The latest parliamentary questions, declarations, proposals and positions concerning industrial pharmacy from the European Parliament.
According to EU legislation, marketing authorisation holders must inform Member State authorities at least two months before temporary or permanent market withdrawals. They are also obliged to ensure continuous supply for medicines placed on a specific EU market.
Following a meeting in 2018, the Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages.
The Commission addresses issues of access and availability through the Pharmaceutical Committee, the Expert Group on Safe and Timely Access to Medicines for Patients and by supporting relevantprojects and initiatives via the EU Health Programme. The Commission also analyses the effectiveness, accessibility and resilience of health systems as part of the European Semester.
In addition, Heads of Medicines Agencies/European Medicines Agency Task Force is working to address shortages and availability of medicines. Shortages with an impact on public health are being shared between Member States in order to increase awareness and facilitate action.
The Commission is currently reflecting on possible additional ways to address shortages of medicines.
According to Directive 2001/83/EC, holders of authorisations to produce medicines are required always to guarantee their availability. However, in practice, it is increasingly common for patients and doctors in the European Union to encounter shortages of certain medicines. This compels them to resort to more expensive medicines, or to order medicines from countries that are not members of the EU and where the same safety requirements do not apply. This has disastrous consequences for patients’ health.
1. Is the Commission monitoring whether shortages are genuine rather than being engineered by businesses with the aim of selling a more expensive alternative medicine?
2. Apart from better coordination between Member States, how else does the Commission intend to overcome the increasing shortages in the short term?
3. As a follow-up to the mission letter to the new Commissioner for Public Health, what measures does the Commission propose in order to tackle dependence on third countries and to increase the production of medicines in the EU?
The Italian Medicines Agency (AIFA) has published further information about the safety of medicinal substances containing fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, pefloxacin, prulifloxacin, rufloxacin, norfloxacin, lomefloxacin) which may produce long-lasting, disabling and potentially permanent adverse side effects, mainly affecting the tendons, muscles or joints and the nervous system.
AIFA has announced, therefore, that medicines containing cinoxacin, flumequine, nalidixic acid and pipemidic acid will be withdrawn from sale.
The German Federal Institute for Drugs and Medical Devices (BfArM) asked the European Medicines Agency (EMA) in 2017 to re-evaluate these medicines, which it did, but this was after it had already given the green light to their being marketed within the EU. In view of that fact, and the final assessments issued by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in 2018 and its Committee for Human Medical Products (CHMP), can the Commission answer the following:
1. Which studies were examined during the marketing authorisation procedures conducted prior to the re-evaluation requested in 2017?
2. Was sufficient weight given to the permanent, disabling adverse side effects on the tendons, muscles and joints and on the nervous system when those studies were examined?
3. Is the Commission going to give patients a straightforward, unambiguous explanation of exactly which medicines will be taken off the market and when?
Familial amyloid polyneuropathy (FAP) is a rare, genetically transmitted neurodegenerative disease that affects around 500 families in Portugal, mainly in the north, Lisbon and in the Serra da Estrela.
The first signs of FAP appear in patients at the age of 20 and the disease severely limits the lives of those affected. Treatment is through a liver transplant, which can take years and cause complications later on in life. A new, highly effective form of medication has recently been discovered, although unfortunately it is not yet available to all patients. There is thus a need to strengthen the role of public health and funding to ensure universal access to medication.
What initiatives could be promoted at EU level to make it easier and cheaper for national authorities to access medication (e.g. negotiations with pharmaceutical companies)?
What aid is available to carry out further research into the disease, investigate possible treatments and find a cure so that medication can be developed that more effectively responds to the different stages of FAP?
Does the Commission share our concerns that the public should be made aware of new developments and products in the area of pharmacology that are not tied in with the commercialisation of health and profits?
The Commission acknowledges that meeting the compliance deadlines of May 2020 for medical devices and May 2022 for in-vitro diagnostic medical devices is a challenging task for the whole sector and all concerned stakeholders. The availability of Notified Bodies is one of the most significant issues in this context.
At the same time, the stricter rules foreseen by the new Regulations must be introduced with no further delay, to ensure a higher level of patient safety. The importance of this has been confirmed in recent discussions in both the European Parliament and the Council. The Commission has been working relentlessly, together with Member States, to ensure that the transition can occur timely and smoothly. In this respect, significant progress has been made.
Up to date, four Notified Bodies have been designated, covering over one third of existing certificates. While progress of the applications depends very much on the level of preparedness of Notified Body applicants, it can be reasonably estimated that a substantially higher number of Notified Bodies will be available before the end of 2019.
The Innovative Medicines Initiative (IMI) has invested EUR 46 million in the pain area referred to by the Honourable Member.
EuropaIN, one of the funded projects, has carried out translational research that aims at understanding pain mechanisms, and at helping to develop novel analgesics and better biomarkers for pain. EuropaIN researchers demonstrated that antidepressants, such as amitriptyline, may relieve fibromyalgia syndrome (FMS) symptoms. However, a remarkable number of patients presents intolerable adverse effects or experience only a small relief of symptoms.
Horizon Europe will be the next Framework Programme investing in Research and Innovation for the period 2021 ‐2027. The implementation of Horizon Europe’s programme-level objectives will be ensured by a multiannual Strategic Planning. This process will set out key strategic orientations for the implementation of Horizon Europe in a transparent and inclusive manner for the period 2021‐2024. Based on the Strategic Planning, a Work Programme will be developed during 2020 that will cover the needs for Research & Innovation for the period 2021‐2022. The Orientation Paper towards the Strategic Planning indicated a possible partnership candidate Innovative Health Initiative (IHI) building upon IMI2.
The Strategic Planning will promote strong engagement with citizens and civil society and include extensive consultations with various stakeholders about research priorities. In the same context, a public consultation is ongoing, which together with the opportunity of participation in the Research & Innovation Days in September 2019 and contributing to the upcoming public consultation on potential future partnerships, represent excellent opportunities also for FMS patients to share their perspectives and expectations.
The Commission recognises the burden of Alzheimer’s disease.
Horizon 2020 is funding brain research with EUR 3.2 billion. The Commission also supports the efforts to coordinate Alzheimer’s research of the Joint Programming Initiative on Neurodegenerative Diseases, and the Innovative Medicines Initiative, a public-private partnership that established a platform where companies and academia collaborate.
In addition the Commission supports Member States and stakeholders in implementing best practices on mental health, including on Alzheimer’s, at national and regional levels. The EU Framework on mental health and well-being and the EU-Compass for action on mental health and well-being provide examples of good practices and policy approaches that Member States may use to complement their national initiatives.
The expert group on dementia, as well as other existing expert groups such as the cancer expert group, are now replaced by the Member States’ Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases that is a high-level group providing guidance and selecting best practices for transfer between countries with the view to support Member States to reach the United Nations Development Goals as well as to pursue a horizontal approach to non-communicable diseases.
The Steering Group agreed that mental health will be a priority area for the selection of best practices in 2019. In May 2019, mental health best practices and implementable research results (including projects funded by the Health Programme and Horizon 2020) were presented to the Member States.
Countries will now be able to select from that group their preferred initiatives for implementation with possible EU funding.
Since 2007, the outermost regions have benefitted from a specific additional allocation implemented in the framework of the European Regional Development Fund, which objectives are to offset additional costs linked to handicaps listed in Article 349 of the Treaty on the Functioning of the European Union.
This allocation may finance operating aid and expenditure covering freight transport services, start-up aid for transport services, operations linked to storage constraints, the excessive size and maintenance of production tools, as well as public service obligations, including those in the transport sector.
The specific transport needs of the outermost regions are fully recognised by the Commission in the strategy adopted in October 2017. The Commission proposed to keep the specific additional allocation at the same level of funding for the programming period 2021-2027.
A study by scientists at the Institute for Quality and Efficiency in Health Care (IQWiG), published in the British Medical Journal in July this year (https://www.bmj.com/company/newsroom/no-evidence-of-added-benefit-for-most-new-drugs-say-researchers/), shows that, in the case of many newly authorised medicines placed on the German market, there is no evidence of any added benefit compared to standard drugs. In total, the Institute examined 216 medicines which had been newly authorised between 2011 and 2017. 58% of them were found to lack any added value.
Is the Commission aware of the findings and recommendations of this study, and will it draw any conclusions from them for the European Medicines Agency’s authorisation procedures?
Many EU companies currently buying chemicals from the UK are classified under REACH as downstream users, not as importers. When the UK leaves the EU, these companies will become importers, and will have to comply with new obligations and registration costs, which will especially affect small distributors.
The UK has introduced a statutory instrument replicating REACH, providing for a transitional period to adapt to the new obligations. However, EU companies buying from the UK won’t benefit from such a transition. The ECHA’s analysis recommended this approach, and focused on substances that are currently only REACH registered in the UK. Unfortunately, it ignores other scenarios, including when mixtures are UK manufactured, but used in the EU, or when mixtures are manufactured outside the EU, but imported via the UK.
Without a transitional arrangement, the EU companies affected might stop importing because they are not registered or because of the cost of registration; or try to continue importing under the existing rules due to ignorance. This would have a substantial impact on EU and other worldwide companies due to repercussions on the supply chain.
Is the Commission aware of these potential ramifications? What discussions have taken place with industry representatives and trade unions?
Will the EU introduce a transitional arrangement, such as that applied to Croatia on their accession to the EU?
The Commission is aware of the growing concerns regarding shortages of medicines and patient care. The reasons for shortages include manufacturing problems, industry quotas, legal parallel trade, or economic reasons such as the price of medicines, which falls under Member States competence.
According to EU legislation, marketing authorisation holders must, other than in exceptional circumstances, inform Member State authorities at least two months before they withdraw their product from the market either permanently or temporarily, including the reasons for the withdrawal. There is also an obligation of continuous supply to cover the needs of patients for medicines placed on a specific EU market.
Following a meeting with Member States in 2018, the Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages. A paper on the obligation of continuous supply to tackle shortages was also agreed with Member States. The Commission is currently reflecting on possible additional ways to address shortages of medicines.
Furthermore, in specific circumstances, the deliberate creation of medicines shortages, for example in the sense of a refusal to supply, may constitute an infringement of both European and national competition rules.
The Commission and/or national authorities are closely following this issue and can further investigate and take enforcement measures in individual cases.
According to Article 168(7) of the Treaty on the Functioning of the EU, the organisation and delivery of health services and medical care is a national competence.
Notwithstanding the above, the EU supports fostering accessible healthcare in Member States. Article 35 of the EU Charter of Fundamental Rights enshrines people’s right of access to treatment and care.
The European Pillar of Social Rights affirms everyone’s right to timely access to affordable, preventive and curative healthcare of good quality. The Commission’s contribution to the future of Europe, stresses that the EU should support Member States to make their healthcare systems effective, accessible and resilient.
The Commission has supported various relevant initiatives through the EU Health programme.
In the Romanian Country Report, published under the most recent European Semester cycle, the Commission has drawn attention to the comparatively low level of spending on healthcare in Romania, notably impacting the coverage of novel medicines.
Under the 2019 European Semester, a Country Specific Recommendation was adopted, that underlines the need for Romania to improve access to healthcare.
Moreover, the Commission engages through different fora with Member States, including its Pharmaceutical Committee, on issues related to the early availability of centrally authorised medicines, for which the marketing authorisation is granted by the Commission.
The Commission is aware of the growing concerns regarding shortages of medicines and the dependence on active substances manufactured in non-EU countries.
To address the security of supply, the Commission, together with the Member States and the European Medicines Agency, is strengthening enforcement and control activities and stimulating the alignment of non-EU countries’ regulatory frameworks with international standards.
