Introduction

The global life sciences landscape has rapidly evolved during the past couple of years, thanks to developments in advanced healthcare technologies. Given that these developments are hardly limited to the Dutch life sciences landscape, and as it goes beyond the scope of this contribution to provide an exhaustive list of these advancements, a few of these will be touched upon here by way of an introduction.

However, two buzzwords that cannot be left out are machine learning and AI. The evolution and application of AI technology has led to some significant advancements in all kinds of medical fields. While developments can be seen in the application of AI in imaging techniques for radiology and pathology, the use AI has already reached even the consulting room of the general practitioner.

Another hot topic and a driving force of progress in healthcare is the field of molecular diagnostics. A recent development in this area concerns a method of analysing non-cellular DNA to look for genomic variants associated with hereditary or genetic disorders. These advancements provide attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring.

Although not necessarily new technologies, there has been a clear acceleration in the adoption of the use of telemedicine and remote monitoring technologies. Technologies such as blood pressure monitors and electrocardiogram (ECG) devices with remote monitoring capabilities enable patients to monitor their health from the comfort of their own homes while staying in contact with their healthcare providers. It is believed that the COVID-19 pandemic has greatly accelerated the adoption of these technologies. The same can be said for wearable devices with medical advantages (eg, smart watches and continuous glucose monitors). These devices provide users with real-time data on their health, as well as the option to share this data with their clinicians without even needing to visit the hospital.

Furthermore, the EU patent litigation landscape saw the greatest change in more than 50 years in 2023. This refers, of course, to the opening of the Unified Patent Court on 1 June 2023 and the option to acquire a unitary patent ‒ thereby creating a single approach to patent registration and litigation currently across 17 participating EU member states. Parties with patents in the life sciences space were eager to kick things off, leading the way in filing cases in the early weeks of the new court’s operation.

Now, following this brief introduction to trends that have affected the Netherlands to a more general extent, it is time to take a closer look at the specific developments in the Dutch life sciences sector: what is going well, what could be better, and in which direction it may be heading.

The Netherlands’ Position Within the EU Clinical Trials Ecosystem

Conducting clinical trials is an essential step in assessing the safety and efficacy of potential new drugs and vaccines. As such, clinical trials are a crucial link between research being done in the lab and the actual advantages it may bring to the patient. It is estimated that around 2,800 clinical trials are authorised each year in the EU/European Economic Area (EEA). So, how is the Netherlands performing in this field?

A recent report has shown that clinical research in the Netherlands is ranked at the top within the EU clinical trials ecosystem. The research was performed by a company called Citeline and focused on ‒ among other things ‒ the amount of clinical trials being performed per country, the quality and areas of research, and the robustness of its logistics.

The report shows that the Netherlands excels in clinical research in oncology, autoimmune diseases, rare diseases and nervous system disorders. Additionally, a relatively large amount of research in the Netherlands is conducted in the field of cardiology when compared with the surrounding countries ‒ the difference being 10% versus 7%. Moreover, the report demonstrates that the Dutch ecosystem harbours innovative leadership and robust infrastructure and logistics.

Besides harbouring a good healthcare system, the Netherlands has a ratio of 41 doctors per 10,000 people. Combined with a relatively large number of hospitals and a high population density, performing clinical research is relatively easier from a logistical standpoint in comparison with other countries. On top of that, the researchers working on clinical trials in the Netherlands are among the most cited scientists in the world (ie, third in Europe and seventh worldwide in 2022).

Naturally, there are areas in which the Dutch clinical trials system can improve. The report states that the Netherlands should more actively engage at international conferences, invest in skilled talent, streamline approval processes, improve key metric reporting and foster better academic‒industry collaboration. The Dutch Clinical Research Foundation has already stated work on a plan to implement these findings, which is scheduled to be published in April 2024.

M&A and Investments

The deals space in the Dutch healthcare sector has not been quiet. More activity was, however, expected as a result of the removal of certain thresholds for the approval of M&A in the healthcare sector. Such deals in many cases require prior approval from the supervising Dutch Healthcare Authority (DHA). In short, the test applied by the DHA verifies whether the intended merger or acquisition could have an adverse effect on the Dutch market ‒ be it for competition or the provision of care in general.

