The Life Sciences Law Review: Netherlands

Introduction

Since the Netherlands is a Member State of the European Union (EU), it has implemented the European legal regimes on medicinal products and medical devices. The following chapter should therefore be read in conjunction with the chapter on the European Union.

Nationally, the regulation of medicinal products has been laid down in the Dutch Medicines Act, the Decree Medicines Act and the Regulation Medicines Act. The regulations on medical devices are covered by the Medical Devices Act, the Decree on medical devices and the Regulation on the Medical Devices Act.

The national competent authority in the Netherlands for medicinal products is the Dutch Medicines Evaluation Board (MEB), an independent administrative body. The MEB evaluates new medicines and acts as a gatekeeper. If new medicinal products need to be authorised by the MEB via the national or decentral procedure, the MEB shall assess the quality, efficacy and safety of such medicinal products.

With the exception of the competence of authorisations exclusively attributed to the MEB, the Dutch Health Care and Youth Inspectorate (IGJ) and the Dutch Food Safety Authority (NVWA) are other competent authorities supervising the Medicines Act.2

The Medical Devices Act, which came into force on 24 October 2019, is an implementation of the European Regulations 2017/745 and 2017/746. The Health Care and Youth Inspectorate is entrusted with the oversight and enforcement of the Medical Devices Act.

Furthermore, the Dutch National Health Care Institute (ZIN) has an advisory role in the content of the healthcare benefits package and the Dutch Health Care Authority (NZA) supervises healthcare providers and healthcare insurers and sets maximum prices for treatments in sectors that are subject to regulated prices.3 Some sectors, including the paramedic sector have deregulated rates and the NZA does not set maximum prices in these sectors.

This chapter provides a summary of the key concepts relating to regulation of medicinal products and medical devices in the Netherlands, where relevant: specifically, mentioning any (local) Dutch differences as compared to the European rules.

The regulatory regime

i Classification

Medicinal product

Pursuant to the definition of a medicinal product as set out above in the Medicines Directive, two criteria are essential: in Article 1 under 2A, the 'presentation criterium' and in Article 1 under 2B, the 'intended or actual function criterium'.

Medical device

An important factor in the classification of a medical device is the purpose as provided by the manufacturer to the device. This entails that when a device does not have a medical purpose, it should not be considered a medical device.4 In borderline cases, it depends on whether the medical device is supported by, for example, a medicinal product. If it is supported by a medicinal product, if falls under the scope of the Medicines Act; if not, it may fall under a specific Commodities Act Decree.

ii Non-clinical studies

In the Animal Testing Act, it has been laid down that it is prohibited to conduct animal testing without an institutional licence granted by the Minister.5 Such a licence may be provided to a company or organisation when the animal testing is aimed at aligning interests for both humans and animals and when it comes to obtaining better health or nutrition.6 Special rules apply with respect to experiments with non-human primates. Due to critical ethical reasons and the overall opinion of Dutch society, experiments with human primates are forbidden.7 In the past, only one temporary exception has been made regarding studies with respect to Hepatitis C vaccinations.

As to Good Laboratory Practice (GLP), the Medicines Act contains a dynamic reference to Directive 2004/10/EC (as amended).8 The IGJ supervises whether the company at hand complies with the rules as set out in the Medicines Act.

iii Clinical trials

The European Clinical Trial Directive has been implemented in the Act on medical-scientific research with human beings and the accompanying decree and regulation. The IGJ is the supervising authority and supervises and enforces the Act on Medical-Scientific Reserach with Human Beings (Wmom). The main focus is to ensure that trials are carried out safely and that the results of clinical trials are traceable, valid and reliable. As to insurance, Dutch legislation contains detailed rules set out in the Decree regarding insurance in clinical trials.

The Medical Devices Regulation 2017/745 (MDR) contains specific rules for submission, assessment and conduct of clinical investigations into medical devices. The Central Committee on Research Involving Human Subjects (CCOO) performs a pre-screening of all incoming documents. After screening the documents, they are sent to the (accredited) Medical Research Ethics Committee (MREC). The reviewing committee is either the CCOO or the MREC, who then, according to classification of the product, lead the clinical investigation.9

iv Named-patient and compassionate use procedures

Pursuant to the European Medicines Directive (Directive 2001/83/EC), the marketing of a medicinal product requires a marketing authorisation. However, the directive contains a few exceptions such as the named-patient and compassionate use procedure.

