Toelichting bij COM(2023)192 - Code van de Unie betreffende geneesmiddelen voor menselijk gebruik - Hoofdinhoud
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| dossier | COM(2023)192 - Code van de Unie betreffende geneesmiddelen voor menselijk gebruik. |
|---|---|
| bron | COM(2023)192  |
| datum | 26-04-2023 |
•Reasons for and objectives of the proposal
EU pharmaceutical legislation has enabled the authorisation of safe, efficacious and high-quality medicinal products. However, patient access to medicinal products across the EU and security of supply are growing concerns, mirrored by recent Council conclusions 1 and resolutions of the European Parliament 2 . There is also a growing problem of shortages of medicinal products for many EU/EEA countries. Consequences of such shortages include decreased quality of treatment received by patients and increased burden on health systems and on healthcare professionals, who need to identify and provide alternative treatments. While the pharmaceutical legislation creates regulatory incentives for innovation and regulatory tools to support timely authorisation of innovative and promising therapies, these medicinal products do not always reach the patient, and patients in the EU have differing levels of access.
Moreover, innovation is not always focused on unmet medical needs, and there are market failures, especially in the development of priority antimicrobials that can help address antimicrobial resistance. Scientific and technological developments and digitalisation are not fully exploited, while the environmental impact of medicinal products needs attention. In addition, the authorisation system could be simplified to keep up with global regulatory competition. The pharmaceutical strategy for Europe 3 is a holistic answer to the current challenges of the pharmaceutical policy with legislative and non-legislative actions interacting together to achieve its overall goal of ensuring EU’s supply of safe and affordable medicinal products and supporting the EU pharmaceutical industry’s innovation efforts 4 . Reviewing the pharmaceutical legislation is key to achieving these objectives. However, innovation, access and affordability are also influenced by factors outside the scope of this legislation, such as global research and innovation activities or national pricing and reimbursement decisions. Hence, not all problems can be addressed by the reform of the legislation alone. Despite this, EU pharmaceutical legislation can be an enabling and connecting factor for innovation, access, affordability and environmental protection.
The proposed revision of the EU pharmaceutical legislation builds on the high level of public health protection and harmonisation already achieved for the authorisation of medicinal products. The overarching aim of the reform is to ensure that patients across the EU have timely and equitable access to medicines. Another objective of the proposal is to enhance security of supply and address shortages through specific measures, including stronger obligations on marketing authorisation holders to notify potential or actual shortages and marketing withdrawals, cessations and suspensions in advance of a foreseen interruption to continued supply of a medicinal product to the market. To support the sector’s global competitiveness and innovative power, right balance needs to be struck between giving incentives for innovation, with more focus on unmet medical needs, and measures on access and affordability.
The framework needs to be simplified, adapted to scientific and technological changes, and contribute to reducing the environmental impact of medicinal products. This proposed reform is comprehensive but targeted and focuses on provisions relevant to achieving its specific objectives; therefore it covers all provisions apart from those concerning advertising, falsified medicinal products, and homeopathic and traditional herbal medicinal products.
Therefore, the objectives of the proposal are the following:
Inhoudsopgave
- General objectives
- Specific objectives
- 2.LEGAL BASIS, SUBSIDIARITY AND PROPORTIONALITY
- 3.RESULTS OF EX-POST EVALUATIONS, STAKEHOLDER CONSULTATIONS AND IMPACT ASSESSMENTS
- General pharmaceutical legislation
- Orphan and paediatric legislation
- 4.BUDGETARY IMPLICATIONS
- 5.OTHER ELEMENTS
- Promoting innovation and access to affordable medicinal products - creating a balanced pharmaceutical ecosystem
- Introduction of variable incentives related to regulatory data protection and rewarding of innovation in areas of unmet medical needs
- Increased competition from earlier market entry of generic and biosimilar medicinal products
- Reducing the environmental impact of medicinal products
- Reducing the regulatory burden and providing a flexible regulatory framework to support innovation and competitiveness
- Specific measures related to quality and manufacturing
–guarantee a high level of public health by ensuring the quality, safety and efficacy of medicinal products for EU patients;
–harmonise the internal market for the supervision and control of medicinal products and the rights and duties incumbent upon the competent authorities of the Member States.
–make sure all patients across the EU have timely and equitable access to safe, effective, and affordable medicines.
–enhance security of supply and ensure medicines are always available to patients, regardless of where they live in the EU.
–offer an attractive, innovation-and competitiveness friendly environment for research, development, and production of medicines in Europe.
–make medicines more environmentally sustainable.
All the general and specific objectives set out above are also relevant for the areas of medicinal products for rare diseases and for children.
