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A new member within EIPG


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

The EU Parliament voted its position on the Unitary SPC


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

Reform of pharma legislation: the debate on regulatory data protection


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

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PGEU annual medicine shortages report

March 4, 2024 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Giuliana Miglierini

The situation of medicine shortages is getting worse, with many countries which in 2023 experienced more issues than the previous years, according to the PGEU annual report on medicine shortages. Community pharmacists are on the front line to find suitable solutions to provide patients with the products they need to treat their diseases.

“Despite pharmacists continued best efforts to find solutions, shortages still leave many patients without their prescribed treatment – said PGEU President Aris Prins. – This situation causes frustration and inconvenience for patients and erodes their trust in pharmacists and in the healthcare system. They also cause stress for pharmacy staff and impose an additional administrative burden on pharmacies daily work”.

The main outcomes of the yearly survey
As every year, PGEU (the association representing community pharmacists at the European level) run a survey among its members to assess the current situation of medicine shortages. The survey was run between 4 December 2023 and 17 January 2024; 26 PGEU’s members provided their contribution to the 15 questions (1 answer per country).

All respondent countries experienced medicines shortages in 2023. Only three respondents reported positive improvements over the previous year (Cyprus, Greece and North Macedonia, representing 12% of the total), some other a stable situation (23%). In the great majority of cases (65%), shortages increased with respect to 2022, confirming the already known trend. Among the more significant data, the Netherlands reported 2.292 medicine shortages in 2023 (in comparison the 1.514 registered in 2022), a negative trend that impacted on 5 out of 13 million medicine users. A similar situation was reported by Sweden, where 2.457 packages were reported to be in shortage in September 2023, compared to the 1.615 in 2022. Spain also reported an increase in 36% of medicine shortages compared to the previous year.

The time spent by community pharmacies to deal with shortages almost tripled over the last 10 years, reaching an average of 10 hours per week in 2023.

The lack of anti-infective for systemic use (i.e. antibiotics) is particularly worrying, as it was experienced in 100% of the respondent countries. Slightly lower are data on shortages of medicines for the respiratory system (96% of countries impacted) and cardiovascular systems (92%). Other therapeutic classes often impacted at a European level are medicines for alimentary tract and metabolism, the nervous system, and antineoplastic and immunomodulating agents (77% of countries impacted, respectively). It is significant to note that, according to the report, there are no categories of medicinal products exempt from shortage issues.

The worsening of this trend is also acknowledged by the fact that in many responding countries (27%) the list of medicines facing shortages exceeded 600 references at the time of the survey, and was between 500-600 references in another 15% of countries.

The problem is not only referred to medicines: medical devices are also concerned, with shortages in community pharmacies reported by 69% (+3% vs 2022) of the countries participating to the survey. In this case too, all classes of medical devices are touched by the problem, with higher percentages for Class I (low risk devices – e.g. bandages, thermometers, surgical face masks) (27%) and Class IIa (medium risk devices – e.g. lancets, needles, short-term contact lenses) (23%). In the case of medical devices, only two countries reported the existence of a specific system to monitor shortages.

The impact for patients and community pharmacies
Patients are hardly impacted by medicine shortages. According to the PGEU report, distress (100% of respondent countries) and interruption of therapeutic treatments (88%) are the more frequent inconvenience. In many cases, patients have no other alternative than to buy other more expensive or non-reimbursable medicines (73%), thus increasing the rate of private expenditure for co-payments. The survey also highlights the occurrence of suboptimal treatment with reduced efficacy (73%), a practice that might negatively impact on patients’ health.

These issues can also lead to patients losing trust in the pharmacy, a negative effect reported by 77% of participating countries; employee satisfaction may be also impacted (73%). A very high percentage of countries (92%) indicated that community pharmacies may experience financial losses linked to medicine shortages, due to the dedicated amount of time needed and increased administrative responsibilities.

According to the report, disruption/suspension of the manufacturing process (65%), national pricing and procurement strategies (62%), and unexpected/high increase in demand of medicines (50%) are the main causes identified by pharmacists leading to medicine shortages. In the majority of countries (69%) there are already reporting systems in place for community pharmacists to report shortages.

Different solutions for different countries
It is worthwhile to note that only 46% of countries participating to PGEU’s survey have a commonly accepted definition of medicine shortages at the national level. This definition is incorporated in the national legislation in 19% of cases. Significantly, 35% of respondent countries still do not apply a standardised definition for shortages.

The PGEU annual report also assessed the solutions available to community pharmacists in different countries. Generic substitution is a very diffuse practice across Europe (92% of respondent countries), while far less often encountered are the preparation of compounding formulations (50%), or the adjustment of therapy and posology with a different strength of the same medicine (50%). Both these practices may require the issuing of a new prescription by the doctor in charge of the patient. Some countries are experiencing new approaches to simplify the process. In Germany, for example, a new legal basis was created to allow pharmacists to deviate from the medical prescription without consulting the prescribing doctor upon certain conditions in case of a shortage.