The named-patient arrangement falls under the capacity of the IGJ. The order has to be made on the initiative of a physician who deems it necessary that the patient is treated with this medicinal product. Furthermore, there should not be any adequate alternative in the Netherlands or otherwise available. The physician should lodge such request with the IGJ and the IGJ stipulates for what time period the medicinal product may be delivered with the physician. The manufacturer, wholesaler or pharmacy should keep a record in which the amount of the medicinal product, the name of the physician and the adverse events shall be registered.10

The compassionate use programme has been set out in Article 3.18 of the aforementioned regulation. A request should be lodged with the Medicines Evaluation Board (CBG-MEB), and it should be accompanied by a programme for the use of the medicinal product and, in case a marketing authorisation application has been lodged, a declaration to this end. The programme should (inter alia) contain: a motivation of the importance of making this medicinal product available; a description of the patient group concerned; and all available information as to the benefit from the risk-benefit assessment of the medicinal products. The MEB may request additional conditions, suspend or withdraw its approval of the compassionate use program.11

v Pre-market clearance

Advanced Therapy Medicinal Products (ATMP) are a different group of medicinal products for somatic cell therapy, gene therapy and tissue engineering.12 ATMPs require a marketing authorisation granted by the European Medicines Agency (EMA).13 An exception is the 'hospital exemption'. The IGJ has to approve the preparation and use of the products used under the hospital exemption. Recently, the IGJ suggested discussing with them beforehand and requesting a 'pre-meeting'. After this, a formal application form may be lodged. The application procedure takes a maximum of six weeks. The approval is granted for a limited number of treatments or batches and for the duration of one year maximum.

vi Regulatory incentives

The regulatory data exclusivity of eight years has been laid down in the Medicines Act. During this period, generic and biosimilar applications may not file a marketing authorisation. Furthermore, there is an additional market protection of two years. This 10-year period may be extended by one year if a new therapeutic indication has been obtained.

The Supplementary Protection Certificate (SPC) provides the option to have additional protection for medicinal products and for pesticides.14 In general, the validity of the SPC follows the validity of the patent. Furthermore, there must be a marketing authorisation for the medicinal product. This means that if the patent is invalid, this also goes for the SPC. The marketing authorisation holder may apply for a SPC with the Patent Centre Netherlands.

Other rewards and incentives provided by way of European law, such as with respect to orphan medicinal products, obviously also apply in the Netherlands.

vii Post-approval controls

In the Netherlands, the IGJ has the task of supervising and enforcing the Medicines Act, which contains rules pertaining to pharmacovigilance, including good pharmacovigilance practice (GPP). Violations of the statutory provisions may lead to administrative fines, whereas infringements of GPP may lead to, for example, critical findings. The IGJ is bound by the policy rules on administrative fines.15

Device vigilance is also overseen by the IGJ. With the implementation of the MDR, the rules regarding device vigilance have become more strict. The Dutch rules regarding medical devices for one-time use only lay down that the re-use of one-time use medical devices may be allowed under some strict rules.16

Finally, the CBG-MEB may suspend or withdraw marketing authorisations. This may have to do with the (im)balance between the benefits and the risks of a medicinal product.

viii Manufacturing controls

If a medicinal product is imported from third countries, such as from outside the European Economic Area (EEA), or the medicinal product is manufactured in the Netherlands, a manufacturing and import licence (MIA) is required. If a medicinal product is 'imported' from another EU Member State, or distributed in the Netherlands, only a Wholesale Distribution Authorisation (WDA) is required The Minister of Health grants these licences and applications are handled by Farmatec, which is part of the Dutch Ministry of Health.

The IGJ is also the supervising authority as to manufacturing and wholesale distribution activities, such as good manufacturing practice (GMP) and good distribution practice (GDP).

