Communication, collaboration and globalisation are the watchwords in new recommendations from an EU regulatory think-tank on removing technical and scientific obstacles to the development of innovative medicines.
The think-tank was set up by the European Medicines Agency (EMEA) and its Committee for Medicinal Products for Human Use (CHMP) as part of the EMEA’s Road Map 2010. One of the key goals of this long-term strategy is to foster research and innovation in the pharmaceutical industry across the European Union (EU). The final report of the EMEA-CHMP think-tank was informed by consultations with pharmaceutical multinationals and small and medium-sized enterprises (SMEs), as well as academic groups and learned societies.
One issue that came across strongly in these consultations was the need for better communication between pharmaceutical companies and regulators, especially during the drug development process. The existing pathways for communicating with the EMEA were regarded as “slow, not sufficiently personalised and too formal or cumbersome”, the report noted.
It recommended that companies make better use of the advice procedures provided by the agency (Scientific Advice and Protocol Assistance for orphan drugs), while meetings during or after major development phases were particularly encouraged. The think-tank also proposed extending to other EMEA working parties the model of less formal and binding ‘briefing meetings’ currently being developed through the agency’s Innovation Task Force with bodies such as the Phamacogenetics Working Party and the Gene Therapy Working Party.
Companies consulted for the report also wanted continuous global harmonisation of scientific guidelines for drug development, particularly in new areas such as validation of biomarkers, novel study designs and statistical methods, advanced therapies, modelling and simulation, and new drugs coupled with diagnostic products.
Here, the think-tank recommended setting priorities for guidelines based on actual scientific needs, in consultation with stakeholders and working-party experts. Other related proposals included rapid publication by EMEA working groups of more limited, targeted guidelines on new or “burning” issues; and organising therapeutic area-specific networks at European level to optimise scientific input into the guidelines.
One of the most important scientific issues for all of the major pharmaceutical companies consulted was qualifying biomarkers and surrogate endpoints. The think-tank recommended that the EMEA commit itself to global collaboration with industry, academia and other regulators such as the US Food and Drug Administration (FDA) on this front, through regular discussion fora and the implementation of global scientific guidance. The research on qualification of biomarkers planned under the 7th Framework Programme/Innovative Medicines Initiative of the European Commission’s Directorate-General for Research “is welcomed and needs long-term support”, the report added.
Most companies also saw a need for interaction and guidance on innovative statistical approaches to clinical trials and novel study designs. These issues should be addressed in the CHMP/Efficacy Working Party (EWP) guideline on ‘Flexible Design’, the think-tank felt. The CHMP/EWP should also consider establishing a specific subgroup to collate overall experience in adaptive/flexible trial designs, while a workshop should be considered to discuss the use of the ‘Bayesian’ methodology in confirmatory clinical trials.
Another issue raised by “most if not all” companies and academic groups in the consultation was the lack of tailored scientific guidance for quality, non-clinical and reporting requirements in clinical trials. This was perceived as a “practical obstacle in conducting research and clinical development in Europe”, especially for certain types of products such as paediatric, orphan and other innovative drugs.
Besides recommending that the CHMP consider developing tailored scientific guidance in these areas, the think-tank said a common EU scientific position on non-clinical requirements prior to conducting early Phase I trials “needs finalisation and urgent implementation”. This should incorporate the final version of the recently published CHMP draft guidance on first-in-man trials with potentially higher-risk medicines, it added.
In a comment on industry trends, the report noted that many of the companies consulted “seemed inclined to continued developing medicinal products ‘as before’, without engaging in too many new, modern, ‘high-risk’ advanced (initially cumbersome) drug development methods/fields”.
On the other hand, many others were “clearly changing their drug development views from [a] conservative ‘one drug fits all’ blockbuster model towards targeted treatment solutions within [a] particular disease and particular molecular-marker profile or otherwise defined disease pathology”. This trend called for new scientific approaches such as validation of biomarkers, identifying biomarker-defined populations in adaptive study designs and increased interaction with regulators to discuss these approaches.
