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Current trends in biosimilar uptake and special focus on automatic substitution – a symposium report

Published on 14 April 2025

Abstract: In December 2023, the University of Helsinki, Helsinki University Hospital (HUS), and University Pharmacy (Yliopiston Apteekki) Helsinki collaborated to present the online symposium titled ‘Current Trends in Biosimilar Uptake and Research with Special Focus on Automatic Substitution’. This provided an overview of global trends in biosimilar use and a systematic examination of the implications of automatic substitution for diverse stakeholders. The symposium proceedings, along with relevant updates, are presented in this paper.

Introduction

In recent years, healthcare systems globally have introduced measures to promote the use of cost-effective biological and biosimilar medicines. With biologicals and biosimilars playing a significant role in treatment plans, policymakers and healthcare professionals have explored strategies such as physician guidance and pharmacist-led substitution to enhance their accessibility and affordability.

To understand more about this transition, and how best to implement in Finland, the December 2023 online symposium ‘Current Trends in Biosimilar Uptake and Research with Special Focus on Automatic Substitution’ was held through collaboration of the University of Helsinki, Helsinki University Hospital (HUS), and University Pharmacy (Yliopiston Apteekki), Helsinki, Finland. This brought together key stakeholders – including physicians, pharmacists, and patients – to discuss national Finnish and international perspectives. The event highlighted the importance of collaboration and structured implementation to ensure positive clinical, economic, and humanistic outcomes. Keynote presentations were followed by a series of ‘short communication’ presentations.

Keynote presentations

International trends in biosimilars: evidence and trust

The symposium opened with a keynote presentation from Dr Alan Lyles, ScD, MPH, PhD (h.c.), Fulbright Specialist and the Henry A Rosenberg Professor of Government, Business and Nonprofit Partnerships, College of Public Affairs, University of Baltimore, in the United States, titled ‘International trends in biosimilars: evidence and trust’. Details of the presentation are outlined as follows.

Balancing access to high-cost pharmaceuticals with affordable sustainability is a global challenge. Each nation’s history, laws, and even regional cultures influence the roles that public and private sectors, professionals, and patients perform in that balance. The United States has an aggressively market-oriented health sector, while Finland’s small role for private healthcare is complemented by birthright access to national health care.

Despite their differences, nations along the continuum from market based to national health care face similar challenges for access to biological products, mainly due to price. Yet price alone is a poor proxy for value – it too often influences pharmaceutical demand when value is the issue. Biosimilar substitution offers a way to reduce this barrier. For example, Norway’s tender for a Remicade® (infliximab) biosimilar in 2015 resulted in a 72% discount offer [1].

In spite of persistent legal battles with innovator companies over intellectual property (‘patent thickets’), small molecule generics have legislative support and a robust history in the US.  These IP challenges extend to biosimilars. For example, the patent on one of the most financially successful pharmaceutical products, Humira® (adalimumab), ended in 2016, but litigation delayed serious biosimilar competition until recently. Even then, the arcane US market structure for pricing and benefits access to biosimilars muted the impact [2].

Influenced by a combination of laws, regulations, the courts, and market competition, biosimilar approval pathways occurred more slowly in the US than in the European Union (EU). There has, however, been movement. The Biologics Price Competition and Innovation Act of 2009(BPCI Act) consulted stakeholders and established a pathway for biosimilars application reviews and marketing decisions [3]. The Biosimilar User Fee Act (2012, with reauthorizations every 5 years) created a funding stream to support the US Food and Drug Administration’s (FDA) hiring additional professionals who perform pre- and post-marketing reviews. As more biosimilars were approved in the US, FDA guidance was updated to acknowledge biosimilars’ role in interchangeability (Labelling for Biosimilar and Interchangeable Biosimilar Products, September 2023), and Considerations in Demonstrating Interchangeability with a Reference Product: June 2024 Update [4, 5].