PGEU also calls the European and national institutions to adopt urgent and ambitious measures to better address medicine shortages. The availability of a timely and adequate supply of medicines to patients should be the first priority, to be included in the ongoing revision of the pharmaceutical legislation. This last one should put patients’ interests over commercial ones. An improved compliance to public service obligations of supply chain actors would be also required, as well as the impact of pricing policies on medicines availability and on the security of the supply chain.

Shared electronic communication tools between pharmacists and prescribers (i.e. electronic health records) may prove important to possibly expand the role of pharmacists to handle shortages, by allowing them to substitute the missing product with the most appropriate alternative. Reporting, monitoring, and communication on medicine shortages should be also improved according to PGEU, with action to be taken both at the central (EMA) and national level, e.g. working at increasing the efficiency and effectiveness of joint notification and assessment practices. A greater transparency on shortages data would be also appreciated by community pharmacists, to be achieved in each country through the connection of all medicine supply chain actors and national competent authorities in consistent reporting systems. Last, but not least, PGEU asks for a better recognition and valorisation of investments made by pharmacists and pharmacies to manage shortages.


The drug shortage situation – EIPG’s point of view

November 24, 2023 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Maurizio Battistini

The shortage of medicines has been a major concern in the countries of the European Union, and elsewhere, for more than 10 years, so much so that the Economic Community has devoted a great deal of effort and increasing attention to this problem in an attempt to mitigate its impact on patient health.

Several factors can be identified as being at the root of the shortage of medicines, some of which intersect with each other, mainly concerning aspects with technical, qualitative, regulatory, forecasting, supply, speculative and economic implications.

EIPG has made its contribution to the various attempts to contain the phenomenon by participating in task forces, round tables and convenings dedicated to identifying the root causes of the issue and, through gap analysis, the consequent mitigation measures. Overall, strengthening the risk-assessment approach to assess and define the risk level of individual deficiencies or the causes to which they pertain in order to rationalize and focus mitigation interventions and identify their level of acceptance with a proactive approach.

Before defining the particularly deserving aspects to be emphasised and consequently acted upon, it is important to mention those that represent, in the opinion of EIPG, but are not limited to, the elements on which priority action should be taken. In analysing the problem, one cannot in fact fail to take proper account of the fact that medicines are not such without their active ingredients and that, for diseases with the widest spread, there are equivalent medicines and alternative therapies. On the basis of the latter assumption, it is understandable that the definition of a shortage of medicines should be restricted to cases where no equivalent medicines or alternative therapies with different medicines are available, so as to concentrate efforts to solve the problem only on those conditions that are worthy of attention because they are not limited to the unavailability of a specific product or to situations for which it is possible to identify an alternative treatment (defining a list of critical medicines and defining risk assessment criteria for assessing whether a product should be on the list or not).

The operation required to bring the production of active ingredients back to Europe, recognising their strategic and central role in the composition of medicines for the entire community and patients, takes longer. The relocation of the manufacturing of active ingredients to third countries, which has been taking place for several years now for mainly economic reasons, has led to the dependence of many other countries, including mainly those of the Union, on supplies that today has the occasional impact that we know of, but which could become much more serious if not systemic. We have been hearing about reshoring the production of active pharmaceutical ingredients for some time now, but so far there do not seem to be any concrete initiatives for its implementation.

As mentioned above, EIPG identified the revision of the definition of drug shortages and the reallocation of strategic production of active pharmaceutical ingredients in Europe as a main key action to mitigate the impact of drug shortages.

Although it is not an aspect of primary interest to the European industrial pharmacist community, EIPG recognises the economic aspects as playing an important role in the origin of shortages, particularly with regard to the low price paid for certain categories of medicines, which induces manufacturers to abandon the manufacture of low-profit products, and the discrepancies in the price of medicines that exist in the different countries of the Union, discrepancies that, coincidentally, make the countries where prices are the lowest or even where volumes are not so attractive as to devote production to shortages.

Having made this necessary digression on the aspects requiring corrective action at source, there are, however, other, mostly ‘occasional’ causes on which to intervene, where possible, in a proactive manner or by means of reaction instruments capable of reducing the impact of shortages. In this regard, some of the elements covered in the introductory part of this discussion, namely: technical-qualitative, regulatory, forecasting and speculative, are taken up and detailed.

As far as the technical quality aspects are concerned, given the vastness of such occasional events in the production cycle of a medicine, a separate, dedicated discussion should be devoted to them. In addition to a few examples, please refer to the chapter ‘Shortages Originating from Manufacturing‘ in the text ‘Pharmaceutical Supply Chains – Medicines Shortages‘ published by Springer and written by the same author as this article. The book, authored by experts in the field, provides an insight of relevant case studies and updated practices in Pharmaceutical Supply Chains (PharmSC) while addressing the most relevant topics within the COST Action Medicines Shortages (CA15105) and it covers uncertainty and risk aspects of supply chain management, carefully combining the scientific level with a pedagogical approach. In industry, proactive strategies such as the adoption of reserve stocks or back-up establishments can be adopted to make up for medicine shortages on an emergency basis, although the expense of sustaining these prudential approaches remains the main problem.