•Consistency with existing provisions in the policy area
The current EU pharmaceutical legislation includes both general and specific legislation. Directive 2001/83/EC of the European Parliament and of the Council 5 and Regulation (EC) No 726/2004 of the European Parliament and of the Council 6 (together ‘general pharmaceutical legislation’) lay down provisions related to medicinal products authorisation and post-authorisation requirements, pre-authorisation support schemes, regulatory incentives in terms of data and market protection, manufacturing and supply, and the European Medicines Agency (EMA). The general pharmaceutical legislation is complemented by specific legislation on medicinal products for rare diseases (Regulation (EC) No 141/2000, the ‘Orphan Regulation’ 7 ), medicinal products for children (Regulation (EC) No 1901/2006, the ‘Paediatric Regulation’ 8 ) and advanced therapy medicinal products (Regulation (EC) No 1394/2007, the ‘ATMP Regulation’ 9 ).The proposed revision of the pharmaceutical legislation will consist of two legislative proposals:
–a new directive, repealing and replacing Directive 2001/83/EC and Directive 2009/35/EC of the European Parliament and of the Council 10 and incorporating relevant parts of the Paediatric Regulation (Regulation (EC) No 1901/2006);
–a new regulation, repealing and replacing Regulation (EC) No 726/2004, repealing and replacing the Orphan Regulation (Regulation (EC) No 141/2000) and repealing and incorporating relevant parts of the Paediatric Regulation (Regulation (EC) No 1901/2006).
The merger of the Orphan Regulation and the Paediatric Regulation with the legislation applicable to all medicinal products will allow for simplification and increased coherence.
Medicinal products for rare diseases and for children will continue to fall under the same provisions as any other medicinal product concerning their quality, safety and efficacy, for example concerning the marketing authorisation procedures, pharmacovigilance and quality requirements. However, specific requirements will also continue to apply to these types of medicinal products in order to support their development. This is because market forces alone have proven insufficient to stimulate adequate research and development of medicinal products for children and patients suffering from a rare disease. Such requirements, which are currently laid down in separate legislative acts, should be integrated into the regulation and this directive in order to ensure clarity and coherence of all the measures applicable to these medicinal products.
•Consistency with other Union policies
The EU pharmaceutical legislation described above has close links with several other related pieces of EU legislation. The ‘Clinical Trials Regulation’ (Regulation (EU) No 536/2014) 11 allows for more efficient approval of clinical trials in the EU. Regulation (EU) 2022/123 12 strengthens the role of the European Medicines Agency in order to facilitate a coordinated EU-level response to health crises. The EMA fees legislation 13 contributes to providing adequate financing for the EMA's activities, including respective remuneration to national competent authorities for their contribution to completing the EMA’s tasks.
There are also links with EU regulatory frameworks for other health products. EU legislation on blood, tissues and cells (BTC) 14 is relevant, as some substances of human origin are starting materials for medicinal products. The EU regulatory framework for medical devices 15 is also relevant, as there are products that combine medicinal products and medical devices.
Futhermore, the objectives of the proposed reform of the pharmaceutical legislation are consistent with those of a number of broader EU policy agendas and initiatives.
In terms of promoting innovation, Horizon Europe 16 , a key funding programme for EU research and innovation, and Beating Cancer Plan 17 both support research and development of new medicinal products. In addition, innovation in the pharmaceutical sector is promoted by the intellectual property frameworks, on patents under the national patent laws, the European Patent Convention and the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement, and on supplementary protection certificates under the EU SPC Regulation 18 . The intellectual property action plan 19 under the Industrial Strategy includes modernising the system of supplementary protection certificates (SPCs). SPCs extend certain patent rights to protect innovation and compensate for lengthy clinical trials and marketing authorisation procedures. With regard to addressing unmet medical needs in the area of antimicrobial resistance, the proposed reform of the pharmaceutical legislation will contribute to the objectives of the European one health action plan against antimicrobial resistance (AMR) 20 .
Concerning access to medicinal products, in addition to the pharmaceutical legislation, the intellectual property frameworks, the Health Technology Assessment (HTA) Regulation (Regulation (EU) 2021/2282, the ‘HTA Regulation’) 21 and the Transparency Directive (Directive 89/105/EEC) 22 also play a role. In addition to extending certain patent rights to protect innovation, SPCs impact the effect of regulatory protection periods provided by the pharmaceutical legislation and therefore the entry of generic and biosimilar medicinal products and ultimately patient access to medicinal products and affordability. Under the HTA Regulation, national HTA bodies will conduct joint clinical assessments that compare new medicinal products to existing ones. Such joint clinical assessments will help Member States take more timely and evidence-based decisions on pricing and reimbursement. Finally, the Transparency Directive regulates procedural aspects of the Member States’ pricing and reimbursement decisions but does not effect the level of price.
In order to enhance security of supply of medicinal products, the proposed reform of the pharmaceutical legislation aims to address systemic shortages and supply chain challenges. The proposed reform therefore complements and further develops the roles of the Member States and competent authorities of the Member States as set out in the extension of the EMA mandate (Regulation (EU) 2022/123), and is aimed at ensuring access to and continued supply of critical medicinal products during health crises. It also complements the mission of the Health Emergency Preparedness and Response Authority (HERA) to ensure availability of medical countermeasures in preparation for and during health crises. The proposed reform of the pharmaceutical legislation is therefore consistent with the package of legislative initiatives related to health security under the European Health Union 23 .