So far, there has been too much focus on the attributes and regulatory pathways for biosimilar products and not enough on understanding the system in which they are used. Price, biosimilar marketing authorization, and technical considerations are not the full explanation for a nation or a region’s adoption and diffusion of biosimilar use. After those concerns and the issue of ‘how similar is similar enough’ are met, transnational comparisons suggest that trust can strongly influence biosimilar use. Patient and physician acceptability are a fifth hurdle for biosimilar adoption, beyond evidence of safety, efficacy, quality, and cost effectiveness [6].

Do low political and social trust doom policies that would increase biosimilar adoption?

Professor James Robinson’s research ‘Social trust and regional variation in the adoption of biosimilars in Italy and Germany’ is an insightful analysis because mathematical economics or technically excellent policy studies alone are insufficient for making effective biosimilar policies [7]. He concludes ‘Overall, the structure of economic incentives would not appear to explain regional variation in adoption of biosimilars’.

In their empiric study comparing biosimilar adoption in provinces and regions in Italy and Germany, Robinson, et al.  (2022) [7] demonstrated critical variations in biosimilar adoption based on ‘social trust’ and ‘political trust’ (using a Quality of Government index) within regions of each nation. Using a Biosimilar Adoption Percentage¹, their analysis demonstrated that regions having low trust had lower percentages of biosimilar use, while regions with high trust had greater biosimilar use. A similar pattern was seen between higher income (greater biosimilar adoption) versus lower income (lower biosimilar adoption).

Italy and Germany’s national policies favour biosimilar use. However, regional and national variations persist. Their healthcare sectors contain multiple components with direct and indirect influences on which products are used, and which are not. For example, Robinson notes that biosimilar choices can be influenced by whether care occurs in an inpatient setting, which agent is the starter pharmaceutical (the originator or the biosimilar), and whether the product is administered by the patient or a provider.

Robinson’s research on factors contributing to variations in biosimilar diffusion within and between Italy and Germany bring a caution. Having identified the roles of political and social trust in the diffusion of biosimilars, a direct campaign to increase that trust could result in the perverse outcome of ‘further mistrust’. Professor Robinson cites Anderson and Griffith ‘that the appropriate response to mistrust in healthcare organizations is not a doubling down on efforts to increase citizen trust but a redesign of those organizations to improve trustworthiness’ [8]. Deliberate, consistent, and reliable performance over an extended time offer greater prospects for change in trust levels.

This applied research makes a compelling argument that variations in ‘trust,’ although previously an omitted consideration, adds to our understanding of why policies to increase the use of biosimilars may be only partially successful.

The research presented in this symposium provides evidence from national approaches to biosimilar use, including automatic substitution. Robinson et al.’s work (2022) on ‘trust’ as an influencer for biosimilar use identifies a promising, underexplored area for productive, actionable research and policies.

The US faces a daunting experience with trust: trust in science, the federal government, the Centers for Disease Control and Prevention, social trust, and trust in news vary by political party affiliation with low or declining recently reported trust in these domains [9]. Unfortunately, global data reveal similar concerns about interpersonal trust and its variation with income [10], suggestingan ongoing challenge for biosimilar adoption.

‘Both individual and institutional trust levels have traditionally been high in Finland’ [11]. High trust suggests that automatic biosimilar substitution may be both more acceptable and successful in Finland.

[1] Biosimilar adoption %: ‘Biosimilars were combined into a sales-weighted index of overall adoption’ in Robinson JC, Schaeff LD. Generics and Biosimilars Initiative Journal (GaBI Journal).2022;11(3):87-8.
doi: 10.5639/gabij.2022.1103.015 http://gabi-journal.net/social-trust-and-regional-variation-in-the-adoption-of-biosimilars-in-italy-and-germany.html

What can medicines’ regulators do to enhance the uptake of biosimilars?

The second keynote presentation, titled ‘What can medicines’ regulators do to enhance the uptake of biosimilars?’, was delivered by speaker Esa Heinonen. The second keynote presentation, titled ‘What can medicines’ regulators do to enhance the uptake of biosimilars?’, was delivered by speaker Esa Heinonen. Dr Heinonen holds the positions of Docent (Drug Development), PhD, and MD, and serves as the Chair of the Heads of Medicines Agencies (HMA) Biosimilar Working Group. He is also a Senior Adviser at the European Medicines Agency (EMA) and works with the Finnish Medicines Agency (Fimea). The key details of his presentation are outlined below.