Pharmaceutical companies are subject to on-site inspections by the IGJ. MIA, WDA, GMP and GDP certificates are to be found in the EudraGMDP database.17

ix Advertising and promotion

The EU rules on advertising and promotion of medicinal products as set out in Directive 2001/83/EC (as amended) have been implemented in Chapter 9 of the Dutch Medicines Act. Advertising a medicinal product for which no marketing authorisation has been granted is explicitly prohibited. Non-compliance with these rules may lead to a high administrative penalty. The exact amounts have been set out in the aforementioned policy rules.18

In the Netherlands, the rules on pharmaceutical advertising are being supervised by way of self-regulation via the Code of Conduct on Pharmaceutical Advertising.

When it comes to medical devices, the rules regarding advertisement and promotion are less strictly regulated when compared to medicinal products. However, just like medicines, there is a code for medicinal products, that is, the Code of Conduct for Medical Devices. This code contains rules regarding advertisement and inducements between suppliers of medicinal products and parties involved in their procurement or application.19

x Distributors and wholesalers

Distributors and importers of medicinal products from Member States of the EU require a WDA. When medicinal products are imported from outside the EEA, a manufacturing authorisation is required.

When in possession of a WDA, medicinal products may be distributed to pharmacists, general practitioners (GPs) holding a pharmacy and other distributors who are also in the possession of a WDA.

The Dutch authority that deals with the requests for this authorisation is the Minister of Health, Welfare and Sports, CIBG, Farmatec.

xi Classification of products

Medicinal products may be divided into four categories: generally available (AV), prescription-only (PO), pharmacy-only (UA) and pharmacies and drugstores-only (UAD). The Dutch CBG-MEB decides which drug belongs into which category.

xii Imports and exports

The Dutch regulations governing the import and export of medicinal products reflect those at EU level.

xiii Controlled substances

Controlled substances are scheduled on either List I (hard drugs) or List II (soft drugs) of the Opium Act. Any action (growing, possession, selling, preparing) with such substance is prohibited unless an Opium Act exemption has been granted.

Lastly, there is a legislative proposal in the Netherlands introducing a new category of controlled substances that are to be placed on the soon to be introduced List Ia. The category of controlled substances concerns 'designer drugs' and these have been described in a dynamic way (e.g., derivatives of 2-fenethylamin). Also, see Section VIII.

Interestingly, the legislative proposal lays down that manufacturers or wholesalers of (List Ia) Active Pharmaceutical Ingredients (API) are exempted from obtaining an opium exemption, as they already fall under the scope of pharmaceutical laws. This discloses how the hierarchy between the European pharmaceutical legislation and the national Opium Act is perceived by the Dutch legislator.

xiv Enforcement

The IGJ supervises and enforces the Medicines Act and accompanying acts, regulations and decrees. The IGJ is competent to impose an administrative fine, recall medicines, confiscate or (temporarily) prohibit the sales in case of violations of the Medicines Act.

Furthermore, the IGJ also supervises the 'collegial delivery of compounded preparations', entailing medicinal products that have been compounded by a pharmacy and are then delivered to other pharmacies that may not have the ability to prepare those medicinal products themselves. The Medicines Directive prohibits this practice, as such medicinal product should have obtained a marketing authorisation. The IGJ has issued a Circular Note20 explaining in which cases collegial delivery is allowed; for instance, when there are no other adequate authorised medicinal products at hand and there is a medical need. The medicinal products should be compounded under GMP.

Pricing and reimbursement

i Pricing

In the Netherlands, the legal framework for the pricing of medicines is set by the Medicines Prices Act, the Health Insurance Act and the Healthcare Market Regulation Act.

Initially, the manufacturer of medicines decides on the price in accordance with the maximum prices set by the government.

Maximum prices are set by the Minister of Medical Care in a ministerial regulation and are based on the average of the prices of comparable medicine in the 'reference countries', aiming to bring the price level closer to the European average price level.21

Currently, the reference countries are Belgium, France, Norway and the United Kingdom.22 The appendix of the Regulation of Maximum Prices of Medicines consists of the maximum prices per medicine and per ml/piece. These prices are established twice a year by Farmatec, a section of the CIBG, an executive organisation of the Ministry of Health, Welfare and Sport.

