n December 2021, the European Commission (EC) adopted the Regulation on Health Technology Assessment (EU HTA Regulation; No. 2021/2282). Its main objectives were to strengthen the quality of HTAs across the EU, ensure efficient use of resources, avoid duplication of industry and national HTA body efforts, and ensure long-term sustainability of EU HTA cooperation. The EU HTA Regulation formally entered into force on 11 January 2022 and will apply to Oncologic & Advanced Therapy Medicinal Products (ATMP) products after a three-year implementation period (i.e., 12 January 2025) in the first instance, followed by Orphan Medicinal Products (OMPs) in 2028, and all other Centrally Approved Medicines from 2030 onward.

In the intervening period (2022-2024), implementation of the EU HTA Regulation will be mainly driven by EUnetHTA21, a consortium of 13 HTA bodies contracted by the EC to support the development of assessment methodologies and procedural guidelines for use by industry, agency assessors, patient representatives, healthcare professionals, and other experts. The EC, which maintains oversight and ownership, will then put forward the EUnetHTA21 deliverables (methods, procedures, templates, etc.), for further refinement/adoption by the Coordination Group or by implementing and delegated acts, before they constitute the basis for the more granular rules, procedures, and methodologies of any future system.

It is imperative that implementation of the EU HTA Regulation does not impede patient access to innovative medicines across all EU Member States. This paper reflects on elements of the HTA Regulation critical to successful implementation and highlights some potential pitfalls.

Key Elements of the EU HTA Regulation

• Phased introduction of JCAs.
• Single “core” submission of clinical data for JCA, including mandatory reuse at national level.
• Single JCA report as input into national HTA processes.
• Introduction of Joint Scientific Advice opportunities (i.e., Joint Scientific Consultations [JSC] with numerous national HTA bodies with/without EMA).

Impact of Joint Clinical Assessments

JCA will impact all Centrally Authorised Products and certain high-risk medical devices. The assessment will then serve as the basis for national value assessments and price negotiations. Despite starting after the EMA regulatory assessment, JCA will run in parallel to, and continue after, the regulatory assessment has concluded. The JCA dossier will be submitted to HTA bodies approximately 45 days prior to CHMP opinion, and the JCA report will be published 30 days after the EC decision (i.e., day 307 of the regulatory procedure). Based on these timelines and the current strain upon the EU system, forward planning to ensure that the required national HTA body resources are available to undertake each JCA will be critical to ensuring timely patient access.

JCA are envisaged to generate high-quality scientific reports that will support Member States in making more evidence-based and timely decisions on patient access to new medicines. Industry hopes that JCA will bring greater clarity and predictability concerning HTA clinical evidence requirements such as further alignment and harmonization of European-focused PICO, particularly regarding populations and comparators.

What Are Joint Scientific Consultations and Why Do They Matter?

EUnetHTA21 is currently undertaking JSC to enable early dialogue between HTA bodies and industry in parallel with EMA scientific advice. The EU HTA Regulation lists prioritization criteria: Products that could address unmet medical needs (no treatment or only unsatisfactory treatment available); first-in-class products; products with significant potential impact on patients, public health, or healthcare systems; products with a significant cross-border dimension; and products which may offer major EU-wide added value or advance EU clinical research priorities.

Regulatory system capacity for JSC has been one of the most significant issues for industry to date. Current JSC availability has been very low and future availability through the Coordinating Group is currently unknown. Notably, only eight JSC slots were opened for industry applications during 2022. The low number of applications for these eight slots was possibly due to factors such as rigid application dates which may not have aligned with internal asset timelines, lack of clarity on current criteria, and uncertainty about the overall process and outcomes.

Applications for JSC slots have also been limited due to resource constraints from the national HTA bodies and EMA, making more obvious the need for all Agencies/Member States to have the necessary resources and expertise to participate—and, importantly, to be incentivized to participate—in European work and ensure a sustainable system.

Maximum flexibility and the opportunity for iterative advice from both regulators and HTA bodies as the clinical development plan evolves is key. Industry has expressed willingness to advocate for sufficient capacity to provide JSC slots to all sponsors along with timely parallel consultations with the EMA, but also multi-HTA interactions without the EMA.

Finally, national advice should also be preserved to allow discussion on specific national economic points, specific national implementation challenges, and/or to complement EU-level JSCs.

Industry Objectives

• Achieving balance between active collaboration and convergence with EMA and HTA bodies during product development, while simultaneously maintaining the distinction between the HTA and the regulatory approval process, reflecting their different roles and objectives;
• Ensuring streamlined, fully integrated expedited processes that improve patient access to innovation across all EU Member States;
• Ensuring EU HTA processes are adequately resourced to uphold a clear, workable, and predictable framework and deliver consistent high-quality outputs;
• Engaging with health technology developers, patients, clinicians, and other experts throughout the entire lifecycle, including post-licensing evidence generation and other real-world evidence; and
• Using state-of-the-art assessment approaches that holistically account for the clinical, regulatory, and patient aspects of the disease and technology in question.

Challenges

EFPIA has also expressed concerns about the visibility of the Coordination Groups and Commissions plans for 2023/2024 (e.g., adoption of final guidelines, processes, methodologies, implementing acts, etc.) as the January 2025 application date inches nearer.

In conclusion, streamlining EMA-HTA body processes will help reduce the burden for Agencies and for industry and bolster Europe as an innovative and attractive first-launch region.