Background

The future availability of ATMPs to EU citizens uniquely requires a partnership between academic/hospital/Contract Manufacturing Organisation (CMO) Good Manufacturing Practise (GMP) facilities and industrial stakeholders.

Some ATMPs will be developed and attain marketing authorisation (MA). Of these, some will be suitable for central manufacture and direct supply to clinicians whilst others will be manufactured centrally but will still require near-patient end-stage processing (thawing/dosing etc), necessitating a partnership between the central industrial manufacturer and a CMO or hospital/academic unit near to the patient.

Finally, there will be many ATMPs which are not suitable for commercialisation and will never obtain a MA but still address a critical unmet clinical need. These should be available as high quality products for EU citizens; otherwise these citizens will be forced to travel outside the EU to receive treatment. A mechanism must be available for production and supply of such ATMPs. However, the pathways needed for the development of ATMPs within the EU are as complex as they are fragmentary, and we aim to simplify the route to ATMP production by dissemination of knowledge, technology transfer and training.

Academic and hospital-based GMP facilities are major contributors to the development of ATMPs. They respond to clinical needs and provide medicinal products in an environment which, albeit compliant with industrial standards, is by definition not industrial. Data from European Medicines Agency show that, currently, more than 85% of clinical trials of ATMPs are academic led (or academic spin out) and have not yet been taken up by industry. This figure suggests that the academic delivery of clinical trials is excellent and that no barriers exist but the reality is that few ATMPs are actually in clinical trial across the EU and the pipeline for development to licensed commercial medicines is poor. Academic trialists fear the cost and complexity of Good Clinical Practice (GCP) and GMP and try to avoid an ATMP classification.

Universities and research funding bodies are reluctant to support formal clinical trials (even at phase I/II) due to the cost, complexity, time and general lack of rapid scientific recognition. The nascent biopharma industry, however, relies on GCP-quality clinical data from first-in-man academic trials to raise funds for further clinical development of an innovative therapy that could ultimately benefit European citizens and strengthen European innovative capacity.

Despite the issues described above, there are many academic clinicians wanting to do trials of novel ATMPs but they generally lack the necessary infrastructure for GCP/GMP compliance. They also report that the regulatory burden hinders the establishment of new and successful facilities; in fact, success relies mostly on those facilities who have manufactured ATMPs prior to the implementation of the current legislation whereas new facilities find it most difficult to enter the stage.

From an industry perspective, the lack of comparability in the application of regulations across the EU is a disincentive to SMEs, funders and big pharma e.g. EVEN when the product attains a marketing authorisation some MS are allowing manufacture of competing products by hospitals under the HEC which devalues the commercial product.

We will generate new knowledge on the impact of advanced therapies regulations by:

– comparing the experience of partners and invited stakeholders;
– conducting a European survey of non-industry facilities in this sector;
– organising workshops, a major conference and a joint meeting with the EBMT for targeted, collaborative discourse;
– establishing a web-based platform for information exchange including the development of a document “tool-box”
– analysing publications and guidance from the perspective of better regulation principles;
– analysing innovation statistics in relation to advanced therapies.

Moreover, the project will establish a common platform that brings together academic researchers, clinicians, quality managers, qualified persons, clinical trials coordinators, legal and regulatory advisors and regulators. The initiative will pursue a strategy of explicit outreach and integration across Europe. It will link academic researchers to existing expertise and highlight the particular issues that can arise when the academic research culture encounters the requirements of ATMP regulations.

Beyond contributing useful data to better assess the consequences of EU legislation, the research process will in itself make a contribution to research excellence in Europe by connecting research participants and stakeholders and by fostering dialogue that will strengthen networks for translational research.