Pharmaceuticals

The principal national legislation governing pharmaceuticals in the Netherlands is the Medicines Act (Geneesmiddelenwet). The Medicines Act regulates matters such as marketing authorisations, the classification of medicinal products, supply and prescription, labelling and package leaflets, advertising, and enforcement. In addition, the Medicines Act Regulations (Regeling Geneesmiddelenwet) and the Medicines Act Decree (Besluit Geneesmiddelenwet) are also relevant.

Directive 2001/83/EC has been implemented into the Medicines Act, together with other relevant EU legislation. Furthermore, the Individual Healthcare Professions Act (Wet op de beroepen in de individuele gezondheidszorg, Wet BIG) regulates certain aspects of the prescribing of medicinal products. Other relevant legislation includes (i) Regulation (EC) No 726/2004, (ii) the Pharmaceutical Pricing Act (Wet geneesmiddelenprijzen), and (iii) the Healthcare (Market Regulation) Act (Wet marktordening gezondheidszorg, Wmg) and the Healthcare Insurance Act (Zorgverzekeringswet, Zvw), which contain rules related to enforcement and reimbursement of (amongst others) medicinal products and medical devices.

Medical Devices

Medical devices are governed by EU law, more specifically the Regulation (EU) 2017/745 (Medical Device Regulation, MDR) (for in vitro diagnostics: Regulation (EU) 2017/746 (In Vitro Diagnostic Regulation, IVDR)). These regulations do not require transposition into Dutch law, as they have direct effect.

National legislation on medical devices is laid down in the Medical Devices Act (Wet medische hulpmiddelen). The Medical Devices Act also regulates national competences and enforcement. In addition, the Medical Devices Decree (Besluit medische hulpmiddelen) and the Medical Devices Regulation (Regeling medische hulpmiddelen) are relevant. Other relevant legislation includes, inter alia, the Wmg and Zvw.

Regulatory bodies governing medicinal products and medical devices

There are various regulatory bodies responsible for overseeing the application and enforcement of the aforementioned legislation.

• The Minister of Health, Welfare and Sport (MoH) is responsible for the overarching pharmaceutical policy (eg, pricing of authorised medicinal products).
• The Medicines Evaluation Board (MEB, College ter Beoordeling van Geneesmiddelen) is responsible for assessing medicinal products, monitoring adverse reactions and risks and promoting the proper use of medicinal products.
• Farmatec (an implementing organisation of the Ministry of Health, Welfare and Sport) is responsible for, amongst others, granting medicinal products authorisation, registration of certain medical devices, issuing certificates for the purposes of export of medicinal products, and setting maximum prices for medicinal products.
• The Dutch Health Care and Youth Inspectorate (IGJ) is tasked with the oversight and enforcement of inter alia the Medical Devices Act and the Medicines Act
• The Dutch Healthcare Authority (Nederlandse Zorgautoriteit, NZa) is tasked with market regulation as well as the supervision of compliance with, inter alia, the Wmg and Zvw.
• The Dutch Competition Authority (Autoriteit Consument & Markt, ACM) is responsible for the oversight of compliance of competition laws, including the markets of medicinal products and medical devices.
• The National Healthcare Institute (Zorginstituut Nederland, ZIN) has an advisory role in relation to the reimbursement of care.
• There are various notified bodies responsible for assessing whether medical devices (of a certain class) satisfy the necessary legal requirements allowing them to be marketed throughout the European Union. These are DEKRA, BSI and Kiwa Dare and Scarlet.

Legal nature and autonomy

The MoH, ZIN, ACM, IGJ and NZa are governmental bodies. The ACM, IGJ, MEB, ZIN and NZA are considered an autonomous administrative authority (zelfstandig bestuursorgaan, ZBO). A ZBO holds a specific position within the central government, as they (i) are not part of any ministry and therefore independent, (ii) exercise public authority and (iii) not hierarchically subordinate to a specific minister.

In general, decisions by the regulatory bodies (eg, a decision to not grant a marketing authorisation or a decision to impose an administrative fine on a marketing authorisation holder) are considered administrative decisions and are governed by the General Administrative Law Act (Algemene wet bestuursrecht, Awb).

These decisions can be challenged by interested parties, within a specific period of time.

• The initial decision by a regulatory body must be objected to within six weeks of notification thereof. The regulatory body is, in principle, obligated to decide on the objection within 12 weeks after the objection has been submitted, but may postpone this period.
• Within six weeks of the date of the objection decision, an appeal may be lodged against such decision with the competent court.
• Within six weeks of the date of a judgment by the competent court an appeal may be lodged with the highest administrative court.

Other regulated markets and/or products have similar (administrative) procedures, as these markets and/or products are typically also under the supervision of a governmental body.

For the sake of completeness: if, for instance, damages are suffered as a result of an unlawful decision by the regulatory body, a claim can also be initiated with the civil court. 

Pharmaceuticals

In the Netherlands, a distinction is made between prescription-only medicines and over-the-counter (self-care) medicines.

Certain medicinal products may only be supplied on prescription; these are referred to as prescription-only medicines (UR geneesmiddelen). The Wet BIG specifies which healthcare professionals are authorised to prescribe medicines. These include physicians, dentists, midwives, physician assistants, and nurse specialists. In addition, certain specialised nurses are authorised to prescribe medicines, namely nurses specialised in diabetes mellitus, oncology, and asthma and COPD.

