HaDEA Archives - European Industrial Pharmacists Group (EIPG)

PIC/S Annual Report 2021


by Giuliana Miglierini The Annual Report of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) resumes the many activities and results achieved in 2021, despite the ongoing pandemic that required remote coordination and on-line virtual meetings. To this regard, a written procedure Read more

Joint implementation plan for the IVDR regulation


by Giuliana Miglierini Regulation (EU) 2017/746 (IVDR), establishing the new legislative framework for in vitro diagnostic medical devices (IVDs), will entry into force on 26 May 2022. The Medical Device Coordination Group (MDCG) has published an updated version of the Read more

Key issues in technical due diligences


by Giuliana Miglierini Financial due diligence is a central theme when discussing mergers and acquisitions (M&A). Not less important for the determination of the fair value of the deal and the actual possibility to integrate the businesses are technical due Read more

A new joint work plan to 2023 for EMA and EUnetHTA 21

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by Giuliana Miglierini

The new Regulation (EU) 2021/228 on Health Technology Assessment (HTA) will assume full validity in January 2025, at the end of the 3-year transition period. To this instance, it is time to define the actions needed to establish the new framework for HTA in the field of medicinal products.

A central point of the new approach is represented by joint scientific consultations (JSCs) to be carried out in coordination between the European Medicines Agency (EMA) and the bodies entitled of HTA at the level of single member states.

After the termination of the European Network for Health Technology Assessment (EUnetHTA) initiative, in 2021, the new consortium EUnetHTA 21 has been created grouping thirteen HTA agencies from The Netherlands, Spain, Italy, Austria, Germany, France, Portugal, Belgium, Ireland, Hungary and Norway. EUnetHTA 21 signed a contract service in 2021 with the Health and Digital Executive Agency (HaDEA) for the provision of joint health technology assessment up to September 2023.

On this basis, EMA and EUnetHTA 21 have now published a joint work plan of the activities to be put in place until 2023; the initiative represents the continuation of the EUnetHTA Joint Actions, started in 2010 and concluded in May 2021.

The document identifies the priority areas of future collaboration between regulators and HTA bodies at European level, with the final goal to “improve efficiency and quality of processes, whilst respecting the respective remits of different decision makers, and ensure mutual understanding and dialogue on evidence needs”.

The transition to the new legislative framework shall be based on a flexible approach to the different tasks; the work plan includes both methodological and operative actions, and it will be monitored in close cooperation with the EU Commission. Progresses will be discussed during the four bilateral meetings planned until September 2023.

Under the new framework, high priority HTA activities related to the service contract will be delivered by EUnetHTA 21. Other voluntary activities can be actioned through individual HTA bodies from a European (EU/EEA) member state that expressed their interest to participate. Should this be the case, the work plan clarifies that the position is that of the individual HTA body, not of EUnetHTA 21. A public consultation on deliverables part of the EUnetHTA’s mandate is also planned.

Actions in support of JSCs

Joint scientific consultations are the core of the new approach to HTA, aimed to generate a robust evidence relative to the entire life cycle of medicinal products, including the post-licensing and launch.

The work plan establishes a new European process of “parallel joint scientific consultation” involving both HTA bodies and EMA, that will take the place of the current procedures of parallel scientific advice, parallel consultation and early dialogue. This action shall make available a single assessment process, reflecting both regulatory and HTA’s needs.

Interested parties can apply to access the EMA/EUnetHTA parallel JSC procedure; a joint guidance on how to apply and the dates of EMA’s Scientific Advice Working Party (SAWP) meetings are available at the dedicated page of the Agency’s website, together with the template of the parallel consultation briefing document and submission deadlines. The joint guideline also provides details for applicants on how to respond to a EUnetHTA 21 open call for joint scientific consultation.

Exchange of information

The setting up of the JSC procedure includes the optimisation of the use of registries to facilitate post-licensing evidence generation (PLEG) and/or launch evidence to support decision making. To this instance, and depending on the specific products selected during the JSC, advice may be provided on requirements for data collection and analysis of disease registries in the context of development plans, or for qualification of registries in disease areas of particular mutual interest (including advanced therapies, ATMPs).

