Mandatory HTAR Implementation in the EU: Part 2

How ProPharma Can Help You Ensure Compliance with the New HTAR Requirements

The new Health Technology Assessment Regulation (HTAR) will set new requirements for pharmaceutical companies seeking registration and market access in the European Union (EU) for their products. This includes preparation and submission of a Joint Clinical Assessment (JCA) report to the European Commission (EC) before product launch. Pharmaceutical companies are also encouraged to request a Joint Scientific Consultation (JSC) with regulatory experts and HTA bodies (HTAb) to exchange information on health technology development plans.

Read Part 1 of our Mandatory HTAR Implementation in the EU series.

Beginning in January 2025, a JCA will be mandatory for all pharmaceutical companies developing new oncology and/or advanced therapy medicinal product (ATMP) therapies who have submitted a centralized Market Authorization Application (MAA) to the European Medicines Agency (EMA). JSCs will be implemented at the same time as the JCA.

ProPharma can support you with all aspects of the new JCA and JSC initiatives throughout the European Union.

The New HTA Regulation

The new HTAR aims to enable a joint perspective on clinical aspects of development of medical products, in vitro diagnostics (IVDs), and high-risk medical devices at an international, European level. It thereby aims to foster innovation and ensure accelerated patient access to new treatments.

The new HTAR covers JCA, JSC, horizon scanning activities, and voluntary cooperation in areas outside the scope of mandatory cooperation. Pharmaceutical company involvement will be required for JCA and strongly recommended for JSC to optimize the success of the JCA.

The implementation of the new HTAR will be a staggered process. As of 2025, all pharmaceutical companies with an ongoing MAA in the EU for health technologies indicated for the treatment of cancer and/or ATMPs will be required to prepare and submit a JCA to the EC. Next in line will be orphan drugs, planned for 2028, and as of 2030, all drugs, IVDs, and high-risk medical devices will need to follow this new process. Vaccines, biosimilars and generics are not in scope.

Additional details regarding the implementation of the new HTAR and specifics on the regulation can be found in our previous blog post, here.

Preparation and Submission of a Joint Clinical Assessment (JCA)

The goal of a JCA is to:

1. Enable a joint perspective on clinical aspects related to the development of health technologies
2. Accelerate the process for patient access
3. Ensure consistency in assessing new technologies

Joint Clinical Assessments will cover safety, epidemiological, and clinical effectiveness. The JCA will outline diverging scientific opinions but will not give recommendations on added value or reimbursement. The latter will remain the responsibility of the individual member state (MS).

Preliminary timelines of the JCA procedure are presented in detail in Figure 1, below. In brief, the health technology developer should provide the HTA secretariat with relevant information for developing the assessment scope of a JCA in parallel with submission of the MAA to the EMA for medicinal products. The EMA shall notify the HTA secretariat of the MAA submission. The HTA secretariat will ensure that all these steps are communicated with the Coordination Group (CG). The pharmaceutical company will be informed of the start of a JCA, the subsequent steps, and the decision of the CG to include the update of the JCA in its annual work program.

Approximately two months following the submission of an MAA to the EMA, the EU member states will begin to discuss and define each country’s assessment scope and PICO framework (population, intervention, comparator(s), clinical outcomes) for the JCA. The assessment scope proposal is prepared by the assessors and will be shared with the members of the JCA Subgroup. The different PICO frameworks are then presented to the health technology developer and the company will have 90 days to develop their JCA dossier, incorporating safety, clinical, and epidemiological data through performance of systematic literature reviews (SLRs) and indirect treatment comparisons (ITCs) following each PICO framework.

After these 90 days, the JCA dossier prepared by the company is submitted to the HTA secretariat. The JCA Subgroup, via the HTA secretariat, shall finalize the revised draft joint clinical assessment at the latest on the date of the adoption of the EC decision granting the marketing authorization and submit them to the CG for endorsement.

Price setting, health economics, and full reimbursement in each market is still performed on a national level and usually commences following CHMP opinion. For transparency, each MS is obliged to report how the JCA was used in national decision making and is not allowed to redo/require analyses already evaluated in the JCA.