The MEB determines whether a medicinal product requires a prescription. In addition, there are over-the-counter (self-care) medicines, which may be purchased without a prescription from pharmacies, drugstores, supermarkets, or petrol stations. Some over-the-counter medicines are available in the Netherlands exclusively through pharmacies, as it is considered important that a pharmacist provides appropriate advice on their use (UA geneesmiddelen). Other self-care medicines may be sold through pharmacies and drugstores only (UAD geneesmiddelen), while certain self-care medicines may also be sold in supermarkets and petrol stations (AV geneesmiddelen).

Medical Devices

Pursuant to the MDR, medical devices in the Netherlands are classified into Classes I (lowest risk), IIa, IIb and III (highest risk), taking into account the intended purpose designated by the manufacturer and the inherent risks associated with the device.

Pursuant to the IVDR, devices are classified into Classes A (lowest risk), B, C and D (highest risk), taking into account the intended purpose and the inherent risks associated with the device.

EU law and domestic laws regulate clinical trials of medicinal products and medical devices. In the Netherlands, the primary regulatory framework for clinical research involving medicinal products is the Clinical Trials Regulation (EU) No 536/2014 (CTR). For research involving medical devices, the MDR is the main framework, while research involving in vitro diagnostic devices is mainly governed by the IVDR.

In the Netherlands, the Medical Research Involving Human Subjects Act (Wet medisch-wetenschappelijk onderzoek met mensen, WMO) is the principal law in this field.

Notably, for clinical trials using genetically modified organisms (GMOs) the Genetically Modified Organisms (Environmental Management) Decree (Besluit genetisch gemodificeerde organismen milieubeheer) and Genetically Modified Organisms Order (Regeling genetisch gemodificeerde organismen) are relevant.

In addition, several other laws, decrees, and regulations may also apply, such as the Embryos Act, the Medicines Act, the Decree on Mandatory Insurance for Medical Research Involving Human Subjects 2015, the Regulation on Medical Research Involving Human Subjects, and the Declaration of Helsinki.

Pharmaceuticals

Clinical trials with medicinal products may fall within the scope of CTR, and the WMO. The Centrale Commissie Mensgebonden Onderzoek (CCMO) is responsible for the implementation and oversight of the WMO in the Netherlands. The CCMO also designates the Medical Research Ethics Committees Medisch Ethische Toetsingscommissie(s) (MREC) that are authorised to review medical-scientific research involving human subjects.

As of 31 January 2023, all new applications for clinical trials with medicinal products must be submitted via the centralised EU portal, the Clinical Trials Information System (CTIS). The sponsor proposes one member state to act as the reporting member state. The reporting member state will then carry out a validation of the application. CCMO carries out this procedure in the Netherlands. After the validation procedure is complete, the evaluation of the application is commenced. This consists of two parts:

• Part I concerns an assessment as regards, inter alia:
1. whether the clinical trial is a low-intervention clinical trial;
2. the anticipated therapeutic and public health benefits;
3. the risks and inconveniences for the subject; and
4. compliance with the relevant requirements concerning:
1. manufacturing and import of investigational medicinal products; and
2. labelling.
• Part II concerns an assessment of the application in relation to, for instance, compliance with the relevant:
1. informed consent requirements;
2. requirements regarding arrangements for rewarding, compensating and recruitment of subjects; and
3. applicable rules for the collection, storage and future use of biological samples of the subject.

For both Part I and Part II, the CTR provides strict timelines. Indeed, after an application by the sponsor, CCMO shall validate the application within ten days. Once the application is validated, CCMO has to provide the assessment report for Part I within 45 days from the validation date. This period can be extended under certain conditions. In terms of Part II, the evaluation report must be submitted within 45 days of validation. The final decision to authorise the clinical trial will have to be made within five days after the conclusion of the assessment period.

Medical Devices

Article 62 MDR sets out the general rules as regards clinical investigations conducted to demonstrate conformity of devices. Article 70(1) indicates that the sponsor of a clinical study must submit an application to the member state(s) concerned, accompanied by the documentation, such as (inter alia): (i) an application form containing a variety of data (eg, name, address, title of the clinical investigation, etc); (ii) an investigator’s brochure containing clinical and non-clinical information on the investigational device; and (iii) the clinical investigational plan setting out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation.

All applications must be submitted via the Research Portal of the CCMO, until the relevant modules of EUDAMED become fully operational. The application procedure depends on whether the application concerns clinical investigations in the context of conformity purposes (Articles 62 and 74(2) MDR), other clinical investigations (Article 82 MDR) or post-market clinical follow-up investigations (Article 74(1) MDR).

• Conformity: The research file will first be validated by CCMO. Indeed, CCMO will review whether the clinical investigation falls within the scope of the MDR and whether the research file is complete (this check is merely administrative; CCMO will not perform a substantive assessment on the completeness). In case of a negative validation, the sponsor can file an objection to CCMO. After a positive decision on the validation, CCMO will transfer the applicant’s file to the review committee (either an accredited MREC or CCMO) for assessment.
• Other Investigations and Post-Market Follow-Up: For other investigations or post-market follow-up investigations, the applicant can submit the file via the Research Portal, after which the file is directly forwarded to the review committee for assessment.