To address environmental challenges, the proposed reform of the pharmaceutical legislation will support initiatives under the European Green Deal 24 . These include the EU action plan ‘Towards Zero Pollution for Air, Water and Soil’ and the revision of: (i) the Urban Waste Water Treatment Directive 25 , (ii) the Industrial Emissions Directive 26 and (iii) the list of surface and groundwater pollutants under the Water Framework Directive 27 . The proposal is also well aligned with the Strategic Approach to Pharmaceuticals in the Environment 28 .
Finally, on the use of health data, the European Health Data Space 29 will provide a common framework across Member States for access to high-quality real world health data. This will promote progress in research and development of medicinal products and provide new tools for pharmacovigilance and comparative clinical assessments. By facilitating access to and use of health data, the two initiatives together will support the competitiveness and innovation capacity of the EU’s pharmaceutical industry.
•Legal basis
The proposal is based on Articles 114 i and 168 i, point (c) of the Treaty on the Functioning of the European Union (TFEU). This is consistent with the legal basis of existing EU pharmaceutical legislation. Article 114 i has as its object the establishment and functioning of the internal market, while Article 168 i, point (c) relates to the setting of high standards for the quality and safety of medicinal products.
•Subsidiarity (for non-exclusive competence)
Common standards of quality, safety and efficacy for the authorisation of medicinal products constitute a cross-border public health issue that affects all Member States and thus can be regulated effectively only at EU level. EU action relies also on the single market to achieve a stronger impact as regards access to safe, effective and affordable medicinal products, and with regard to the security of supply across the EU. Uncoordinated measures by Member States may result in distortions of competition and barriers to intra-EU trade for medicinal products that are relevant for the entire EU, and would also likely increase administrative burden for pharmaceutical companies, which often operate in more than one Member State.
A harmonised approach at EU level also provides greater potential for incentives to support innovation and for concerted action to develop medicinal products in areas of unmet medical needs. Moreover, simplification and streamlining of processes under the proposed reform are expected to reduce administrative burden for companies and authorities and hence improve the efficiency and attractiveness of the EU system. The reform will also have a positive influence on the competitive functioning of the market through targeted incentives and other measures that facilitate early market entry of generic and biosimilar medicinal products, contributing to patient access and affordability. Nevertheless, the proposed reform of the pharmaceutical legislation respects Member States’ exclusive competence in the provision of health services, including pricing and reimbursement policies and decisions.
•Proportionality
The initiative does not go beyond what is necessary to achieve the objectives of the reform. It does so in a way that is conducive to national action, which would otherwise not be sufficient to achieve those objectives in a satisfactory way.
The principle of proportionality has been reflected in the comparison of different options evaluated in the impact assessment. For example, trade-offs are inherent between the objective of innovation (promoting the development of new medicinal products) and the objective of affordability (which is often achieved by generic/biosimilar competition). The reform maintains the incentives as a key element for innovation, but they are adapted to better encourage and reward product development in areas of unmet medical needs and to better address timely patient access to medicinal products in all Member States.
•Choice of the instrument
The proposed directive introduces a large number of amendments to Directive 2001/83/EC and incorporates part of the current provisions and amendments to Regulation (EC) No 1901/2006. A new directive repealing Directive 2001/83/EC (rather than an amending directive) is therefore considered the appropriate legal instrument. A directive remains the best choice of legal instrument to avoid fragmentation of national legislation on medicinal products for human use, given that the legislation is based on a system of national and EU marketing authorisations. National authorisations are granted and managed on the basis of national laws implementing the EU law. The evaluation of the general pharmaceutical legislation has not found that the choice of legal instrument has caused specific problems or reduced the level of harmonisation. In addition, a REFIT Platform opinion 30 from 2019 showed that there was no support among the Member States to turn Directive 2001/83/EC into a regulation.
•Ex-post evaluations/fitness checks of existing legislation
For the reform of the general pharmaceutical legislation, stakeholder consultation activities were carried out as part of ‘back-to-back’ evaluations and impact assessments of the general pharmaceutical legislation and of the Orphan and Paediatric Regulations 31 .
For medicinal products for rare diseases and for children a joint evaluation on the functioning of the two pieces of legislation was carried out and published in 2020 32 .
For the general pharmaceutical legislation the evaluation of the legislation showed that the legislation continues to be relevant for the dual overarching objectives of protecting public health and harmonising the internal market for medicinal products in the EU. The legislation delivered on the objectives of the 2004 revision, albeit not to the same extent for all. The objective of ensuring quality, safety and efficacy of medicinal products was achieved to the largest extent, while patient access to medicinal products in all Member States was achieved only to a limited extent. As to ensuring the competitive functioning of the internal market and attractiveness in a global context, the legislation has performed to a moderate extent. The evaluation found that the achievements or shortcomings of the 2004 revision vis-a-vis its objectives depend on many external factors outside the remit of the legislation. These include R&D activities and international location of R&D clusters, national pricing and reimbursement decisions, business decisions and market size. The pharmaceutical sector and the development of medicinal products are global; research and clinical trials conducted on one continent will support development and authorisation in other continents; global are also the supply chains and manufacturing of medicinal products. International cooperation to harmonise requirements to support authorisation exists, e.g. the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 33 .