From 2018, specific lower turnover thresholds were in force for companies in the healthcare sector, with the effect that healthcare providers were more likely to meet the criteria of needing to seek regulatory approval before proceeding with a deal. As of 1 January 2023, the lower turnover thresholds were removed ‒ as a result of which, the generic higher turnover thresholds applied to healthcare providers, as they also apply in other economic sectors. This meant that, from that date onwards, considerably fewer M&A within the healthcare sector require regulatory approval.

Despite this change, there has not been an increase in the number of M&A within the Dutch healthcare sector. In the first half of 2023, 95 M&A took place, whereas a total of 170 deals took place in the same period of 2022. It is still unclear what has led to this noticeable difference. As in earlier years, most M&A occurred in the oral healthcare sector.

Private equity

What has increased is the influx of private equity in the Dutch healthcare sector. In 2019, about 50% of the investments in large healthcare institutions were done by private equity. By 2022, however, this percentage had increased to about 60% in total. Private equity has thus become a dominant force for transactions in the Dutch healthcare sector.

The desirability of this development is highly debated. Critics believe that providing care and making a return on investments do not go hand in hand and that healthcare can or may not be seen as a revenue-generating model. Proponents, however, believe that investors’ capital can actually be used to invest in improving healthcare, as private equity frequently also brings networks and knowledge to the market.

As a result of these discussions, research is currently being conducted to determine the effects of private equity on the Dutch healthcare landscape. The results of this research are expected to be presented by the end of the first quarter of 2024 and hopefully provide insights into the desirability of this development.

Dutch Inventors and the Patent Litigation Landscape

For such a small country, the Netherlands continues to make a name for itself when it comes to being a hub for innovation ‒ at least based on the number of patents filed by Dutch companies. In 2023, Dutch companies and inventors filed 7,033 EU patent applications, which is an increase of 3.5% compared to 2022. This increase also supersedes the average EU-wide increase of 1.5%. Patents in the medical technology field dominate among Dutch inventors ‒ although the chemical and biotechnology sectors also show significant growth.

Dutch patent litigators were, moreover, kept aptly entertained with regard to one specific topic in the past year. At conferences, in articles and in case law reviews, one topic was invariably on the agenda: the test of plausibility. In short, this test plays a role in patents where the issue is whether the patent makes sufficiently clear what the technical contribution of the invention is to the state of the art. After much litigation and uncertainty concerning the interpretation of this test, debate still persists among scholars and professionals. Naturally, the authors are following the developments on this topic closely.

However, the impression should not be given that there was a lack of attention on other patent cases at the Dutch courts. In fact, the number of patent cases that are being handled by the courts in The Hague shows a rising trend. After a record low of only 116 cases handled in 2021, presumably due to the COVID-19 pandemic, plaintiffs filed 149 new patent cases in 2022. Although not as high as the numbers in 2017, which rose to 172 cases in total, the trend upwards is a good sign of the value and persisting appreciation of the Dutch patent litigation system.

Kinks in the Supply Chain and the Option of Circularity

In the past two years, the Dutch pharmaceutical landscape has seen more issues with the availability of pharmaceuticals. In 2023, as a short-term solution to the shortages, the Dutch Medicines Evaluation Board (College ter Beoordeling van Geneesmiddelen, or CBG) and the Health and Youth Care Inspectorate (Inspectie Gezondheidszorg en Jeugd, or IGJ) granted permissions to pharmacists, manufacturers and wholesalers to import alternative products on a total of 140 occasions for 46 different drugs. In 2022, such permissions were granted in 132 instances for a total of 54 drugs.

In those two years, delay in production or release of end products caused more than half of all delivery problems. For long-term shortages, manufacturers reported that the problems were mainly due to a shortage of raw materials or long-term production issues. Specific to the global shortage of Ozempic was its off-label use as a weight-loss drug and the media attention this received. Recent articles (such as “CBG en IGJ: Beperkte Alternatieven Antibiotica voor Kinderen Beschikbaar” (CBG and IGJ: Limited Antibiotic Alternatives Available for Children), which was published in Pharmaceutisch Weekblad) have further stressed that there were limited supplies of alternatives to antibiotics for the treatment of children available, owing to shortages of liquid antibiotics.