The following deadlines apply:

• For the validation phase, the deadline is a maximum of ten (+ five) days for the initial review of the scope and completeness of the dossier. If the dossier is complete, the research file is forwarded to the review committee for assessment. Depending on the class of medical devices, specific review committees are accredited.
• For the assessment phase, the deadlines are (i) a maximum of 45 calendar days (+ 20 in case of expert consultations) for assessments regarding class IIa invasive, Class IIb invasive, Class III devices; and (ii) a maximum of 2 x 56 calendar days regarding Class I, Class IIa non-invasive and Class IIb non-invasive devices.

The accredited MREC or CCMO can call a clock stop to request further information.

Pharmaceuticals

An application for a clinical trial must be registered in CTIS. Regardless of the outcome of a clinical trial, the sponsor must submit a summary of the results of the clinical trial within one year after the end of the clinical trial in the member states concerned. This must be accompanied by a summary that is understandable to a layperson. For clinical trials initiated prior to 31 January 2022, access to information is provided via the EU Clinical Trials Register.

Medical Devices

At the moment, there is no publicly available database that provides insight into clinical investigations or performances studies under the MDR and IVDR. However, once the Clinical Investigations and Performance Studies module of EUDAMED becomes operational, the registration becomes mandatory. This mandatory registration requirement shall take effect six months after publication of the notice confirming the functionality of the module in the Official Journal of the EU. 

In addition to the General Data Protection Regulation (EU) 2016/679 (GDPR) and related laws and regulations (see 2.6 Personal or Sensitive Data), the WMO is also relevant with regard to the use of online tools in clinical research. Recruitment materials (including online tools) and digital monitoring methods must be submitted to and approved by a MREC or the CCMO. Online tools must not mislead participants and must ensure sufficient transparency.

Under Dutch law, data resulting from clinical trials qualifies as personal data within the meaning of the GDPR insofar as the data relates to an identified or identifiable research subject. As clinical research involves information about a person’s health, physical or mental condition, such data will, in principle, constitute special categories of personal data (sensitive data) under the GDPR. Coded or pseudonymised data is, in principle, still considered personal data as re-identification of individuals is usually reasonably possible.

Transferring non-anonymised data to a third party or an affiliate is permitted, provided that the requirements of the GDPR are met. In the context of clinical trials, this is typically complied with by obtaining consent from the data subject (Article 6(1)(a) GDPR). For the purposes of processing sensitive data, an explicit consent from the data subject is required (Article 9(2)(a) GDPR). Additional requirements apply where data is transferred outside the EU/EEA.

If the research data is fully anonymised and can no longer be traced back to a natural person, such data falls outside the scope of the GDPR and is no longer considered personal or sensitive data. In that case, the GDPR restrictions on processing and transfer do not apply.

Since 25 May 2018, the GDPR has been directly applicable in the Netherlands. Where the GDPR allows room for national choices in its implementation, these have been elaborated upon in the GDPR Implementation Act (UAVG). The GDPR provides that the processing of personal data relating to health or mental condition is permitted only if there is a lawful basis. Such a basis may be laid down in law; otherwise, consent is required to process health data. The GDPR privacy statement and the use of data are also assessed as part of the application for a medicinal product study.

The Database Act (Databankenwet), based on the Database Directive 96/9/EC, and the Copyright Act apply to the database itself.

Pharmaceuticals

The criteria of medicinal products are laid down in Directive 2001/83/EC and the Medicines Act. A medicinal product is (i) any substance or combination thereof presented for treating or preventing disease in human beings or (ii) any substance or combination thereof which may be administered to human beings with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in human beings. In other words, a product can be qualified as a pharmaceutical based on either its “presentation” or its “function”.

Medical Devices

With regard to medical devices, the MDR provides that any (amongst others) instrument, apparatus, implant or other article (i) intended by the manufacturer to be used for human beings for specific medical purposes (Article 2(1) MDR) and (ii) which does not achieve its principal intended action by pharmaceutical, immunological or metabolic means, but may be assisted in its function by such means. In other words, of importance are the intended purpose provided by the manufacturer and the mechanism of action of the device.

Whether a product classifies as one of the two is determined on a case-by-case basis. For instance, if a device does not have a medical purpose (assigned by its manufacturer), it would not be considered a medical device. Similarly, if a device is intended by its manufacturer to be used for specific medical purposes, but achieves such purposes because of its pharmaceutical, immunological or metabolic means, it would, in principle, be considered a pharmaceutical under the Directive 2001/83/EC (and the Medicines Act). In that respect, it should be noted that a product that has been classified as a medical device in another member state does not necessarily mean it will be classified as such in another member state.

Dutch law does not provide for specific authorisation procedures in relation to biological medicinal products. However, where an application concerns a biological medicinal product for which the applicant can demonstrate that it is generic vis-à-vis the reference medicinal product, a fast-track procedure becomes available. Furthermore, it should be noted that (i) medicinal products developed by means of biotechnological processes, as listed in Annex 1(1) of Regulation (EC) 726/2004, and (ii) certain ATMPs, as listed in Annex 1(a) of Regulation (EC) 726/2004, are subject to a centralised procedure.

Validity (and Renewal) of Marketing Authorisation

A marketing authorisation is valid for a period of five years (Article 47(1) Medicines Act).

The marketing authorisation can be renewed at the request of its holder. Nine months prior to expiration of the marketing authorisation, the marketing authorisation holder is required to submit to the MEB a consolidated version of the registration file. Such consolidated file is required to include (i) the changes made since the marketing authorisation was first granted and (ii) the review of suspected adverse reaction reports and periodic safety reports. After carrying out a risk-benefit assessment the MEB may decide to grant a renewal for an indefinite period or a (once-only) renewal of five years. A reason why the MEB may decide to not grant a renewal for an indefinite period of time is if the pharmaceutical has been exposed to an insufficient number of patients.