The evaluation identified the main shortcomings that the pharmaceutical legislation has not adequately addressed, while recognising that these also depend on factors outside its remit. These main shortcomings are as follows:
–Medical needs of patients are not sufficiently met.
–Affordability of medicinal products is a challenge for health systems.
–Patients have unequal access to medicinal products across the EU.
–Shortages of medicinal products are an increasing problem in the EU.
–The medicinal product lifecycle can have negative impacts on the environment.
–The regulatory system does not sufficiently cater for innovation and in some instances creates unnecessary administrative burden.
Concerning medicinal products for rare diseases and for children, the evaluation showed that overall the two specific pieces of legislation have achieved positive results by allowing more medicinal products to be developed for these two population groups. However, it also identified important shortcomings, which are similar to the ones identified for the general pharmaceutical legislation:
–Medical needs of patients with rare diseases and of children are not sufficiently met.
–Affordability of medicinal products is a growing challenge for health systems.
–Patients have unequal access to medicinal products across the EU.
–The regulatory system does not sufficiently cater for innovation and in some instances creates unnecessary administrative burden.
•Stakeholder consultations
For the reform of the general pharmaceutical legislation, stakeholder consultation activities were carried out as part of the ‘back-to-back’ evaluation and impact assessment 34 . A single consultation strategy was prepared for this exercise, including consultation activities looking backward and forward. It aimed to collect inputs and perspectives of all stakeholder groups both on the evaluation of the legislation and for the impact assessment of different possible policy options for the reform.
The following key stakeholder groups were identified as priority groups in the consultation strategy: the public; organisations representing patients, consumers and civil society active in public health and social issues (‘CSOs’); healthcare professionals and healthcare providers; researchers, academia and learned societies (academics); environmental organisations; the pharmaceutical industry and their representatives.
As part of the internal policy work process supporting the revision, the Commission collaborated with the European Medicines Agency (EMA) and the competent authorities of the Member States (NCAs) dealing with the regulation of medicinal products. Both actors play a pivotal role in implementing the pharmaceutical legislation.
Information was collected through consultations that took place between 30 March 2021 and 25 April 2022. These consisted of:
–feedback on the Commission’s combined evaluation roadmap/inception impact assessment (30 March-27 April 2021);
–Commission online public consultation (28 September - 21 December 2021);
–targeted stakeholder surveys with public authorities, the pharmaceutical industry including SMEs, academia, civil society representatives and healthcare providers (survey) (16 November 2021-14 January 2022);
–interviews (2 December 2021-31 January 2022);
–a validation workshop on the evaluation findings (workshop 1) on 19 January 2022;
–a validation workshop on the impact assessment findings (workshop 2) on 25 April 2022.
There was broad consensus among stakeholders that the current pharmaceutical system guarantees a high level of patient safety on which the revision can build to address new challenges and improve supply of safe and affordable medicinal products, patient access and innovation, especially in areas where the medical needs of patients are not met. The public, patients and civil society organisations expressed their expectation of equitable access to innovative therapies across the EU, including for unmet medical needs, and continuous supply of their medicinal products. Public authorities and patient organisations opted for a variable duration for the current main incentives, as reflected in the preferred option. The pharmaceutical industry argued against any introduction of variable incentives or the shortening of existing ones and favoured the introduction of additional or novel incentives. Industry also highlighted the need for stability in the current legal framework and predictability for incentives. The elements on the environment, regulatory support for non-commercial entities and repurposing of medicinal products included in the preferred option were supported by key stakeholders such as healthcare providers, academia and environmental organisations.
Concerning the revision of the legislation on medicinal products for children and for rare diseases, specific consultation activities were carried out in the context of the impact assessment procedure: a public consultation ran from 7 May to 30 July 2021. Furthermore, targeted surveys, including a costing survey both for pharmaceutical companies and public authorities, were conducted from 21 June to 30 July 2021 (late responses were accepted until the end of September 2021, due to the summer break). An interview programme with all relevant stakeholder groups (public authorities, pharmaceutical industry including SMEs, academia, civil society representatives and healthcare providers) was conducted at the end of June 2021, while focus groups met on 23 February 2022 to discuss some of the main issue of the reform.
