework. The EU cross-border healthcare framework is placing a disproportionate burden on patients and fails to meet their needs. Removing the barriers to cross-border healthcare has the potential to enable patients access to life-saving therapies regardless of their country of residence.

[1] Braendstrup, P., Levine, B. L., & Ruella, M. (2020). The long road to the first FDA-approved gene therapy: chimeric antigen receptor T cells targeting CD19. Cytotherapy, 22(2), 57–69. https://doi.org/10.1016/j.jcyt.2019.12.004