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A new member within EIPG


The European Industrial Pharmacists Group (EIPG) is pleased to announce the Romanian Association (AFFI) as its newest member following the annual General Assembly of EIPG in Rome (20th-21st April 2024). Commenting on the continued growth of EIPG’s membership, EIPG President Read more

The EU Parliament voted its position on the Unitary SPC


by Giuliana Miglierini The intersecting pathways of revision of the pharmaceutical and intellectual property legislations recently marked the adoption of the EU Parliament’s position on the new unitary Supplementary Protection Certificate (SPC) system, parallel to the recast of the current Read more

Reform of pharma legislation: the debate on regulatory data protection


by Giuliana Miglierini As the definition of the final contents of many new pieces of the overall revision of the pharmaceutical legislation is approaching, many voices commented the possible impact the new scheme for regulatory data protection (RDP) may have Read more

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EMA, new features for the PRIority Medicines (PRIME) scheme

May 19, 2023 , , , , , , , , , , , , , , , , , , , , , , , , , , ,

By Giuliana Miglierini

Based on the review of results obtained in the first five years of implementation of the PRIority Medicines (PRIME) scheme, the European Medicines Agency has launched a set of new features to further enhance the support to developers of new medicinal products in areas of unmet medical needs (see the revised guidance for applicants seeking access to PRIME scheme).

The guideline complements contents of other documents, i.e. EMA’s Guidance on accelerated assessment, the guidance on the preparation of the PRIME kick-off meeting and submission readiness meeting, the one specific for applicants seeking scientific advice and protocol assistance, and the toolbox guidance for robust CMC data packages.

The new set of measures to speed up approval

The major goal of the PRIME scheme, introduced by EMA in 2016, is to accelerate the regulatory pathway for new medicines seeking approval and that may have a high impact on severe conditions currently lacking treatment options. The scheme aims to facilitate the generation of robust data packages supporting the compliance to regulatory requirements for all aspects of development and production of a new medicine.

A critical aspect to ensure efficiency of this process is the ability to build a constructive and continuous dialogue between regulators and sponsors, fundamental for the continuous monitoring of development activities. To this regard, EMA will establish a new roadmap for each PRI-ME development, that will parallel and complement the already existing product development tracker. The combination of the two should allow the optimisation of early scientific advice and regulatory support provided by EMA committees. It should also facilitate the prompt identification of critical aspects and emerging issues in the development, requiring further discussion between regulators and sponsors to positively solve them.

Should issues occur with a specific programme that has already received comprehensive initial advice, EMA is now entitled to provide expedited scientific advice specifically for PRIME developments. The new approach will be tested in a one-year pilot project started in March 2023. Requests of expedited scientific advice have to meet some criteria: the request is a follow-up advice, subsequent to the initial scientific advice procedure; it refers to issues with a specific, well-defined scope; and its urgency has to be justified, in comparison to standard scientific ad-vice timelines. The PRIME Scientific Coordinator is the first point of contact for sponsors to discuss these requests, which have to be submitted via IRIS, as well as all other issues referred to the PRIME scheme.

The pilot phase also includes the new roadmap and tracker to replace the previous PRIME annual update for any products that have not yet been discussed in a Kick-off meeting. Contents of both the roadmap and development tracker are detailed in the updated guidance.

Submission readiness meetings are the third new measure introduced by EMA. The meetings will serve as the final checking point to assess the status of development, with respect to the implementation of the regulatory advice previously provided by the Agency, and the resulting data package intended to support the MA application. Mature plans for post-marketing evidence generation should also be presented, as needed. Applicants are expected to start organise the submission readiness meeting approx. 15 months prior to the intended MAA submission date; the meetings should occur approx. 9-12 months prior the same date. Confirmation of eligibility to accelerated assessment should be checked 2-3 months before submission of the MA application.

Key features of PRIME scheme

At the end of 2022, the PRIME scheme supported the development and final recommendation for approval for 26 medicines. Sponsor can voluntarily file an application to access the scheme, providing evidence the eligibility criteria are met, in particular with reference to a potential major public health interest. These include conditions for which there is an unmet medical need in prevention, diagnosis or treatment, a new therapeutic method is introduced providing significant benefit over the existing ones or bringing a major therapeutic advantage to patients in a given indication.