European Medicines Agency (EMA) is the leading regulatory agency regarding biosimilar medicines. It has created the concept of biosimilar medicines and the guidelines for their development and pharmacovigilance. EMA guidelines have been the basis for those developed later by FDA in the US, other authorities and the World Health Organization (WHO). At the time of writing of the report, 90 biosimilars have marketing authorization in the EU.

During the EU Presidency of Finland, Fimea organized a multistakeholder meeting on biosimilars in 2019. In this meeting, it was concluded that the uptake of biosimilars was still very low in many countries although, from the regulatory point of view, EU is the leading region, and the more cost-effective biosimilars have been shown to be as effective and safe as the originator products. It was also concluded that the National Competent Authorities (NCA) regulating medicines should take more responsibility to enhance the uptake of biosimilars in the EU. The Heads of Medicines Agencies (HMA) Biosimilar Working Group (BSWG) was then established, with 15 NCAs and EMA joining the group. The main activities have been to develop and promote the use of objective information on biosimilars to increase the trust of healthcare professionals on biosimilars. Another important goal has been to share experiences on various strategies to enhance the uptake of biosimilars at national level.

An analysis was made by the BSWG on the websites of NCAs in 2020, showing that 10 out of the 30 NCAs did not have any information on biosimilars on their website. This finding was in line with a previous academic study by Barbier et al in 2022 [12]. The BSWG created a recommendation on a minimal set of information to be made available at each website of NCAs, which was accepted by the HMA Plenary in 2022. The group also noted that on the website of EMA, where the regulatory information on biosimilars is abundant, there was no information on the interchangeability of biosimilars. The BSWG had previously conducted a comprehensive analysis on the interchangeability of biosimilar monoclonal antibodies, where it was shown that interchangeability of biosimilars with the originator products is safe and does not compromise the efficacy of the products [13]. This is in line with the very basic regulatory concept of biosimilars, where the regulatory documentation (pharmaceutical-biological, non-clinical, clinical data) of biosimilar medicines are compared with that of the originator products to prove the sufficient similarity of the products. The statement on interchangeability of biosimilars on EMA’s website was realized in 2022 [14], which has had a major positive effect in many countries to enhance the trust on biosimilars. The BSWG also carried out an extensive analysis on the current information packages provided by various health authorities such as EMA, FDA and some other authorities. The conclusion was that there is the need to update EMA’s information package on biosimilar medicines to reflect the current scientific information especially about the interchangeability issue but also to make the information more structured and digestible using infographs and other communication methods. Two information packages, one for the healthcare professionals and one for patient groups, are being currently prepared. These will be ready by the second quarter of 2025.

At the national level, there have been various strategies to enhance the uptake of biosimilars. These have included information campaigns, pricing policies, prescription rules, procurement and tendering processes, and legislative measures. For example, in Ireland a targeted information campaign was used to enhance the uptake of selected biosimilar monoclonal antibodies. Information and debate meetings were held in major hospitals. Also, a gain-sharing policy was launched: a major part of the savings gained by using biosimilar products is given to the responsible clinical teams. Such a campaign was very successful but needed also a major resource allocation from national authorities. Tendering processes, where various biological products compete for the monopoly of the product to be used in a hospital or even a whole country like in Denmark, have been usually very effective to lower the price of biologicals. When such processes have been implemented and all the stakeholders well informed, they are very cost-effective methods. When the prices have been lowered thanks to competition, the use of such products is also increased, i.e. more new patients can be treated. Sometimes also the originator products can win the tenders when they lower the price sufficiently.