In addition, the Dutch Healthcare Authority is entrusted with price and performance regulation in healthcare.23 This also includes the price and performance regulation of pharmaceutical care. The performance regulations of pharmaceutical care act as a basis for negotiations between health insurers and pharmaceutical caregivers.24

Furthermore, the Authority for Consumers and Markets (ACM) is tasked with regulating the competition in markets, including the healthcare market. The ACM is proficient in monitoring excessive prices of prescription-only medicines in the pharmaceutical industry.25

ii Reimbursement

Health insurance is mandatory in the Netherlands and the basic care package is determined by the government. There is a distinction between extramural pharmaceutical care on the one hand, which is characterised by a closed system with a positive list of reimbursed medicines and intramural pharmaceutical care on the other hand. Authorised medicines are eligible for reimbursement if they are listed in the Medicine Reimbursement System and are on the appendix of the Health Insurance Regulation. This regulation divides medicines in groups of mutually replaceable medicines and determines how the limits of reimbursement are calculated.26

In the Medicine Reimbursement System, medicinal products are either listed in Appendix 1a or Appendix 1b. Medicinal products that are mutually replaceable are clustered in group a and are listed in Appendix 1a, whereas non-mutually replaceable medicinal products are listed in Appendix 1b. Medicinal products are considered to be mutually replaceable if they are useable for the same indications, have the same route of administration and are intended for the same age group.27

Appendix 1a is characterised by a reimbursement limit, whereas Appendix 1b does not have a reimbursement limit. If the reimbursement of medicinal products requires additional conditions, these products are listed in Appendix 2 of the Health Insurance Regulation, aiming to induce effective use of these medicinal products.28

On the other hand, the reimbursement of intramural medical care is characterised by the notion of 'the established medical science and medical practice'. Expensive medicines can be placed in the 'lock chamber'. The Minister of Medical Care is then entrusted with negotiating the price of the pharmaceutical product. There is no delimitation in time in which a medicinal product can be held in the lock chamber, and as a result it can be uncertain when an expensive medicinal product is eligible for reimbursement.

Lastly, The National Healthcare Institute performs Health Technology Assessment and has an advisory role in the reimbursement of medicine.29

In the Netherlands, a preference policy for medicinal products is wielded. Health insurers may indicate a preferential medicinal product in a group of mutually replaceable medicinal products that are designated by the Minister of Health, Welfare and Sport. The health insurer only has to reimburse the preferential medicinal products, unless the non-preferential medicinal product is medically necessary for the patient.30

Of all the active substances mentioned in the ministerial regulation, at least one medicinal product must be available for reimbursement.31 In a recent judgment, the Dutch Supreme Court ruled that if multiple medicinal products with the same active substance, but differences in dosage or strength are mentioned in the ministerial regulation, health insurers also have the discretionary power to select one dosage or strength of the medicinal product. Physicians are still able to prescribe a non-preferential dosage or strength of the medicinal product if such use can be medically justified for the patient.32

Administrative and judicial remedies

The MEB, IGJ, ACM, Dutch Health Care Authority and the National Health Care Institute are administrative bodies and therefore administrative law is applicable.

If an interested party does not agree with the decision of an administrative body in the Netherlands, he or she may object with the administrative body. However, a notice of objection needs to be submitted within six weeks after the decision, under penalty of inadmissibility. If the governing body upholds its decision, the interested party may lodge an appeal, within six weeks after the governing body posted the decision, with the administrative law department of the district court. If the court does not rule in favour of the interested party, the party may appeal, in accordance with the appendix of the General Administrative Law Act, to the administrative law department of the Council of State.33

The General Administrative Law Act also regulates the relative competence of the administrative law department of the district court. If the interested party lodges an appeal against a decision of a Minister and the interested party does not have a registered office in the Netherlands, the administrative law department of the district court of the Hague is exclusively competent.34

Financial relationships with prescribers and payers

To promote innovation, cooperation between the pharmaceutical industry and healthcare professionals is essential. However, the financial relationships between these parties may have a negative effect on the patient's perception of impartial healthcare. Therefore, the Dutch Central Transparency Register (DCTR) was created in April 2013, providing insight into financial relations between the pharmaceutical companies and the prescribers of medicine, as well as the medical devices sector.

The DCTR contains information about the financial transactions of the parties regarding service agreements, sponsoring agreements and individual hospitality.35 It does not contain information about clinical research or financial ties that do not exceed the threshold of €500 a year.

