Embarking on the EU HTAR realization journey: Key insights from the first of six implementing acts
By Mareike Konstanski, MSc, Susanne Kossow, PhD, Ruairi O'Donnell, PhD, Kim Joline Schmidt, MSc
Less than one year before the implementation of the European Union Health Technology Assessment Regulation (EU HTAR), industry and national HTA bodies are still missing clarity on the Joint Scientific Consultation (JSC) and Joint Clinical Assessment (JCA) procedures. The first implementing act of JCA has now been published, but does it address the stakeholders’ concerns?
The long-awaited draft implementing act on procedural rules for JCA of medicinal products has been published in March 2024 (European Commission, 2024). The act essentially confirms the timelines and procedures previously laid out by the European Commission (EC) and the JCA dossier and report templates established by EUnetHTA 21. Meanwhile, the public consultation period has been finalized and the implementing act was agreed during the meeting of the HTA Comitology Committee on the 26th of April. The implementing act will enter into force once translations for all languages of the member states are available.
Timelines
The implementing regulation specifies that “in order to allow sufficient time for a high-quality JCA,” the clinical assessment should start at the same time as the marketing authorization procedure, and, more specifically, upon the confirmation by the European Medicines Agency (EMA) of a valid submission of an application for marketing authorization. In addition, the final JCA report is to be endorsed by the HTA Coordination Group (HTACG) no later than 30 days following the adoption of the EC decision granting marketing authorization for the medicinal product under assessment. The EC thereby confirms the fully parallel process with the EMA, and the act further highlights the close collaboration and information exchange with the regulatory authority throughout the assessment. If changes occur during the regulatory process, such as changes in the therapeutic indication compared to the initially submitted one or a variation to the terms of existing marketing authorization, timelines for the JCA may be significantly delayed, depending on the extent of the impact of such changes. In some cases, this may even imply the preparation of a new assessment scope upon the decision of the JCA Subgroup.
Manufacturer involvement
As expected based on previous guidance, the involvement of the manufacturer laid out in the draft implementing act during the JCA scoping process was minimal. At the time of submission of the marketing authorization application, the manufacturer should submit information to the HTA Secretariat relevant to the development of the assessment scope, including the Summary of Product Characteristics, and the clinical overview section of the submission file to the EMA. The JCA Subgroup will then finalize the assessment scope at latest 10 days after the Committee for Medicinal Products for Human Use adopts its list of questions. Industry stakeholders have previously requested a stronger involvement in the preparation of the assessment scope, ie the definition of the PICOs (population, intervention, comparator(s), outcomes). However, the draft implementing act laid out that manufacturers would have the possibility to contribute to the development of the assessment scope only if the JCA Subgroup considers it necessary to invite them to provide further information in a meeting with the JCA Subgroup before assessment scope finalization, or an explanation meeting after assessment scope finalization. Based on feedback during the public consultation period, manufacturers are now able to proactively request an assessment scope explanation meeting with the JCA Subgroup. The meeting should take place up until 20 days after the finalization of the assessment scope by the JCA Subgroup.
The manufacturer is expected to inform the HTACG in case new clinical data become available during the JCA process. The EC will set a deadline by which such new data should be submitted for them to be considered in the draft JCA reports. However, after publication of a completed JCA, the manufacturer can still request an update if new evidence becomes available at a later time point.
JCA dossier template and submission timeline
The JCA dossier is set to be submitted within 100 days from the date of the notification of the first request to the manufacturer, or 60 days in case of an accelerated regulatory process or the variation to the terms of an existing marketing authorization. The manufacturer will be notified within 15 days from dossier submission if the EC considers the JCA dossier to meet the formal requirements laid down in the HTA regulation. Upon the second request to the manufacturer, the latter will have 15 days to submit missing information, data, analyses, and other evidence requested by the EC. The timeline will be reduced to 10 days for products with accelerated regulatory process or variation to the terms of the existing marketing authorization, and to 7 days if only minor information is missing. The implementing act further states that the assessor and co-assessor may request additional specifications, clarifications, data, analyses, and other evidence at any time during the preparation of the draft JCA and summary reports. Such information will need to be provided within 7 to 30 days (depending on the nature of the request) from the date of the notification of the request.
The detailed timelines specified in the implementing act confirm that little time will be available to customize the JCA dossier to the EC’s and JCA Subgroup’s requirements, thus highlighting the need for early strategic preparation to optimize JCA timelines and outcomes.
