The regulatory regimei Classification
Medicines for human use are defined as:
any product that (a) is presented as a suitable product for the treatment or prevention of diseases in human beings, or (b) may be used in or administered to human beings to restore, change or modify physiological functions by a pharmacological, immunological or metabolic effect or to make a medical diagnosis.
The decision as to whether a product will be deemed a medicine, a medical device or another regulated product depends largely on the presentation and the product's demonstrated mode of action. The DMA determines whether medicines should be classified as over-the-counter medicines (OTCs) or prescription medicines. The decision as to whether approved medicines should be restricted for use in specific patient groups and prescribing status is also decided by the DMA. Medicines approved by the European Medicines Agency (EMA) will maintain their classification status in Denmark. Natural medicines, traditional herbal medicines and homeopathic products are also regulated by the DMA, whereas complementary medicines and vitamins are regulated by the Danish Veterinary and Food Administration. Prescription medicines may be dispensed only by pharmacies, but it is permitted for some OTCs to be sold elsewhere. As of 1 January 2018, some OTCs are placed freely in pharmacies, shops and retail stores, and are no longer be placed behind a counter or locked in a cabinet. A list of these OTCs can be found on the DMA website.ii Non-clinical studies
Non-clinical studies of compounds must be conducted in compliance with the principles of good laboratory practice (GLP). GLP defines the standards for the planning, conducting, monitoring, recording and reporting of in vitro and in vivo studies. All animal studies must be carried out in accordance with the principles of Directive 2010/63/EU. Permissions to conduct animal studies on vertebrate animals and foetuses of mammals must be granted by the Animal Experiments Inspectorate (AEI). The AEI approves all animal experiments in Denmark and undertakes inspections of all facilities where animal experiments are carried out.iii Clinical trials
Clinical trials on human beings are regulated by Directive 2001/20/EC and Regulation (EU) No. 536/2014 as implemented into Danish law. All clinical trials must be conducted in accordance with the principles of good clinical practice (GCP)., Before initiation of the study, the protocol may be subject to approval by the DMA and an ethics committee. Trial subjects must receive proper written and oral information about the trial before consenting to participate. Informed consent forms must be signed by the trial subjects and stored by the primary investigator. As clinical trials may be subject to inspection by the DMA, participants must be informed about this before consenting to participate. The informed consent form must contain a section describing the DMA's unconditional access to all trial and patient data. Injuries occurring in clinical trial subjects are covered by a publicly funded compensation scheme (see Section VI).Sponsor
In Danish law, the clinical trial sponsor is defined as the individual, company, institution or company that takes the overall responsibility for the initiation, management and, in some cases, financing of the clinical trial. The trial sponsor has several legal obligations, such as registration of the trial in EudraCT, reporting of trial results to EudraCT and reporting of adverse events occurring during the trial to the DMA. The definition of the term 'sponsor' in Danish law (as stated above) is not the same as in Directive 2001/20/EC, which defines a sponsor as an individual, company, institution or organisation that takes responsibility for the initiation, management or financing of a clinical trial.iv Named-patient and compassionate use procedures
In special cases, the DMA may authorise the prescribing of unlicensed medicines, such as those approved but not marketed in Denmark or pharmacy compounds. Hence compassionate use permissions are only granted in situations where the unlicensed medicine cannot be substituted by a medicine already marketed in Denmark. Physicians, dentists and veterinary surgeons may apply for a single permission for use of unlicensed medicines in specific patients or apply for a general permission that allows use of an unlicensed product for all patients affiliated with a specific hospital department or general practice. When applying for compassionate use permissions, the DMA usually requires information about the name of the medicine, active ingredients, medical form, strength, producer, distributor, indication for use and medical justifications for the application. Medicines prescribed for compassionate use are also subject to the rules for reporting adverse events to the DMA.v Pre-market clearance
Medicines must be approved by the EMA or DMA and included on the medical register (www.medicinpriser.dk) before they can be marketed in Denmark. The applicant for and holder of a marketing authorisation must be established in an EEA country, or represented in Denmark by another EEA company. Generic medicines may be authorised according to the abridged application procedure, in which applicants may omit some or all of the preclinical and clinical trial data if bioequivalence can be documented with a reference product and regulatory data exclusivity for the reference product has expired.vi Regulatory incentives