The PRIME scheme articulates its support through different actions along the planned pathway. Depending on the type of medicinal product under development, the early appointment of a Rapporteur from the Committee for Medicinal Products for Human Use (CHMP) or the Committee for Advanced Therapies (CAT) allows for the discussion of all preparatory aspects of the ap-plication from both a technical and scientific perspective. Opinions may be also provided by other relevant EMA’s Committees and Working Parties, as needed.

Sponsors can also benefit from an initial Kick-off meeting with all the above-mentioned regulators and experts, to obtain preliminary guidance on the overall development plan. Key development steps subject to future scientific advice and the recommended regulatory strategy should be addressed during this meeting.

Special provisions are set forth to facilitate access to the PRIME scheme for SMEs and academic applicants. Upon demonstration of proof of principle, these may be granted Early Entry PRIME status, allowing for introductory meetings to raise awareness on regulatory requirements, and provide early advice on the overall development plan and relevant milestones. The requested proof of principle should be based on compelling non-clinical data in a relevant model providing early evidence of promising activity, and first-in-human studies indicating adequate exposure for the desired pharmacotherapeutic effects and tolerability.

Advice on the generation of proof of concept data is also provided at this stage by the EMA pro-duct team, and it must be fulfilled in order to confirm transition to full PRIME eligibility. In this instance, appointment of the CHMP/CAT Rapporteur is also activated.

The main steps of the procedure

Upon a first checking of acceptability of the application and related documentation, a Scientific Advice Working Party (SAWP) reviewer and a EMA scientific officer are appointed (plus a CAT reviewer in case of advanced-therapy products), and sponsors are informed of the start of the procedure and expected timelines. The SAWP committee should provide its comments to the reports by day 30, followed by final adoption by CHMP by day 40. A flowchart describing the criteria to determine eligibility is reported in Annex 1 of the guideline. The opinion of the CHMP is followed by the issuing of a letter detailing the reasons for the positive/negative decision. The outcomes of the CHMP meetings including discussions of PRIME developments are published as part of the highlights on the monthly adopted recommendations.

The confirmation of eligibility to the centralised procedure triggers the appointment of the CHMP Rapporteur, according to the specific procedure. A letter of intent to submit an MAA (approximately 6-7 months prior to submission of the MAA) is also requested.

In the case of SMEs accessing Early Entry PRIME, the appointment of the Rapporteur follows the generation of data confirming eligibility at proof of concept stage. SMEs or academic applicants also benefit from a full fee waiver for scientific advice or follow-up requests.

The Kick-off meeting is usually scheduled around 3-4 months after granting of the PRIME eligibility; submission of relevant background information and a detailed regulatory roadmap is requested to applicants in order to prepare the meeting.


Steps forward towards the new framework for HTA

November 26, 2021 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

By Giuliana Miglierini

The long-waited European regulation on Health Technology Assessment (HTA) was adopted by the Council of Europe on November 9, and it has now to pass through the final endorsement of the European Parliament as the last step before publication in the EU Official Journal. The regulation will entry into force three years and twenty days after publication.

The first proposal of a new HTA regulation was made in January 2018 by the EU Commission; the final political agreement between the Council and the EU Parliament was reached in June 2021. The position of the Council of Europe on the draft regulation at first reading was also published.

The provisions of the new HTA regulation will apply to medicinal products, medical devices (for example pacemakers, dialysis equipment or infusion pumps) or medical and surgical procedures, as well as measures for disease prevention, diagnosis or treatment used in healthcare.

“The adoption of this law is another demonstration of how EU countries, when acting together, can achieve very practical results for their citizens. This new law will benefit patients, producers of health technologies and our health systems.”, said Janez Poklukar, the Slovenian minister for health.

Cooperation and joint activities

Joint clinical assessments and joint scientific consultations are central concepts of the HTA regulation: a target that would require the active cooperation of all member states in order to efficiently identify emerging health technologies. Administrative procedures shall be greatly simplified and become more cost-efficient, as manufacturers of health technologies (especially small companies) should be required to submit once-only all data and documentation for a certain technology at the EU level. These will form the basis for national competent authorities to run all joint activities, including scientific advice and clinical assessment.

The added value of new health technologies compared to the existing ones will be a main driver to guide the assessment activities, so to take informed decisions on pricing or reimbursement.

Joint scientific consultations may also include the exchange of relevant information between national authorities and manufacturers on development plans for the technology under assessment, so to favour the availability of all the evidence required to meet regulatory expectations.