The annexes of the implementing act include the JCA dossier and JCA report templates. Compared to the previous templates established under EUnetHTA 21, no major structural changes have been implemented. It is thus confirmed that the JCA dossier will have a similar structure to the current German AMNOG dossier. Importantly, the manufacturer will need to explain any deviations from the recommended proposition for evidence generation in the framework of a JSC or PICO(s) identified by the JCA Subgroup during the scoping process (find more considerations on the JCA dossier requirements here).
Patient and clinician involvement
Patients and clinical and other relevant experts will be involved as early as possible in the JCA process. The stakeholder selection should start whenever the HTACG becomes aware of upcoming submissions for EMA marketing authorization. The HTA Secretariat, in cooperation with the JCA Subgroup and the appointed assessor and co-assessor, shall identify patients and clinical and other relevant experts to be consulted based on the disease, the therapeutic area concerned, and other relevant expertise for the specific JCA. For the identification of relevant stakeholders, the HTA Secretariat may further consult the members of the HTA stakeholder network, the European reference networks for rare and complex diseases and their respective European patient advocacy groups, the portal for rare diseases and orphan drugs (“Orphanet”), the national contact points designated, and the EMA. Priority will be given to patients and clinical and other relevant experts with expertise in the therapeutic area of the specific JCA, covering several Member States. Capacity building of patients in the framework of the European Patients Academy on Therapeutic Innovation (EUPATI) HTA4Patients and the European Capacity Building for Patients (EUCAPA) is currently ongoing and planned to be run until 2026 (find more details on the programs here).
Conclusions
In summary, the implementing act on procedural rules for the JCA of medicinal products provides more details on timelines and rules and responsibilities throughout the JCA. Even though no major procedural or structural changes have been implemented compared to previous guidance, industry feedback given during the public consultation was taken into account. Thereby, main concerns of the industry regarding minimal possibility to engage in the process and short timelines have been somewhat addressed. With the JCA requirements having been confirmed and only eight months left until the implementation of the EU HTAR, manufacturers need to strategically prepare for their products’ JCA procedures to anticipate potential procedural and evidence generation challenges and optimize their JCA outcomes. It will be further important to monitor implications of upcoming implementing acts to be adopted throughout 2024 (see Table 1).
Table 1. Implementing acts to be adopted by 2025
| Implementing act | Deadline | Status |
|---|---|---|
| Procedural rules for JCA of medicinal products | Q1 – Q2 2024 | Prefinal version published in April 2024 |
| Procedural rules for the management of conflict of interest | Q2 – Q3 2024 | In preparation |
| Rules on cooperation by exchange of information with the EMA | Q2 – Q3 2024 | In preparation |
| Procedural rules for JSC of medicinal products | Q2 – Q3 2024 | Planned |
| Procedural rules for JSC of medical devices and IVD medical devices | Q4 2024 | Planned |
| Procedural rules for JCA of medical devices and IVD medical devices | Q4 2024 | Planned |
Key: EMA – European Medicines Agency; IVD – in vitro diagnostic; JCA – Joint Clinical Assessment; JSC – Joint Scientific Consultation.
Source: European Commission. The EU regulation on health technology assessment: what’s in it and why it matters? Accessed 12 April 2024. https://health.ec.europa.eu/document/download/855247c3-cda9-4645-99f7-7098836f314c_en?filename=ev_20240409_co01_en.pdf
Upcoming events
- 11 June 2024: Third meeting of the stakeholder network
Sources
European Commission. Health technology assessment – joint clinical assessments of medicinal products. Accessed 2 April 2024. https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/13708-Health-technology-assessment-joint-clinical-assessments-of-medicinal-products_en
European Commission. Implementation rolling plan. 2023-2024. Accessed 27 March 2024. https://health.ec.europa.eu/document/download/397b2a2e-1793-48fd-b9f5-7b8f0b05c7dd_en
European Commission. The EU regulation on health technology assessment: what’s in it and why it matters? Accessed 12 April 2024. https://health.ec.europa.eu/document/download/855247c3-cda9-4645-99f7-7098836f314c_en?filename=ev_20240409_co01_en.pdf
European Commission. Draft Commission Implementing Regulation on Joint Clinical Assessments of Medicinal Products. Accessed 6 May 2024. https://ec.europa.eu/transparency/comitology-register/screen/documents/096863/2/consult
This article summarises Cencora’s understanding of the topic based on publicly available information at the time of writing (see listed sources) and the authors’ expertise in this area. Any recommendations provided in the article may not be applicable to all situations and do not constitute legal advice; readers should not rely on the article in making decisions related to the topics discussed.