As a result of these issues, Dutch Minister for Medical Care Pia Dijkstra has stated that she wants to lead the way in the debate on drug shortages with her position in the EU. In her announcement, Dijkstra has stressed that the Netherlands is a small country dependent on other countries for the supply of raw materials. Specifically with regard to the shortage of antibiotics for children, Dijkstra has called on Dutch producers of antibiotics to come forward to provide short-term relief for the shortages. In the long term, a team consisting of suppliers, pharmacists, wholesalers, health insurers and the Dutch Medicines Evaluation Board has been enacted to investigate how antibiotics should be distributed in the future.

Reissuance of drugs

Nonetheless, drug shortages could possibly be resolved via other methods. One of the suggested methods is to reissue unused drugs. In theory, it is possible to reissue drugs. In practice, however, drug reissuance is only allowed for use in scientific studies at the present time. Several obstacles, such as laws and regulations and the lack of a sustainable reimbursement system for reissuance, currently stand in the way. Various parties in the pharmaceutical supply chain are therefore exploring how these obstacles could be removed.

By way of example, a roundtable discussion was held, to which all parties in the chain ‒ from manufacturers to patients ‒ were invited. The conclusion was that there appeared to be a great incentive to join forces. As such, Dutch demissionary Minister for Health, Welfare and Sport Ernst Kuipers has sent a letter to the EC, pleading for EU law to be amended so that reissuance might be possible in the future.

In his letter, Kuipers drew particular attention to the Falsified Medicines Directive (FMD). Even though the FMD has proven effective in the fight against falsified drugs and is important to ensure the safe use of drugs in the European Union, he believes it is necessary to re-examine this EU Directive, given the current unprecedented drug shortages and the desire to combat the waste of drugs. Kuipers stressed that he does not want to tamper with the core of the FMD, nor does he advocate a large-scale reissue of all returned drugs. His main focus is the examination of the conditions under which reissuance is a safe and beneficial option. According to Kuipers, a sustainable approach to the pharmaceutical supply chain is indispensable in securing the future resilience of the Dutch healthcare system.

Prevention, Prevention, Prevention

Another notable trend in the Dutch healthcare landscape is the increasing move towards preventative care, rather than retrospective cure. The focus on prevention is an important means of keeping healthcare accessible and affordable. Earlier in 2024, two motions on medical prevention were adopted in the House of Representatives. These motions require the government to:

• propose ways in which budgets for new vaccines can better reflect positive opinions from the Dutch Health Council confirming the effect of the vaccine; and
• develop a set of tools that can quantify the broad costs and benefits of prevention in the short, medium and long term.

With these adoptions, the majority of the MPs have spoken out in favour of structural attention to the social benefits of (medical) prevention.

The same call to move towards prevention is being heard from the Dutch Hospital Association (Nederlandse Vereniging van Ziekenhuizen, or NVZ). Earlier in 2024, the NVZ handed over a consultation document entitled “Open Hospitals” to Pia Dijkstra. In this document, the NVZ identified pre-conditions that it believes are crucial to continue in order to enable accessible and quality care, such as:

• the recruitment and retention of sufficient healthcare professionals;
• appropriate funding;
• the realisation of good data exchange; and
• the removal of competition rules that hinder or delay co-operation.

Digitalisation is also frequently mentioned in the document as one of the solution-based approaches. As touched upon in the introduction to this article, the provision of hybrid or digital care will play an ever-increasing role in and is an important way of delivering care at home, be it via home monitoring or remotely ‒ thereby partly overcoming the issue of shortages of staff.

Beyond the political aspects of moving towards prevention, a new project involved in the development of antiviral drugs commenced in March 2024 at the Dutch Leiden University Medical Center. The aim of this new project, called PanViPrep, is to be able to better protect Europe in case of any following. The combined knowledge of the experts involved in the project cover the areas of virology, protein chemistry, medicinal chemistry, pharmacology and AI systems. The research project focuses on antivirals, as they can be developed with a broader possible effect than that of vaccines.

Forthcoming Developments

In the Netherlands, most drugs are reimbursed through the basic health insurance scheme. In recent years, there has been an uptick of very expensive drugs on the market and those that are intended to enter the Dutch market may temporarily be placed in the so-called lock system. Once there, the Dutch National Health Care Institute assesses whether the new and expensive drug is effective, complies with the standards of science and practice, and has a proportionately reasonable price. Following the assessment, the Health Care Institute advises the Minister for Medical Care whether or not to admit the drug to the insured package under certain conditions. The Minister for Medical Care may then decide to negotiate the price with the manufacturer and decide whether to reimburse the drug though the national insurance scheme.