There was broad consensus among stakeholders that the two pieces of legislation have had a positive effect on the development of medicinal products for children and the treatment of rare diseases. However, concerning the Paediatric Regulation, all the current structure of the paediatric investigation plan and of the condition allowing the waiver of the obligation to draw up such a plan were considered as possible obstacles to the development of certain innovative products. All stakeholders highlighted that for both the medicinal products for rare diseases and the medicinal products for children, medicinal products addressing unmet medical needs of patients should be better supported. Public authorities supported a variable duration for market exclusivity for medicinal products for rare diseases as a tool to better focus development in areas where treatments are not available. The pharmaceutical industry argued against any introduction of variable incentives or the shortening of existing ones and favoured the introduction of additional or novel incentives. As for the revision of the general pharmaceutical legislation, industry also highlighted the need for stability in the current legal framework and predictability for incentives.
•Collection and use of expertise
In addition to the extensive stakeholder consultation described in previous sections, the following external studies were conducted to support the ‘back-to-back’ evaluation and impact assessment of the general pharmaceutical legislation and the evaluation and impact assessment of the orphan and paediatric legislation:
–Study supporting the Evaluation and Impact Assessment of the general pharmaceutical legislation. Evaluation Report, Technopolis Group (2022).
–Study supporting the Evaluation and Impact Assessment of the general pharmaceutical legislation. Impact Assessment Report, Technopolis Group (2022).
–Future-proofing pharmaceutical legislation - Study on medicine shortages, Technopolis Group (2021).
–Study to support the evaluation of the EU Orphan Regulation, Technopolis Group and Ecorys (2019).
–Study on the economic impact of supplementary protection certificates, pharmaceutical incentives and rewards in Europe, Copenhagen Economics (2018).
–Study on the economic impact of the Paediatric Regulation, including its rewards and incentives, Technopolis Group and Ecorys (2016).
•Impact assessments
The impact assessment for the revision of the general pharmaceutical legislation 35 analysed three policy options (A, B and C).
–Option A builds on the status quo and achieves the objectives mainly through new incentives.
–Option B reaches the objectives through more obligations and oversight.
–Option C adopts a ‘quid pro quo’ approach in the sense that positive behaviour is rewarded and obligations are only used when there are no alternatives.
Option A maintains the current system of regulatory protection for innovative medicinal products and adds additional conditional periods of protection. Priority antimicrobials benefit from a transferable exclusivity voucher. Current requirements on security of supply are retained (notification of withdrawal at least two months in advance). The existing requirements on the environmental risk assessment continue with additional information obligations.
Option B provides for a variable duration of regulatory data protection periods (split into standard and conditional periods). Companies must either have an antimicrobial in their portfolio or pay into a fund to finance the development of new ones. Companies are obliged to launch medicinal products with an EU-wide authorisation in the majority of Member States (small markets included) and to provide information on public funding received. Current requirements on security of supply are retained and companies are obliged to offer their marketing authorisation for transfer to another company before withdrawal. The environmental risk assessment results in additional responsibilities for companies.
Option C provides for a variable duration of regulatory data protection (split into standard and conditional periods), striking a balance between providing attractive incentives for innovation and supporting timely patient access to medicinal products across the EU. Priority antimicrobials can benefit from a transferable exclusivity voucher subject to strict eligibility criteria and conditions for use of the voucher, while prudent-use measures further contribute to addressing antimicrobial resistance. Marketing authorisation holders are required to ensure transparency on public funding for clinical trials. Reporting of shortages is harmonised and only critical shortages are brought to the attention of authorities at the EU level. Marketing authorisation holders are obliged to notify possible shortages earlier and to offer their marketing authorisation for transfer to another company before withdrawal. Requirements on the environmental risk assessment and conditions of use are strengthened.
All options are complemented by a set of common elements aimed at simplifying and streamlining regulatory procedures and future-proofing the legislation with a view to accommodating novel technologies.
The preferred option is based on option C and also includes the common elements mentioned above. The preferred option was considered to be the best policy choice, taking into account the specific objectives of the revision and the economic, social and environmental impacts of the proposed measures.
The preferred option and its introduction of variable incentives is a cost-effective way of achieving the objectives of improved access, addressing unmet medical need and affordability for health systems. It is expected to provide 15% increased access, meaning 67 million more people residing in the EU who can potentially benefit from a new medicinal product, and more medicinal products addressing unmet medical needs at the same cost for the public payers as today. In addition, savings are expected for companies and regulatory authorities through the cross-cutting measures that would allow for better coordination, simplification and accelerated regulatory processes.
Measures to incentivise the development of priority antimicrobials are estimated to entail costs for public payers and the generic industry but could be effective against antimicrobial resistance if applied under strict conditions and with tight measures for prudent use. These costs must also be seen in the context of the threat of resistant bacteria and current costs incurred from antimicrobial resistance including deaths, healthcare costs and productivity losses.
The originator companies would have additional costs and benefits from the incentives and the market launch conditionality, and overall they would see an increase in their sales. Some increased costs will be associated with the reporting on shortages. Regulatory authorities will incur costs to perform additional tasks in the areas of shortage management, strengthened environmental risk assessment and enhanced pre-authorisation scientific and regulatory support.