The Commission is currently reflecting on possible ways to address these challenges to health security by enhancing oversight of the global manufacturing and supply chain and boosting industrial policy.
In addition, the Heads of Medicines Agencies/European Medicines Agency Task Force is working to develop and coordinate actions to address shortages and availability of medicines. It is currently piloting a system for internal cooperation and information sharing between national authorities. Shortages with an impact on public health are being shared through this system in order to increase awareness and facilitate Member State actions.
As the Honourable Member rightly states, Directive 2001/83/EC obliges that the labelling and the package leaflet of medicinal products placed on the market shall be in an official language (or languages) of the Member State where the medicinal product is placed on the market.
Where the medicinal product is not intended to be delivered directly to the patient, or where there are severe problems in respect of the availability of the medicinal product; or in case of certain medicinal products for rare diseases, the competent authorities may, subject to measures they consider necessary to safeguard human health, grant a full or partial exemption to the abovementioned obligation. This may be the case in Member States with smaller markets where there is an issue of availability of the medicinal product.
The enforcement of the directive is the primary responsibility of the Member States’ competent authorities. These authorities check marketing authorisation holders’ compliance with the terms of the marketing authorisation, for instance by conducting inspections and imposing applicable sanctions. If consumers believe companies do not comply with the terms of a marketing authorisation they can contact their respective national medicine regulator.
The role of the Commission consists of monitoring the Member States’ implementation of EC law and ensuring that national legislations and practices comply with EC law, in line with the communication from the Commission ‘EC law: Better results through better application’. In its communication, the Commission explains its strategic approach to enforcement and the important role that the national authorities play in securing the rights of individuals when EC law is breached.
The relocation costs of the European Medicines Agency are part of the total costs to the Agency’s budget related to the United Kingdom’s withdrawal from the EU.
These costs will be incurred during the years 2018 to 2020 and, at this time, can only be estimated by the Agency.
The Commission has therefore sent to the European Medicines Agency the request of the Honourable Member on costs related to its move from London to Amsterdam. The Commission will transmit the reply as soon as it is available.
The Commission is aware of the shortages of the nationally authorised medicines Sinemet and Sinemet Plus. The company announced the shortage in September 2018 and recommendations to healthcare professionals and patients on suitable alternatives were issued in individual Member States.
According to EU legislation, marketing authorisation holders must, other than in exceptional circumstances, inform Member States’ authorities at least two months before they withdraw their product from the market either permanently or temporarily, including the reasons for the withdrawal. As correctly stated by the Honourable Members, there is also an obligation of continuous supply to cover the needs of patients once a medicine is placed on a specific EU market.
The Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages, following a meeting with Member States on 25 May 2018. A paper on the obligation of continuous supply to tackle shortages was also agreed with Member States in this meeting.
In addition, Heads of Medicines Agencies/European Medicines Agency Task Force is working to develop and coordinate actions to address shortages and availability of medicines. It is currently piloting a system for internal cooperation and information sharing between national authorities. Shortages with an impact on public health are being shared through this system in order to increase awareness and facilitate Member State actions.
EU legislation on homeopathic medicines was introduced in 1992 with the aim of ensuring their quality and safety whilst at the same time providing a clear indication of their homeopathic nature.
At the time of adoption of the legislation, it was considered that despite the differences in recognition between Member States, consumers across the EU should be adequately protected if they choose to use homeopathic medicines.
Under the current simplified registration procedure, homeopathic medicines must not mention specific therapeutic indications and must be diluted to a sufficient degree to ensure their safety. Furthermore, their labelling must clearly mention that they are ‘homeopathic medicinal products without approved therapeutic indications’ and shall bear a warning advising to consult a doctor if symptoms persist.
There are currently no plans to revise Directive 2001/83/EC as regards homeopathic medicinal products or change their designation to ‘homeopathic substances’.
Protecting people exposed to low quality medical products requires a holistic approach that strengthens pharmaceutical systems both globally and locally, tackling issues such as adequately resourced health systems, the regulatory framework and its enforcement, quality manufacturing and distribution, and the availability of qualified health workers.
The EU promotes access to medicines in developing countries through a health-in-all-policies approach and various initiatives, programmes and financial support. The Renewed Partnership on Strengthening pharmaceutical systems aimed to improve the quality and availability of pharmaceutical supplies including safety and quality of medicines. In particular the EU MEDISAFE project supports the fight against the production and trafficking of falsified medicines and pharmaceuticals in Eastern and Central Africa. The EU also provides support to the World Health Organization (WHO) to work on access to medicines that includes the prevention, detection and response to sub-standard and falsified products.
Furthermore, the EU contributes to global initiatives that provide quality assured medicines such as the Global Fund to fight Aids, Tuberculosis and Malaria, Gavi, the Vaccine Alliance, the United Nations Population Fund, and supports partner countries’ bilateral health programmes on medical product quality. The EU and Member States also play an active role in the WHO Member State mechanism on substandard and falsified medicines, with WHO supporting countries through its activities on medicines quality assurance.
In order to help fight the dissemination of counterfeit medicines, the EU prepares a biannual Report on the protection and enforcement of intellectual property rights in third countries and the Counterfeit and Piracy Watch List. The EU also has cooperation programmes with China, South-East Asia and Latin America among others to reduce the import of such medicines.
Genome-editing technologies can cure or treat patients affected by life-threatening diseases. In order to support these technologies, the EU has already invested more than EUR 450 million in research projects, including more than EUR 166 million since the start of Horizon 2020.
Examples include the projects Cell-PID and UPGRADE, always complying with our framework’s ethical principles and relevant national and international legislation. Remaining calls in Horizon 2020 further support genome editing approaches and support will continue in Horizon Europe through the ‘Health’ Cluster of Pillar II, paving the way for their swift uptake into health systems.
Regulation No 1394/2007 governs the use of genome editing techniques in medicinal products for human use. The regulation provides for strict controls of quality, safety and efficacy and a centralised assessment by the Committee for Advanced Therapies.
Recognising the potential of gene therapy medicinal products — including genome-editing approaches, the Commission is working with the Committee and Member States to support developers while ensuring a high level of public health protection.
Examples are the recent Guidelines on Good Manufacturing Practices (GMP) for Advanced Therapy Medicinal Products and the ongoing development of scientific guidelines for gene therapy medicinal products, including genome editing approaches.
The Commission is exploring different activities to stimulate and inform the scientific and social debate on the applications of genome editing technologies for healthcare. A public survey such as Eurobarometer could be considered.
The Commission supports proactively EU citizens’ access to innovative cancer medicines along the steps from product discovery to a patient.
The EU plays an important role in supporting cancer research, including funds for the development of innovative cancer drugs. Overall, EU’s long-term investment in cancer research totals more than EUR 2.8 billion since the beginning of the 7th Framework Programme in 2007.
The pharmaceutical legislation provides mechanisms for earlier access to promising medicines, including treatments for cancer. A marketing authorisation can be granted to fulfil an unmet medical need based on more limited evidence and medicines of major interest for public health and therapeutic innovation may undergo an accelerated assessment.
The European Medicines Agency (EMA) offers developers opportunities for an early dialogue through scientific advice or the PRIority MEdicines (PRIME) scheme, under which 14 oncology products have been granted access.
The pricing and reimbursement of medicines are competency of the Member States. However, the Commission has adopted a proposal for a Regulation on cooperation on Health Technology Assessment, which is being negotiated in the European Parliament and Council. The proposal provides for joint clinical assessments of new health technologies, including innovative cancer medicines. High quality, timely joint clinical assessments would support Member States in taking timely and evidence-based decisions on patient access, and contribute to improving patient access to innovative health technologies across the EU.
The relocation of EMA was handled efficiently and will not impact the high quality and safety of medicines that patients in the EU expect.
The Commission has been in frequent contact with the European Medicines Agency (EMA) over the Agency’s efforts to find a new tenant for the London building and to keep the related costs under control.
EMA signed its rent contract in 2011 without a break clause, bearing in mind that negotiating such a break clause would have increased the rental costs considerably. The absence of a break clause in the rent contract was a conscious choice to achieve savings, at a time when a potential United Kingdom withdrawal was not under discussion. On this basis the European Parliament and the Council (“the budgetary authority”) approved EMA’s building file in 2011.
Following the submission of its request to the budgetary authority on 4 March 2019, the EMA obtained the European Parliament’s approval on 18 March 2019 and Council approval on 2 April 2019, to enter into a sub-lease contract for the London building. Negotiations with the landlord and the sub-tenant are currently ongoing.
Shortages of pharmaceutical products are a serious problem that can affect many patients across the EU. The Commission is aware of the concerns regarding shortages of pharmaceutical products for human use. The reasons for shortages include manufacturing problems, quotas from industry, legal parallel trade, or economic reasons such as the price of medicines, which falls under the competence of the Member States.
As a response to calls from the co-legislators to monitor the obligation of continuous supply laid down in EU legislation), the Commission held a meeting with experts from EU countries on 25 May 2018.
After the meeting, the Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages. At the meeting, a document was also agreed to assist Member States to implement and enforce the obligation of continuous supply.
The European Medicines Agency and Heads of Medicines Agencies network are working on measures to address this problem, including agreeing a definition of a shortage and improving the reporting of shortages of medicines.
The Commission also addresses issues of access and availability through the Pharmaceutical Committee, the Expert Group on Safe and Timely Access to Medicines for Patients and by supporting relevant projects and initiatives via the EU Health Programme.
Generally speaking, the organisation and delivery of health services and medical care and the pricing and reimbursement decisions that closely influence access to medicines are a Member State competence. The Commission, however, closely follows this issue and analyses the effectiveness, accessibility and resilience of health systems as part of the European Semester.
The Commission is aware of the matter at hand. The Dutch and the Belgian competition authorities, which, as part of the European Competition Network, also enforce EU competition rules, are analysing the situation as a follow up to complaints.
Therefore, the Commission is at this stage not in a position to provide further information with regard to the questions raised. The Commission will however continue to monitor the pharmaceutical sector in close cooperation with the national competition authorities, and take action, if necessary.
The Commission notes that although medicines authorised at EU level can be placed on the market in all Member States, this is not always the case, as placing on the market depends on the decision of companies and on pricing and reimbursement decisions.
Pricing policies for medicinal products are Member States’ competence. However, the Commission promotes the exchange of information among Member States on their pricing policies, for example through the European medicine price database (EURIPID) and projects by the Organization for Economic Co-operation and Development (OECD). The Commission also facilitates the exchange of best practices and knowledge among Member States through a network of competent authorities.
As part of its competition policy, the Commission monitors pharmaceutical markets and investigates, where appropriate, possible breaches of EU competition rules. In addition, the Commission supports national competition authorities in Europe that can investigate possible breaches of EU competition rules, including as regards excessive pricing.
The Commission started in May 2017 with Brexit preparedness activities in the pharmaceutical sector to ensure continued and safe access to medicinal products for patients, including in case of a disorderly withdrawal of the United Kingdom from the European Union. While no legislative preparedness proposals were necessary, the Commission worked closely together with Member States and the European Medicines Agency (EMA) to minimise any potential risk concerning supply of medicines in a no-deal scenario.
For example, with regard to the batch control testing, the Commission has informed the authorities and stakeholders that, for a specific period of time and in justified cases, competent authorities may allow justified cases controls of imported medicines to be carried out by third parties in the United Kingdom, provided that the batch is released by a qualified person established in the EU. This is based on the applicable legislation given the particular circumstances of Brexit.
Subject to these conditions, a temporary exemption may be given to the concerned companies by the national competent authorities or EMA.
As regards Brexit preparedness at the Union’s borders, the Commission has published a wealth of information on customs procedures, including links to relevant websites and additional information from national authorities. On 10 April 2019, the Commission published additional practical guidance for a no-deal scenario, including with regard to medicines and medical devices.
