Sähköisen pakkausselosteen (ePL) edut ja haasteet – katsaus ePL-pilotteihin sairaalaympäristöissä Euroopassa

20.10.2023 | Camilla Skogman-Lindqvist (Novartis), Outi Lapatto-Reiniluoto (HUS), Mari Sirviö (PIF), Mia Sivén (Helsinki University)

Sähköisen pakkausselosteen (ePL) edut ja haasteet – katsaus ePL-pilotteihin sairaalaympäristöissä Euroopassa

Artikkeli on alun perin julkaistu European Journal of Pharmaceutical Sciences -lehdessä lokakuussa 2023.

Benefits and challenges of electronic package leaflet (ePL) - review of ePL pilots in hospital settings in Europe


Inclusion of package leaflets in paper format is a legal requirement in European Union (EU), therefore the electronic package leaflet (ePL) is a relatively unknown phenomenon in medicinal products in Europe. Introduction of ePL only would be a more sustainable format of providing the product information than paper package leaflet. Furthermore, ePL would support health care professionals’ comprehension of product use through electronic searchability and facilitate access to up-to-date product information in respective language used. It could also help us to tackle the availability issues and be a further step towards common packages.

With this commentary, our aim is to review the ongoing ePL pilots in hospital settings in Europe and identify the benefits and challenges of ePL. Based on our review, there is a broad general support for the removal of paper package leaflets from hospital products. Packages without paper package leaflets are considered more sustainable due to savings in production and materials. Furthermore, ePL could be a facilitator for common packages in EU-countries with the benefit of reducing pharmaceutical waste and drug shortages. The most important benefit from both pharmaceutical industry and healthcare professionals’ interest is that current and on-line updated product information is always electronically available, especially from drug safety perspective.

1. Introduction

Current European legislation requires the Marketing Authorisation Holders in pharmaceutical companies to include a package leaflet (PL) in every pharmaceutical package. These leaflets must be understandable to patients and written in official languages of the destination country (European Commission EC, 2023). In most European countries, the latest approved package leaflet can also be found on the several authorized webpages.

However, during the life cycle of a product a process to review and update the product information to the patient is required and this is quite cumbersome. New quality and safety information is collected constantly from e.g. Periodic Safety Update Reports, Development Safety Update Reports and Risk Management, and transferred via a regulated process to the summary of product characteristics (SPC) and to the package leaflet (PL) (European Commission EC, 2023). This regulatory process can take couple of years and sometimes a new regulatory process has been started before finalizing the previous one. Furthermore, some EU countries have national requirements for mandatory reserve supplies to be kept up in warehouses, causing a further delay in implementing the newest product information details for some essential medicines due to inventory turnover (Finnish Medicines Agency, 2008).

The paper package leaflet has been under discussion for a long time in the pharmaceutical industry, now especially due to the revision of the pharmaceutical legislation in Europe (European Commission Proposal, 2023). There is pressure to produce accurate, comprehensive and legible information to patients during the whole lifecycle of the product. A transition to a more digital world is envisaged to lead to cost reductions and environmental benefits (European Commission, 2020). Digitalization is also supported by moving from traditional prescriptions and medical health records to electronic systems in many countries (European Commission, 2023; Social Insurance Institution of Finland, 2023).

The European Pharmaceutical strategy stated already in 2020 that a better use of electronic product information (ePI), which is a combination of both the broader summary of product characteristics (SPC) and the shorter package leaflet (PL), would support a wider availability of medicines across European member states (European Commission EC, 2020). Very low prices and small sales volumes are the two most significant factors why products are not brought to a market despite approved marketing authorization. ePL could act as an incentive to bring a product to market as a survey done in the summer 2022 amongst pharmaceutical companies showed (Sundgren et. al., 2023).

A clear benefit of an ePL would be a possibility to mitigate drug shortages. Multilingual packages, with ePLs available in different languages, would increase availability of medicines across borders. This could be achieved already as part of the marketing authorization approval and the importance is significant with e.g. orphan drugs (EMA Key Principles, 2020; Nagaoka et. al, 2022; EFPIA, 2020; Sundgren et. al., 2023; Wang et al., 2023).