The impact assessment on the revision of the orphan and paediatric legislation also analysed three policy options (A, B and C) per legislative act. The different policy options vary as to the incentives or rewards to which medicinal products for rare diseases and for children would be entitled. In addition, the revision will include a series of common elements present in all options.
For medicinal products for rare diseases, option A keeps the 10 years of market exclusivity and adds - as an additional incentive - a transferable regulatory protection voucher for products addressing a high unmet medical need (HUMN) of patients. Such a voucher allows for a one-year extension in the length of regulatory protection or can be sold to another company and used for a product in that company’s portfolio.
Option B abolishes the current market exclusivity of 10 years for all orphan medicinal products.
Option C provides for a variable duration of market exclusivity of 10, 9 and 5 years, based on the type of orphan medicinal product (for HUMN, new active substances and well-established use applications respectively). A ‘bonus’ market exclusivity extension of one year can be granted, based on patient accessibility in all relevant Member States, but only for HUMN products and new active substances.
All options are complemented by a set of common elements aimed at simplifying and streamlining regulatory procedures and future-proofing the legislation.
Option C was considered to be the best policy choice, taking into account the specific objectives and the economic and social impacts of the proposed measures. This option is expected to provide a balanced positive outcome contributing to the achievement of the four objectives of the revision. It will aim to refocus investments and boost innovation, in particular in products addressing HUMN, without undermining the development of other medicinal products for rare diseases. The measures provided for under this option are also expected to improve the competitiveness of EU pharmaceutical industry, including of SMEs, and will lead to the best results in terms of patient access (due to: (i) the possibility for generics and biosimilars to enter the market earlier than they do today; and (ii) the proposed access conditionality for extending the market exclusivity). Furthermore, more flexible criteria to better define an orphan condition will make the legislation more ‘fit’ to accommodate new technologies and reduce administrative burdens.
The total balance of yearly costs and benefit calculated per interested stakeholder group for this preferred option compared to the baseline are: EUR 662 million cost savings for public payers from accelerated generic entry and a EUR 88 million profit gain for the generic industry. The public will benefit from an additional one or two HUMN medicinal products and overall broader and faster access for patients. Originators will see an estimated EUR 640 million gross profit loss from earlier generic entry, but savings are expected for companies through the cross-cutting measures in the general pharmaceutical legislation that would allow for better coordination, simplification and accelerated regulatory processes.
For medicinal products for children, in option A the six month supplementary protection certificate (SPC) extension is kept as a reward for all medicinal products completing a paediatric investigation plan (‘PIP’). Furthermore, an extra reward benefiting products addressing unmet medical needs of children is added. This will consist of either 12 extra months of SPC extension or a regulatory protection voucher (duration one year), which could be transferred to another product (possibly of another company) against payment, allowing the receiving product to benefit from extended regulatory data protection (+one year). In option B, the reward for completing a PIP is abolished. Developers of every new medicinal product would continue to be obliged to agree with the EMA and conduct a PIP, but the extra costs incurred would not be rewarded. In option C, like today, the six month SPC extension remains the main reward for completing a PIP. All options are complemented by a set of common elements aimed at simplifying and streamlining regulatory procedures and future-proofing the legislation.
Option C was considered the best policy choice, taking into account the proposed measures’ specific objectives and economics and social impacts. Option C is expected to yield to an increased number of medicinal products, in particular in areas of unmet medical needs of children, which are expected to reach children faster than today. It would also ensure a fair return of investment for medicinal products developers who fulfil the legal obligation to study medicinal products in children, as well as reduced administrative costs linked to the procedures that follow from the obligation.
New simplification measures and obligations (for example those linked to medicinal product’s mechanism of action) are expected to cut time to access to children’s versions of medicinal products by 2-3 years and to bring three more new medicinal products for children yearly compared to the baseline, which in turn results in additional rewards for developers. These new medicinal products for children will result, on a yearly basis, in costs for the public estimated EUR 151 million, while originator companies would gain EUR 103 million in gross profits to compensate their efforts. Thanks to simplification of the rewards scheme linked to the study of medicinal products for use in children, generic companies will find it easier to predict when they will be able to enter the market.
•Regulatory fitness and simplification
The proposed revisions aim to simplify the regulatory framework and improve its effectiveness and efficiency, thereby reducing the administrative costs borne by companies and competent authorities. Most of the envisaged measures will act on core procedures for the authorisation and lifecycle management of medicinal products.
Administrative costs will fall for competent authorities, business and other relevant entities, for two overarching reasons. Firstly, procedures will be streamlined and accelerated, for example in connection with the renewal of marketing authorisations and the submission of variations or the transfer of the responsibility for orphan designations from the Commission to the EMA. Secondly, there will be enhanced coordination of the European medicines regulatory network, for example in terms of the work of different EMA committees and interactions with related regulatory frameworks. Further contributions to cost reductions for business and administrations are expected to come from adaptations to accommodate new concepts such as adaptive clinical trials, a medicinal product’s mechanism of action, use of real world evidence, and new uses of health data within the regulatory framework.