How ProPharma Can Support with a Joint Clinical Assessment

Based on the JCA timelines and discussion above, a health technology developer will need to take the following steps for the preparation and submission of a JCA:

• Prepare information for the HTA secretariat for developing the assessment scope of a JCA
• Develop an SLR taking MS PICO frameworks into consideration
• Develop an ITC taking results from the SLR into consideration
• Present epidemiological data
• Prepare and submit the JCA dossier

ProPharma can support you with all the steps required in the JCA process. In addition, our team of expert European regulatory affairs consultants can also assist with all necessary activities related to a national HTA submission in each European member state following the CHMP opinion, and can provide further assistance at a local level (e.g., health economic modeling, local clinical input, and price calculations and negotiations).

Joint Scientific Advice Meetings Between EMA and HTAb

Joint scientific advice meetings will be offered to health technology developers as an opportunity to engage with either multiple HTAb representatives from different MSs alone or jointly with EMA representatives. Joint scientific consultations will be implemented in January 2025, at the same time the JCA requirements take effect. However, prior to next year’s JSC implementation, Joint Scientific Consultations can also be requested in parallel with EMA Scientific Advice, via the Parallel EMA/HTAb Scientific Advice procedure.

The overall aim of these joint advice procedures is to foster early dialogue between health technology developers and HTAb, encouraging them to exchange relevant information and create a better understanding of the new technology being assessed. Several criteria need to be met to qualify for early joint consultations (e.g., high patient volumes, high unmet need, high impact on the health care system, etc.).

Requesting the JSC Meeting

The exact meeting procedure for JSC is yet to be disclosed. However, for ongoing Parallel EMA/HTAb Scientific Advice procedures, the application is initiated after the health technology developer submits the request to the EMA and sends the draft briefing package to the applicable HTA-CG Contact. A common briefing document template is used, and each question can be addressed to the Regulators, the HTAbs alone, or to both. Documents with written answers to the company’s questions will be compiled accordingly.

A list of issues will then be prepared and raised by EMA and the HTAb to facilitate the discussion during the meeting. The list of issues from the HTAb are also exchanged between EMA and HTA-CG Contact.

Preparing for the JSC Meeting

The next step is the preparation for the meeting’s discussion. The pharmaceutical company should send any written responses to the list of issues in advance of the meeting takes place. The aims of these meetings are to discuss issues of concern from EMA and/or HTAbs with the company’s proposal regarding major aspects of clinical trial designs, and to discuss potential solutions that could facilitate a consolidated development plan.

Importantly, parallel EMA/HTAb Scientific Advice and JSCs include information exchange and synchronized timing guidance. The outcome of these procedures is not legally binding, but deviations should be explained in the JCA submission.

ProPharma: Your Partner for Joint Scientific Advice Meetings

Based on the Joint Scientific Advice discussion above, a pharmaceutical company will need to take the following steps to successfully prepare for and participate in a joint consultation meeting:

• Prepare an application form (with strategy for advice)
• Prepare a briefing document (with formulations of questions to pose, formulation of positions for each question etc.)
• Written response to the list of issues to be raised during the discussion meeting
• Meeting preparation and participation

ProPharma can support you with each of these steps to ensure you maximize the exchange of relevant information and create a better understanding of the new technology being assessed.

We can also support you with early regulatory and market access strategic advice support and with strategic decisions regarding how to best implement EMA’s/HTAb’s feedback in a JCA dossier and national HTA submissions.

Expert European Regulatory Affairs Consultants

ProPharma is uniquely positioned to provide comprehensive support for the upcoming HTAR initiatives in January 2025. Our team combines in-house specialists in both regulatory affairs and HTA, enabling us to offer clients unrivalled joint support throughout the entire process. Furthermore, our consultants remain at the forefront of the field by closely monitoring the latest EU guidance and actively engaging with national stakeholders, regulatory bodies, and HTA organizations.