In some countries bolder approaches have already been developed. In Australia ePL (consumer medicines information, CMI) have been in use for several years, and they have recently updated their template for better readability, that will be implemented by 2025 (Australian Government, Therapeutics Goods Administration, 2020). In addition, from Sep 2023, ePL only is accepted in injectable medicines administered by health care professionals (Australian Government, Therapeutics Goods Administration, 2023). In Japan the inclusion of ePLs were introduced using GS1 coding and the paper package leaflets will be abolished by the end of July 2023 (Nagaoka et. al, 2022). Singapore is following the same way on a voluntary basis (Singapore Health Sciences Authority, 2021).

The aim of this commentary is to collect as much information as possible and introduce the readers to different ePL pilots in hospital settings or other projects already ongoing in this field, and to identify the benefits and challenges of ePL. With this commentary we also try to encourage people involved to communicate with each other and share their experiences.

2. Background

The regulators, physicians and industry would like the patients to read and understand the information in the package leaflet but providing the information in paper format does not mean that the patients will use it as a source of information about their medicines. Internet is becoming increasingly popular in accessing up to date information about health and medicines. (Hämeen-Anttila et al., 2018; Liu et al., 2022; European Commission, 2022) In the hospital setting, it is reported that the majority of patients currently do not receive the package leaflet to read, but they receive the information directly from the healthcare professionals who administer the medication (EAHP, 2022). The report doesn't, however, reveal if the patients have asked for it in written form.

One pathway to get the most up to date and reliable information quicker to the targeted groups is via a trusted source of an electronic version of the package leaflet.

Reducing paper would also have an environmental effect, which is important to people and society. Sustainable medicine and sustainable use of pharmaceuticals should be a common target to all of us. Introducing ePL would save environment in many different ways starting from less energy and materials needed to produce packages without a paper package leaflet, smaller package dimensions, less storage capacity, less paper waste and less pharmaceutical waste. If an update is required, repacking the packages with valid paper package leaflets and scrapping the outdated material is more costly than destroying the packages, which may lead to more drug shortages (European Commission Green Deal, 2023; Alajärvi et al., 2022).

3. Overview of the ongoing ePL pilots in EU/EEA

At the moment, there are numerous piloting projects ongoing in Europe focusing on ePL. EU countries like Belgium, Luxembourg, Spain and the Baltics have ongoing initiatives relating to the implementation of ePL for some hospital products (Nauwelaerts et al., 2022).

3.1. Belgium and Luxembourg

The initially planned 2 year-pilot in Belgium and Luxemburg was initiated in 2018 with an aim to demonstrate the equivalence of replacing the paper package leaflet with an ePL in hospital products. The main idea of the leaflet must remain the same, i.e. to provide the information of the safe and effective use of the medicine (Lambot et. al., 2022). The pilot required a derogation to Article 58 of Directive EU/2001/83 of the legal obligation in inserting a paper package leaflet in the packaging of a medicinal product. Following the calls to include medicines in the pilot, 42 medicinal products from 17 pharmaceutical companies participated in the Belgian/Luxembourg pilot.

In the beginning of the pilot, a survey was conducted among the participating hospital pharmacists to demonstrate a baseline. Follow-up surveys are performed throughout the project at set intervals to oversee the results from the entire pilot. The interim results confirmed that the patients in the hospitals rarely request the package leaflet from the healthcare professionals. Most of the pharmacists (98%; 24mths survey) had never been asked by patients for the package leaflet and 95% (48mths survey) would agree to remove the package leaflet from the medicinal packages in the hospital setting. In situations where the hospital pharmacists needed to consult the PL regarding the medicines in the pilot, 96% (24mths survey) answered that they consulted the electronic version of the PL, not the paper (Lambot et. al., 2022; pharma.be, 2022). During the pilot, the hospital pharmacists did not find the lack of paper leaflets inconvenient in any way (opinion of 97% of respondents at 48mths).

During the first 48 months of the pilot an estimation of over 1.000.000 units of medicines, exclusively used in hospitals, have been sold in Belgium and Luxemburg. The hospital pharmacists also recognized the positive impact on the environment.

The European commission is informed of the Belgian/Luxembourg pilot interim results. More data will be collected as the steering committee would like to obtain more data to confirm the currently obtained results. An application to extend the pilot 7 years until Aug 2025 and to include more products has been granted (Innovative Medicines Luxembourg, 2023).