With the outpatient care products like insulins there are currently generally quite low levels of the use of biosimilars, partly since in most of the countries there are no tendering systems for outpatient care products. It should also be noted that originators have also often lowered their prices and/or brought new competitive pharmaceutical forms into the market. Prescription quotas are used in some countries like in Germany, where a certain percentage of prescription on biological medicines should be biosimilars. In Finland, an ordinance has been in force for the prescribers to use the cheapest products in the market. These measures defining the prescribing patterns have not proven, however, to be very effective to increase the use of biosimilar medicines.

Automatic substitution is one legislative measure which has been piloted in various countries. In this procedure typically a biological medicine is switched to the cheaper one by a pharmacist without consulting the prescribing physician. In most of the EU countries this implies only to the outpatient care products. In Norway, insulin glargine and teriparatide have been the first piloted products, in France filgrastim and pegfilgrastim. In Finland the law on automatic substitution was passed in 2023 stating that in principle all biological medicines can be included into the automatic substitution. Fimea must, however, check if there are any product-specific, especially device-specific reasons which would make the automatic switching cumbersome or would create a risk for patient safety. The law will be implemented in phases, the first phase including the low-weight heparin products in 2024.

There is still a great variability in the use of biological medicines in the EU as there is high general usage in Western and Northern Europe, but less in Eastern and Southern Europe [15]. In the future, quite many expensive orphan biological medicines will lose their patent exclusivity. Developing biosimilars to the orphan biologicals is, however, economically challenging if comparative clinical trials would be requested as basically stated in the regulatory guidelines. The UK medicines regulatory agency, MHRA published a new development guideline for biosimilars stating that large comparative clinical trials may not be requested automatically [16]. Also, at EMA there are preliminary preparatory discussions on this matter [17]. If – and I believe when – in the future comparative clinical trials would be requested only in exceptional cases, this will enhance the development also to the orphan biologicals, but on the other hand, it may create an extra challenge to convince the prescribers and patients on the efficacy and safety of biosimilars. Therefore, information campaigns and evidence-based open dialog with healthcare professionals and patients are needed now, especially in countries where the uptake of biosimilars has been low. This needs collaboration of all parties, EMA, NCAs, NCAPR (national authorities responsible for pricing and reimbursement) and healthcare professional and patient groups at national and EU level representing various therapeutic groups. Objective information on biosimilars is available, one needs to use it.

Short communications

Implementation of automatic substitution of biologicals in Finland: status of preparations

Following the two keynote presentations, a series of short communications were delivered. The first presentation, titled ‘Implementation of automatic substitution of biologicals in Finland: status of preparations’, was given by Hanna M Tolonen, MSc (Pharm), PhD. Dr Tolonen serves as Quality Manager at HUS Pharmacy, HUS Helsinki University Hospital, and is a Visiting Scientist with the Clinical Pharmacy Group in the Division of Pharmacology and Pharmacotherapy at the University of Helsinki’s Faculty of Pharmacy, Finland.

Before implementation of automatic substitution of biologicals in Finland, several preparatory studies were carried out mainly by regulatory authorities. The prospective medication safety aspects of biological substitution were studied by a multidisciplinary team led by the Finnish Medicines Agency using semi-structured stakeholder interviews in 2018 [18]. The study identified potential benefits and risks and risk mitigation measures. The study outlined that substitution may introduce new tasks and communication needs to those involved in the actual medication use process, see Figure 1. This concerns particularly community pharmacists who will be responsible for the substitution and counselling the patients.  The study also evaluated the impact of the substitution interval on safety and market attractiveness.

Figure 1: Illustration of new tasks and communication needs for patients and health professionals introduced by the implementation of automatic substitution of biological medicines

This stakeholder interview research, particularly Figure 1, has been used in the preparation of legislation along with several other national measures preparing the landscape for these legislative changes [19]. Fimea introduced the position paper on the interchangeability of biosimilars in 2015. As a part of the Rational Pharmacotherapy Action Plan 2018‒2022, based on the Government Programme [20], physicians were mandated to prescribe the most affordable price biological medicine.