Suspension and Other (Enforcement) Measures

Article 51 Medicines Act lays down several circumstances under which the MEB will suspend, vary or withdraw a marketing authorisation, for instance if:

• a pharmaceutical is harmful;
• the therapeutic effect is absent or the risk-benefit assessment is unfavourable;
• the requirements relating to labelling or the package leaflet have not been observed; or
• the obligations regarding pharmacovigilance have not been complied with.

The MEB can also withdraw a marketing authorisation upon the request of its holder. Furthermore, if a pharmaceutical has not been marketed for a consecutive period of three years, the marketing authorisation will be deemed invalid.

Medical Devices

A CE certificate is valid for a maximum period of five years. Upon the request of the manufacturer, this period can be extended (each time for a maximum period of five years). A declaration of conformity by the manufacturer of a medical device is valid for an indefinite period, though it should be re-issued in case the medical device has undergone significant changes.

The notified body may suspend or withdraw a CE certificate (or impose restrictions on it) if it finds that the requirements imposed by law are no longer met by the manufacturer (Article 56(4) MDR). The IGJ can demand that the notified body suspend or withdraw a CE certificate.

Procedure for Obtaining a Marketing Authorisation (Medicinal Products)

Every pharmaceutical that is marketed in the Netherlands must have a marketing authorisation (Article 40 Medicines Act). A marketing authorisation can be obtained through several procedures which are outlined below:

• a national procedure that is under the responsibility of the MEB and which, if completed successfully, will result in a marketing authorisation that is only valid for the Dutch market;
• a decentralised procedure, which is a European authorisation procedure that – on the basis of identical documentation – allows for a marketing authorisation to be granted simultaneously in two or more EEA countries;
• a mutual recognition procedure, which allows for the extension of a marketing authorisation already issued in another member state (the reference member state) to one or more EEA countries; and
• a centralised procedure, which is under the responsibility of EMA and allows for the provision of a marketing authorisation that is valid across all EU countries; this procedure is compulsory for, for instance, orphan medicines.

For the purposes of the national procedure, an application must be submitted to the MEB that includes information about the quality, safety and efficacy of the pharmaceutical. Based on the provided information and documents, the MEB will conduct a risk-benefit assessment. The applicant is responsible for the accuracy of the submitted information and documents (Article 45(3) Medicines Act). A decision by the MEB on whether a marketing authorisation will be provided has to be made within 210 days after receiving the application (Article 44(2) Medicines Act). This period can, in principle, be suspended if the MEB requests the applicant to provide additional information regarding the application. 

Applications for variations must be submitted to the MEB. A template cover letter (and recommendations for what to include in such letter) has been published on the MEB website. There are various types of variations: Type IA, Type IB, Type II (and extensions), as mentioned in the Variation Regulation 1234/2008 (and as amended by Regulation (EU) 2024/1701). After an application for variations, the applicant receives a confirmation of receipt of the application. The following timelines apply:

• For type IA variations, the MEB applies 60 days: 30 days for the validation and 30 days for any administrative change for the marketing authorisation that might be required.
• For type IB variations, the MEB applies 30 days for the validation and assessment of the application, 30 days for any clock-stop period and 30 days for the second assessment round. Type IB variations should be approved by the MEB before the marketing authorisation holder may implement the changes.
• For Type II variations, the MEB applies either 164 days or 194 days (for a new indication).

In order to assist market parties with applications for variations, the MEB has published a useful Q&A on its website.

Transfer of marketing authorisation requires prior authorisation. It is required to submit:

• an accompanying letter and change request form;
• a declaration that marketing authorisations are being transferred;
• a statement that, with the exception of a new pharmacovigilance system, there are no changes to the marketing authorisation dossier;
• an abstract from the Chamber of Commerce of the transferee;
• authorisations where applicable (eg, manufacturer/retail/wholesale) to a new marketing authorisation holder; and
• a modified SPC, labelling and package leaflet.

Medical Devices

There are no marketing authorisations in relation to medical devices. However, medical devices are divided into four classes: Class I, IIa, IIb and III. The classification rules are set out in Annex VIII of the MDR. In short, the class of a medical device is determined based on the level of invasiveness, the part of the body it is in contact with as well as the duration of the contact. In vitro diagnostic medical devices are also divided into various classes: Class A, B, C and D. The classification rules are provided for in Annex VIII of the IVDR. The classification of an in vitro diagnostic medical device depends on the intended purpose of the device as well as its risk profile.

A medical device must bear a CE certificate if it is to be placed on the market in the Netherlands.

Article 40 Medicines Act provides for several exceptions from the requirement of a marketing authorisation. These include, inter alia:

• pharmacy preparations;
• investigational medicinal products;
• medicinal products that fall under the named patient arrangement;
• medicinal products under the compassionate use programme (this requires the approval from the MEB);
• ATMPs under the “hospital exemption” (their preparation and use is subject to approval from the IGJ);
• parallel imports;
• medicinal products that are provided with temporary approval by the MoH (for distribution) in response to the suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation; and
• in-transit/export medicinal products (related to wholesale activities), which are not allowed to be placed on the market in the Netherlands (unless they have a marketing authorisation).