Patents may be granted for medicines for 20 years from the date of filing as provided in the Patent Act, Section 40. When granted a marketing authorisation for a medicine, the marketing authorisation holder may benefit from a data protection period of eight years from the first marketing in the EEA., If new indications are approved later, the data protection period may be extended to 11 years. Danish law concerning supplementary protection certificates (SPCs) is harmonised with EU Directives. The duration of an SPC is limited to a maximum of five years without the possibility of extension. Supplementary protection for medicines may in turn be extended by an additional six months if the patentee has tested the suitability of the medicines for children in accordance with Regulation (EC) No. 1901/2006 and Regulation (EC) No. 1 902/2006., Article 36 of Regulation (EC) No. 1991/2006 allows for a further six-month extension of the SPC if a paediatric indication is approved by the regulatory authorities. An application for a paediatric extension should also be filed with the Danish Patent and Trademark Office (DKPTO).Patented indications
When dispensing medicines, pharmacies are legally obliged to substitute the cheapest medicine within the relevant substitution group. If a medicine has a patented indication, it may have an effect on how the DMA establishes the substitution group to which the medicine belongs. Consequently, the marketing authorisation holder of a medicine with a patented indication must inform the DMA about the patent or SPC and its expiry date, and the DMA will subsequently verify the patent or SPC in collaboration with the DKPTO. If the patent or SPC affects the substitution rules and groups, these will be changed accordingly. This means in practice that the pharmacy should dispense the medicine with the patent protected indication.vii Post-approval controls
Marketing authorisation holders of medicines are legally obligated to establish and maintain a pharmacovigilance system, have access to a qualified person situated in the EEA and to comply with national rules on reporting suspected adverse reactions. The reporting requirements of adverse events from medicine use are described in Executive Order No. 1823 of 15 September 2015. According to Section 4(1) thereof, physicians, dentists, midwives, veterinary surgeons and pharmaceutical companies are legally obliged to report all suspected adverse events and exposure reactions in patients or animals they are treating. It is not mandatory to report adverse events caused by medication errors to the DMA. Pharmacists, consumers, patient relatives and lawyers may all report adverse events directly to the DMA. All serious adverse events must be reported to the DMA no later than 15 days after a physician, dentist, midwife or veterinary surgeon becomes aware of the event. During the first two years of marketing, all adverse events must be reported. After the two-year period, reporting obligations cover serious or unexpected adverse events only. For generic medicines, only serious or unexpected adverse events and exposing reactions must be reported; the reporting requirements apply from the time when marketing of the medicines has begun. Additionally, the DMA has introduced strict reporting of all adverse events occurring for medicines under special surveillance. A list of these medicines can be found on the DMA website.viii Manufacturing controls
Manufacturers of medicines must have a manufacturing authorisation, under Section 39 of the Medicines Act. Medicines are to be manufactured in accordance with Good Manufacturing Practice (GMP) guidelines and the European Commission's guidelines listed in Volume 4 of the Rules governing medicinal products in the European Union. Manufacturers must have at least one qualified GMP person permanently and continuously at their disposal. Permissions will be granted by the DMA, and the DMA will regularly inspect the companies.
Distributors and wholesalers must also be authorised by the DMA, under Section 39 of the Medicines Act, and may also be inspected by the DMA. Information about authorised distributors and wholesalers may be found on the DMA website. Transport companies that only provide transportation of medicines do not need an authorisation. However, pharmaceutical companies must ensure that medicines are transported in compliance with the GDP rules. Distributors and wholesalers must approve and review their suppliers regularly to monitor the suppliers' compliance with the GDP rules.ix Advertising and promotion
Advertising of medicines is regulated in Part 7 of the Medicines Act and Executive Order No. 1153 of 22 October 2014 on advertising rules for medicines. The main purpose of the legislation is to protect the public against misleading and prohibited advertising of medicines and to ensure that the public have access to objective and adequate information about medicines. Advertising for prescription medicine to the general public is not allowed, but direct advertising to healthcare professionals (HCPs) is permitted.x Controlled substances
Manufacturers, wholesalers and others who handle medicines classified as euphoriants (e.g., narcotics or psychotropic substances) need a manufacturing, import or wholesale licence that specifically includes those substances. Authorisation of narcotics or psychotropic substances may be granted if the substances are prescribed to drug addicts for medical purposes. Dispensing of the medicines may be made by physicians, pharmacists and institutions involved in treatment of drug addicts. A list of euphoriants subject to control by the Danish authorities is available on the DMA website.