Since 2023, biological prescriptions have been restricted to being valid for one year instead of the standard two years. The same year, national legislation allowing biologicals substitution was approved [21]. According to the legislation, biologicals have a six-month substitution interval, a reference pricing system, and a stepwise implementation that started with the substitution of enoxaparin in April 2024, see Figure 2. Note that fast-acting insulins and patients under 18 years will be excluded from the substitution.

Figure 2: Schedule of the stepwise implementation of the legislation allowing automatic substitution of biological medicines in community pharmacies in Finland

The Ministry of Social Affairs and Health has set up a national working group to coordinate implementation of the new legislation and is working on practical guidelines for implementation. The national Social Insurance Institution of Finland (KELA), also abbreviated as SII – the major third-party payor – will evaluate the impact of substitution on direct drug costs. Implementation at the pharmacy level has been supported by continuing education and providing resources to learn more about biologicals and their self-managed administration at home for counselling purposes. In addition to initiating a nationally coordinated education for community pharmacists, a multidisciplinary research consortium has been established to evaluate substitution outcomes. The implementation is also supported by collaboration with international partners.

Preparedness of patients for automatic substitution of biologicals: issues to be considered in community pharmacies

The second short communication was delivered by Dr Kari Linden, Docent, MSc (Pharm), MSc (Econ), PhD, Research Manager at the University Pharmacy (Yliopiston Apteekki) Research Unit in Helsinki, Finland. Titled ‘Preparedness of patients for automatic substitution of biologicals: issues to be considered in community pharmacies’, the discussion explored key factors for pharmacies to address regarding biological substitutions.

The use of lower-priced biological medicines is intensively promoted to curb the increasing medicine costs in many countries. Biosimilars are biological medicines that are highly similar, comparable, and often more affordable compared to their approved reference products. The effective and safe uptake of biosimilars is impacted by the perceptions and actions of healthcare professionals (HCPs) and patients [22-26]. Recently, increasing attention has been given to the role of the patient and the pharmacist [25-29]; biologicals can often be transitioned through a switch by a physician, or in some countries, through a substitution by a pharmacist.

Many patients are not aware of biosimilars and biological medicines in general [25-26, 29-30]. However, the majority of patients express a neutral or positive perception of biosimilars for non-medical (economic) reasons, but doubts about their clinical efficacy, safety, and quality are common. This  uncertainty increases on the substitution of biologicals, particularly if the substitution is conducted without a physician’s involvement or at a stable phase of the patient’s treatment [25, 28-29, 31]. The patient’s perceptions are determined by several psychological and socioeconomic factors, as well as by knowledge and experience of biologicals and even generic medicines [25, 29, 32]. Patient perceptions affect patients’ trust in biosimilars, willingness to accept the substitution, treatment adherence, nocebo effect, and finally, the therapeutic and economic outcomes of the treatment [25, 29, 33].

National biosimilar implementation strategies and plans emphasizing the importance of medicines information and concerning all stakeholders such as HCPs, patients, patient associations, and medicines information providers are strongly recommended by the literature [22-25].  Appropriate medicines information for patients and HCPs should be easily accessible, reliable, coherent, customized, and actively communicated [25, 31, 34-35].

Medicines information on biologicals and their substitution has some specific characteristics. First, many patients and even HCPs are not familiar with the biosimilar concept [25, 29-30], and misinformation about biosimilars is common [25, 36]. Second, it is a prerequisite for effective medicines information to patients that HCPs are aware and convinced of the substitution. The non-inferiority of biosimilars and the rationale for the non-medical substitution must be clearly communicated to the patients. Comprehensive information should be actively disseminated and readily available to all patients [35]. Many patients want information on biosimilars’ therapeutic equality with reference products, efficacy, safety, and dosing devices. Even minor changes in the style or focus (‘framing’) of the information provision may have major effects on the patient’s attitudes towards biosimilars [35]. The first experiences of mandatory biological switching, for example, in New Zealand, have also shown the need to consider practical treatment issues, such as the provision of alcohol wipes and sharp bins for injection devices, and the continuation of a patient support programme [37]. Third, it is widely recognized that the impacts of implementing biological substitution strategies must be systematically evaluated from different stakeholder perspectives with therapeutic, humanistic, and net economic measures.