Medical Devices

Medical devices without a CE marking may, in certain circumstances, be used. Indeed, there is a specific consent procedure for medical devices and in vitro diagnostic medical devices, under which the MoH – advised by the IGJ – may provide an exemption. In order to qualify for such exemption, a manufacturer has to submit an application with the Central Information Point for Healthcare Professions (Centraal Informatiepunt Beroepen Gezondheidszorg, CIBG), which is an executive organisation of the Ministry of Health, Welfare and Sport.

An exemption is, in principle, only provided if (i) in the absence of such exemption, an unacceptable risk will arise for patient care in the Netherlands, (ii) no equivalent alternative is available, and (iii) if the manufacturer has made it plausible that the device is safe and meets the quality and safety requirements as described by applicable laws and regulations.

Pharmaceuticals

The marketing authorisation holder is required to carry out pharmacovigilance. In that respect, the holder of a marketing authorisation is required to, inter alia: 

• have (per medicinal product) a pharmacovigilance system in place (Article 76a Medicines Act), which is required to tie in with the pharmacovigilance system of the MEB (which keeps its own, more abstract, pharmacovigilance system);
• keep up to date a pharmacovigilance system master file (PSMF);
• implement a risk management system (that is documented in an up-to-date risk management plan);
• conduct audits and designate a qualified person that is responsible for pharmacovigilance;
• register all suspected adverse effects that appear in the EU (or third countries) and that the marketing authorisation holder is notified of;
• (electronically) submit periodic safety update reports (PSUR) to the EMA;
• keep up to date the product information based on up-to-date scientific knowledge; and
• give public notice (on the basis of pharmacovigilance information) of risks concerning the use of medicinal products.

Furthermore, the MEB is authorised to impose a range of additional obligations on a marketing authorisation holder, including requirements to carry out post-authorisation efficacy studies or to comply with enhanced registration and notification obligations that go beyond standard pharmacovigilance requirements. These (additional) obligations can be imposed during the application procedure (for a marketing authorisation), but can also, if needed, be imposed after a marketing authorisation has been provided.

Medical Devices

A manufacturer is required to conduct post-market surveillance in order to monitor the safety and performance of the medical device that has been placed on the market. For that purpose, a post-market surveillance system (PSM system) needs to be implemented by the manufacturer. Such PSM system includes the collection of data ensuring the device’s performance and safety, and is used, inter alia:

• to verify whether the benefit/risk ratio has remained favourable;
• for clinical evaluation purposes;
• to assess when modifications or corrective actions need to be made;
• to assess what it can do to improve the usability, performance and safety of the device; and
• to monitor the design and the production process.

Furthermore, the manufacturer must notify the Inspectorate if (i) there is an incident in which its medical device is involved and (ii) a corrective action has been performed in relation to the medical device. A manufacturer or distributor is also obligated to report any expected supply interruptions to the Healthcare Procurement Network Netherlands. Importers are required to keep a register of complaints, recalled and withdrawn devices, and devices that do not meet the requirements. Finally, importers and distributors must (i) inform the manufacturer, the authorised representative (and/or the importer) immediately, if they receive a complaint or report about a product they imported or sold (or if such product does not meet the requirements) and (ii) report to the Inspectorate if a medical device presents a serious risk.

Pharmaceuticals

The MEB discloses information on (i) whether there is an application pending for (parallel import) marketing authorisations for a specific active substances and (ii) withdrawn and refused applications for marketing authorisations. As regards the latter, the MEB provides the name of the medicinal product, the relevant active substance, the type of procedure (eg, national), whether the application is withdrawn or refused, and the public assessment report. 

Furthermore, the MEB also publishes official product information of all medicinal products that have marketing authorisation in the Netherlands. The information includes an overview of:

• new marketing authorisations;
• new homeopathic marketing authorisations;
• withdrawn and suspended marketing authorisations;
• new marketing authorisations with a new active substance in the Netherlands;
• new marketing authorisations authorised by the European Commission;
• revised SmPC’s or package leaflets;
• (revised) public assessment reports;
• approved compassionate use programmes; and
• scientific substantiation for suspended, refused and withdrawn marketing authorisations.

The above is published in the Medicines Information Bank (Geneesmiddeleninformatiebank), which is updated on a weekly basis.

Medical Devices

In the context of medical devices, it is of note that EUDAMED may provide for access to certain information (eg, clinical performance). EUDAMED is not yet fully functional, as not all modules have been rolled out.

Pharmaceuticals

In the Netherlands, medicinal products are primarily regulated under the Medicines Act and at EU level.

As marketing authorisation procedures are largely harmonised within the European Union, accelerated pathways are generally pursued within the European regulatory framework. One such mechanism is the accelerated assessment procedure, based on Article 14(9) of Regulation (EC) No 726/2004. Pursuant to this provision, the assessment period under the centralised marketing authorisation procedure may be reduced from the standard 210 days to 150 days, provided that the medicinal product is of major interest from the perspective of public health and, in particular, represents therapeutic innovation.

In addition, Article 14a Regulation (EC) No 726/2004 provides for the possibility of a Conditional Marketing Authorisation. On the basis of this provision, a medicinal product intended for the treatment, prevention or diagnosis of seriously debilitating or life-threatening diseases may be granted a marketing authorisation prior to the submission of comprehensive clinical data, provided that: (i) an unmet medical need exists; (ii) the benefit of immediate availability outweighs the risk inherent in the fact that additional data are still required; and (iii) the applicant undertakes to submit the outstanding data within an agreed timeframe.