Enhanced digitisation will facilitate the integration of regulatory systems and platforms across the EU and support for the re-use of data, and is expected to reduce costs for administrations over time (although it may induce initial one-off costs). For example, electronic submissions by industry to the European Medicines Agency and competent authorities of the Member States will deliver cost savings to industry. Moreover, the envisaged use of the electronic product information (as opposed to paper leaflets) should also lead to administrative cost reductions.
SMEs and non-commercial entities involved in the development of medicinal products are expected to benefit in particular from the envisaged simplification of procedures, wider use of electronic processes and reduction of administrative burden. The proposal also aims at optimising the regulatory support (e.g. scientific advice) to SMEs and non-commercial organisations, resulting in additional reductions of administrative costs for these parties.
Overall, the envisaged measures for simplification and burden reduction are expected to reduce costs for businesses, supporting the ‘one in one out’ approach. In particular, the proposed streamlining procedures and enhanced support are expected to yield cost savings for EU pharmaceutical industry.
•Fundamental rights
The proposal contributes to achieving a high level of human health protection and is therefore consistent with Article 35 of the Charter of Fundamental Rights of the European Union.
The financial impact is shown in the Legal Financial Statement attached to the proposal for a Regulation of the European Parliament and of the Council, laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006.
•Implementation plans and monitoring, evaluation and reporting arrangements
The development of new medicinal products can be a long process that can take up to 10-15 years. Incentives and rewards therefore have an influence many years after the marketing authorisation date. The benefit for patients also needs to be measured over a period of at least 5-10 years after a medicinal product is authorised. The Commission intends to monitor relevant parameters that enable assessment of progress of the proposed measures with a view to reaching their objectives. The majority of indicators are already collected at the EMA level. Furthermore, the Pharmaceutical Committee 36 will provide a forum for discussing issues related to the transposition and monitoring progress. The Commission will report on the monitoring periodically. A meaningful evaluation of the results of the revised legislation can only be envisaged after at least 15 years from the deadline for its transposition.
•Explanatory documents (for directives)
Following the ruling of the European Court of Justice in Commission vs Belgium (Case C-543/17), Member States must accompany their notifications of national transposition measures with sufficiently clear and precise information, indicating which provisions of national law transpose which provisions of a directive. This must be provided for each obligation, not only at article level. If Member States comply with this obligation, they would not need, in principle, to send explanatory documents on the transposition to the Commission.
•Detailed explanation of the specific provisions of the proposal
The proposed revision of the pharmaceutical legislation consists of a proposal for a new directive and a proposal for a new regulation (see previous section ‘Consistency with existing provisions in the policy area’), which will also cover orphan and paediatric medicinal products. Provisions for orphan medicinal products have been integrated in the proposed regulation. While procedural requirements applicable to paediatric medicinal products are primarily integrated in the new regulation, the general framework for the authorisation and rewarding of these products have been included in the new directive. The main areas of the revision under the proposed new regulation are covered by the explanatory memorandum of the accompanying proposal for a regulation.
Annex II to the directive contains the existing text of Annex I. Annex II will be updated by delegated act. The delegated act will be adopted and applied before the deadline for the transposition of the directive.
The proposed directive includes the following main areas of revision:
Promoting innovation and access to affordable medicinal products - creating a balanced pharmaceutical ecosystem
To enable innovation and promote the competitiveness of the EU pharmaceutical industry, in particular SMEs, the provisions of the proposed directive work in synergy with those of the proposed regulation. In this respect, a balanced system of incentives is proposed. The system rewards innovation, especially in areas of unmet medical needs, and innovation reaches patients and improves access across the EU. To make the regulatory system more efficient and innovation-friendly, measures are proposed to simplify and streamline procedures and to create an agile and future-proof framework (see also measures under ‘Reducing regulatory burden and providing a flexible regulatory framework to support innovation and competitiveness’ below and in the proposed regulation).
Introduction of variable incentives related to regulatory data protection and rewarding of innovation in areas of unmet medical needs
The current standard period of regulatory data protection will be reduced from eight years to six years. Nevertheless, this remains competitive given what other regions offer. Furthermore, marketing authorisation holders will benefit from additional periods of data protection (beyond the standard six years) if they launch the medicinal products in all Member States covered by the marketing authorisation (+two years), if they address unmet medical needs (+six months), if they conduct comparative clinical trials (+six months) or for an additional therapeutic indication (+ one year).
Prolongation of data protection for the market launch will be granted if the medicinal product is supplied in accordance with the needs of the Member States concerned within two years from the marketing authorisation (or within three years in the case of SMEs, not-for-profit entities or companies with limited experience in the EU system). Member States have the possibility to waive the condition of launch in their territory for the purpose of the prolongation. This is expected to be the case particularly in situations where launch in a particular Member State is materially impossible or because there are special reasons why a Member State wishes that launch takes place later. Such a waiver does not mean that a Member State is not interested in the medicinal product altogether.
