Good quality RWD/RWE give insights on the real-life impact of medicines and health care. RWE has shown its value in assessing effectiveness, efficacy and safety of vaccines/medicines when traditional randomised clinical trials are unethical or impossible to conduct9. This has been particularly visible for COVID-19 treatments and vaccines.RECOMMENDATIONS
EMA/Heads of Medicines Agencies (HMA) to develop and adopt guidance, together with other stakeholders10,11, for a RWD/RWE framework with clear principles for data quality and interoperability, access, analysis and regulatory acceptance. A key aspect will be to support the joint advice with HTA bodies to ensure their readiness to accept alternative evidence generation for market access decisions.
An application for approval of a new medicine contains a large amount of data collected over many years but is evaluated in 1 dossier. Without ongoing dialogue, medicine developers might not identify limitations or gaps that could undermine the medicine approval. Iterative scientific dialogue with Authorities during the collection of data would help reduce uncertainties and optimise the development and application process.RECOMMENDATIONS
EMA to work with stakeholders, including the industry, to design a regulatory pathway which includes a process for seeking early and iterative dialogue on data as they are generated. EMA and stakeholders to consider leveraging international data standards and technology, including cloud-based submission as an enabler. EMA and HTAs to ensure there is a readiness to accept iterative data generation as part of their evaluation procedures.
1 in 4 medicines approved at EU level includes a medical device component. This is likely to increase in future years.
While EMA assesses medicines, other authorities (i.e. national regulatory authorities and Notified Bodies) are responsible for assessing the performance of medical devices and in vitro diagnostics used in combination with these medicines. Experience gained by US FDA underlines the importance of an integrated approach and clear roles and responsibilities of assessing bodies.RECOMMENDATIONS
EMA to ensure the possibility for a parallel advice with Notified Bodies and adopt an integrated EU pathway for the assessment of drug-device combinations and in vitro diagnostics. Long-lasting impact can be achieved through legislative changes in particular for certain types of drug-device combinations (see recommendation 11).
Innovative clinical trials approaches, including complex clinical trials (CCTs) and decentralised trials (DCTs), lead to greater efficiencies and diversity of patients joining a trial. They can combine studies and shorten the time needed to get the evidence to support medicine’s authorisation.
Biomarkers are increasingly important to test a response to the treatment and to develop personalised medicines. EMA qualification is needed to use biomarker results, but current procedures are cumbersome.RECOMMENDATIONS
Continue the multi-stakeholder dialogue to increase awareness and acceptance of CCTs and DCTs and further develop guidance. This dialogue should involve patients and address implications for Health Technology Assessment (HTA) bodies and payers.
The implementation of the new EU Clinical Trial Regulation should be an enabler of innovative CTs rather than a hurdle. EMA to work with stakeholders to streamline the biomarker qualification process and produce guidance.
While the global response to the COVID-19 pandemic has shown the potential of digital health and accelerated a greater reliance on telemedicine, the life science industry has been surprisingly slow to join the digital revolution. Digitalisation can speed up and increase quality in the R&D and manufacturing processes as well as ease the compilation and assessment of data.RECOMMENDATIONS
EU regulatory authorities to ensure that all aspects of the regulatory system are ‘digitally enabled’. This means working with policymakers, regulators, healthcare providers and industry to ensure that the infrastructure, data security framework, and mindset required are in place to embrace the digital opportunities.
Pharmaceutical supply chains are spanning across continents, and involve many actors: material/API suppliers, manufacturers, wholesalers, traders, pharmacies and hospitals. Supply chains need to cope with different potential disruptions to ensure patient needs are met. For example, the COVID-19 pandemic revealed the need to have real-time patient-demand data by countries to react to sudden changes in medicines demand.RECOMMENDATIONS
EMA and the EU Commission (EC) to set up a reporting system, with a common definition of ‘shortage’. The system should collect real time information and ensure a streamlined alert system. To avoid duplication, the existing European Medicines Verification System could be used. The European Centre for Disease Control (ECDC) should release epidemiological modelling, patients’ needs and hospital capacity data in the Member States.