Regardless of the structures of the national implementation strategies and guidance for biological substitution, community pharmacies are on the frontline in enhancing the effective and safe uptake of biologicals [23-26, 38-39]. Pharmacists meet patients using biologicals more frequently than any other HCPs and provide them with comprehensive and customized information on biologicals, substitution, prices, and other treatment options. The extended use of biologicals will increase the need for closer collaboration between pharmacies and other healthcare players enhancing the rational use of biologicals and patients’ health outcomes.

Preparedness of physicians for automatic substitution of biologicals: issues to be considered

The third short communication, titled ‘Preparedness of physicians for automatic substitution of biologics: issues to be considered,‘ was delivered by Dr Sinikka Sihvo, Docent (Public Health), PhD. At the time of the symposium, she served as a Health Policy Advisor at Finnish Medical Association.

Although physicians consider biosimilars equal to other biological medicines, too few (about a half) would voluntarily prescribe them as their first choice [40]. Further, according to a systematic review, the attitudes of physicians toward automatic substitution of biosimilars in community pharmacies were negative, 65%–95% being against it [41]. Therefore, national policies are needed to make a shift towards use of more affordable biologicals.

A prescription is a powerful treatment tool in the doctor–patient relationship. However, the physician’s obligation to prescribe the lowest price biological product could be seen as a reduction of physician’s autonomy. The physician can still prohibit the substitution of biological medicine by ticking a box ‘Do not substitute’ in the prescription but the reasons must be unambiguously stated. In the case of biologicals this could be, for example, related to a patient’s difficulties in learning how to use a new administration device. However, physicians very seldom use this prohibition.

Issues that need attention

Physicians need more information about the reform and its related obligations. They need to receive repeated information at various stages of the reform: which biologicals become substituted in pharmacies, timetables for changes and rules of prescribing and reimbursement. There can be confusion among physicians about which products pharmacies can substitute automatically. It should be clarified that it is a question of substitution of certain medical substances not of therapeutic substitution. Biological medicine will not be substituted without a biosimilar option available.

It should be emphasized that automatic substitution of biologicals in pharmacies does not leave the responsibility for drug information on biologicals solely to pharmacists. Physicians should inform patients that the prescribed biological medicine can be substituted in the pharmacy for an interchangeable medicine, see Figure 3. Advice on how to use a new device can be provided in the pharmacy but the responsibility for guidance about how to inject the dose (proper use of the device) remains with the physicians and the nurse.  Further, patients should always know who to contact in health care and how to act in case of further questions or problems.

Figure 3: Aspects that are essential in implementing automatic substitution of biologicals in the pharmacy from physicians’ perspective

Automatic substitution in pharmacies calls not only for national guidelines but also local collaboration between physicians and pharmacies. Fast-track communication channels would be useful. It is well known that reaching the physician in case of questions concerning a prescription can be troublesome and time consuming for pharmacists while dispensing.

To conclude, there is evidence that physicians’ attitudes towards biosimilars have become more positive. Similarly, once positive real-life experiences with automatic substitution are reported that will most likely shape physicians’ (and patients’) perceptions about the automatic substitution of biologicals in pharmacies to the positive direction.

Landscape of biological medicines for pharmacist-led substitution

The final presentation of the symposium, titled ‘Landscape of biologic medicines for pharmacist-led substitution,’ was delivered by Kati Sarnola, Docent in Pharmaceutical Policy and Pharmacoeconomics. Dr Sarnola holds an MSc in Pharmacy, an MSc in Economics, and a PhD, serves as a Senior Researcher at KELA.

Biological medicines significantly impact reimbursement expenditure

In outpatient care in Finland, biological medicines accounted for an average reimbursement of €150 million per quarter in 2022‒2024, as shown in Figure 4 [42]. In each quarter, an average of 212,000 patients received reimbursements via the national reimbursement scheme. In 2022, seven out of 10 medicines with the highest reimbursement expenditure were biological medicines, accounting for the expenditure of €218 million or 12% of all medicine reimbursements in 2022 [43]. Furthermore, biological medicines for which biosimilars were available accounted for the costs of €171 million and reimbursements of €151 million in 2023 [42].