In a number of situations, shortages can occur due to underestimated sales forecasts or problems with the supply of raw materials, and in particular APIs.

A particular case in point is parallel trade, which by its very nature can have such contrasting effects that it has been dubbed ‘The double face of the parallel trade’. While on the one hand, this method is useful in dealing with shortages in a relatively short time (import in the country where the shortage needs to be filled and export from the country where the availability exists), on the other hand, it has often encouraged the migration of products from countries where they are cheap to others where they guarantee a higher margin, in which case it could be the source of the problem and not its solution.

Last but not least, it should be pointed out that the phenomenon of shortages has an economic implication, as it is more likely to affect drugs with low profitability or movements of drugs from countries with low margins or sales volumes to those with high margins or higher market shares.

Heads of Medicines Agencies and the European Medicines Agency on improving availability of human and veterinary medicines invited the EIPG to attend the key stakeholders’ table at the Workshop on Shortages Prevention Plan held on 1 and 2 March 2023. The EIPG was represented by Jane Nicholson and Maurizio Battistini. Staff from the EMA, the European Commission and members of national authorities presented their current initiatives and future plans. Representatives from the research and generics industry, wholesalers, pharmacists from the EIPG and PGEU, and several organizations representing patient groups had the opportunity to present and discuss ideas for shortage prevention, permanent market withdrawals, and shortage communication and transparency.

The meeting had breakthrough sessions on biosimilars (the EMA is publicly encouraging their use) immunoglobulins and veterinary medicines. The EIPG commented on the low prices of medicines that cause shortages and called for more accurate definitions of ‘medicine shortages’ and to focus efforts on essential product shortages where there is no equivalent medicine or alternative therapy to ensure patient access to adequate treatment.

Shown below is the action plan that EIPG submitted to the group at the meeting; an action plan that largely reflects what is the topic of this article.

  • Establish pro-active risk management plan
  • Prepare list of medicinal products of clinical importance that lack therapeutic alternatives • Undertake regular checks on market availability of alternative products especially those with low pricing due to cap measures
  • Criticality in the procurement of all starting materials with particular attention to APIs
    • How to mitigate?
  • Quality and manufacturing aspects that could have an impact on medicines’ shortages
    • How to manage them preventively?
  • Appropriate agreements on quality and capacity of CMOs
  • Need to review quality management systems throughout life cycle (including those for older products)
  • Consideration of batch release and transportation impact on the time to deliver products to the market
  • Review impact on production planning of potential weaknesses in sales forecasting

Everyone in industry agrees that problems of shortages are complex with no quick solutions, and it was interesting to hear staff from Agencies agree that one of the main problems of shortages for older products is the impact of low pricing of products by national healthcare systems. Also, product dumping of medicines at an extremely low price was mentioned as occurring in some countries and everyone present agreed this must not be tolerated. There were 100 participants in the main meeting room at the EMA and 200 who were connected online.

In opening the meeting, Emer Cooke Executive (Director EMA) explained the aim was to inform stakeholders about the HMA/EMA Task Force activities and deliverables and share stakeholders’ perspectives on ongoing and planned initiatives to address availability issues. She explained the long-term position of the EMA is to focus on prevention and to become more proactive, particularly since the EMA after Covid was given an extended mandate for emergency situations. The EU joint action for shortages has been launched to improve capacity at national level and the single point of contact (SPOC) working party is really helping to ensure suitable structures are in place to assist with shortages. The EMA is working with the European Commission, DG SANTE (medicinal products unit, quality, safety and innovation) and DG HERA (intelligence gathering, analysis and innovation unit) both of whom made presentations during the meeting.

In October 2023, released documents about Commission steps up actions to address critical shortages of medicines and strengthen security of supply in the EU.

The work done by the European community is aimed at addressing the shortages of the most critical medicines by emphasising the role of logistical aspects but overlooking certain critical elements that go beyond supply chain management and concern the upstream management of the concrete problems for which medicine shortages continue to occur (root causes). For the time being, the Commission seems to be oriented towards a predominantly top-down approach, even if there are spaces where opportunities for a multidisciplinary discussion involving all stakeholders in the supply chain are offered. However, it remains important to note that the Community is taking an active interest in the problem albeit adopting containment measures aimed at containing the problem rather than solving it at its root.

Given the role entrusted to Italy to find solutions to this important problem, the author is convinced that the face-to-face meeting that EIPG will have in Rome with the Italian Medicines’ Agency, on the occasion of the EIPG’s Annual General Assembly, will serve as a constructive basis for working together to find longer-term solutions to medicines’ shortages main causes.