Duing the next two years, the number of drugs being placed in the lock is expected to rise sharply. Besides autonomous growth in the number of “locked” drugs, the proposed adjustment of the lock criteria – to essentially lower the price threshold for a drug to be in scope for placement in the lock – is seen as a reason why pressure on the lock system might be increased in the coming years. However, it has been shown that the lock system does have an overall positive effect on the Dutch national healthcare system.

Duration reimbursement process

To provide insights regarding the status of drugs that are put in the lock system, the Ministry of Health, Welfare and Sport launched the Dashboard Doorlooptijden Geneesmiddelen (“the Dashboard”). The Dashboard provides patients, prescribers and drug manufacturers insight into which stage of the reimbursement process (submission, review or negotiation) expensive new drugs are at.

Horizon Scan

Further insights with regard to the pharmaceutical landscape have been provided by the publishing of the new Horizon Scan by the National Health Care Institute in late 2023. The Horizon Scan maps the potential impact of new drugs on patient treatment and healthcare costs. In addition, the Horizon Scan monitors indication extensions for existing drugs. This provides patients, practitioners, hospitals, health insurers and government bodies with early information on developments in the field of these drugs.

The Horizon Scan shows that, before the end of 2025, 104 indication extensions and 83 new drugs are expected to enter the market for various cancers (mostly lung and breast cancers). It is also notable that more than 10% of the drugs expected to receive European Medicines Agency approval in the next two years will be gene, cell and tissue therapies.

Long-Term Outlook

In conclusion, it is worth looking a bit further ahead to what is expected to happen in the Dutch life sciences landscape.

Vision for first-line care

Dutch Minister for Health, Welfare and Sport Conny Helder has presented the Primary Care Vision 2030 to the House of Representatives. The aim of the Primary Care Vision 2030 is to strengthen the organisation of primary care, assuring that care will always accessible to everyone who needs it. In addition to contributions from the Patient Federation Netherlands, the Royal Dutch Pharmacists Association (Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie, or KNMP), the Netherlands Society of General Practitioners, the Federation of Medical Specialists, Health Insurers Netherlands and Social Work Netherlands (among others), the input from citizens’ platforms proved very helpful in shaping the Primary Care Vision 2030 document.

The main aims of the Primary Care Vision 2030 document can be summarised as follows.

• The co-operating parties will work together in the coming years to reduce the unwanted pressure on primary care and better prepare and guide patients to primary care.
• Capacity within primary care should also be better utilised by organising tasks differently where necessary.
• There will be a point of contact for primary care in the region and a 24/7 infrastructure for crisis situations.
• Healthcare professionals want more sustainable co-operation within primary care, both between primary care and other domains and between primary care and its financiers. The focus here will be less on competition ‒ co-operation and contracting should be based more on continuity and mutual trust.

A total amount of EUR104 million has been made available for the programme to be implemented according to what the parties have set out in the Primary Care Vision 2030 document before 2026. It has been agreed that a number of concrete scenarios for the bolstering of primary care will be worked out before the summer of 2024.

Vision for future-proof long-term care

In addition to plans for primary care, plans are also being made to ensure a sustainable system for long-term care. Demand for this type of care is high and continues to grow under the pressure of an ageing population. For this purpose, the Dutch Care Assessment Centre (Centrum Indicatiestelling Zorg, or CIZ), the National Health Care Institute, the DHA and the Dutch Central Administration Office set out ‒ in a joint work agenda ‒ to tackle the steps needed to keep long-term care available in the future. The four areas in which the stakeholders believe the system of care and welfare should be adjusted can be summarised as follows.

• A patients’ social network currently does not play a role in the Long-Term Care Act (Wet langdurige zorg, or Wlz). This should be incorporated.
• The Wlz should remain available for the most vulnerable ‒ meaning that, if appropriate care and support for others can be well established in other domains, this should be possible and preferably encouraged.
• In several regions of the county, the availability of healthcare is already constrained ‒ for example, owing to a greater presence of elderly patients in that region. The agenda sets out to think of solutions to help with distribution issues in regions with scarcity.
• Lastly, the agenda sets out to explore how to reduce complexity in the care/system with the Ministry of Health, Welfare and Sport.

These four themes will be fleshed out in the coming period.