The new Heads of Agencies Group

While waiting for the formal adoption of the new HTA regulation by the EU Parliament, other activities are ongoing to set up the operative framework needed to guarantee the smooth activation of all planned collaborative efforts.

The newly formed Heads of Agencies Group (HAG) is an initiative aimed to support the implementation of common joint work approach on all HTA activities at the EU level, according to the new model of cooperation among national authorities established by the regulation.

The new HTA-focused collaborative network for high-level strategic exchange and discussion was launched on 29 September 2021 by the heads of 19 European HTA agencies, which elected Prof. Rui Santos Ivo (INFARMED, Portugal) as its Chair, and Prof. Dominique Le Guludec (HAS, France) and Dr. Trygve Ottersen (NIPH, Norway) as Vice-Chairs. The secretariat of the Group has been established at the Dutch Health Care Institute (ZIN).

All HAG’s activities will be based on a joint Memorandum of Understanding. The Group will work during the next three years to support national systems to be prepared for the entry into force of the HTA regulation, including the availability of the needed capacity. HAG will also support the joint technical and scientific work performed by HTA bodies across Europe, and it will advise policymakers and other relevant institutions – both at the EU and national level – on issues related to cooperation in HTA.

Current members of the group include the following national authorities involved in HTA activities: AEMPS (Spain), AIFA (Italy), AGENAS (Italy), AIHTA (Austria), INFARMED (Portugal), KCE (Belgium), NIPH (Norway), G-BA (Germany), HAS (France), HIQA (Ireland), IQWiG (Germany), FIMEA (Finland), NCPE (Ireland), REDETS (Spain), RER (Italy), RIZIV-INAMI (Belgium), NOMA (Norway), TLV (Sweden) and ZIN (The Netherlands).

The EUnetHTA 21 consortium

After the closing of its third Joint Action (2016-2020), which paved the way to the permanent HTA working structure for Europe (encompassing more than 80 HTA bodies), the European Network for Health Technology Assessment (EUnetHTA) has published a HTA White Paper as the final document resuming lessons learned up to now that may prove relevant for the implementation of the next phase of the HTA joint cooperation.

This new phase in the life of the Network, that now goes under the name of EUnetHTA 21, is no more a Joint Action; a joint consortium has been created instead, led by the Dutch HTA body ZIN and including the following HTA agencies: AEMPS (Spain), AIFA (Italy), AIHTA (Austria), GBA (Germany), HAS (France), INFARMED (Portugal), IQWIG (Germany), KCE (Belgium), NCPE (Ireland), NIPN (Hungary), NOMA (Norway) and TLV (Sweden). The consortium will provide support to the future European HTA system to be established according to the upcoming regulation.

EUnetHTA 21 is funded by a two-years’ Service Contract for the Provision of Joint Health Technology Assessment (HTA) Work Supporting the Continuation of EU Cooperation on HTA, signed on 17 September 2021 by the European Health and Digital Executive Agency (HaDEA).

The first Stakeholder Kick-Off online meeting of the consortium is scheduled on 3 December

2021; the discussion will focus on the illustration of the governance principles, the planned interactions with stakeholders in the form of public consultations and the presentation of deliverables planned for the next two years.

The first Open Call for consultation

EUnetHTA 21 has already launched its first Open Call , targeted to the pharmaceutical industry with reference to four different Joint Scientific Consultations (JSC, previously referred to as Early Dialogues). The Call is open until 7 December 2021; some other four slots for JSC are expected to be activated during the period of activities of EUnetHTA 21.

The medicinal products to access these four first slots will be selected on the basis of the results of the Open Call, within two weeks from its closure; the following Joint Scientific Consultations are expected to start in January 2022. According to EUnetHTA, the procedure to be used for JSC shall remain essentially unchanged, with just minor adjustments; an updated guidance document should be soon available.

JSCs are a pillar of the new HTA regulation, aimed to provide non-binding scientific advice to developers of new products, after completion of the feasibility or proof of concept studies and prior to the activation of pivotal clinical trials, in order to improve the quality and appropriateness of the data to be used for future HTA assessment. This type of evaluation will run in parallel to EMA’s scientific advice procedures.

Early exchange of relevant information between applicants and both regulatory (EMA) and HTA agencies represents the core of the process, so to optimise the integration of the different requirements to be included in the study design across multiple European member states. These might refer, for example, to the choice of comparators or relevant outcomes, to the quality of life and/or patient groups (both for pivotal trials and post-launch studies), as well as to the economic evidence generation plan.