Figure 4: Biological medicines in outpatient care in Finland in 2023 (Source: Statistics of the Social Insurance Institution of Finland 2024 [1-2])

Biological medicines may significantly benefit patients with diabetes or rheumatic diseases, for example, but they often come with high costs. These therapies are often reimbursed via a national reimbursement scheme and thus, biological medicines significantly contribute to reimbursement expenditure.

Savings can be achieved with active price competition of biological medicines

Figure 4 clearly shows the need for a higher uptake of less expensive biological medicines.  To change prescribing patterns, Finnish physicians were first obliged in 2017 by a decree to prescribe the least inexpensive version of a biological medicine, but no supervision nor sanctions were introduced at the time.  This measure did not increase the uptake of less expensive biologicalmedicines in outpatient care as expected. The shares of biosimilars prescribed remained modest, especially in insulins [44].

Savings can, however, be achieved by the introduction of less expensive biological medicines and with active price competition. In 2023, active price competition resulted in savings and enabled the treatment of more patients with adalimumab, golimumab and etanercept [42-43]. Examples of savings in 2023: paid reimbursements for adalimumab decreased 16%, while the persons receiving reimbursements increased 10% [42-43, 45]. The corresponding numbers were +0.6% and +4% for golimumab, and -15% and +4% for etanercept, respectively.

Finland introduced novel measures to support the uptake of less expensive biological medicines

As a cost containment measure, Finland introduced new measure to support the uptake of less expensive biological medicines in 2023 and in 2024, see Figure 5 [46-47]. Since 2023, physicians have been obliged by the law to select the least expensive biologicalproduct, except for patient or treatment-related causes, the Social Insurance Institution of Finland (SII) steers and supervises prescribing, [46-47]. In 2024, Finland introduced pharmacist-led substitution of all biological medicines except for short-acting insulins. Automatic substitution will be implemented in stages by 2026.

Figure 5: Measures to support the uptake of less expensive biological medicines in Finland since 2023

While the effects of pharmacist-led substitution remained unseen at the time of the symposium in December 2023, we have already seen the first results of the steering and supervision of the prescribing of biological medicines. For example, from April to November 2023, it was observed according to national SII data that 1,090 physicians prescribed biological medicines in which price differences between products existed [42, 47]. During the same period, a total of 6,000 prescriptions were prescribed and 52% (n = 3,100) of them were written for the least expensive product. Thus, almost half of the physicians (48%, n = 520) received a guidance letter from SII to steer their prescribing towards lower-price products. During this steering period from April to September in 2023, we observed an increase from 8% to 52% in the proportion of prescriptions with the least expensive alternative, keeping in mind that other factors may have affected the markets as well.

Although the effects of steering prescribing seem promising in the short term, the long-term effects of steering and automatic substitution on the prices, markets, availability and accessibility of biological medicines need to be investigated.

Conclusions and closing remarks

The symposium’s conclusions and closing remarks were delivered by Dr Hanna M Tolonen, Dr Kari Linden, and Dr Marja Airaksinen, Professor (Emerita) and Visiting Scientist in the Clinical Pharmacy Group, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland).

Biological medicines accounted for 12% of all Finnish medicine reimbursements in 2022. In 2023 and 2024, Finland introduced novel measures to support the uptake of less expensive biological medicines by the steering and supervision of physicians by the SII of Finland starting in 2023, and by pharmacist-led substitution of biological medicines excluding short-acting insulins starting in 2024. Medicines information enhances patients’ awareness and knowledge of biological medicines, treatment success, and outcomes, and pharmacies will continue to play an important role in this medicine information chain.