3.2. Baltics – Estonia, Latvia, Lithuania

The industrial 2-year-project in the Baltic countries, Estonia, Latvia and Lithuania, started in 2021 and was restricted to medicinal products for hospital use. It aimed at evaluating whether the use of ePLs ensures safe use of medicinal products and whether the use of ePL could improve the availability of hospital products (Republic of Estonia Agency of Medicines, 2021). An extension to the project has been applied for in 2023.

An interview study regarding the Baltic project was done in 2022. It consisted of a group of interviewees, considered as subject matter experts, from health authorities, industry and hospital pharmacies and received a positive outcome as all participants felt generally supportive of removing the paper package leaflet from the selected hospital products (Sirkas et. al, 2022). Future environmental aspects were already seen as important and substantial in this project, though only 13 hospital products from 9 companies that were selected could not provide an actual picture.

Package leaflets vary in size, and some can be measured up to a meter long, as the countries regulatory requirements and the nature of the medicinal product affects the amount of information in the package leaflet. Significant amount of paper can be saved if the package leaflet would be removed. In addition, the rest of the packaging material, can be decreased in size when the package leaflets are removed.

3.3. Spain

In January 2022, a one-year pilot was started in Spain, with possibilities for extension. The aim of this national pilot is to assess the impact of the removal of the paper package leaflet in hospital products. The results are used to guide future reviews of pharmaceutical regulation, especially taking into account the advancement of new technologies and their implementation in the pharmaceutical sector (AEMPS, 2021).

In the Spanish pilot the product information is accessed via a datamatrix code on the primary packaging material, that will allow direct access to the package leaflet in the Centro de Información online de Medicamentos Autorizados (CIMA) [Online Information Center of Authorized Medicines] application. The introduced datamatrix code also enhances drug safety as it reduces errors at several levels such as dispensation, administration and preparation (AEMPS, 2021).

The second phase of the pilot started June 2023, and 100 products from 21 marketing authorization holders are participating. According to the Spanish Health Authority the interim results of the first year of the pilot were very good. A survey done by the Spanish Society of Hospital Pharmacy (SEFH) to selected hospitals, rated the satisfaction level of this initiative to be 4.75 out of 5. In addition, hardly any patient or healthcare professional requested the package leaflet printed on paper (AEMPS, 2023; Herranz-Alonso et al., 2022).

3.4. Iceland

The Icelandic ePL pilot is planned to take 3 years and it started in 2022. It focuses more on access of medicines especially to hospitals. It will be assessed whether the pilot will lead to an increase of marketed hospital products on the Icelandic market. Surveys directed to the healthcare professionals in this pilot was conducted in Sep 2022 and will be conducted at the end of the pilot to assess possible problems and questions around access, use and reading of ePLs. The project will also evaluate whether the use of ePLs ensures safe medicinal treatments of patients. Forty-six medicinal products from different pharmaceutical companies were participating in March 2023.

Interim results show that products brought onto market in Iceland has increased by 8,4% from the start of the pilot. Surveys are planned to be conducted throughout the project, covering topics on access, use and reading of the PL. At this point of time further information is not available, and no official results have been published regarding the Icelandic pilot, the results here are from an oral presentation given by the Icelandic health authorities to industry stakeholders in spring 2023 (IMA, 2023).

4. Overview of other ePL projects in EU

Several other initiatives from different stakeholders are being conducted in EU that have a clear focus on electronic product information. EU is preparing to launch its own structured database to cover the digitalization demands. The EU (EMA) database will undergo a pilot testing starting 2023 and ending in 2024, using a common technical standard (FHIR), with a group of EU national competent authorities, to support harmonized electronic product information on medicines in EU (European Commission EC, 2023). This is based on the Key Principles published by EMA in 2020 to guide the development and use of electronic product information on human medicines (EMA Key Principles, 2020).