Prolongation of data protection for addressing unmet medical need will be granted if the medicinal product is for a life-threatening or seriously debilitating disease with remaining high morbidity or mortality, and the use of the medicinal product results in a meaningful reduction in disease morbidity or mortality. The various elements of this criterion-based definition of unmet medical need (e.g. “remaining high morbidity or mortality”) will be further specified in implementing acts, taking into account scientific input by the EMA, to ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases.
The period of regulatory data protection is followed by a period of market protection (two years), which remains unchanged under the proposed directive as compared to the existing rules.
With the additional conditional protection periods, the period of regulatory protection (data and market protection) can add up to 12 years for innovative medicines (if a new therapeutic indication is added after the initial marketing authorisation).
In addition, for a medicinal product addressing an unmet medical need, a company will benefit from an enhanced scientific and regulatory support scheme (‘PRIME’) and from accelerated assessment mechanisms. The PRIME support scheme will boost innovation in areas of unmet medical needs, allow pharmaceutical companies to speed up the development process and allow earlier patient access. The various elements of this criterion-based definition of unmet medical need (e.g “remaining high morbidity or mortality”) will be further specified in implementing acts, taking into account scientific input by the EMA, to ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases.
The ‘Bolar exemption’ (under which studies can be carried out for subsequent regulatory approval of generics and biosimilars during the patent or supplementary protection certificate protection of the reference medicinal product), will be broadened in scope and its harmonised application in all Member States ensured. In addition, procedures for the authorisation of generics and biosimilars will be simplified: as a general rule, risk management plans will no longer be required for generic and biosimilar medicinal products, considering that the reference medicinal product already has such a plan. The interchangeability of biosimilars with their reference medicinal products is also better recognised based on accumulated scientific experience with such medicinal products. In addition, the act provides an incentive for repurposing off-patent, added value medicinal products. This supports innovation, resulting in a new therapeutic indication that offers significant clinical benefit in comparison with existing therapies. Taken together, these measures will facilitate earlier market entry of generics and biosimilars, thus increasing competition and contributing to the objectives of promoting affordability of medicinal products and patient access.
Increased transparency on the contribution of public funding to research & development costs
Marketing authorisation holders will be required to publish a report listing all direct financial support received from any public authority or publicly funded body for the research and development of the medicinal product, whether successful or not successful. Such information will be easily accessible to the public on a dedicated webpage of the marketing authorisation holder and in the database of all medicinal products for human use authorised in the EU. Greater transparency around public funding for medicinal products development is expected to help maintain or improve access to affordable medicinal products.
Strengthening the requirements for the environmental risk assessment (ERA) in the market authorisation of medicinal products will drive pharmaceutical companies to evaluate and limit potential adverse effects to the environment and public health. The scope of the ERA is extended to cover new protection goals such as the risks of antimicrobial resistance.
Reducing the regulatory burden and providing a flexible regulatory framework to support innovation and competitiveness
Reduction of the regulatory burden will be ensured by measures simplifying regulatory procedures and improving digitisation. These include provisions on electronic submission of applications and electronic product information (ePI) on authorised medicinal products, the latter being an option that Member States can opt for based on their particular readiness to replace the paper leaflet. Measures to reduce regulatory burden also include abolishing the renewal and the sunset clause. The reduction of administrative burden through simplification and digitisation measures will benefit in particular to SMEs and not-for-profit entities involved in developing medicinal products. The various measures to reduce the regulatory burden will strengthen the competitiveness of the pharmaceutical sector.
Adapted frameworks with specific regulatory requirements tailored to the characteristics or methods inherent to certain, especially novel, medicinal products will ensure an agile and future-proof regulatory environment while keeping the existing high standards of quality, safety and efficacy. Such adapted frameworks could draw on the results of the regulatory sandboxes established in the proposed regulation.
The proposed directive provides rules for products which combine a medicinal product and a medical device and specifies the interplay with the medical devices legal framework. These provisions improve legal certainty in order to accommodate increasing innovation in this field. In addition, the interplay with the legislation on substances of human origin (‘SoHO’ as defined in the ‘SoHO Regulation’) is further clarified with a new definition of ‘SoHO-derived medicinal product’ and the possibility for the EMA to make a scientific recommendation on a medicinal product’s regulatory status, under the classification mechanism proposed in the regulation, in consultation with the relevant SoHO regulatory body. The proposed directive also introduces measures to improve the application of hospital exemptions for advanced therapy medicinal products.
Specific provisions for new platform technologies 37 will facilitate the development and authorisation of such types of innovation for the benefit of patients.
The advent of new therapeutic approaches that have features such as very short shelf-lives, and which may be highly personalised, enable decentralised manufacture and use of patient-specific medicinal products. These paradigms of decentralised or personalised manufacturing require a shift away from existing regulatory frameworks that are designed to meet the regulatory expectations for large-scale centralised manufacture. The new legal framework incorporates a risk-based and flexible approach that will enable the manufacture or testing of a wide range of medicinal products in close proximity to the patient.