As a response to calls from the co-legislators to monitor the obligation of continuous supply laid down in EU legislation, the Commission held a meeting with experts from EU countries on 25 May 2018. After the meeting, the Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages. A document on the obligation of continuous supply to tackle shortages, including the general principles to be considered by Member States planning to introduce restrictions on the supply of medicines at risk of shortage, was also published in order to improve enforcement by national authorities. The European Medicines Agency and Heads of Medicines Agencies network are also working on various measures to address this problem, including improving the reporting of shortages of medicines.
The enforcement of EU medicines legislation is the responsibility of the Member States. An overview of Member State penalties in relation to shortages is included in the summary report of Member States’ measures to ensure continuous supply mentioned above.
EU legislation requires an authorisation to manufacture or import medicines and active ingredients. There is no requirement in the marketing authorisation regarding the number of manufacturing sites or production capacity.
The compatibility of national legislation banning the mail order sale of prescription medicines for human use with the relevant EU legislation (in particular Articles 34 and 36 of the Treaty on the Functioning of the EU and Directive 2001/83/EC of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use), would have to be assessed on a case-by-case basis.
This assessment would consider the modalities of the national legislation and would include an appreciation of whether such legislation is necessary to pursue legitimate objectives of public health protection, and appropriate for securing the attainment of the objective pursued.
The assessment would also examine whether the legislation is not going beyond what is necessary to attain the legitimate objectives of public health protection.
According to EU medicines legislation, a marketing authorisation is required to place a medicine on the market in the EU, including online. In 2011, stricter rules for online sales of medicines were introduced in the EU to address increasing concerns with falsified medicines being sold online to citizens.
EU legislation requires online pharmacies to obtain an authorisation to supply medicines at a distance and to notify the national authorities where they are established of their intention to sell medicines online. Member States are responsible for enforcing the legislation and ensuring that only legal economic operators are offering medicines for sale in the EU.
In addition, Member States cooperate with other jurisdictions around the world to tackle illegal online sales. In 2018, the INTERPOL operation Pangea shut down 3 671 websites with illegal online offerings. The operation led to the seizure of ten million units of medicines and 859 arrests around the world.
Since 1 July 2015, a common EU-wide logo is mandatory for all online pharmacies legally operating in the EU(5). The logo makes it easier for EU citizens to identify legal online pharmacies.
The main objective of the EU Regulation on orphan medicinal products is to provide incentives for research, development and placing on the market of orphan medicines to ensure that patients suffering from rare conditions have the same quality of treatment.
The Commission is currently evaluating the functioning of the EU Orphan Regulation, which will provide insight in how the various incentives (including market exclusivity) have been used in practice and the financial consequences this has resulted in.
Pricing policies for medicinal products are outside the EU remit and fall under the Member States’ competences. However, the Commission is promoting the exchange of information among Member States on their pricing policies. This can enhance price competition for medicines and help minimise potential negative effects on accessibility. The Commission also facilitates the exchange of best practices and knowledge and supports the strengthening of cooperation on a voluntary basis, in particular through tools such as a European medicine price database.
As part of its competition policy, the Commission also monitors pharmaceutical markets and investigates, where appropriate, possible breaches of EU competition rules that may entail high prices. Article 102 of the Treaty on the Functioning of the EU also applies to abusive practices in the context of medicines benefitting from patent protection and regulatory exclusivity. That said, competition law enforcement has to take due account of the efforts and incentives to innovate. The Commission supports national competition authorities in Europe that can investigate possible breaches of EU competition rules, including excessive pricing.
1. The Commission has taken note of the report of France Assos Santé. The reasons for shortages include manufacturing problems, quotas from industry, legal parallel trade, or economic reasons such as the price of medicines, which falls under the competence of the Member States.
According to EU medicines legislation, there is an obligation for companies to ensure continuous supply of medicines to cover the needs of patients once a product is placed on a specific EU market. Furthermore, in specific circumstances, the deliberate creation of medicines shortages, for example in the sense of a refusal to supply, may constitute an infringement of both European and national competition rules. The Commission and/or national authorities are closely following this issue and can further investigate and take enforcement measures in individual cases.
2. Marketing authorisation holders must, other than in exceptional circumstances, inform Member States’ authorities at least two months in advance if they plan to withdraw their product from the market either permanently or temporarily, including the reasons for the withdrawal. There is also an obligation of continuous supply to cover the needs of patients once a medicine product is placed on a specific EU market and an obligation to comply with competition rules. The sudden withdrawal of marketing authorisations should, therefore, not be a common occurrence. There is, however, no obligation to market medicines in a particular or all Member State(s) by pharmaceutical companies.
As mentioned above, EU legislation requires an authorisation to manufacture or import medicines and active ingredients. There is no requirement in the marketing authorisation regarding the number of manufacturing sites.
The European Parliament,
– having regard to Rule 133 of its Rules of Procedure,
A. whereas, in its resolution of 2 March 2017 on EU options for improving access to medicines, Parliament states that ensuring patient access to essential medicines is one of the core objectives of the EU and the WHO;
B. whereas the agenda of the WHO plenary meeting to be held in Geneva from 20 to 28 May 2019 lists, among the strategic priority matters to be discussed, item 11.7 ‘Addressing the global shortage of, and access to, medicines and vaccines’; whereas the Italian Government has tabled a comprehensive resolution on this topic;
C. whereas it is of the utmost importance to address properly the global shortage of, and access to, medicines and vaccines;
1. Calls on the EU and all Member States to agree on a common position supporting, at the upcoming 72nd WHO plenary meeting, the resolution entitled ‘Improving the transparency of markets for drugs, vaccines and other health-related technologies’, which sets out a number of measures designed to achieve this objective.
The main objective of the EU Regulation on orphan medicinal products is to provide incentives for research, development and placing on the market of orphan medicines to ensure that patients suffering from rare conditions have the same quality of treatment.
The Commission is currently evaluating the functioning of this regulation. The evaluation will include an assessment of measures at national and EU level ensuring accessibility to affordable medicines and will provide insight into the use of various incentives in practice and its financial consequences.
Pricing policies for medicinal products are Member States’ competence. However, the Commission promotes the exchange of information among Member States on their pricing policies, for example through the Euripid database. It also facilitates the exchange of best practices and knowledge among Member States through a network of competent authorities.
As part of its competition policy, the Commission monitors pharmaceutical markets and investigates, where appropriate, possible breaches of EU competition rules that may entail high prices. Article 102 of the Treaty on the Functioning of the EU also applies to abusive practices in the context of medicines benefitting from exclusivity, like the one resulting from patent law and orphan medicines regulation.
That said, competition law enforcement has to take due account of the efforts and incentives to innovate. The Commission supports national competition authorities in Europe that can investigate possible breaches of EU competition rules, including as regards excessive pricing.
The Commission is aware of the concerns regarding shortages of pharmaceutical products for human use. Shortages are a serious problem that can affect many patients across the EU. The main reasons for shortages include manufacturing problems, quotas from industry, legal parallel trade, or economic reasons such as the price of medicines, which falls under the competence of the Member States.
The Commission has not carried out an impact assessment on shortages but held a meeting with experts from EU countries on 25 May 2018. The meeting was a response to calls from the co-legislators to monitor the obligation of marketing authorisation holders to ensure continuous supply of medicines as laid down in EU legislation.
The Commission published a summary of Member States’ measures to ensure continuous supply, including national measures addressing shortages. A meeting document on the obligation of continuous supply to tackle shortages, including the general principles to be considered by Member States planning to introduce restrictions on the supply of medicines at risk of shortage, was agreed at the meeting. The European Medicines Agency and Heads of Medicines Agencies network are also working on various measures to address this problem, including improving the reporting of shortages of medicines.
On 25 January 2019 the Commission asked the European Medicines Agency (EMA) to review as soon as possible the available evidence on the safety and efficacy of the use of Lartruvo (olaratumab) in combination with doxorubicin. In this review the EMA is seeking clarification of the discrepancy between the results of the phase II and III trials. The outcome of the full review will be published on the EMA website. Any regulatory action if necessary will be based on the outcome of the review and will be in the interest of patients.
Regarding clinical trials, the marketing authorisation holder informed the EMA that they stopped enrolling new patients into clinical trials where the active substance olaratumab is used in combination with doxorubicin, and that patients already treated in such a clinical trial are asked to confirm their consent. Research is continuing in those clinical trials of olaratumab where it is used in combination with other agents, in patients with a soft tissue sarcoma or in other cancers.
Soft tissue sarcoma may require surgery, radiation therapy and/or systemic anti-cancer medicines (“chemotherapy”) for treatment. Each patient’s situation is evaluated with respect to best option(s) as part of the patient’s treatment. Public information on treatment options is readily available through healthcare professional guidelines.
Patients with a soft tissue tumour are closely and regularly followed for evaluations and treatment by healthcare professionals. Recommendations for systematically monitoring of patients are also included in the information accompanying the medicine.
Summary of petition: The petitioner argues that Spanish Law 29/2006 of 26 July on guarantees and the rational use of medicines and health products (as amended by Royal Legislative Decree 1/2015 of 24 July) subjects official formulas or preparations to an additional and more restrictive requirement not provided for in Directive 2001/83/EC. This Directive concerns the Community code relating to medicinal products for human use. This additional requirement means that official preparations must be listed and described in the National Formulary, which is a different resource to the pharmacopoeia. For this reason, the petitioner states that Spain is failing to comply with Directive 2001/83/EC.
Conclusion: As the EU legislation clearly leaves to the Member States the competence to decide on the requirements to be applied on officinal preparations, the Commission is not in a position to intervene in favour of the petitioner.
The Commission would like to inform the Honourable Member that there is a pending assessment of a marketing authorisation application via the EU centralised procedure for a medicinal product containing an active substance lifitegrast for use in ophthalmology.
The assessment by the European Medicines Agency’s (EMA) scientific Committee for Medicinal Products for Human Use (CHMP) is expected to be finalised in 2019. In case of a positive CHMP opinion the next standard step is a decision-making process at the Commission level, with involvement of the Member States, potentially leading to a marketing authorisation valid across the whole EU. As the procedure is in its early stage, more precise estimation of timelines of the process in question cannot be provided.
In response to the Honourable Member, we can confirm that the European Medicines Agency (EMA) is currently evaluating an extension of indication for Lynparza in the first-line maintenance treatment of BRCA-mutated advanced ovarian cancer.
This procedure (for a variation of the marketing authorisation of Lynparza) is expected to be finalised later this year. In view of the pending scientific assessment, a more precise timing is not possible.
EMA’s Business Continuity Plan has been put in place to ensure that any activities directly related to authorisation, maintenance and supervision of medicines are not affected by EMA’s relocation to the Netherlands. As a result of this policy, this authorisation procedure is following the foreseen timetable and there have been no unexpected delays.