Furthermore, an application can be made for a duplex marketing authorisation (if specific conditions are met – eg, the reference product has not been granted a marketing authorisation via a duplex procedure or via the centralised procedure). A duplex marketing authorisation is a marketing authorisation for a medicinal product for which the dossier at the time of the application for the marketing authorisation is identical to that of a previously registered product (see policy document “MEB 16: Duplex marketing authorisation”). In principle, the issuance of the duplex marketing authorisation is carried out within 45 days.

In emergency situations, a marketing authorisation may even be granted in the absence of complete pre-clinical or pharmaceutical data.

Medical Devices

Dutch law – in line with the MDR – does not provide for a formal fast-track registration procedure for medical devices. Market access is obtained through the regular CE conformity assessment system. Limited and temporary derogation mechanisms (such as Article 59 MDR) do exist for urgent public health interests; however, these do not constitute a structural accelerated pathway.       

Pharmaceuticals

EU-based reliance

Within the EU, regulatory reliance is structurally embedded in three main procedures, as mentioned in 3.4 Procedure for Obtaining a Marketing Authorisation.

Non-EU-based reliance

The Netherlands does not automatically recognise a marketing authorisation issued outside the EU. An EU-compliant application is always required. However, the EU has concluded Mutual Recognition Agreements with certain countries, which primarily concern the recognition of GMP inspections and, in some cases, batch testing. The MEB also participates in various pilot programmes of mutual regulatory reliance managed by the EMA.

Medical Devices

EU-based reliance

If a device has obtained a valid CE marking in accordance with the MDR or IVDR, it may be placed on the market in all EU member states, including the Netherlands, and no additional national product approval is required.

Non-EU-based reliance

There is no automatic recognition. An independent EU-compliant conformity assessment is mandatory. Such conformity certificate at EU level (granted by an EU notified body) is also required when a marketing authorisation for the device has been obtained from a third-country regulatory agency. However, the relevant EU notified body may take the findings of such third-country regulatory agency into account when conducting its conformity assessment.

Pharmaceuticals

Under Dutch law, manufacturing sites/manufacturers of medicinal products are subject to a prior manufacturing authorisation pursuant to the Dutch Medicines Act. Without such authorisation, it is prohibited to manufacture, package, label, test, release or import medicinal products from third countries. The authorisation is granted by Farmatec on behalf of the MoH, while the IGJ is responsible for inspections and supervision.

The authorisation is obtained by submitting an application to Farmatec. Following a positive assessment, the authorisation is granted for an indefinite period and remains valid as long as the statutory requirements are met. However, it may be suspended or revoked in case of non-compliance.

Medical Devices

Manufacturers of medical devices are not subject to a prior authorisation requirement. They must, however, comply with the MDR or, where applicable, the IVDR. In addition, manufacturers are required to register in accordance with the applicable regulatory framework (see Article 31 MDR and Article 28 IVDR).

Pharmaceuticals

Parties that are engaged in the wholesale distribution of medicinal products in the Netherlands are subject to a wholesale distribution authorisation.

In order to obtain a wholesale distribution authorisation, an application must be submitted to Farmatec. A wholesale distributor must appoint a Responsible Person (RP) and show that the GDP will be complied with. The procedure is similar to that of the manufacturing authorisation; reference is therefore made to 5.1 Requirements for Authorisation for Manufacturing Plants. The authorisation covers procuring (within the EER), having in stock, supplying or exporting medicinal products into (or taking out of) Dutch territory.

The costs of the application procedure amount to EUR1,700. The application will only be taken into consideration after payment of this fee. Furthermore, the holder of a wholesale distribution authorisation is obliged to pay a yearly fee of EUR1,600. The wholesale distribution authorisation is, in principle, provided for an indefinite period.

Medical Devices

For medical devices, no separate wholesale distribution authorisation is required. However, obligations do apply under, inter alia, the MDR and IVDR – eg, distributors must comply with specific quality, compliance, and traceability requirements (Article 14 MDR and IVDR).

See 1.3 Categories of Pharmaceuticals and Medical Devices.

In the Netherlands, the import and export of pharmaceuticals and medical devices are regulated by a combination of national legislation (Medicines Act / Medical Devices Act), EU pharmaceutical legislation (including Directive 2001/83/EC), EU regulations (MDR, IVDR) and Customs legislation (UCC). Customs supervises and controls goods at the border. The Inspectorate exercises substantive supervision and enforces compliance both at the border and within the market.

Any company that has a manufacturing authorisation or a wholesale distribution authorisation can act as an importer of record. In that respect, it should be noted that importing medicinal products from outside the EEA requires a manufacturing authorisation.

In terms of medical devices, any natural or legal person established within the European Union that places a device from a third country on the market can act as an importer of record. The importer must comply with the obligations set out in the MDR or IVDR, including, inter alia, registration obligations.

In order to import medicinal products, a wholesale distribution authorisation (if medicinal products are imported from EEA countries) and/or manufacturing authorisation is required (if medicinal products are imported from third countries). Furthermore, for import purposes it is also required to provide an import declaration to customs.

There are several exemptions from the prior authorisation requirements, for instance:

• The Inspectorate can grant an import exemption in case of a severe shortage of a medicinal product. Whether such exemption is necessary is to be assessed by the Inspectorate in consultation with the MEB. The exemption only concerns medicinal products that are not registered in the Netherlands, but have a marketing authorisation in another member state or a third country (with which a mutual recognition agreement is in place).
• An exemption applies to medicinal products authorised under compassionate use programmes.
• Finally, an exemption also applies to in-transit/export medicinal products (related to wholesale activities), which are not allowed to be placed on the market in the Netherlands (unless they have marketing authorisations).