Reference: Battistini, M. (2019). Shortages of Medicines Originating from Manufacturing. In: Barbosa-Povoa, A., Jenzer, H., de Miranda, J. (eds) Pharmaceutical Supply Chains – Medicines Shortages. Lecture Notes in Logistics. Springer, Cham. https://doi.org/10.1007/978-3-030-15398-4_5


EC Communication (part 1): How to address critical medicines shortages

October 27, 2023 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Giuliana Miglierini

As announced on 3 October in the speech given by Commissioner Stella Kyriakides at European Parliament Plenary Session, the EU Commission has published on 24 October its Communication on medicine shortages and strategic healthcare autonomy.

The planned actions are firstly targeted to prevent and mitigate on the short-term critical medicine shortages, thus avoiding the reoccurrence of situations such as those experienced in the 2022. Mid- and long-term actions have been also addressed to support the strategic autonomy of the European pharmaceutical supply chain. Among these is the creation of a Critical Medicines Alliance, to start operations in early 2024.

“Improving the management of critical shortages of medicines and ensuring a steady security of supply for the EU has been our priority since day one. We need a single market for medicines in the EU and a new approach to better tackle shortages of critical medicines. Today we are putting forward collective actions to work closer with the industry and help Member States improve the security of supply for the coming winter and in the long-term.” said Stella Kyriakides, Commissioner for Health and Food Safety.

In this first post, we will examine actions in the field of medicines shortages, leaving the medium and long-term ones to a following article (part 2).

Prepared for future winters

The first goal of the EU Commission is to avoid situations of shortages of critical antibiotics such as those that occurred last year. To this instance, the Health Emergency Preparedness and Response Authority (HERA) and the European Medicines Agency (EMA) have already identified key antibiotics potentially at risk of critical shortages in the winter season, also in future years.

Immediately after the release of the Communication by the Commission, EMA published the details of the announced new European Voluntary Solidarity Mechanism for medicines, the MSSG Solidarity Mechanism.

The mechanism was developed by EMA’s Medicines Shortages Steering Group (MSSG), on the basis of the informal experience made during the pandemic. In case of critical shortages escalated to the MSSG for coordination at European level to request assistance, other member states may be of help through the rescEU stockpile mechanism to redistribute medicines from available stocks. The activation of the Union Civil Protection Mechanism (UCPM), via its 24/7 available European Response Coordination Centre (ERCC), aims to coordinate and logistically support the voluntary transfer of medicines, and it should represent the last resort, after the interested member state had exhausted all other possibilities.

The MSSG also developed a Toolkit including recommendations on how to tackle shortages of critical medicines. Among others are the monitoring of available stocks, supply and demand, interactions with marketing authorisation holders and manufacturers for increasing the manufacturing capacity and for the fair distribution of medicinal products, the implementation of regulatory flexibilities and actions aimed to improve communication to the public and international cooperation with other regulators to early identify critical shortages.

The other actions to tackle shortages

The first version of the Union list of critical medicines is expected to be released by the end of 2023. It will allow the development of further actions, on the basis of the analysis of the vulnerabilities of the supply chain of selected medicines to occur by April 2024.

In addition to the practical recommendations relative to demand forecasting at national level, the Commission is working on an EU Mechanism for Demand Signalling that should better support the collective EU public sector in its decisions. A new European Shortages Monitoring Platform for reporting information regarding available stocks and shortages of medicines is expected to start operating in 2025. Many future actions shall be supported using artificial intelligence to extract information about trends in demand and supply from existing data.

At the regulatory level, a new Joint Action has been announced for early 2024 to promote the effective use of flexibility as well as of measures applied at national level (i.e. magistral preparations of local pharmacies). Regulatory flexibilities may include, among others, the quick authorisation of alternatives, the approval of alternative suppliers of raw materials or finished products, or the temporary extension of shelf-life.

Another initiative announced for 2024 should see the issuing of an EU guidance on procurement of medicines, better detailing the already existing tools and practices supporting the security of supply. In the meantime, an EU joint procurement for antibiotics and treatments for respiratory viruses should be activated for the incoming winter.

The Communication contains some recommendations for member states and the pharmaceutical industry. The former are called to monitor and fully enforce the supply obligations of companies, to develop effective communication plans, and to consider how national procurement rules and criteria can increase security of supply. Industrial stakeholders should continuously monitor the evolution of demand and supply of critical medicines, assuring to the full the supply obligation under EU law. Early communication of critical situations to regulators should also occur, as well as the implementation of recommendations, both on regulatory flexibilities and on the elements of the pharmaceutical revision that could already be applied.

Comments from the stakeholders

The interested pharmaceutical associations promptly reacted to the EU Commission’s Communication.