Special attention should be provided to a subset of critical medicines. In these cases, manufacturers would collaborate with regulators on shortage prevention plans.
Today there is no alignment on the concept of unmet medical need (UMN). What is considered an UMN depends on the perspective that is taken; from patient, healthcare systems or a societal point of view.
UMN definition is used throughout the value chain, from drug discovery to pricing and reimbursement. UMN designation can offer prioritisation and acceleration of regulatory processes, as seen in EMA’s PRIME scheme.RECOMMENDATIONS
The EC and EMA to include all relevant stakeholders in determining what constitutes an UMN, and notably the patient perspective. An inclusive approach is also important to identify criteria for applicability of accelerated regulatory procedures which are context-specific.
Information submitted to regulators doesn’t stop at the approval of a medicine. Manufacturers need to constantly update their terms of a marketing authorisation to demonstrate a medicine is safe, efficacious and manufactured respecting the highest quality standards. The current framework, including the EU Variations Regulation, managing these updates, is inflexible and carries too high administrative burden both for industry and for regulators.RECOMMENDATIONS
EC and EMA to evolve the variations system and legislation to incorporate the principles and tools described in ICH Q12 guidance. This includes extending risk-based approaches for well-characterised products, and developing vaccine-specific annex to EU Variations guideline.17 It should also enable a lifecycle management of medicines being more efficient and adapted to digitalisation.
Europe is the slowest region to approve new medicines in comparison to the US, Japan, Canada and Australia3. EMA’s committee structure does not provide for efficiencies nor it allows Member States to bring forward their best experts. The Commission decision-making process takes in average 67 days whilst during the pandemic it took only one day. A recent report shows that for 11 oncology products 18.600 years of potential life could have been saved if it was not for these 67 days step embedded in the legislation.RECOMMENDATIONS
EC and EMA to reconsider the committee structure to enhance Member States ability to bring forward their expertise. It is imperative that the EMA and the EU Regulatory network ensure the upskilling of staff expertise and are provided with the needed resources. The decision-making process from EMA approval to EC decision to be made more efficient.
There are several EU regulatory tools that can be described as expedited regulatory pathways (ERP) such as PRIME and accelerated assessment. To date, their use has been limited. By the end of 2021, EMA accepted only 25% of the 382 requests for PRIME eligibility. Effective ERPs are needed for a future-proof regulatory framework to deliver the wide range of innovative treatments in the pipeline.RECOMMENDATIONS
EC to embed PRIME in legislation to ensure its optimal use and allocation of sufficient resources in the EU Medicines Regulatory network, including EMA permanent staff. A suite of effective ERPs should be put in place to be leveraged and combined as needed. Eligibility criteria should be consistent and apply to new indications/line extensions.
As mentioned under n. 4, Europe is missing an integrated approach to evaluate drug-device combinations, which represent >25% of the current pipeline. This creates uncertainty and puts the European patients in disadvantage in comparison to the US.RECOMMENDATIONS
EC to create a new legal category for combinations of medicines and medical devices so that they are regulated as medicinal products. This will streamline their regulatory pathway. The new legal category will be a driver for an extended EMA remit, with sufficient staff and expertise, to coordinate and arbitrate for drug-device combination products intended to be used as medicines.
Under current EU legislation the paper version of a medicine leaflet is mandatory. Many studies of electronic product information (ePI) are showing the feasibility and benefits of electronic information. ePI contains the most updated, regulatory approved information without any delay. This contributes to increased patient safety, improves health literary and adherence to the treatment.RECOMMENDATIONS
EC to ensure legislative readiness to transition from paper leaflets to ePI while considering the elderly population and those who may not have access to computers or mobile technology. EC and stakeholders to consider further improvements to health literacy by removing any barriers in the legislation.
Any new and centralised ePI repository / database to be constructed as state-of-art in terms of privacy aspects and to be free of any commercials.