Meeting Highlights: DIA Europe 2022
How to Future-Proof the EU Medicines Regulatory System
Nick Sykes

n its Pharmaceutical Strategy, the European Commission intends to “future-proof” the EU medicines regulatory system. What does that mean for a system that has existed for more than two decades but has constantly evolved as science, technology, and societal expectations have changed? DIA Europe 2022 featured much discussion on what “future-proofing” looks like.

The innovation industry provided suggestions for changes to the EU regulatory system in response to the Commission’s open public consultation during the fourth quarter of 2021. These proposals were discussed throughout the DIA Europe 2022 meeting and included the following priorities for the Commission to focus on.

Better Use of Available Expedited Regulatory Pathways

The European regulatory system provides several pathways that can expedite the development and approval of innovative medicines (Conditional Marketing Authorisation, PRIME, Accelerated Assessment). However, they have been underutilized by regulators in the EU, particularly when one considers the use of comparable pathways in other regions. The EMA’s PRIME scheme is a case in point; entry into the scheme is unclear, with most applications denied entry. In addition, it is the author’s view that PRIME’s value in accelerating patients’ access to innovative products has yet to be truly determined. Giving PRIME some legislative legitimacy, with better-defined high-level criteria for entry and guaranteed eligibility for the Accelerated Assessment programme, may help to drive PRIME status to the level of a US Breakthrough Therapy Designation (BTD).

At DIA Europe 2022, several regulators agreed that expedited regulatory pathways need to be used in a smarter way. However, acceptance needs to come with safeguards for regulators to be able to stop the assessment of applications based on immature dossiers. Most pharmaceutical companies strive to ensure that their MA (Marketing Authorisation) dossiers are mature enough to “tell the story”; therefore this simple, resource-saving ask from regulators should be acceptable.

Process, Time, and Responsibility for Issuing the MA Decision

Since 1985, medicines authorized at the EU level have had to endure several months’ delay before being made available to patients after the EU’s regulators have declared the product to be safe, efficacious, and manufactured to a high-quality standard due to the Commission decision-making process. One group has estimated that for just 11 recent oncology products this delay could account for 18,600 years of lives lost. During the COVID-19 pandemic, the process was expedited to less than one day for vaccines, demonstrating that it is possible to shorten timelines significantly without affecting the quality and rigor of scientific review. A more radical approach would be to transfer the authority to issue the Marketing Authorisation decision to the EMA, removing an unnecessary and delaying point of handover.

EU Regulators’ Participation in Global Benefit-Risk Assessment Collaborations

Several sessions at DIA Europe 2022 referred to the recent and increasing trend for regulators from countries with more mature regulatory systems to collaborate on benefit-risk assessments. Such approaches include the ACCESS Consortium (collaboration among Australia’s Therapeutic Goods Administration, Health Canada, Singapore’s Health Sciences Authority, the Swiss Agency for Therapeutic Products [Swissmedic] of Switzerland, and the Medicines & Healthcare products Regulatory Agency of the UK) and FDA’s Project ORBIS (with all of the ACCESS agencies plus Brazil’s National Health Surveillance Agency and the Israel Ministry of Health Pharmaceutical Administration). Participants at DIA Europe 2022 highlighted that the EMA and EU regulators are absent from these collaborations.

During the pandemic, the EMA introduced its OPEN pilot as a way for a small group of regulators to collaborate with the Agency on the benefit-risk assessment of COVID vaccines and therapeutics. Post-pandemic, further development of this collaborative approach is encouraged. In addition, ICMRA (the International Coalition of Medicines Regulatory Authorities) became an important global forum for regulators to cooperate during the pandemic. Although EMA takes a leading role in ICMRA, the focus of the coalition is directed toward education and sharing learnings between regulators and not benefit-risk assessment collaboration.

Currently, EU assessment timelines are set in law and this, arguably, means that EMA’s participation in collaborative benefit-risk assessments such as ACCESS and ORBIS is difficult. Future-proof legislation should ensure that the language used to define assessment processes and timelines provides EU regulators with the flexibility for participation in future international collaborations.

Replacing Paper Patient Leaflets with Electronic Patient Information

A recurring theme throughout DIA Europe 2022 was the need for a future-proofed regulatory system to embrace digitalization. Nowhere is this need more urgent than in the provision of medicines information to patients. The current approach to providing paper patient leaflets is outdated from both a technological and an environmental perspective. Digital approaches to providing medicines information to patients can tailor both the information and the way that information is delivered to better meet the needs of the patients taking that medicine and thus delivering a better patient experience.

We must acknowledge that not all patients in the EU currently have digital access or a high level of digital literacy. However, solutions (e.g., paper leaflet provided upon patient’s request) are available (and were shown to work during the pandemic) that will ensure that those patients can still be provided with the information they need to understand the medicines they take. Over time, limitations on digital access and digital literacy levels should be addressed, meaning those interim solutions will eventually be unnecessary. Failing to use this opportunity to review the legislation to address existing limitations and embrace digitalization risks leaving the EU regulatory system and patients behind the approaches taken by other countries.

Define Regulatory Processes but Allow for Regulatory Agility for Highly Novel Technologies Where Legislation Creates Barriers to Development and Approval

During the pandemic, EU regulators did everything they could to expedite approval of vaccines and therapeutics and should be congratulated for the role they played in protecting public health. However, their actions were hindered by the limitations of the legislation; for instance, there is no provision in the legislation for an EU Emergency Use Authorisation. The legislation, like the rest of us, had not anticipated the pandemic’s rapid onset and impact. The legislation had also not anticipated industry’s ability to respond so rapidly, and to develop and make vaccines and therapeutics available for regulatory review.

A future regulatory system must have the agility that allows regulators and developers to pilot and adapt regulatory procedures for new cutting-edge product developments that would otherwise be hindered by existing rules, so patients can rapidly receive the innovative treatments they need. This agility, perhaps in the form of a “sandbox,” is needed not only during public health emergencies but also to ensure that the development and regulatory review of truly novel interventions are not impeded by legislation that has not anticipated them.

Review Should Look to the 2030s

The impending review of the pharmaceutical legislation is a “once in a generation” opportunity to update the EU regulatory system. Since any revision is unlikely to take effect until the latter half of this decade, the legislation must ensure that the system is ready to support the development and regulatory assessment of innovations anticipated to arrive in the 2030s and 2040s. It is important to look at this review through this lens and not just as a means of fixing today’s problems. The EU needs a future-proof regulatory system to maintain its globally influential status and, more importantly, to ensure that patients in the EU rapidly benefit from innovative medicines to come.