EFPIA particularly welcomed the structural measures to address the industrial dimension of medicines shortages in the medium and long term, as the Critical Medicines Alliance. The development of solutions targeting the specific root causes of shortages, and measures aimed at mitigating shortages in the short term should be “proportionate and provide efficient, workable solutions that serve public health needs”. EFPIA asks for the industry to be included in the design and implementation of new processes and highlighted the “missed opportunity” represented by sharing of the information stored in the European Medicines Verification System (EMVS).

“In response to Member State and Parliament calls for a Critical Medicines Act, this communication is a positive first step for the security of supply of medicines. Medicines for Europe will partner with the EU to implement these important reforms”, said Medicines for Europe President, Elisabeth Stampa. The associations ask, among others, for a strategic EU reserve of essential medicines, and EU funds and State aid projects to incentivise investments in greener and more secure manufacturing processes for essential medicines and active pharmaceutical ingredients (APIs). Digitalisation of the regulatory system and harmonisation of pack sizes and presentations would be also helpful.

European community pharmacists also welcomed the Communication, as it may help to avoid new, severe medicine shortages like the one experienced last winter. “PGEU’s annual survey confirms that shortages exist in all EU countries across all types of medicines, causing detriment to patients’ health, waste of resources and frustration. Every day, we spend hours managing shortages and finding solutions to guarantee continuity of treatment for our patients”, commented PGEU President Koen Straetmans. As for the common strategic approach to stockpiling, according to PGEU it should be guaranteed that stocks will not be to such an extent as to jeopardize the general supply of medicines, nor they should generate unnecessary waste.

EuropaBio, representing the biotech industry, positively commented on the Communication and highlighted that EU actions should not be limited to essential medicines, but should target also the growing dependency on third countries for innovation medicines.


Some perspectives on green pharmaceuticals

January 20, 2023 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Giuliana Miglierini

The central role the green agenda plays within the EU Commission’s transformative policies impacts also on the development and availability of pharmaceutical products characterised by a improved sustainability. The concept of “Pharmaceuticals in the environment” (PiE) is entering the new legislative framework; the undergoing revision of the pharmaceutical legislation, for example, may include among other the request of environmental risk assessment and urban wastewater treatment. But also, the goal of a circular economy at net zero emission and the revision of the chemical legislation.

As explained by Dr Bengt Mattson, Policy Manager at the Swedish research-based pharmaceutical industry association Läkemedelsindustriföreningen (Lif) during a recent EIPG’s webinar, the EU Commission Action plan on environment for years 2021-2023 includes twenty legislative and non-legislative files impacting also the pharma sector.

The theme of the so-called “green pharmaceuticals” is also part of the broader approach to environmental sustainability of the chemical industry. The topic is not new, for example the EU and IMI-funded CHEM21 project in years 2012-2017 focused on the development of new manufacturing processes for the pharmaceutical industry to reduce the use of expensive and toxic materials. Another target of the project included the development of environmentally friendly methods useful to save time and costs, while reducing waste.

Activities focused on the antimicrobial drug flucytosine, with the final goal to use flow chemistry and biocatalyst techniques to make it more easily available also in lower income countries to treat a fungal form of meningitis in HIV/AIDS patients. The new, cleaner and safer method developed under the project allowed to reduce the need for expensive toxic chemicals and other raw materials, with a corresponding decrease both in costs and wastes. As a side activity, the CHEM21 project also explored more efficient screening methods to find new enzymes potentially useful as biocatalysts in industrial chemical reactions.

A Green-by-design future for pharmaceutical processes

At the EIPG’s webinar, Dr Mattson discussed from many different perspectives how R&D initiatives may influence green manufacturing. The attention moved from packaging and energy in the ’90-ies to APIs released in the environment at the beginning of the new millennium. The ’20-ies shows a greater attention to API-related emission and to aspects linked to the efficient use of resources and the resulting carbon footprint. From this point of view, it may result not easy to correctly estimate the expected environmental impact of a pharmaceutical product. Biological substances, for example, may be more easily biodegradable than synthetic small molecules, but they may also require more energy to ensure the correct storage conditions.

The development of green processes represents a great challenge for chemists and pharmacists working in the pharmaceutical industry. A possible approach to Green Drug Design has been explored, for example, by another IMI project, Premier. Results have been recently published in the Environmental Science & Technology Letters.

The “Greneer” approach includes among others, criteria aimed to achieve avoidance of non-target effects and of use of persistent, bioaccumulative, and toxic (PBT) substances, and exposure reduction. The final goal would be the development of “green-by-design” active pharmaceutical ingredients.

Green pharmaceutical processes should also prefer more eco-friendly, renewable raw materials, with a particular attention to the choice of solvents and reagents. Waste water treatment to eliminate residues of pharmaceuticals is a typical example of downstream measures put in place at the industrial level to reduce the environmental impact of manufacturing activities. As noted during the webinar, the main source of this type of pollutants remains excretion by patients, followed by inappropriate disposal.