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D. whereas healthcare systems in the EU are facing challenges due to an ageing population, budgetary constraints, the increasing incidence of chronic and rare diseases, difficulties in ensuring basic healthcare in rural areas and the high prices of medicines; whereas Member States are responsible for developing, keeping and exchanging across borders information on an updated catalogue of medicine shortages to ensure the availability of essential medicines;
E. whereas the healthcare that citizens need may sometimes be best provided in another Member State, on account of proximity, ease of access, the specialised nature of care or a lack of capacity, such as a shortage of essential medicines, in their own Member State;
AA. whereas there is considerable room for improving and simplifying the reimbursement procedures in a number of Member States, particularly with regard to prescriptions, orphan drugs, pharmaceutically compounded medicinal products and follow-up therapy and procedures;
7. Stresses that the Member States should transpose the directive correctly in order to ensure high-quality and accessible cross-border healthcare for patients, in full compliance with the implementation deadlines laid down in the legislation; recognises that specific improvements can be made with regard to access to prescribed medicines and continuity of treatment; calls on the Commission to explore the possibility of expanding the scope of the directive to include vaccination programmes;
28. Calls on the Member States to urge healthcare providers and hospitals to supply patients, in advance, with an accurate and up-to-date estimate of the cost of treatment abroad, including medicine, honoraria, overnight stays and supplementary fees;
36. Recommends building on the steps already taken to increase public awareness and understanding of rare diseases and rare cancers and to increase funding for R&D; asks the Commission to further guarantee access to information, medicine and medical treatment for patients with rare diseases throughout the EU, and to strive for improved access to early and accurate diagnosis; urges the Commission to address the low registration rate of rare diseases and to further develop and promote common standards for sharing and exchanging data in rare disease registries;
42. Regrets the difficulties faced by patients, especially those in border areas, in securing access to and reimbursement for medicines in other Member States, owing to differing availabilities and administrative rules across the EU; calls on the Member States and their respective health authorities to address the legal and practical issues that are hindering the mutual recognition of medical prescriptions across the EU, and urges the Commission to take supportive action in this regard;
43. Regrets the difficulties faced by patients in securing access to and reimbursement for medicines in other Member States, owing to differing availabilities and rules across the EU;
44. Calls on the Commission to draw up an action plan to systematically address excessively high medicine prices and the great disparities in them between the various Member States;
The relocation costs of the European Medicines Agency are part of the total costs to the agency’s budget related to the United Kingdom’s withdrawal from the EU. These costs will be incurred during the years 2018 to 2020 and, at this time, can only be estimated by the agency. The Commission has therefore sent to the European Medicines Agency the request of the Honourable Member on costs related to its move from London to Amsterdam. The Commission will transmit the reply as soon as it is available.
The main objective of the EU Regulation on orphan medicinal products is to provide incentives for the research, development and placing on the market of orphan medicines in order to ensure that patients suffering from rare conditions have the same quality of treatment as any other patient. These incentives, however, are one of the factors influencing prices for orphan medicines, and, hence, potentially, access to such medicines.
The Commission is currently evaluating the functioning of the regulation. The example of the orphan medicine Chenodeoxycholic acid Leadiant is part of this evaluation.
Pricing policies for medicinal products fall under the Member States’ competence. However, the Commission is promoting the exchange of information among Member States on their pricing policies. This can enhance price competition for medicines and help minimising potential negative effects on the accessibility of medicines.
The Commission supports the strengthening of Member States’ cooperation on a voluntary basis in this context, in particular through tools such as a European medicine price database(3). It also facilitates the exchange of best practices and knowledge among Member States through the Network of competent authorities responsible for pricing and reimbursement.
Furthermore, as part of its competition policy, the Commission monitors pharmaceutical markets and is ready to take action, where appropriate, against breaches of the EU competition rules, including excessive pricing that may be in breach of Article 102 of the Treaty on the Functioning of the EU.
The Commission is also supporting national competition authorities across the EU (within the European Competition Network) that also investigate into excessive pricing concerns.
Access to timely, high-quality and affordable healthcare is one of the building blocks of the European social model. As one of its 20 principles, it is at the heart of the European Pillar of Social Rights, which is mobilising efforts at European and national level to move towards better healthcare systems. Though the organisation of healthcare systems is according to Article 168 of the Treaty on the Functioning of the EU the responsibility of Member States, the Commission provides support through policy co-ordination in the framework of the European Semester and through the European Funds to build more accessible, effective and resilient healthcare systems across Europe.
Challenges posed by cost sharing for medicines were highlighted by the Commission in the Semester’s Country Report for Spain in 2018. This problem, along other challenges, will be followed up in the 2019 Semester cycle.
The Commission has not received representatives from the United Kingdom government or health agencies on the implications of a no-deal Brexit for the medicines/medical equipment sector. The Commission services have met relevant European trade associations and individual companies on a number of occasions to discuss the consequences of the United Kingdom withdrawal from the European Union. The Commission’s consistent message has been that all companies must prepare for all withdrawal scenarios as a matter of urgency, on the basis of the extensive guidance provided by the Commission and the European Medicines Agency. As regards the supply of medicines and medical equipment, of which emergency and trauma equipment are part, the Commission together with the European Medicines Agency and national regulators prepared Questions & Answers documents and information notices, and organised stakeholders meetings to ensure that the sector is prepared for all withdrawal scenarios.
The Commission provided an overview, which is publically available, of the latest state of play in the medicines/medical equipment sector in a preparedness seminar with Member States on 12 December 2018.
The Commission is aware of the potential risk to public health caused by Brexit, in particular as regards the supply of medicinal products, included vaccines, to patients.
The Commission services together with the European Medicines Agency (EMA) and the national competent authorities have taken preparedness measures since the early stages of the Brexit process to mitigate risks of supply shortages. Dedicated questions and answers have been published and regularly updated on the websites of the Commission, EMA2 and the Heads of Medicines Agencies.
EMA conducted an industry survey to identify possible products that could be at risk of supply shortage. National competent authorities are currently carrying out similar preparedness activities for nationally authorised products.
Vaccines are part of this assessment. Regulators and industry representatives are discussing the matter regularly in technical meetings.
The Commission has consistently called on all stakeholders in all sectors to take all the necessary measures so that they are ready for all possible scenarios. In this context, companies are expected to engage with the regulatory authorities as necessary and bring to their attention any specific issues related to vaccines, including seasonal and pandemic influenza vaccines.
Regarding the future relationship between the EU and the United Kingdom (UK), the Commission refers the Honourable Member to the “political declaration setting out the framework for the future relationship between the EU and the UK”
The organisation and delivery of the health services and medical care fall within the competence of each Member State, including the funding. Member States are fully responsible for the decisions on pricing and reimbursement of medicinal products. However, they have to comply with the “EU Transparency Directive” that lays down a series of procedural rules applicable to any national measure regulating prices of medicines and their inclusion in the scope of public health insurance systems. This Directive, without touching upon the substance of pricing and reimbursement, aims at ensuring that national decisions in the area of prices of medicines are taken in a transparent way and within certain time limits.
To date, the issue of pricing and reimbursement has not been raised in the current discussions with the United States (US). As the European Commission considers that the issue of pricing and reimbursement should not be covered in any trade negotiations with the US in light of the significant differences in EU and US healthcare systems, it does not intend to seek an authorisation to negotiate on this matter.
According to point 3 of Annex III of the Value Added Tax (VAT) Directive, Member States may apply a reduced rate of VAT to pharmaceutical products of a kind normally used for health care, prevention of illnesses and as treatment for medical and veterinary purposes. Point 3 covers medicaments classified under heading 3004 of the Combined Nomenclature as long as they are finished goods, which can be used directly by final consumers.
Member States may also choose to apply a reduced VAT rate to specific pharmaceutical products among those mentioned in point 3, while applying the standard rate to other such products.
Concerning the principle of fiscal neutrality, it follows from settled case-law of the Court of Justice of the European Union (CJEU) that, this principle precludes similar goods or services which are in competition with each other being treated differently for VAT purposes. As regards an assessment of the similarity of medicaments, it is clear from the Court’s case-law that account must be taken primarily of the point of view of an average consumer. Products are similar where they have similar characteristics and meet the same needs from the point of view of consumers, the test being whether their use is comparable, and where the differences between them do not have a significant influence on the decision of the average consumer to use one or the other product. The assessment of whether certain products are similar and whether they are in competition with each other, is first and foremost a matter for a national court to determine, taking into account the guidance provided by the CJEU.
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J. whereas in its strategic work in 2017, the Ombudsman’s office closed four strategic inquiries and opened four new ones on Council transparency; on the ‘revolving doors’ issue concerning former European Commissioners; on the accessibility of Commission websites for persons with disabilities and on pre-submission activities linked to medicine assessments by the European Medicines Agency (EMA); whereas in 2017 the Ombudsman opened eight strategic initiatives on, among other subjects, European Council lobbying transparency, improving the European Citizens’ Initiative (ECI), and revolving doors rules at various EU institutions and bodies, and closed six strategic initiatives;…
35. Urges the Ombudsman to launch a strategic inquiry in order to assess whether EU Institutions, offices and agencies, such as the European Chemicals Agency (ECHA), the European Food Safety Authority (EFSA) and the EMA, ensure that the collection, examination and publication of scientific evidence is fully independent, transparent, impartial, accurate and free from conflict of interests, and whether the proper policies and procedural safeguards are in place, notably when dealing with GMOs, glyphosate, pesticides, phytosanitary and biocidal products and medicines; suggests, in this regard, a further inquiry into the composition and selection procedures of the scientific committees and panels of these agencies, in order to ensure that they are completely independent and to put into place the most stringent mechanisms preventing any possible conflict of interests;
The economic and social situation is improving throughout the EU, including in Italy. However challenges and regional divergences remain.
To address these challenges, in the context of the European Semester, Italy was recommended, among others, to step up implementation of the reform of active labour market policies and to foster research, innovation, digital skills and infrastructure through better-targeted investment and increase participation in vocational-oriented tertiary education.
Sicily is one of the least developed Italian regions and is still affected by the consequences of the crisis; for example the employment rate in 2017 was less than 50%, among the lowest of the EU. The EU supports regional development in Sicily over the 2014-2020 period through the European Regional Development Fund and the European Social Fund.
The European Regional Development Fund for 2014-2020 foresees around EUR 457 million to finance the Research and Innovation interventions. A share of these resources will be devoted to initiatives on the life sciences industries and the pharmaceutical, medical devices and biotechnology in the framework of the regional smart specialisation strategy.
The European Social Fund operational programme for Sicily, with a budget of EUR 820 million, prioritises investments in projects to boost people`s chances of getting work through better skills and qualifications, in social inclusion measures and in improvements in education and training systems.
Paragraph 15 of the Guidelines for Brexit negotiations of the European Council (Article 50) of 29 April 2017 states that ‘the future location of the seats of EU agencies and facilities located in the United Kingdom is a matter for the 27 Member States to settle rapidly’. On the basis of a procedure endorsed by the Heads of State or Government of all 27 Member States for the relocation of the London-based EU agencies, after three rounds of voting, on 20 November 2017, the 27 Member States selected Amsterdam as the agency’s new seat. On 17 October 2018, the European Parliament and the Council agreed on a compromise text for a regulation, which determines that the location of the seat of the European Medicines Agency shall be in Amsterdam.
As regards costs for the European Union budget associated with the need of the Agency to occupy temporary premises before moving into its permanent premises, the Commission informs the Honourable Member that as agreed with the Agency, such costs are to be borne by the Netherlands. The Commission has transmitted the Agency the request by the Honourable Member on costs already incurred by the Agency in its move from London to Amsterdam. The reply will be transmitted by the Commission as soon as possible. Finally, the Commission cannot provide estimates on costs associated with the possible loss of the ongoing court case to Canary Wharf.
In its reply to Written Question P-003774/2018 the Commission stated that as it is represented on the Management Board of the European Medicines Agency, it ‘closely follows the Agency’s proposed measures to mitigate the related business continuity risks arising from its relocation to Amsterdam’.
The Board was informed on 4 October 2018 that cooperation with the Netherlands is running smoothly and preparations for the interim and the permanent buildings are on track.
This and other information on Brexit preparedness is available on the Agency’s website. In addition, as of three months following the entry into force of the Agency’s amended Regulation, the Netherlands will be required to report on progress on the building to the European Parliament and Council.
As stipulated by the co-legislators in a recital to the regulation amending the Agency’s Regulation, ‘the authorities of the Netherlands are making efforts to ensure the operational effectiveness, continuity and uninterrupted functioning of the Agency during and after the relocation. Nevertheless, given the extraordinary situation, the Agency may have to temporarily focus on its core tasks and prioritise other activities according to their impact on public health and the Agency’s ability to function.’