Concurrently, various auxiliary solutions are being developed at national level in many countries, like websites and apps. In Germany, a mobile phone application has been launched and implemented via trade associations. The app was tested by all stakeholders; authorities, patients, senior citizens, visually impaired citizens, individual users, industry and pharmacists; and feedback was collected from them. Afterwards, an online survey was sent for all these participants and positive feedback was received. The product information is presented in a structured way that has been validated by the pharma companies (Lang, 2018). Also other countries, like the Nordic countries (Finland, Sweden, Norway, Denmark), have developed websites or apps that are already in use by the healthcare professionals and patients (examples of such websites www.fass.se, www.pharmacafennica.fi; www.terveysportti.fi, www.felleskatalogen.no, www.indlaegssedler.dk).

5. Discussion

Digitalization took a giant leap forward during the CoViD-pandemia and this development should not be lost but harnessed and improved. According to Eurostat, internet penetration in Europe was up to an average of 93% in 2022. Health-related information (e.g. diseases, injuries, improving health) was sought over the internet by 52% of EU individuals. In four European countries health-related information was sought by over 70% of individuals via the internet (European Commission, 2022). In hospital settings, electronic package leaflet is used much more regularly by healthcare professionals than by patients at home. Utilizing electronic product information would benefit patient safety by the availability of updated information. It is important that the information is reliable and provided through known channels (Liu et al. 2022).

This commentary and short review of ePL pilots is concentrating on the hospital products. The whole pharmaceutical field is too wide to tackle in one action and ePL of all products including OTC-pharmaceuticals must still wait. There will always be patients and citizens who need the package leaflet in paper format or without any electronical equipment. However, if the patients are hospitalized, product information can easily be provided for them by healthcare professionals by printing the newest version of ePL or giving the information face-to-face in person.

All this has led to a pressure to update the European medicines legislation and its regulations, which proves to be a very lengthy process. The proposal of the Directive and Regulation was published in April 2023, containing a section for an EU wide database for the public. The legislation will still take probably years to become effective in all EU member states (European Commission Proposal, 2023). In the proposal it is stated that new technologies should facilitate equal or better quality of product information compared to paper format. An important factor is utilization of existing information, according to EMAs SPOR-initiative on reusing data (SPOR = substances, products, organizations and referentials).

From an industry perspective, the total amount of material used for the package leaflets and packaging materials in general is enormous, not to mention water usage in the paper manufacturing. However, at the moment the packaging process is configured and tested with paper PL included as the paper is not only for information but also for protecting e.g. glass vials during transportation. Packages without this paper protection may require some new innovations for this protection (European Medicines Agency, 2023).

Regulatory requirements should support the environmental aspects and patient safety. It is important to recognize that the electronic product information is an improvement of the availability of updated information (Sirkas et. al, 2022). However, it should not be a driver to make the PLs even longer than they are now, but should focus on the legibility, searchability and quality of the information. The inclusion of ePL should be a smooth process from a regulatory perspective. Based on the current knowledge from hospital pilots, the absence of paper PLs has not caused inconvenience in the daily practice for pharmacists or other healthcare professionals (Lambot et. al., 2022).

Implementation should however consider the current IT infrastructure in different healthcare settings in different countries regarding the technical equipment's using ePL in daily routine (EAHP, 2022). There should also be enough incentives for the industry to bring products to market and hospitals, to increase accessibility to medicines. The ePL has been suggested as one, for example for low-volume products that would benefit from electronic language versions (Sundgren et. al., 2023).

There is also a need for simultaneous implementation, as due to increasing manufacturing costs and desire to drive down unnecessary pharmaceutical waste, there is a pressure to increase common packages, a legislative change must be coordinated throughout Europe to facilitate this. A summary of these benefits and challenges have been listed in the Table 1.

6. Conclusion

There is a clear demand to improve access to medicines. ePL could function as one significant tool to achieve this goal by smoothing the way for common packages. However, also other aspects speak for the rapid implementation of ePL such as immediate access to up-to-date product information (incl. safety aspects) for health care professionals, environmental aspects, manufacturing and shipping costs only naming a few. The possibilities of utilizing different languages in a world with many minorities in several countries is a huge opportunity to increase knowledge of pharmaceuticals.

The current situation has led many countries to build their own electronic solutions and if a common structured database in EU takes too long to be implemented, we will have an even more shattered picture in the near future regarding product information. Hospital medicines could act as a pilot with a pure ePL solution and pave the way for other pharmaceuticals to follow.


Linkki artikkelin alkuperäiseen julkaisuun.