The pharmaceutical supply chain, and in particular community pharmacists represented by PGEU, is also active to inform patients, develop national and regional collection schemes for expired and unused medicines, and to make available more sustainable packing materials and transports.

A call to action from the UK

In the UK, the request emerging from a report by the Office of Health Economics (OHE), commissioned by the Association of the British Pharmaceutical Industry (ABPI) is for the government and other stakeholders to take immediate action “to secure the era of green pharmaceuticals”.

The report highlights the challenges for the pharmaceutical industry in order to reach the ambitious target of net zero carbon. Among these is the difficulty to quickly change processes to increase sustainability while maintaining product safety, the need to collaborate at all levels along the complex global pharmaceutical supply chain, the high waste-to-product ratio on the supply side of the medicines market, the new environmental impact profile of innovative drug products compared to established small molecule technologies, and the lack of reward for sustainability.

The report also suggests high-priority activities, including investment in decarbonisation and a long-term energy strategy for transition away from fossil fuels. Common regulatory standards and environmental reporting standards should be agreed upon by regulators of different geographic areas, including the EU and US. Financial support for the adoption of greener technologies by both the industry and the NHS is also suggested. Improvements to the NHS’s supply chain may come by the Supplier Roadmap and more sustainable procurement processes and health technology assessment methods. Public-private partnerships may represent the tool to launch proof of concept pilots for sustainability schemes or co-invest on key infrastructure projects.

Standardised metrics to be used to publicly disclose emissions and progress against targets are suggested as a useful tool for the industry, together with the life cycle analysis (LCA) of products, and the development of innovative solutions for waste management and efficiency improvement.

Other insights on green pharmaceuticals

Many other things may be said on green pharmaceuticals, but we are running out of space. We then highlight some useful links readers may refer to deepen the topic.

An outcome of the CHEM21 project is represented by the CHEM21 online learning platform, managed by the ACS Green Chemistry Institute. The platform offers many free educational and training materials in the field of the sustainable synthesis of pharmaceuticals.

The Green Chemistry Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) has elaborated a Green Aspirational Level (GAL) metrics to assess the green efficiency for a given API’s manufacturing process, based on the complexity of its ideal synthesis route.

The industrial associations also committed to take action in the field of Environment, Health, Safety and Sustainability (EHS&S). The three main European groups representing, respectively, the research-based industry (EFPIA), the auto-cure (AESGP) and the generic and biosimilar sectors (Medicines for Europe) have developed the Eco-Pharmaco-Stewardship (EPS) framework. The initiative takes into consideration the entire life-cycle of a medicinal product, including roles and responsibilities of all parties involved.

The Medicine Maker’s editor Stephanie Sutton interviewed some industrial experts on different aspects of sustainability (here the link to the article). Some other comments from industrial representatives have been reported by Cynthia A. Challener in an article published on PharmTech.com


The main contributions to the consultation on the revision of the pharmaceutical legislation

March 4, 2022 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Giuliana Miglierini

The European Commission has published the summary of the outcomes of the public consultation on the Evaluation and revision of the general pharmaceutical legislation, which closed on 21 December 2021. A total of 478 contributions were received, mostly by companies and business organisations (25.10%), non-governmental organisations (19.67%) and business associations (14.02%). At the geographical level, Germany contributed the 18.2% of feedbacks, followed by Belgium (16.7%), and France (9.2%); 12.8% of contributions came from non-EU countries.

Almost half of the respondents (48.1%) are registered in the EU Transparency Register; one third (33.1%) provided also separate position documents. The Summary Report and single contributions to the consultation are available at the Commission’s dedicated webpage.

Large companies represented the main industrial contributors (39%). Feedback from the pharmaceutical sector accounts for 28.4%, those from patient or consumer organisations 13.8%. A great part of the comments from public authorities (26 respondents in total) came from public authorities at national level (82.6%).

The main themes emerged from the answers

The Summary Report provides an outlook of the received comments from the perspective of the different categories of stakeholders.

Key topics of interest for the Industry included the decline of R&D investment and clinical trials in Europe, paralleled by the need of a more attractive regulatory framework for global investment and a facilitated access to value-added products and over-the-counter switching. Slow response rates of regulatory agencies, high administrative costs, convergence of data requirements of EMA and HTA, digitalisation of regulatory processes and optimisation of regulatory pathways for vaccines are other issues looking for solutions.

The impact of parallel trade on the security of supply, a predictable system of incentives for innovative products and unmet medical needs, a strong framework for intellectual property (IP) protection, and attention to the EU manufacturing of active pharmaceutical ingredients (APIs) were also reported.

Some of these topics were also addressed under the perspective of public authorities and healthcare payers. Comparative safety assessments, coherence with the blood, tissues and cells (BTC) legislation, affordability issues due to high prices/monopoly positions, transparency of medicinal product R&D and market launch costs, and abuse of existing incentives are other issues on the table, together with incentives for APIs manufacturing in the EU and a clear framework for medicine repurposing. On the clinical perspective, regulators ask for the inclusion of up-to-date clinical information in the Summaries of product characteristics, and for patient involvement in the definition of unmet medical needs.