The Agency is working closely with the Commission on the prioritisation of activities, in order to ensure protection of public health in the European Union.
The Commission has sent the Agency the request of the Honourable Members on costs related to its move from London to Amsterdam. The Commission will transmit the reply as soon as possible.
Paragraph 15 of the Guidelines for Brexit negotiations of the European Council (Article 50) of 29 April 2017 states that “the future location of the seats of EU agencies and facilities located in the United Kingdom is a matter for the 27 Member States to settle rapidly”.
On 22 June 2017, the Heads of State or Government of the 27 Member States endorsed a procedure leading up to a decision on the relocation of the European Medicines Agency and the European Banking Authority, including six criteria which interested Member States should address in their offers to host one or both of the agencies.
The Commission was invited to examine the offers submitted by the Member States and to present by 30 September 2017 its assessment to the Secretary-General of the Council. This assessment was exclusively based on the information contained in the offers and for the purpose of the procedure leading up to a decision on the relocation by the 27 Member States. On 20 November 2017, following a series of presentations in the Council and after three rounds of voting, the 27 Member States selected Amsterdam as the Medicines Agency’s new seat.
On 17 October 2018, the European Parliament and the Council agreed on a compromise text for a Regulation, which determines that the location of the seat of the European Medicines Agency shall be in Amsterdam.
In that legislative act, the co-legislators also welcome “that the authorities of the Netherlands are making efforts to ensure the operational effectiveness, continuity and uninterrupted functioning of the Agency during and after the relocation. Nevertheless, given the extraordinary situation, the Agency may have to temporarily focus on its core tasks and prioritise other activities according to their impact on public health and the Agency’s ability to function.”
1. The organisation and delivery of health services and medical care and the pricing and reimbursement decisions that closely influence access to medicines are a Member State competence. The Commission, however, closely follows this issue and analyses the effectiveness, accessibility and resilience of health systems as part of the European Semester. A recent study on the economic impact of pharmaceutical incentives on innovation, availability and accessibility has also examined the reasons for selective market launches of medicines.
The Commission facilitates exchanges between Member States on shortages of medicines. A meeting with Member State experts on 25 May 2018 addressed shortages of medicines and clarified the obligation for industry and wholesalers to ensure a continuous supply of medicines. The Heads of Medicines Agencies/European Medicines Agency task force on availability of authorised medicines for human and veterinary use continues to work to address shortages of medicines and market access in the Member States.
2. According to EU legislation, companies lose their marketing authorisation if they do not place their products on the market in a Member State within three years. There is, however, no obligation to market medicines in a particular or all Member State(s) and no criteria to define ‘commercial interest’.
Marketing authorisation holders must inform Member States’ authorities at least two months in advance if they plan to withdraw their product from the market either permanently or temporarily, including the reasons for the withdrawal.
The Commission is currently working on a strategic approach to pharmaceuticals in the environment, which is expected to address gaps in knowledge of the risks from pharmaceuticals in the environment and may include further actions relevant to antimicrobial resistance (AMR) at EU level.
As regards the observation from the Scientific Steering Committee that the introduction of AMR genes into the environment changes microbial ecology, and its suggested areas of investigation, the Commission is focusing on how the presence of antimicrobials in the environment might increase the maintenance and spread of AMR, and what levels of antimicrobials could trigger AMR development. At the same time, it will learn more about the changes that occur in microbial ecology generally, and about whether there are indications of any other effects on the environment.
The Good Manufacturing Practice Guide for active substances was adopted primarily to ensure the quality of medicines to be placed on the European market. The guide does not cover environmental protection as such, because this is generally governed by other legislation. However, the guide requires waste in and from factory buildings to be disposed of in a safe, timely and sanitary manner. The facilities have to comply with local regulations to minimise the risk of contaminating the environment. The Commission promotes dialogue and EU external action with the main pharmaceutical-producing countries to ensure environmentally sound production practices.
Information on the progress, achievements and budget for all projects of the ‘New Drugs 4 Bad Bugs’ programme is already available on the the Innovative Medicines Initiative website. Additional information is available on the Cordis website.
1) The Commission is not aware of similar requests from other Member States calling for the amendment of the current legislation concerning homeopathic medicinal products.
2) The Commission considers that the current regulatory framework for homeopathic products takes into account their specific nature and strikes a balance between ensuring their quality and safety and informing consumers including health professionals, while at the same time giving citizens access to these products. In particular, producers shall not associate clinical claims with homeopathic products without demonstrable therapeutic efficacy. In addition, the label of these products shall include “homeopathic medicinal product without approved therapeutic indications” and a warning to “consult a doctor if the symptoms persist”. There are no plans in the Commission at this time to evaluate or amend the legislation on homeopathic products.
3) Directive 2001/83/EC requires that homeopathic and conventional medicinal products have the same scrutiny in terms of their manufacture, distribution and pharmacovigilance and lays down specific safety provisions for homeopathic products without therapeutic claims. It specifies what information may be used for the advertisement of these products and it does not allow the use of information on clinical efficacy. It is Member State competence to monitor that the advertisement of medical products is compliant with the legislation. Finally, Member States remain free to take actions at national level to raise awareness of the specific characteristics of homeopathic medicines.
Two Commission guidelines establish the requirements of Good Distribution Practice (GDP) for Medicinal products and their active substances.
The Commission guidelines on GDP of medicinal products for human use, were first published in 1994 and revised in 2013 to take into account recent advances in appropriate storage and distribution practices. The guidelines are applicable since 24 November 2013.
In 2015, a second set of guidelines were published on principles of GDP of active substances for medicinal products for human use for importers and distributors of active substances for medicinal products for human use. The guidelines are applicable as of 21 September 2015.
The Commission believes these two sets of guidelines are up to date and do not need to be amended in the near future.
Although the Commission has not conducted any specific studies on the practical implementation of the GDP guidelines by Member States, the Commission and the European Medicines Agency hold regular meetings with competent authorities where GDP in the EU is often discussed.
The Commission closely follows the work of the ‘Heads of Medicines Agencies/European Medicines Agency’ task force on availability of authorised medicines that deals with access and possible shortages of medicines in the Member States. The Commission also contributes in other ways to addressing issues of access and availability, for example through the expert group on Safe and Timely Access to Medicines for Patients.
The Commission proposal on Health Technology Assessment has the aim and the potential to contribute to a better availability of innovative health technologies, including medicines. It foresees the development of joint clinical assessments at EU level that identify which treatments bring real added value for patients.
In relation to patient waiting times, the organisation and delivery of health service and medical care are the responsibility of the Member States, as well as the management of medical treatment. However, the Commission follows and analyses the effectiveness, accessibility and resilience of health systems as part of the European Semester.
Concerning cancer prevention, the Commission has adopted a number of tobacco control measures to reduce the risk of respiratory diseases. The Commission helps Member States to promote smoke-free policies and healthy life styles, and provides EU best practices and guidelines in the areas of cancer screening, quality assurance in cancer management, integrated cancer control, after-care at community level, and survivorship and rehabilitation.
Finally, Horizon 2020 has supported research on lung cancer prevention, diagnosis, treatment as well as quality-of-life of lung cancer patients and will provide further funding opportunities in its last call for proposals(9).
The Commission has necessarily prioritised legislative procedures over recent months. It has also been considering which initiatives it can still carry through to completion during its remaining time in office, and has now decided that the European Union Strategic Approach to Pharmaceuticals in the Environment will be among those initiatives. It is aiming to adopt the Approach as soon as possible.
The Commission notes that the European Medicines Agency (EMA), like other EU actors, has prepared business continuity plans to address certain consequences stemming from the United Kingdom leaving the Union. For more information on these plans, the Commission invites the Honourable Member to directly address the Agency.
The Commission notes from the Agency’s plans that core activities related to the evaluation, maintenance and supervision of medicines, including its activities on Anti-Microbial Resistance (AMR) are currently being safeguarded and that therefore the Agency is continuing its contribution to the fight against AMR both at international and European level.
The Commission will continue its collaboration with international partners in order to meet the AMR Action Plan’s objectives. It will also support EMA in the implementation of its strategy to modernise the Summary of Product Characteristics of old Antibiotics.
A review of existing scientific literature on the subject of medical cannabis provides conclusive or substantial evidence that cannabis and cannabinoids have therapeutic effects: they treat chronic pain in adults, work as an antiemetic when treating chemotherapy-induced nausea and vomiting, and improve muscle spasticity symptoms in multiple sclerosis. Moreover, in December 2017, the WHO officially recommended that the cannabis compound cannabidiol (CBD) should not be internationally scheduled as a controlled substance. One cannabis-based medicine has been authorised through the mutual recognition procedure and marketed in 17 Member States, but no Member State has authorised the smoking of cannabis for medical purposes, given that smoking can pose health risks. The issue of medical cannabis use often gets lumped in with the use of cannabis as a recreational drug, which should be considered a separate issue. The regulatory landscape is changing fast both in the EU and worldwide. In light of the above:
– Which actions has the Commission taken to support quality research on cannabis-based medicines? Which actions does the Commission plan for future research and how much funding does it plan to allocate for such research under the next Framework Programme 9 (Horizon Europe)? Does the Commission consider that the regulatory environment across the EU is conducive to quality research on medical cannabis?
– Even in the Member States where medical cannabis is legal, conditions for access, prescription, purchase, pricing, refunding – in addition to the level of knowledge among healthcare professionals on the use of such medicines – differ widely and present a challenge for patients. Does the Commission consider that it should improve patient access to medical cannabis?
– Does the Commission intend to establish standards for non-pharmaceutical medical cannabis in order to ensure consumer safety? Has the Commission investigated what would be the appropriate limit of tetrahydrocannabinol (THC) present in medical cannabis in order to protect consumers?
The Commission notes that the European Medicines Agency’s (EMA), like other EU actors, has prepared business continuity plans to address certain consequences stemming from the United Kingdom leaving the Union. For more information on these plans, including on the Agency’s participation in stakeholder meetings, the Commission invites the Honourable Member to directly address the Agency.
The Commission notes from the Agency’s plans that core regulatory tasks on marketing authorisation related opinions and surveillance of individual medicinal products are currently not being targeted and that the timeframes laid down in the legislation are therefore currently not being questioned. As regards international collaboration, and in particular harmonisation activities, the Commission and the Agency are working closely on the prioritisation in order to maintain the EU’s leading role at global level, despite the temporary scaling down of some identified tasks of the Agency.
The Commission supports the Agency’s focus on key stakeholders meetings and rational use of resources for the smooth running of its core tasks.
In accordance with EU treaties, the provision of healthcare is the responsibility of Member States, while the Commission provides policy guidance and support to Member States. Access to timely, high-quality and affordable healthcare is one of the principles of the European Pillar of Social Rights, and has been fully integrated into the European Semester process. The European Semester is the Commission’s tool to analyse the economic and social developments in the Member States, monitor relevant reforms and propose every year country-specific recommendations. In 2018, twelve Member States have received a country specific recommendation regarding their healthcare system.
Knowledge-building, including in health, is a Commission priority. The Joint Assessment Framework (JAF) for Health includes a set of indicators agreed with Member States in the context of the Social Protection Committee2 covering the four dimensions: health outcomes, access, quality and non-health determinants. The reading of these indicators is meant to provide a first-step quantitative screening to detect possible major challenges in each Member State’s health systems in the context of the Social Open Method of Coordination. Complementarily, the “State of Health in the EU” cycle produced country profiles for all Member States in 2017. The Commission is also co-funding the Organisation for Economic Co-operation and Development Patient-Reported Indicators Survey which will fill the knowledge gap on quality of healthcare from the patients’ perspective. On demand of Member
States, the Commission’s Structural Reform Support Service provides technical support to raise quality of healthcare.