The DCTR is characterised by a self-regulatory regime and therefore has no formal basis in Dutch legislation. It is built around the engagement of the pharmaceutical and medical devices industry through the Pharmaceutical Advertising Code and the Code of Conduct Medical devices, binding its stakeholders through membership.36

In March 2020, the legislative proposal Transparency Register Care was submitted by Dutch member of the House of Representatives Lilianne Ploumen. This legislative proposal aims to amend the Medicines Act, the Medical Devices Act and the Individual Healthcare Professions Act, resulting in a formal legal basis of a mandatory public register that would monitor financial relationships between the pharmaceutical industry and the medical devices industry on the one hand and healthcare professionals on the other.37 All transactions between pharmaceutical companies and healthcare professionals exceeding the threshold of €50 must be reported if the legislative proposal will enter into force. This legislative proposal is currently still in the preparation phase.38

Special liability or compensation systems

In the Netherlands, there is no legislation specifically designed to compensate people injured by medicines or medical devices, besides legislation based on the Council Directive on the approximation of the laws, regulations and administrative provisions of the Member States concerning liability for defective products (85/374/EEC). These provisions have been implemented into provisions 6:185-6:193 of the Dutch Civil Code. It concerns a strict liability. Furthermore, Article 6:77 of the Dutch Civil Code has laid down that the person using an unsuitable ancillary item, such as a medical device or a medicinal product, is also strictly liable.

Furthermore, Article 6:162 of the Dutch Civil Code on the wrongful act could also entail liability for medical devices and medicinal products, especially when the limitation periods based on product liability have lapsed.

Transactional and competition issues

i Competition Law

The European legislation on the prohibition of cartels and the abuse of a dominant economic position is directly implemented in the Dutch Competition Act. The Authority for Consumers and Markets is the competent body to enforce action when cartels or an abuse of a dominant position are suspected. The ACM also assesses joint ventures and mergers after a report is filed. As the ACM is tasked with enforcing action to improve competition, it has the power to impose fines when an infringement is observed.

In July 2021, the ACM imposed a fine of €19,569,500 on the pharmaceutical manufacturer Leadiant based on an infringement of the abuse of a dominant position, as a result of the excessive prices of CDCA-Leadiant, which was prescribed to patients with a chronic metabolic disease. Leadiant applied for an orphan drug status for the drug, which had been used for another indication for a long time and raised the price of CDCA-Leadiant to €14,000. The ACM concluded that the excessive price was not attributable to the costs of producing the drug, to the costs of the attainment of orphan drug status, or to the costs of attaining the marketing authorisation. In addition to their dominant economic position, the ACM ruled that Leadiant violated the Dutch competition rules.39 Leadiant has announced an objection to the decision of the ACM, but it is unknown what the outcome of this objection is and if Leadiant will lodge an appeal.

ii Transactional issues

In 2020, mergers and acquisitions in the life sciences sector in the Netherlands have slightly increased, despite the impact of the covid-19 pandemic. The international transactions remained on the same level as that of 2019 and the life sciences sector accounted for 23 deals, including 17 deals attributable to biotech companies.40

Current developments

i Compulsory licensing

As a response to the covid-19 crisis and in particular the patents on covid-19 vaccines, a legislative proposal has been submitted in April of 2021, aiming to amend the Dutch Patent Act 1995. Currently, the Minister of Economic affairs has the power to issue a compulsory licence if it serves the public interest. However, in this legislative proposal, the Dutch Minister of Health, Welfare and Sport (instead of the Minister of Economic Affairs) will become competent to grant a compulsory licence for a pharmaceutical product during a crisis or emergency.41

The goal of the proposal is to create a legal basis to induce the pharmaceutical companies with patent rights to lower their prices, improving the availability of the medicines.42

The proposal is currently under consideration in the Dutch House of Representatives and as a result of this proposal, pharmaceutical companies may be obligated to tolerate an impairment on their patent rights in the foreseeable future.43 However, the court shall be requested to assess whether compensation is reasonable.

The legislative proposal is furthermore questionable as it seems in violation of European law as to data and market exclusivity.

ii The Opium Act

Currently, the Dutch Opium Act regulates the prohibiting of the production, possession and sale of controlled substances. It consists of two Schedules, typically dividing the substances by severity of damage on the health of the user.