The Summary Report also provides feedback on comments received by academics and research institutions, civil society organisations, citizens, healthcare professionals and other respondents. A total of six different campaigns were identified through the statistical analysis of the received answers, addressing respectively the need to update the radiopharmaceutical legislation, medicines shortages and the role of wholesale distribution, incentives for the innovative pharmaceutical industry and for generic manufacturers, access to treatments for rare diseases from the patient perspective, and the integration of microbiome science in the legislation.

EFPIA’s contribution

EFPIA, representing the innovator industry, highlighted the “significant interdependencies between the R&D policy environment and the manufacturing ecosystem downstream”. At the regulatory level, suggestions include the reinforcement of expertise-driven assessment and a more agile centralised authorisation framework, the improvement of expedited pathways framework supporting innovation, an expanded role of EMA in the assessment of drug-device/diagnostic combination products, and the replacement of the paper patient information leaflets with electronic versions.

The impact of further modifications of the EU SPC framework would need a careful assessment, while a Regulatory Data Protection (RDP) would support a better evaluation of products with lower development times, insufficiency/inadequacy of patent protection and new indications.

EFPIA also provides its vision on the sustainability of the off-patent market, including procurement practices and interchangeability of medicinal products. Actions to prevent and mitigate medicines shortages should be differentiated and coordinated at the European level, on the basis of a harmonised definition of shortage. Harmonisation should also represent a target for quality requirements at the global level, as well as for supply chain and GDPs. Other identified barriers at the manufacturing level include manufacturing site authorisations referring only to the local premises specified, full import testing, Official Medicines Control Laboratory testing for vaccines and biologics, and the revision of the Variations Regulation.

Comments from Medicines for Europe

Medicines for Europe, representing the off-patent industry, asks for a fit-for-purpose, efficient and fully digitalised regulatory framework. Among the priorities at the regulatory level are the optimisation of the Decentralised and Repeat Use Procedures. The regulatory framework should also avoid the unnecessary and unethical repetition of clinical studies, so to encourage generic and biosimilar medicines development. Global access and competition in the field of off-patent medicines should benefit of a single global development framework for multiple jurisdictions.

According to Medicines for Europe, the revision of the pharmaceutical legislation should also address the absence of rewards for manufacturers, in order to find a balance with their obligations of supply. As for IP protection, the association asks for the clarification of the Bolar exemption and the legal ban of patent linkage in all EU member states. The availability of multiple API suppliers should be encouraged through a single and efficient assessment of ASMP (Assembling Surfactants-Mucoadhesive Polymers) and API authorisations, and the separation between the regulatory dossier (regulatory assessment-subject of variations) and GMP (subject of inspection) should be introduced; a broader use of virtual inspections should also be promoted.

Other comments from industrial associations

AESGP, representing the self-care industry, considers the incentive of one added year of data protections not sufficient to reward investment in innovative switches. The burden posed by the Sunset Clause is also critical with regard to un-marketed licences, as well as extending the data exclusivity for a new indication or a switch. Stringent pharmacovigilance and post-approval change requirements are considered by AESGP unjustified or disproportionate, due to the limited gains in patient protection. The suggestion is for a risk-based approach for the submission of Risk Management Plans as a part of Market Access Authorisation, based on existing API safety info and provided there are no great differences in conditions of use. At the regulatory level, the applicant should be free to choose the procedure to authorise the product, and all procedures should perform equally and according to defined timelines. A broader definition of unmet needs would allow for more non-prescription medicines to be accessed; differences in the legal status of this type of medicines in different EU’s countries may also affect their availability to patients.

The European Healthcare Distribution Association (GIRP) addressed mainly issues related to medicines shortages. Among these are the need to strengthen the existing obligations for supply chain actors, and a better framework for the implementation of Article 81, paragraph 2 and 3 of Directive 2001/83 in member states legislation, so to place obligations on both marketing authorisation holders (MAHs) and pharmaceutical full-line wholesalers. The latter should be appropriately and continuously supplied by MAHs with the full range of products. Unjustified supply quotas based on legal and ethical grounds should be abolished.

A legal basis should be established for a EU-wide early warning system for anticipated/potential and verified/confirmed shortages for critical medicines. EU-wide harmonised categories for root causes of shortages should be implemented in the shortages databases managed by member states. GIRP also addressed access to market, suggesting pricing and reimbursement for centrally registered products should be separated from the availability of centrally registered products on national markets.