Regarding medical devices, as any medical device has to fully comply with the relevant EU regulatory requirements, the importation thereof from third countries requires the importer to, inter alia, verify that (i) the devices have a valid CE marking and Declaration of Conformity, (ii) the manufacturer of the medical device is identified and (iii) the labelling of the device is carried out in accordance with the MDR/IVDR.

In the Netherlands, non-tariff regulations and restrictions applicable to the importation of pharmaceuticals and medical devices are imposed on the basis of their classification under the Combined Nomenclature (CN), pursuant to Council Regulation (EEC) No 2658/87, and their qualification under the applicable sector-specific legislation.

As part of the customs territory of the European Union, imports are governed by Regulation (EU) No 952/2013 (Union Customs Code). Customs authorities may verify compliance with product-specific requirements upon importation.

Pharmaceuticals are regulated under the Medicines Act. Importation from third countries requires, inter alia, a manufacturing/import authorisation, compliance with GMP and a valid marketing authorisation.

Medical devices are regulated under the MDR and IVDR, as enforced in the Netherlands through the Medical Devices Act. Imported devices must bear CE marking and comply with the applicable conformity assessment requirements.

The Netherlands, through its EU membership, is a party to free trade agreements containing provisions on trade and regulatory facilitation that are relevant to medicinal products and medical devices. The Netherlands is also a member of the WTO.

Pharmaceuticals

The specific rules in relation to pricing of medicinal products are mainly laid down in the Pharmaceutical Pricing Act (and underlying regulations). In that regard, it is ultimately the Dutch government, more specifically the MoH, that is responsible for regulation of pricing for authorised medicinal products. Indeed, while the MoH does not set fixed prices for medicinal products, the MoH does set the maximum allowable price for medicinal products by using a system of external reference pricing and reference countries. The reference countries are currently France, Norway, Belgium and the United Kingdom. In order to determine the maximum price, the following steps are observed:

• For each reference country, the comparable medicines are classified into a product group.
• For each country, the package size(s) with the lowest unit price are selected based on the brand name of the relevant comparable medicine. If the selected package size(s) of that medicine appears multiple times in the price list, the average price(s) thereof are included in the calculation.
• The prices of the selected packages are averaged per country.
• If necessary, the average price will be converted into euros.
• The maximum price is set at the arithmetic mean of the (converted) averages of the reference countries.

The MoH then prepares a decision to amend the list of maximum prices by (twice a year) publishing draft regulations with the amended prices in the Government Gazette (Staatscourant). The draft regulations are also published on Farmatec’s website. As the decision to amend prices is subject to a uniform public preparatory procedure, any interested party can, within six weeks after the publication of the draft regulations in the Government Gazette, submit an opinion (zienswijze) in relation to the proposed maximum prices. After the procedure has been completed, the MoH sets the maximum price for each authorised medicinal product (per quantity and pharmaceutical form, including brand name or generic) and includes them in the Annex to the Pharmaceutical Pricing Regulation. It is prohibited to sell (or buy) a medicinal product at a higher price than the maximum price (Article 4 Pharmaceutical Pricing Act).

Furthermore, Article 3(2) of the Pharmaceutical Pricing Act allows, in special cases and upon (substantiated) request, for the amendment of the maximum price of a medicinal product. This concerns medicinal products (that fall within a specific product group) with a total annual turnover in the Netherlands of less than EUR1 million (Article 2 of the Temporary Policy Rule 2024 (Tijdelijke beleidsregel maximumprijzen geneesmiddelen 2024). If granted, the maximum price will be increased by 15% (Article 3(1)(b) Temporary Policy Rule 2024).

Medical Devices

The pricing of medical devices is, in principle, not subject to similar legal control mechanisms. 

See 8.1 Price Control for Pharmaceuticals and Medical Devices.

Reimbursement

In the Netherlands, there is a private healthcare system that is heavily regulated and consists of various healthcare-related acts, of which the Healthcare Insurance Act (Zorgverzekeringswet, Zvw) is the most prominent (though the Long-Term Care Act (Wet langdurige zorg, Wlz) is also a substantial contributor to the Dutch healthcare system).

In short, all types of care (i) to which the insured is entitled and (ii) that healthcare insurers are obliged to offer pursuant to the Zvw (and underlying regulations) are referred to as the basic package (basispakket). What is included in the basic package is determined by the government and can change on a yearly basis. The ZiN advises the MoH on the contents of the basic package.

Reimbursement in the context of Zvw-care is carried out by private healthcare insurers that have a duty of care vis-à-vis their insured population. This means that they should ensure that their insured receives the care to which they are entitled, within reasonable time and travel distance. To that end, healthcare insurers must purchase sufficient care from healthcare providers, for which they usually conclude annual agreements. Healthcare that is provided by healthcare providers that are contracted by healthcare insurers is generally fully reimbursed. If the insured opt to receive healthcare from non-contracted providers, such care will usually not be fully reimbursed.