In April of 2020, a legislative proposal was drafted, aiming to adjust the Opium Act: The Decree Opium Act and the Regulation Execution Decree Opium Act. The adjustment of the Opium Act will consist of the addition of a list (Ia) of substance groups instead of individual substances, aiming to help act proactively on the rapid innovations in the drug industry. The substance groups, namely 2-phenethylamine, cannabimimetics or synthetic cannabinoids and 4-aminopiperidine will be prohibited under the new legislative proposal and all (new) derivatives will be prohibited as well.44

This legislative proposal has finished consultation and thereafter an advice of the Council of State will presumably be drafted.45 After this, the Dutch House of Representatives will address the legislative proposal before it will be handed to the Senate. If the Senate rules in favour, the law will be ratified, published and will come into force. Also, see Section II.xiii.

iii Pilot parallel procedures

The Dutch Medicines Evaluation Board, which is responsible for the authorisation of new medicines, and the National Health Care Institute, which is tasked with reimbursement, joined forces in the pilot parallel procedures to improve the availability of innovative medicines in the Netherlands.46 This pilot redefines the procedures that are necessary for the registration and reimbursement of medicines by letting the different procedures run parallel to one another to shorten the timespan from registration to reimbursement.

Marketing authorisation holders can register their medicine for the pilot themselves. Currently, seven marketing authorisation holders have enrolled in the pilot and three medicines have effectively completed the parallel procedure. By means of the parallel procedure, The National Health Care Institute was able to review the reimbursement of the three medicines rapidly, fulfilling the goal of the pilot. Unfortunately, it is unclear how much time was approximately saved with the parallel procedure. The project is expected to continue until the end of 2021.

Footnotes

1 Hanneke Later-Nijland is a partner at Genome Lawyers.

2 Article 100, Medicines Act.

3 Article 16, Paragraph a, Health Care Market Regulation Act.

4 Snoek, T&C Health Law, comment on Article 1 Medical Devices Act.

5 Article 2 of the Act on Animal Tests.

6 Kamerstukken I 1975/76, 10 589, pp. 7-8 (MvT).

7 Lexplicatie, Introduction to Animal Testing Act.

8 Article 100d Medicines Act.

9 Leidraad MDR: Review of a clinical investigation with a medical device – guidance document for MRECs, p. 24.

10 Article 3.17 Regulation Medicines Act.

11 Article 3.18 Regulation Medicines Act.

13 Regulation (EC) 1394/2007.

14 Regulation (EC) 469/2009.

16 Article 23(3)(d–e) Medical Device Act.

18 Appendix to the Ministry of Health, Welfare and Sport's Penalty Policy Rules 2019: Medicines Act.

22 ibid.

23 Dutch Healthcare Authority: www.nza.nl/over-nza/wat-doet-de-nza.

26 See footnote 20.

30 Article 2.8, Paragraph 4, Health Insurance Decree.

31 Article 2.8, Paragraph 3, Health Insurance Decree.

32 Dutch Supreme Court 9 July 2021, ECLI:NL:HR:2021:1111.

33 Or, in some cases, to the Board of Appeal for Business or the Central Board of Appeal.

34 Article 8:7, Paragraph 2, General Administrative Law Act.

35 Transparency Register Care: www.transparantieregister.nl/homepage/zoek-uw-zorgaanbieder/wat-is-wel-en-niet-geregistreerd. A financial relationship regarding hospitality must only be disclosed in the DCTR if mandatory according to the Pharmaceutical Advertising Code.

37 Explanatory memorandum of legislative proposal 35410.

40 D Enklaar and M van Thiel de Vries, Healthcare & Life Sciences M&A onderzoek 2020, Amsterdam: February 2021. www.deloitte.com/content/dam/Deloitte/nl/Documents/life-sciences-health-care/deloitte-nl-healthcare-life-sciences-m-a-onderzoek-2020.pdf.

41 Explanatory memorandum of legislative proposal 35809.

42 ibid.

43 ibid.

44 Explanatory memorandum of legislative proposal of the amendment of the Opium Act.

46 National Health Care Institute:

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