Biological medicine costs have stimulated a search for mechanisms to control these costs, with a lot of interest in using automatic substitution of biologicals in community pharmacies in Finland. The online symposium ‘Current Trends in Biosimilar Uptake and Research with Special Focus on Automatic Substitution’ took place in December 2023 and it reached a wide audience with lively discussions.

The symposium provided an overview of national preparations for the change, both from an international perspective and from domestic perspectives – including those of physicians, pharmacists, patients, and major third-party payors.

One of the key lessons learnt from organizing the symposium was that we need more events and discussion forums like this to share experiences and expectations between parties involved. Automatic biological substitution is a change that does not only concern community pharmacists, but it also concerns physicians and nurses, as well as patients who benefit from treatments with biological medicines. Therefore, implementation of change requires actions and coordination at the local and regional level to build up feasible structures and processes for positive clinical, humanistic and economic outcomes.

As a follow up, since December 2023 when the online symposium took place, community pharmacies started officially following the substitution of biologicals in April 2024 with enoxaparin products. However, the need for substitution of enoxaparin products has been low because of harmonization of prices of interchangeable products. More substitutions and savings are anticipated for the year 2025 when the substitution will extend to cover major groups of biological medicines users, such as adalimumab and etanercept users in January 2025, and insulin glargine users in April 2025.

Concerning preparations for the larger-scale implementation, community pharmacies have continued in-house preparations and training with the support of national stakeholders, such as the Association of Finnish Pharmacies and the Pharmaceutical Learning Centre.  Fimea released the first practical guidelines for substitution in 2024.

The progress of automatic substitution’s implementation will be continuously evaluated by research using, e.g. registers and safety incident reports. These can indicate needs for systemic changes in the substitution process to manage risks and optimize the process involving several actors and organizations.

Competing interests: Lyles A, Heinonen E, Sihvo S, Sarnola K, and Airaksinen M have no competing interests to declare. Tolonen HM received lecture fees from the Association of Finnish Pharmacies, and Pharmaceutical Learning Centre. Linden K received lecture fees from Viatris Oy, the Finnish Society for Rheumatology, the Pharmaceutical Learning Centre, and Pfizer Oy.

Provenance and peer review: Not commissioned; internally peer reviewed.

Authors

Marja Airaksinen, MSc (Pharm), PhD
Professor (Emerita), Visiting Scientist, Clinical Pharmacy Group, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
ORCID 0000-0002-6077-5671

Esa Heinonen, Docent (Drug Development), MD, PhD
Chair of the Heads of Medicines Agencies (HMA) Biosimilar Working Group, European Medicines Agency EMA
Senior Adviser, Finnish Medicines Agency (Fimea), Finland

Kari Linden, Docent, MSc (Pharm), MSc (Econ), PhD
Research Manager, University Pharmacy (Yliopiston Apteekki), Research Unit, Helsinki, Finland
ORCID iD: 0009-0008-8571-6804

Alan Lyles, ScD, MPH, PhD (h. c.), Fulbright Specialist
Henry A. Rosenberg Professor of Government, Business and Nonprofit Partnerships, College of Public Affairs, University of Baltimore, USA
ORCID: 0000-0003-2927-4489

Kati Sarnola, Docent (Pharmaceutical Policy and Pharmacoeconomics), MSc (Pharm), MSc (Econ), PhD
Senior Researcher, Social Insurance Institution of Finland (KELA), Helsinki, Finland
ORCID ID: 0000-0003-1300-7482

Sinikka Sihvo, Docent (Public Health), PhD
Health Policy Advisor, Finnish Medical Association (at the time of the Symposium)

Hanna M Tolonen, MSc (Pharm), PhD
Quality Manager, HUS Pharmacy, HUS Helsinki University Hospital, Helsinki, Finland
Visiting Scientist, Clinical Pharmacy Group, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
ORCID: 0000-0002-6824-7566

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Author for correspondence:: Alan Lyles, ScD, MPH, PhD (h.c.), Henry A. Rosenberg Professor of Government, Business and Nonprofit Partnerships, College of Public Affairs, University of Baltimore, USA

Disclosure of Conflict of Interest Statement is available upon request.

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