As to medicinal products (in the context of extramural care), it is of importance to note that only medicinal products that are included in the Medicine Reimbursement System (Geneesmiddelenvergoedingssysteem, GVS) can fall within the scope of the basic coverage. Indeed, the MoH (advised by ZiN) (i) decides which medicinal products are included in the GVS, and (ii) divides the medicinal products into two lists, which are included in the Regeling Zorgverzekering (Rzv) as Annex 1A (interchangeable medicinal products) and Annex 1B (medicinal products that are not interchangeable). Medicinal products included in Annex 1A have a reimbursement limit (the insured must pay an additional sum, if the price exceeds this limit). Some medicinal products are only reimbursed when specific conditions are met (eg, specific indications); these are included in Annex 2 of the Rzv.

Healthcare insurers typically purchase medicinal products via preferential purchasing procedures, where they designate at least one variant of all active ingredients that the MoH designated as interchangeable (Article 2.8(3) Besluit zorgverzekering, Bzv). Healthcare insurers also have the power to limit the coverage to a specific strength per active ingredient (if the Rzv includes medicinal products with different strengths of the same active ingredient). If a medical practitioner indicates that it would be medically unjustifiable to treat the patient with the preferential product and prescribes a specific different variant of the medicinal product, that variant will have to be reimbursed (Article 2.8(4) Bzv).

Article 2.8(1) Bzv provides for a reimbursement route for unauthorised medicinal products, if these medicinal products can be considered rational pharmacotherapy (generally relevant in the context of pharmacy preparations). This is the case if the medicinal product (i) has a suitable pharmaceutical form for the specific patient, (ii) is proven to be working and effective, and (iii) is the most cost-effective option for, respectively, the healthcare insurer or the patient.

For medicinal products utilised for inpatient purposes, a different mechanism applies. Article 2.4 Bzv stipulates that insured patients have a right to “medical care” (geneeskundige zorg) that is commonly provided by medical specialists (medische specialisten). If such medical care includes the use of medicinal products, these medicinal products will generally be reimbursed as part of the received medical care.

In short, whether care is (fully) reimbursed depends on a variety of circumstances, such as whether:

• the care falls within the scope of the basic package;
• the received care is contracted by the healthcare insurer;
• the medicinal product is designated by the MoH;
• the healthcare insurer designated the specific medicinal product; and
• a medical practitioner issues a statement indicating that:
1. treatment with the preferential product is medically unjustifiable; and
2. the insured requires a specific (other) medicinal product; and
• some of the (other) exceptions apply.

Medical Devices

Medical devices are treated somewhat differently to medicinal products as it is generally up to the healthcare insurers to determine whether a specific medical device is eligible for reimbursement from the basic package. In that respect, healthcare insurers will generally assess whether (i) new devices meet the legal requirement of “established medical science and medical practice” (stand van de wetenschap en praktijk, SW&P) (Article 2.1(2) Bzv) and (ii) the insured is reasonably reliant (or better: requires) on a specific medical device (Article 2.1(3) Bzv). However, in terms of the latter criterion, the professional autonomy of the medical practitioner (the referrer) is generally leading.

As mentioned in 8.3 Reimbursement From Public Funds, ZiN is tasked with advising the MoH on reimbursement of, inter alia, medicinal products. Indeed, ZiN is responsible for performing HTA, including cost-benefit analyses. Such cost-benefit analyses therefore play an important role for both the price and reimbursement status of a medicinal product. For the purposes of (amongst others) these cost-benefit analyses, ZiN is assisted by the Scientific Advisory Board (Wetenschappelijk Adviesraad).

The price of medical devices is generally decided as a result of negotiations between healthcare insurers and providers of medical devices. Such price negotiations generally (also) result in parties agreeing on an “all-in price”, where the price not only includes the specific medical device but also includes adjacent services (eg, monitoring, customer service, etc).

Article 61 Medicines Act provides a prohibitory provision for, inter alia, the dispensing of prescription-only and pharmacy-only medicinal products. Furthermore, pursuant to Article 36(14) of the Individual Healthcare Professions Act (Wet BIG), only a limited number of healthcare professionals (eg, medical practitioners, dentists) can prescribe medicinal products. In general, the following is of note in the context of prescribing and dispensing medicinal products:

• The Wet BIG includes disciplinary rules that must be complied with by healthcare professionals, including pharmacists. In that respect, healthcare professionals must comply with the principle of good care (Article 40 Wet BIG).
• In order to satisfy their “good care” obligation, pharmacists must comply with specific professional guidelines, which typically set out what constitutes “good care”. Adhering to these professional guidelines is not voluntary, as competent authorities (as well as, for instance, healthcare insurers) can use these guidelines to assess whether pharmacists act in compliance with the principle of good care.
• Dispensing medicinal products (as well as advising patients on their use and monitoring such use) is one of the legally defined areas of expertise of pharmacists (Article 23 Wet BIG).
• Furthermore, Article 67 Medicines Act prohibits prescriptions via the internet of medicinal products to persons that the prescriber (i) has never personally seen, or (ii) does not know, or (iii) does not have the medical history of. However, a temporary tolerance policy has been introduced based on which prescriptions via the internet are allowed under strict circumstances (prescribing policy rules via the internet, Beleidsregel voorschrijven via internet).
• Additionally, off-label prescriptions are only allowed if the relevant professional groups have developed protocols and standards for that purpose. If such protocols and standards are still in development, consultations between the treating medical practitioner and the pharmacists are necessary (Article 68 Dutch Medicines Act).

It is not allowed for pharmacists to pay more than the maximum price as set by the MoH. See 8.1 Price Control for Pharmaceuticals and Medical Devices and 8.2 Price Levels of Pharmaceuticals or Medical Devices.