This exchange of information between EMA and EUnetHTA 21 may lead to discussions in order to monitor progress in the identification of PLEG. Under this action, a voluntary pilot might be activated to explore the feasibility of earlier engagement with an HTA agency during regulatory assessment, including evidence sharing and managing of uncertainties. A main outcome of this area of cooperation shall see the initial drafting of the rules for the exchange of information on the preparation and update of joint clinical assessment of medicinal products.

Capturing patient relevant data and information

The ability to generate patient relevant data and information is key to support the process of decision making. The joint work plan aims to develop new methodologies to improve reliance of patient relevant data. To this instance, the cooperation with EUnetHTA is expected to contribute to EMA’s initiative to establish an EU network of experts on Patient Reported Outcomes (PROs). The work plan also includes voluntary actions focused on the discussion and exchange of relevant data in bilateral meetings, in parallel with the development of the respective guidelines, and a workshop on patient experience data planned in June 2022.

The work plan shall also favour a better engagement of patients and healthcare professionals in areas of mutual interest. To this regard, EMA and EUnetHTA 21 will share their best practices as for compensation for expert participation and how to incorporate the input received in regulatory and HTA deliverables.

Preparedness for future challenges

The need to better understand challenges arising from the development of innovative treatments will benefit the sharing of horizon scanning activities between EMA and EUnetHTA 21. This may include, on a voluntary basis, joint discussions on data requirements and preparative measures relative to high-impact innovative medicines for patients with high unmet needs. Other voluntary activities by individual HTA bodies may focus on the optimisation of regulatory assessment reports in order to facilitate the uptake of their outcomes as part of the HTA process. Sharing of experience and guidance on the optimisation of information on subpopulations (e.g. labelling and EPARs) may also be considered, as well as the improvement of Orphan Medicines Assessment Reports (OMARs). Under the methodological perspective needed to make real-world evidence more available, a main goal of the plan shall achieve HTA representation in the advisory board of Darwin EU, the Data Analysis and Real World Interrogation Network established and coordinated by EMA to provide timely and reliable evidence on the use, safety and effectiveness of medicines for human use from real-world healthcare databases across the EU.

Other voluntary activities in this area may include multi-stakeholder discussions aimed to optimise the design, quality and utilisation of disease registries and the training on new guidance on registry-based studies. Joint methodological work may be also carried out to identify key concepts supporting the acceptance of extrapolation and/or evidence transfer, and to share best practices and experiences in the field of the integrated assessment of companion diagnostics, or other diagnostics for targeting therapeutics not directly related to the use of specific medicines.


Steps forward towards the new framework for HTA

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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.


First steps of the HERA Authority and comments from industrial and medical associations

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by Giuliana Miglierini

The new European Health Emergency preparedness and Response Authority (HERA) has started its operative phase. Initially launched in February 2021, HERA has been modelled by the European Commission on the example of the US’s DARPA agency, and it will be in charge of anticipating threats and potential health crises.

The first three calls for tender to support HERA’s setup have been published on the Commission’s website and will remain open until 29 October 2021. They are targeted towards addressing different aspects of the management of Covid-19 therapeutics and antimicrobial resistance.

A total sum of €7 million from the EU4Health programme will fund these activities. An info session on the three calls was delivered on 14 October 2021 by European Health and Digital Executive Agency (HaDEA) in collaboration with DG Santé (see more at this link). A summary of HERA’s activities in the field of crisis preparedness and emergency response is also available here. A budget of €6 billion from the current Multiannual Financial Framework 2022-2027 is available to fund HERA’s setup and activities, plus additional support from other EU programmes, for a total of almost €30 billion. HERA will be part of the internal Commission structure, and it is expected to become fully operational in early 2022.