The European Parliament
9. Welcomes the agreement on the Veterinary Medicinal Products Regulation reached on 5 June 2018; welcomes the provisions laid down to restrict the use of antibiotics for meta- and prophylaxis; recalls its position on preventive measures and the EMA/EFSA joint scientific opinion calling for: the use of breeding stock that grows more healthily and slowly, stocking densities that do not increase the risk of disease, smaller groups, isolation of sick animals (Article 10 of Regulation (EU) 2016/429), and implementation of existing welfare laws; trusts that the regulation will facilitate the much-needed action on antimicrobial resistance (AMR) and stimulate innovation in the field of veterinary medicine; considers that the European poultry sector and national authorities are undertaking initiatives to reduce the use of antibiotics through the modernisation of poultry farms;
In the European Union, a disease is considered rare when it affects no more than one person in 2 000. While individual rare diseases are all characterised by their low prevalence, they affect all biological systems. There are between 6 000 and 8 000 different rare diseases that in total affect an estimated 30 million people in the European Union.
A limited but increasing number of so-called orphan drugs reach patients. However, the majority of rare diseases still lack any effective treatment. The field of rare diseases suffers from insufficient medical and scientific knowledge. One specific group of rare diseases is characterised by its quick progression and extremely debilitating effects, including, if left untreated, rapid death. The medicines currently available for these diseases only slow the progression of the disease. Early diagnosis is therefore vital, as any delays between the first symptoms and actual diagnosis will impact negatively upon that patient’s life expectancy. Research is also needed for effective treatment. In addition, patient access to medicines for rare diseases varies largely across Europe.
In light of the above:
1. What measures has the Commission taken so far to ensure accurate and timely diagnosis of rare diseases, as well as access to affordable medicines required to treat them, across the EU? How does the Commission promote research in the field of rare diseases and into the development of new or improved methods for early diagnosis? How does it intend to further these efforts and achieve measurable improved outcomes for rare disease patients in all EU Member States?
2. How does the Commission intend to guarantee access to information and to medicines and medical treatment for rare disease patients throughout the EU? How does the Commission promote better coordination and learning across Member States, given that access to early and accurate diagnosis can have a significant impact on the patient’s prognosis and quality of life?
3. What are the Commission’s plans to ensure sustainable funding of patient organisations supporting the European Reference Networks on rare diseases, for example by means of the European Joint Programme on Rare Diseases?
The Commission proposal for a regulation of the European Parliament and of the Council amending Regulation (EC) No 469/2009 concerning the supplementary protection certificate (SPC) for medicinal products balances the interests of the whole spectrum of stakeholders, including patients as well as generic and originator companies.
While the first objective of the proposal is to foster competitiveness of EU-based manufacturers of generics and biosimilars, the proposal will also benefit EU patients. Supplying the EU market as soon as the SPC expires will be facilitated by the existence of manufacturing facilities in the EU, set up in order to produce and export medicinal products during the term of the SPC.
The Commission considers that the approach to applicability in time of the proposal represents a suitable compromise between the need for, on the one hand, legal certainty for SPC holders and respect of the Charter of Fundamental Rights of the European Union and, on the other, for swift applicability of the waiver so as to avoid delaying benefits for EU-based manufacturers of generics and biosimilars and for patients.
The Commission understands that Germany is still considering how it will implement the judgment of the Court of Justice of the European Union in Case C-148/15. At this stage and based on the information available, the Commission is not in a position to comment nor assess the compatibility of the possible options. The legislative solution chosen to implement the judgment will need to be compliant with the relevant EU rules such as the freedom of movement of goods.
The EU and Ukraine have in their Association Agreement agreed on patent rules that reflect the EU legislation and comply with the international provisions in this area. Notably, the provisions in the Agreement ensure innovators’ capacity to build on prior knowledge to develop valuable new and improved treatments (second and further medical indications or new therapies) that can improve health outcomes.
Furthermore, the Agreement recalls the flexibilities provided for by international trade law, notably the right to grant compulsory licenses and the freedom to determine the grounds upon which such licenses are granted in line with the letter and spirit of the World Trade Organisation (WTO) Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement.
The new Ukrainian draft law on patents would prohibit patents on certain types of biopharmaceutical inventions. The Commission has already raised its concerns about such restrictions at the last EU-Ukraine Intellectual Property Rights (IPR) Dialogue in Kyiv (on 20 June 2018), because they undermine innovation and seem to not comply with Article 27(1) of the WTO TRIPS Agreement.
On 26 June 2018, the European medicines regulatory network consisting of national competent authorities (including Hungary), the European Medicines Agency (EMA) and the Commission were notified through the rapid alert system about the presence of the impurity N-nitrosodimethylamine (NDMA) in valsartan active substance manufactured by a Chinese supplier.
The regulatory network operates an incident management plan with the aim to take appropriate action whenever incidents which could have a serious impact on public health arise in relation to medicines. Following the Incident Review Network teleconference with EMA and Member States, on 5 July 2018 the Commission immediately initiated an EU wide review procedure of the products concerned.
The Commission asked EMA to evaluate with priority the potential impact on patients of the exposure to NDMA from valsartan medicines. The analysis of available data is ongoing.
In parallel and since the products concerned are nationally authorised medicines, the Member States have taken regulatory actions to recall affected medicines. In addition to pharmacy level recall, the Hungarian national authorities have advised patients not to stop treatment and to go to their doctor at an early opportunity so that an alternative treatment can be prescribed for them.
In addition to dealing with the consequences of the specific incident now, the Commission together with EMA and the European medicines regulatory network will study the lessons learned from this case.
With regard to the effectiveness of the EU system to monitor the continuous safety of medicines once they are authorised (pharmacovigilance — PhV), it should be stressed that medicines in the EU are subject to strict post-marketing surveillance for which obligations to marketing authorisation holders and competent authorities are set by EU legislation and therefore harmonised. These obligations have been further strengthened following revisions in 2010 and 2012.
As a result, the EU PhV system is one of the most advanced and comprehensive in the world and represents a robust and transparent instrument to ensure a high level of public health protection throughout the EU.
Concerning Levothyrox, the Commission would like to refer to its answer to question E-003511/2018. In the context of the formulation change, national competent authorities sought advice from the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) on any potential safety concerns with the new formulation.
Based on the available information, the PRAC agreed that there is no difference in the pattern of adverse events reported before and after the switch to the new formulation.
The PRAC also advised to undertake close monitoring and supervision during the transition period for all patients to ensure that the patient’s individual dose remains appropriate.
The Commission disagrees with the suggestion that the EU marketing authorisation system should be replaced by a global system. Medicines are not goods like any other and require a strong and comprehensive regulatory system within the jurisdiction of the EU. This does not exclude continuous cooperation with partner authorities in other regions of the world, which is already underway.
The European Parliament,
– having regard to Rule 133 of its Rules of Procedure,
A. whereas the first CAR therapy for treating diffuse large B-cell lymphoma in adults and acute lymphoblastic leukaemia in children and young people has received community approval;
B. whereas the drug agencies in individual countries need to reduce the cost of the therapy and identify clinics where it can be carried out, potentially leading to a very long waiting period;
C. whereas, to select these clinics, it will be necessary to establish a set of requirements and features with which the authorised clinics must comply, and that during the waiting period, pharmaceutical companies producing the treatment will administer it to a limited group of volunteers;
D. whereas the potential side effects of the therapy may be serious, and studies into treatments to eliminate them are already in progress;
1. Calls on the Commission to create a research and testing hub for cancer cell therapies similar to CAR-T and for treatments able to eliminate their potential side effects;
2. Calls on the Commission to set up public clinics authorised to administer such treatments during the negotiation period and to work to implement clear deadlines on the waiting time between the approval of a treatment and its commercialisation.
Summary of petition: The petitioner is calling on the European Parliament to implement a Single Protocol in relation to informed consent for Human papillomavirus (HPV) vaccination in the European Union with the active participation of the EU health authorities. He refers to several principles in the Charter of Fundamental Rights, including the right to integrity and, in the field of medicine, the free and informed consent of patients. The petitioner claims that not enough information about the risk associated with HPV vaccine is being given to parents before the vaccination of their daughters, and that concerns about adverse reactions of the vaccine have been ignored.
Conclusion: The Commission can only act within the framework of its competences, and most of the issues raised by the petitioner are beyond them. The Commission is currently not considering further actions in light of the principles of subsidiarity and proportionality, and considers that the relevant actions and objectives can be better achieved at the level of the Member States. As regards the safety of HPV vaccines, the Commission reiterates that a solid legal framework is already in place which ensures that only safe and effective vaccines are authorised for use in the EU and which requires marketing authorisation holders, national competent authorities and the European Medicines Agency to follow strict pharmacovigilance processes after a vaccine has been authorised.
The Commission’s website on the online pharmacies logo and on falsified medicines had 573 294 unique views between 2016 and 2018. It aims to raise awareness of the common logo, enable citizens to identify legitimate pharmacies and provide information on the potential dangers of using online pharmacies.
The Member States’ websites are the primary source of information, including verification of the logo. Almost all Member States have published the list of registers of online medicine retailers and many publish information on the dangers of falsified medicines. The Commission does not have statistics on the use of Member States’ websites. The Commission is in regular dialogue with Member States on their national information campaigns and on raising public awareness on this issue.
In order to further prevent the introduction of falsified medicines in the legal supply chain, the Commission also introduced legislation to develop a verification and traceability system based on a unique identifier and an anti-tampering device. The rules outlined in Delegated Regulation (EU) 2016/161 will apply as of 9 February 2019 and will require pharmacies (including online pharmacies) and hospitals to use safety features to verify the authenticity of prescription medicines.
In 2018, a Commission report outlined Member States’ transposition measures and assessed their effectiveness in relation to the Falsified Medicines Directive (2011/62/EU). The report provides an overview of the penalties that Member States have in place or have taken to fight falsified medicines. This will help Member States, who have an important role to play in the enforcement of the legislation to identify best practices to discourage the falsification of medicines.
The Commission is very much aware of the necessity for the European Medicines Agency (EMA) to deliver its public and animal health activities continuously to ensure that medicinal products (for human and veterinary use) authorised in the EU meet the criteria of safety, efficacy and quality. As a member on its Management Board, the Commission closely follows the Agency’s proposed measures to mitigate the related business continuity risks arising from the relocation of EMA to Amsterdam.
In the framework of the 2019 budgetary procedure, EMA requested 40 additional contract agents for a temporary period. This request and the supporting information provided by EMA were particularly carefully analysed by the Commission services. The request and information provided by EMA were judged as not being sufficiently documented to support such an increase in staff, even for a temporary period, taking into account also the relatively large size of the Agency.
It should be noted that any requests for staff increase need to be very well substantiated via the budgetary procedure.
The Commission remains in close contact with the Agency as regards the departure of key staff and its impact on the capacity of EMA to deliver on its high priority activities.
It is widely recognised that advanced therapeutic medicinal products (ATMPs) have the potential to address some of today’s unmet medical needs and provide novel solutions to diseases such as cancer or neurodegenerative disorders. For example, the European Medicines Agency (EMA) recently issued a positive opinion on the first two marketing authorisation applications for chimeric antigen receptors (CAR) T-cells medicines in the EU. These belong to a new generation of personalised cancer immunotherapies that are based on collecting and modifying patients’ own immune cells to treat their cancer.
The regulation of this field is complex. The protection of patients requires a rigorous examination of risks and benefits while ensuring that obligations of developers are realistic. However, that does not mean that further legislative changes are necessary. With the 2007 Regulation (EC) 1394/2007 the field is already governed by a clear and specific framework addressing the particular challenges of this product category.