Market access has been addressed also by Affordable Medicines Europe, representing parallel distributors. The suggestion is for the Commission to develop a guidance on the launch of centrally approved products by parallel distributors in markets where the MAHs have not launched. An obligation for MAHs to supply entities launching in markets not covered by MAHs is also envisaged. To better manage withdrawals, Art 123 (2) of Directive 2001/83 should be amended, and a notification by MAHs should be made no less than 12 months before the withdrawal for commercial reasons. MAHs should also compulsory supply entities continuing marketing in markets undergoing commercial withdrawal; in this instance, guidance to member states should be provided on how to delegate pharmacovigilance tasks to another member state where pharmacovigilance data are available, so to limit technical measures aiming to reduce availability and ensure that products can still enter the market.

The Alliance of Regenerative Medicines (ARM), representing producers of advanced therapy medicinal products (ATMP), highlights the risk for Europe of loose positions in the competitive scenarios due to policy and regulatory barriers. According to ARM, all medicines falling under the ATMP definition should undergo the same regulatory requirements. A mandatory centralized procedure of authorisation should be maintained, in order to provide the level of expertise needed for the assessment of these complex products. GMP and pharmacovigilance aspects should be also coordinated at EU level. Bedside manufacturing models or other schemes should be avoided in order to prevent a two-tiered regulatory framework for ATMPs, leading to different quality and safety standards. Hospital Exemption (HE) should also be strictly regulated and harmonised across member states, with application only to individual patients on a case-by-case basis. Accelerated market approval procedures are expected to maintain rigorous regulatory requirements and high-quality standards for ATMPs. A pan-EU infrastructure and standards for collecting, storing and using ATMP-related real-world data, also for regulatory decision-making, is supported. The association asks for changes to the regulatory requirements for medicines containing genetically modified organisms (GMOs). Implementation of the EU cross-border healthcare legislation would support the administration of ATMPs to patients; HTA should be also coordinated at the EU-level.

Obligations accompanying any novel incentives should carefully take into considerations differences compared to traditional pharmaceuticals, as well as withdrawals due to market failures. A new business model is also recommended by ARM to address the shift in cost from chronic to one-time treatment. No modification of the current definition of ATMP to differentiate with respect to BTC products would be needed.

The position of community pharmacists

The Pharmaceutical Group of the European Union (PGEU) also contributed to the consultation with a position paper, providing the perspective of community pharmacists. The document suggests that issues of medicine shortages and patients’ access would require a “bold, ambitious, and coordinated actions at all policy levels”. According to PGEU, the revision of the pharmaceutical legislation should take the form of a new Directive, so to better respect the existing social, cultural and economic differences between European countries, which are reflected in the organisation of their healthcare systems.

An expanded role for EMA in the prevention and management of shortages, in coordination with the HMA, and the availability of a centralised EU monitoring system for (anticipated) shortages of all medicines in the EU would support the improved availability and access for patients. PGEU also asks for a better transparency and timely communication on shortages to affected stakeholders, as community pharmacists are deeply impacted; clarification of European and national laws related to the public service obligations of supply chain actors would also help to improve compliance.

A more effective redistribution mechanism for medicines available on the European market, irrespective of the country of residence of the patient, would help to face health crises and other special circumstances (i.e. the Brexit and its impact on medicines supply in Malta, Ireland and Cyprus). PGEU also suggests that pharmaceutical companies asking for a centralised marketing authorisation for their products should then commercialise them in all member states. Unmet needs of small patient populations may find an answer in pharmaceutical compounding by community and hospital pharmacists; this practice may also help to face shortages in cases where no suitable alternatives are available.

On their regulatory perspective, PGEU suggests that electronic Product Information (ePI) should complement, and not completely replace, printed leaflets. Digitalisation is deemed important also with respect to the exploitation of real-world data for regulatory decision making and Health Technology Assessment. To this instance, the association suggests to consider a rewarding for evidence generation in community pharmacies at the national level, so to better intercept data useful to evaluate the effectiveness, safety, off-label use and therapeutic added value of medicines in practice. According to PGEU, pharmacy organisations should also be better involved in integrated medicines development and post-authorisation activities, in coordination with other actors.

Repurposing of off-patent medicines should be targeted to areas where important public health benefits are likely to be achieved, but attention should be paid not to limit patients access to these medicines for the currently authorised indications. The association of community pharmacists also supports the reshoring of pharmaceutical manufacturing in the EU (e.g. active ingredients, excipients and basic chemical compounds particularly critical in terms of supply), a goal to improve European competitiveness and reduce the direct dependence from extra-EU countries. An improved diversification of the medicines supply chain is also envisaged.

Environmental issues should be tackled by the availability of innovative incentive and business models for the development of new antimicrobials and antibiotics, and a full compliance with environmental quality standards for pharmaceuticals. A coordinated approach among member states to the evaluation of cost-effectiveness and added therapeutic value of new therapies, including HTA, would support the affordability and fiscal sustainability of medicines. According to PGEU, pricing decisions in one country should not negatively impact on patient access in other countries. Cost-effective pharmaceutical care services at national level should be promoted as a mean to support the rational use of medicines through the adequate remuneration.