HERA’s role is to improve the EU’s development, manufacturing, procurement and distribution of key medical countermeasures said the Commissioner for Health, Stella Kyriakides, following the recent Informal Meeting of Health Ministers in Ljubljana, Slovenia -. HERA will also be crucial in ensuring accessibility and availability of medicines. As I said to Ministers today, HERA is a joint undertaking, with Member States, EU Agencies, the European Parliament and other concerned stakeholders, including industry and civil society. HERA’s strength and success will come from our joint preparedness and joint response, and our capacity to bringing joint solutions. HERA is now operational and should be fully up and running early next year.

HERA’s first activities

The call for tender on antimicrobial resistancerefers to a service contract to run a study comprehensive of a technological review of the latest AMR medical-countermeasures (e.g.; medicines, medical devices, vaccines) and a gap analysis and assessment of needs amongst the EU Member States and key stakeholders. The study shall also include options for possible actions, funding and provision of support mechanisms, and exploration of available tools suitable to ensure the availability of safe and effective products in the European market. These products are expected to be immediately available to the EU and member states in the event of a public health emergency. The estimated total value of the tender is €1 million.

Stockpiling of medical countermeasures in the area of AMR is the subject of the second feasibility study (estimated total value €1 million). The study shall analyse physical stockpiling solutions compared to other options, providing identification and assessment of all available opportunities. The needs and availability of AMR countermeasures shall be also assessing, both at member states and EU level, as well as the mapping of relevant stockpiling systems currently operated at EU and/or global level (e.g. WHO). Possible funding mechanisms (including procurement options), identification and assessment of operational deployment mechanisms and considerations on liability and regulatory aspects and/or constraints are also to be included in the study.

The third feasibility study has the higher estimated total value (€5 million) and will focus on the design and prototype development for a mapping platform on Covid-19 therapeutics in the EU. The platform is expected to map the production capacity and supply of products intended to treat Covid-19, both already on the market and in R&D phases. Possible examples include ICU medicines, heparin, dexamethasone and antibiotics, in vitro diagnostics devices and/or companion diagnostics.

Comments from stakeholders

Many stakeholders released their comments to welcome the creation of the new Authority.

The creation of HERA is a first step to putting Europe on the front foot in addressing global health threats.”, said EFPIA Director General, Nathalie Moll. “The speed at which Europe became the epicentre of the Covid-19 crisis meant, as a region, we were simply reacting to issues as they arose, working together to find solutions as quickly as possible”.

The lessons learnt during the pandemic revealed a number of weaknesses in Europe’s ability to respond to a public health crisis. HERA’s ability to balance coordination and unity with agility and responsiveness as threats emerge shall be central to its success, according to EFPIA. The Federation, together with Vaccines Europe, supports an end-to-end approach to govern HERA’s activities, and a collaborative, partnership-based model to maximise the strength of each stakeholder in a highly coordinated approach.

The association representing the generic and biosimilar industry, Medicines for Europe, wrote in a note that HERA should “be an efficient agency with strong links to healthcare industries”. A joint industrial cooperation forum to coordinate interactions of manufacturing associations and EU authorities, a regulatory framework able to prioritise the supply of essential medicines and the elimination of the proposal for redundant manufacturing capacity are just some suggestions made by the Association, which is more favourable towards manufacturing investment in a wide range of medicine production types, as outlined in the Structured Dialogue.

Reserve policies should be also revised in order to avoid waste, costly destruction, and distorting supplies of medicines to certain (smaller) EU countries. The functioning of joint procurement system should be also addressed and improved by the Commission, to avoid distortions in the internal market and provide accurate demand estimates.

The Federation of the European Academies of Medicine (FEAM) published in May 2021 a report jointly prepared with the Wellcome Trust, highlighting the opportunity in the short term not to overstep HERA’s role in relation to others European authorities (e.g. the European Centre for Disease Prevention and Control) as a pre-requirement to ensure its success.

The new-born Authority should also try to harmonise the European research and development landscape for pandemic preparedness and response, in order to remain “relevant and active between emergencies”.