At the same time, the application of the existing provisions can be optimised. The joint action plan between the Commission and the EMA, mentioned by the Honourable Members, serves this purpose. For example, the guidelines on good manufacturing practices have already been delivered, providing clear benefits to the sector. Other actions of the plan are still ongoing or in preparation.
The Commission is aware of the epidemiological data of fibromyalgia syndromes including the impact of the disease on employment of affected people.
As regards a marketing authorisation of a medicinal product in the EU, according to the pharmaceutical legislation, it is granted only after the quality, safety and efficacy of the product has been evaluated and a positive benefit-risk balance related to its use has been concluded.
Three medicines (pregabalin, milnacipran, and duloxetine) have been approved in the United States of America for the treatment of fibromyalgia. Applications of these medicines for the indication concerned were also submitted to the European Medicines Agency (EMA).
After careful examination, EMA was of the opinion that the benefits of these medicines in the treatment of fibromyalgia did not outweigh the risks and therefore recommended that the marketing authorisation be refused in this indication.
As regards the diagnosis and treatment of fibromyalgia, Article 168 of the Treaty Union on the Functioning of the EU stipulates that organisation and delivery of health services and medical care, including diagnostic services and pain management, fall under the responsibility of Member States.
The issue of the contamination of certain medicines with N-Nitrosodimethylamine (NDMA) is a serious concern. On 5 July 2018 the Commission triggered a review (commonly called referral) of valsartan medicines in relation to NDMA found in the active substance from Zhejiang Huahai Pharmaceuticals. The review is being carried out by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) which will adopt the Agency’s opinion. The CHMP opinion will be sent to the Commission for a final legally binding decision applicable in all EU Member States concerning whether marketing authorisations of the medicines under review should be maintained, varied, suspended or revoked. In the meantime, as a precaution, Member States are recalling the concerned medicines.
The European Directorate for the Quality of Medicines and HealthCare (EDQM) is responsible for the certification of suitability to the monographs of the European Pharmacopoeia (CEP procedure) for pharmaceutical substances. The EDQM does not change the manufacturing process for active substances. It is the manufacturer who introduces such changes, validates them and submits them for approval. The EDQM has strict procedures for the evaluation of dossiers submitted to obtain a CEP and relies on the expertise of experienced quality assessors nominated by competent authorities for their evaluation.
The risk of the presence of the NDMA impurity in other sartans (the class of active substances) is being assessed by the EDQM for those active substances covered by CEPs, and the holders of these CEPs have been contacted by EDQM. National competent authorities and the EMA are being regularly updated on progress of this review by the EDQM, which should be completed soon.
1. As the Honourable Member stated, the Commission adopted in 2017 an assessment report on the current shortcomings in the summary of product characteristics (SmPC) and the package leaflet (PL) with recommendations on how these leaflets could be improved to better meet the needs of patients and healthcare professionals.
Regarding readability of the product information, the Commission’s report recommended to consider revising the existing guidelines including the Commission’s guideline on the readability of the labelling and package leaflet of medicinal products for human use.
The Commission is working with the European Medicines Agency (EMA), the network of national competent authorities and in close collaboration with other relevant stakeholders towards the implementation of the recommendations of the report. As a follow-up, the EMA published an action plan with identified deliverables and timelines to implement the recommendations of the Commission’s report.
However, the completion of the work is currently impacted by the forthcoming move of the EMA from London to Amsterdam and the need for EMA to focus on core business priorities for the time being.
2. The current guideline of readability includes indeed a reference to the type size of 9 points, but as a minimum. It does not prevent a bigger size. When the guideline was last updated in 2009, the minimum size was increased from 8 points up to 9 points following a public consultation and a discussion with the competent authorities in Member States.
The Commission is aware of the risks of falsified medicines through Internet sales. Since 1 July 2015, a common, EU-wide logo is mandatory for all online pharmacies or retailers legally operating in the EU. This makes it easier to distinguish between legal and illegal online pharmacies throughout the EU.
The Commission led a proactive communication campaign for the introduction of the EU common logo to identify legal online pharmacies. This included a Commission toolbox in all EU languages that was shared with Member States in order to ensure that a consistent message is given to EU citizens.
The communication materials, explained the legal framework for online sales in the EU including the fact that Member States are free to prohibit online sales of prescription medicines. It warned that a legally operating EU online retailer, if authorised or entitled to supply a prescription medicine, will always require a prescription. It stressed that a compliance with this legal requirement is one of the guarantees that the medicine bought online is authentic and safe.
The Commission website remains a key tool to keep citizens informed of the ongoing work to address counterfeit and falsified medicines.
The change to a new formulation of Levothyrox was requested by the French authorities to reduce deterioration of the active substance over time during storage of the tablets. This change also provided the opportunity to avoid lactose, unsuitable for patients with lactose intolerance, in tablets’ composition.
The marketing authorisation holder for Levothyrox has initiated a procedure to make the same formulation changes to most of its levothyroxine medicines across the EU. In this context, the German regulatory authority, Das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), which is leading the procedure, sought advice from the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) on any potential safety concerns with the new formulation. Based on the available information, the PRAC agreed that there is no difference in the pattern of adverse events reported before and after the switch to the new formulation.
In general, side effects associated with a switch to a new formulation of levothyroxine are expected in some patients because this medicine has a narrow therapeutic index, which means that the difference between the therapeutic dose and a dose which may trigger side effects is very small.
In January 2018, the PRAC recommended issuing specific advice to healthcare professionals on how to manage patients when switching from one formulation to another. This includes blood tests to ensure that the dose is adjusted to the individual patient situation. Particular attention should be paid to vulnerable groups, including patients with thyroid cancer and cardiovascular disease, pregnant women, children, and the elderly.
Medicines in the EU are subject to a post-marketing surveillance for which obligations to marketing authorisation holders and competent authorities are set by the legislation. Signals on safety risks are evaluated by the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) and a regulatory action is taken, as appropriate.
A recent scientific review by the EMA recommended new measures to avoid valproate exposure in pregnancy (e.g. ban on use for migraine or bipolar disorder during pregnancy, a ban on treating epilepsy during pregnancy unless no other effective treatment available). These recommendations are reflected in the summary of product characteristics that is the basis of information for healthcare professionals on how to use the medicinal product safely and effectively.
The Commission does not have figures on the number of people affected in the EU. However, data may be available in some Member States.
Regarding compensation, it should be stressed that health policy, as well as the organisation and delivery of healthcare, is a Member State competence under Article 168 of the Treaty on the Functioning of the EU.
Overall, the Commission takes the view that the legal framework to monitor medicines has been continuously strengthened to ensure that the medicines which are made available to patients in the EU correspond to high standards of quality, safety and efficacy.
The Commission did not draw up an assessment of the impact of the withdrawal of the United Kingdom from the European Union in the area of medicines and healthcare products. The Commission would like to recall that the decision of the United Kingdom to withdraw from the Union was a unilateral decision of the United Kingdom. The Commission regrets, but respects, this decision. The Commission, the European Medicines Agency and EU 27 national competent authorities are taking all necessary measures to ensure preparedness of the European Union with regard to medicines and healthcare products. In particular, Commission services have published ‘preparedness notices’ to stakeholders as regards medicinal products (jointly with the European Medicines Agency) and medical devices. More information is available on the respective website of the Commission services and of the European Medicines Agency.
On 25 April 2018, the Commission adopted a Communication on digital health and care, which includes a key section on better data to promote research, disease prevention and personalised health and care. In the Communication, the Commission presents, as area for piloting, the use of real-world data by healthcare professionals, public authorities and industry to ensure that healthcare products, innovative technologies and therapies meet patients’ needs and lead to favourable health outcomes.
The Commission aims to take this pilot forward, by leveraging existing work and optimizing use of real-world data by researchers, healthcare professionals, health technology assessment agencies, regulatory and other public authorities. Therefore as a first step, the Commission will take into account the existing programmes and ongoing initatives in the field such as Horizon 2020 and Innovative Medicines Initiative research projects, EUnetHTA and GAPP Joint Actions, projects led by the European Medicines Agency and feedback from all relevant stakeholders. Objectives will be to improve the common understanding on how the value of real-world data can be best captured and to provide practical guidance for its use.
The Commission introduced stricter rules for online sales of medicines in 2011 to address the increasing concerns of falsified medicines sold to consumers in the EU via the internet. These include a common EU logo for online pharmacies, and the requirement for online pharmacies to obtain an authorisation to supply medicines at a distance and notify the Member State authorities where they are established of their intention to sell medicines online. At the same time, Member States are allowed to maintain prohibitions of online sales of prescription medicines in order to safeguard public health.
The Commission and the Member States have worked together in recent years to enable healthcare providers to exchange patient data (ePrescriptions and patient summaries) across borders by setting up an eHealth Digital Service Infrastructure (eHDSI). Thanks to this infrastructure, 22 Member States will eventually exchange patient data by 2020.
With the recently adopted Communication on enabling the digital transformation of health and care, the Commission commits to further support this infrastructure, and to expand the exchange of data to cover full electronic health records. This will give healthcare providers and patients cross-border access to medical data and increase interoperability between health systems at larger scale.
In addition, the cross-border healthcare Directive includes the recognition of medical prescriptions issued in a Member State other than the Member State where the prescriptions are dispensed.
The Commission is aware of the number of people affected by Down syndrome and their plight. The prevalence of Down syndrome in Europe is monitored by the European Surveillance of Congenital Anomalies (EUROCAT), the European network of population-based registries for the epidemiologic surveillance of congenital anomalies.
The Joint Research Centre of the European Commission manages the Central Registry and European level coordination as part of the European Platform on Rare Diseases Registration.
Over the past 10 years, the EU has dedicated some EUR 70 million to research on intellectual disabilities and Down syndrome in 61 research projects. The EU will continue to support research in these areas to improve the quality of life of people with intellectual disabilities and their carers, and to eliminate stigmatisation and alleviate the social and economic burden.
In the Horizon 2020 Societal Challenge 1, most topics addressing non-communicable diseases do not specify any diseases in particular and therefore are open to less prevalent diseases, including those involving clinical trials. For instance, the 2019 Work Programme contains a topic on mental and non-mental comorbidities that could support research on the links between Down syndrome and Alzheimer’s disease or autism.
It is the intention of the Commission that the next Framework Programme — Horizon Europe, should maintain this approach of very open competitive calls for proposals. Thus, the Health cluster would not address specific diseases, but two areas of intervention would address the needs of people with disabilities, i.e. area 1 ‘Health throughout the Life Course’ and area 5 ‘Tools, Technologies and Digital Solutions for Health and Care’, while area 3 would address ‘Non-Communicable and Rare Diseases’.
Vaccines like all medicines are authorised according to EU legal requirements and only after their quality, safety and efficacy have been evaluated. Vaccines are monitored for safety and adverse reactions through their lifecycle. Signals on safety risks are reported at the EU level and evaluated by the European Medicines Agency (EMA) and regulatory actions are taken, as appropriate.
The EMA provides guidelines with the requirements on clinical evaluation of vaccines. It addresses the studies to be performed of new vaccines and may also be applicable to the further development of already licensed vaccines.
Experience with vaccine development has shown that the pharmacokinetic (PK) properties of antigens included in vaccines do not provide useful information for determining dose recommendations and this is the main purpose of doing such studies.
Vaccines are biological medicines that have different characteristics from chemical substances. Since the metabolic pathways of vaccines are generally understood (they are metabolised into small peptide and eventually to amino acids), and the action of vaccines is mediated locally at the site of injection and draining lymph nodes, PK studies are generally not required for vaccines.
However, in some cases PK evaluation is needed in particular when vaccines contain novel adjuvants/excipients or when delivered in the body using new delivery systems. This will have to be evaluated on a case-by-case basis, taking into account the expected impact on efficacy and safety and available preclinical information.
There are estimates of the possible reduced timeline regarding market access for health technologies as a result of a more efficient Health Technology Assessment process.
This is of course dependent on the current procedures in a given Member State. A recent study found that within a sample of 16 countries, the availability of joint clinical assessment at the time of marketing authorisation can speed up market access in 12 of them by a period ranging from 2 to 6 weeks.
The impacts of this 2-6 weeks of earlier access can have significant benefits for all relevant stakeholders. Notably, patients could receive treatment more quickly with an impact on improving their health condition.
Unless otherwise provided for in the legal bases establishing them, the general rules governing the use of languages of the European Union apply to EU decentralised agencies as regards their external communication.
Moreover, as stipulated in the Common Approach on EU Decentralised Agencies, agencies’ websites should be made as multilingual as possible. It is therefore important that agencies strive to implement, to the best of their ability, the principles of openness, transparency and good administration, while having regards to the sound financial management of their resources.
This may entail prioritisation of translation activities so as to reconcile competing demands, while reaching out to more stakeholders and citizens.
As agencies are separate legal entities, the Commission has asked those agencies mentioned by the Honourable Member to provide answers to the questions raised by the Honourable Member. The Commission will forward the agencies’ answers to the Honourable Member as soon as possible.
The Impact Assessment on the Commission’s proposal on Health Technology Assessment (HTA) showed that there are important differences in the processes and definitions of health technology assessments in the Member States. Therefore, it is not appropriate to give one figure for the number or for the cost of HTAs undertaken in the EU. Nonetheless, it can be concluded that the cost of producing a single-technology HTA by Member States authorities ranged from EUR 4 000 to EUR 135 000.
1. The number of assessments carried out by national HTA bodies range from 5 HTAs per year to up to 390 HTAs per year. However, as mentioned above, they vary greatly in methodology and therefore it would not be appropriate/ adequate to provide a consolidated annual figure.
2. The costs for joint health technology assessments were modelled on the experience of the EUnetHTA Join Action, where a joint assessment on relative effectiveness assessment (REA) for pharmaceuticals has a cost of EUR 117 000. However, these are the costs in the framework of the pilot exercises and once conducted routinely the unit cost is expected to markedly decrease. In fact, a study showed that the cost savings related to the joint REA are estimated at EUR 1 560 000 to EUR 2 670 000 per year for HTA bodies. This is in line with the results of the focus group meeting with public administrations carried out in the context of the study. The participants agreed that a stronger EU cooperation would lead to a cost decrease per joint output (once the system is well established and running). The saving will of course depend on the number of joint assessments carried out.
Further to the announcement in the 2015 Single Market Strategy, a legislative proposal to fine-tune the EU supplementary protection certificates (SPC) system was adopted by the Commission on 28 May 2018. This initiative, called for by European Parliament in its Resolution on the Single Market Strategy in May 2016, proposes a targeted adjustment to the existing SPC Regulation, through the introduction of a manufacturing waiver for export purposes. This proposal follows an inception impact assessment in February 2017, a public consultation in autumn 2017, and a series of independent studies related to SPCs.
A wider review is underway in the context of the analysis of pharmaceutical incentives called for by the Council in 2016, which the Commission is currently undertaking. This is based on various sources of evidence, including a recent study on the economic impact of supplementary protection certificates, pharmaceutical incentives and rewards in Europe, conducted by Copenhagen Economics, published on 28 May 2018, and the ongoing evaluation of the EU paediatric and orphan legislations. The Commission will engage in further discussions with all stakeholders about the outcome of this analysis.
Healthcare is a sector exposed to specific corruption risks. As noted in the Commission’s reply to E-000040/2017, the Commission has prioritised sharing of good practices in fighting corruption in this sector in its EU anti-corruption experience sharing programme and supported relevant work at the European Partners against Corruption (EPAC) — European contact-point network against corruption (EACN).
The Commission has also recently published an updated study of corruption in the healthcare sector(2) that includes, inter alia, an analysis of improper marketing practices and corruption in the procurement of medical devices and pharmaceutical products as well informal payments in healthcare.
In addition, the Commission has encouraged Member States to take steps to address the issue of corruption also in healthcare in the framework of the European semester of economic governance.
EU legislation on homeopathic medicines was introduced in 1992 with the aim of ensuring their quality and safety whilst at the same time providing a clear indication of their homeopathic nature. At the time of adoption of the legislation, it was considered that despite the differences in recognition between Member States, consumers across the EU should be adequately protected if they choose to use homeopathic medicines.
Under the current simplified registration procedure, homeopathic medicines must not mention specific therapeutic indications and be diluted to a sufficient degree to ensure their safety. Furthermore, their labelling must clearly mention that they are ‘homeopathic medicinal products’.
There are no plans to revise Directive 2001/83/EC as regards homeopathic medicinal products or change their designation to ‘homeopathic substances’.
EU legislation on homeopathic medicines was introduced in 1992 with the aim of ensuring their quality and safety whilst at the same time providing a clear indication of their homeopathic nature. At the time of adoption of the legislation, it was considered that despite the differences in recognition between Member States, consumers across the EU should be adequately protected, if they choose to use homeopathic medicines.
Under the current simplified registration procedure, homeopathic medicines must not mention specific therapeutic indications and be diluted to a sufficient degree to ensure their safety. Furthermore, their labelling must clearly mention that they are ‘homeopathic medicinal products’.
Regarding the second question, the regulatory framework for homeopathic medicines and vaccines is different under Directive 2001/83/EC. Vaccines can only be authorised subject to an in-depth assessment of quality, safety and efficacy.
The Council Conclusions of June 2016 on ‘Strengthening the balance in the pharmaceutical systems in the European Union and its Member States’ invite the Commission to perform, among other things, an analysis of the impact of pharmaceutical incentives on innovation, availability and accessibility of medicinal products in the European Union. As part of this effort, a holistic, in-depth and evidence based analysis of those incentives has been carried out by an external consultant, Copenhagen Economics, contracted by the Commission. The final report of Copenhagen Economics is available on the website of the European Commission.
The Commission is aware of the submissions by Pharmaceutical Research and Manufacturers of America (PhRMA) and Biotechnology Innovation Organisation (BIO) in the context of stakeholder consultations on the 2018 Special 301 Report by the Office of the United States Trade Representative (USTR). The EU was not placed on the watch list in the report, neither does the report mention the matter brought up by PhRMA and BIO.
The Commission conducts its policy based on evidence, in consultation with the relevant stakeholders, in a transparent manner and independently of any administrative procedures carried out by third countries. It will engage in further discussions with all stakeholders about the outcomes of this study and analysis.
Valproate-containing medicines have been approved nationally in the EU to treat epilepsy and bipolar disorder and in some countries for prevention of migraine. It is known that if taken during pregnancy they can cause malformations in the baby and developmental disorders after birth.
It is therefore important to avoid exposure of babies to valproate medicines in the womb.
As with any medicinal product, the side effects (and their frequency) related to valproate used during pregnancy are clearly reflected in the summary of product characteristics and patient leaflet.
A recent scientific review by the European Medicines Agency recommended new measures to avoid valproate exposure in pregnancy (e.g. ban on use for migraine or bipolar disorder during pregnancy, a ban on treating epilepsy during pregnancy unless no other effective treatment available). These recommendations were sent to the Commission at the end of March 2018 which will be followed up with a legally binding decision.
The Commission does not have figures on the number of people affected in the EU. However, data may be available in some Member States.
Regarding compensation, it should be stressed that health policy, as well as the organisation and delivery of healthcare, is a Member State competence under Article 168 of the Treaty on the Functioning of the EU.
Overall, the Commission takes the view that the legal framework to monitor medicines has been continuously strengthened to ensure that the medicines which are made available to patients in the EU correspond to high standards of quality, safety and efficacy.
As the Commission pointed out in its reply to the Written Question E-005260/2017, the competence for vaccination policies and how they are organised lies with the EU Member States.
As the Commission pointed out in its reply to the Written Question E-003125/2017, the number of Europe-wide studies analysing the impact of mandatory vaccination on vaccination coverage is limited. Mappings conducted in the EU indicate that there are no striking differences in vaccination coverage between countries that recommend certain vaccinations and countries that make vaccinations mandatory for the general public. However, the Commission has no information on single national vaccination programmes as regards their impact on public trust.
The Commission has recently presented a policy initiative on strengthened cooperation against vaccine-preventable diseases by which it proposes to establish a European Vaccination Information Sharing system to monitor online vaccine misinformation and develop evidence-based information tools and guidance to support Member States in countering vaccine hesitancy. In addition, the Commission proposes to convene a Coalition for vaccination, including European associations of healthcare workers, to combat myths about vaccination.
Building on the existing EU pharmacovigilance system the Commission proposes with the new vaccination initiative to establish, with support of the European Medicines Agency, a European vaccination information portal to provide objective, transparent and updated evidence on vaccines, their benefit and safety, and the pharmacovigilance process.
1. Vaccines may contain small amounts of aluminium acting as adjuvants. They are authorised nationally or centrally. The European Medicine Agency (EMA) is in contact with the French National Agency for Medicines and Health Products Safety (ANMS), which financed the research referred to by the Honourable Member. In September 2017, ANMS communicated that the results of the new studies, as well as the available publication, do not change the positive benefit/risk ratio of vaccines. EMA, in collaboration with the EU Member States, continuously monitors the safety of aluminium-containing vaccines, including studies reported in the worldwide scientific literature, and will take any necessary action in case a safety issue is identified.
2. Through the Innovative Medicines Initiative (IMI), the Commission funds research on vaccine safety. The IMI projects ADVANCE and BioVacSafe work to deliver reliable data on the benefits/risks of marketed vaccines, and to improve testing and monitoring of vaccine safety, respectively.
The agreement of 29 December 2016 between the pharmaceutical industry (Farmindustria) on the one hand and on the other the Spanish Ministries of Finance and Public Service and of Health, Social Services and Equality, is a state measure to control public expenditure on medicines. It caps the growth of Spanish public expenditure on originator (branded) medicines relative to the evolution of Spanish gross domestic product (GDP). This is an example of so-called ‘payback/clawback’ policies to prevent deficits in public budgets.
The agreement does not oblige the Autonomous Communities to purchase branded medicines. It only sets conditions in case sales of such medicines are higher or lower than a certain cap. In case the cap is not reached, the Monitoring Committee for the agreement (composed of representatives of the above Ministries, Farmaindustria and the Autonomous Communities adhering to the agreement) ‘may’ propose incentives under the framework of Royal Decree-Law 8/2010 (which among others envisages deductions to be applied by the industry on sales of medicines to the national health service). To date, to the Commission’s understanding, no such measures have been proposed. Thus making financing from the Spanish Government’s Autonomous Liquidity Fund contingent on acceptance of this agreement (by the Autonomous Communities) as such does not appear to create a barrier to entry for generic medicines or to raise concerns under EU competition rules.
The Commission has no current plans to submit a new proposal for the revision of Directive 89/105/EEC. It is now working to ensure the appropriate implementation of the existing Directive by the Member States.
The Commission has no current plans to develop common cost accounting and pricing methods for medicines in the European market.
However, the Commission is supporting improved exchange of information among Member States and promoting their cooperation on a voluntary basis for example through the Network of competent authorities responsible for pricing and reimbursement (CAPR), by supporting a European medicine price data base focusing on the appropriate use of current data sets of product prices and implementing effective application of reference pricing to participating Member States and by supporting a Project on Sustainable Access to Innovative Therapies.