The regulatory regime
The Medicinal Product Act and the Medicinal Products Ordinance are based on Directive 2001/83/EC, and the Medical Devices Act and the Medical Devices Ordnance are based on Directives 90/385/EEC, 93/42 EEC and 98/79/EC. There are additional regulations and guidelines issued by the MPA.
Notably, on 5 April 2017, two new regulations on medical devices were adopted within the European Union; Regulation (EU) 2017/745 on medical devices and Regulation (EU) 2017/746 on in vitro diagnostic medical devices. They entered into force on 26 May 2017, replacing the existing directives. However, the new rules will only apply after a transitional period of three years after entry into force for the regulation on medical devices (in spring 2020), and five years after entry into force for the regulation on in vitro diagnostic medical devices (in spring 2022).i Classification
The definition of a medicinal product corresponds with the definition found in Directive 2001/83/EC. According to Chapter 2 Section 1 of the Medicinal Products Act, a medicinal product is:
- any substance or combination of substances having properties for treating or preventing diseases in human beings; or
- any substance that may be used in or administered to human beings or animals either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.
The two primary determining factors for classifying a medicinal product are the content of the product and the intended use of the product. Other factors that may affect the classification of the product are, for example, (1) the formulation of the product, (2) how the product is marketed, and (3) whether or not the product meets the requirements of medical devices, in which case the legislation on medical devices will apply.
A product that does not fall under the definition of a medicinal product according to the above definition and determining factors, can nevertheless, because of its characteristics, purpose and use, be covered by the Medicinal Products Act, in line with MPA Regulation LVFS 2011:15. For instance, a product can be classified as a medicinal product even without containing any active substances (e.g., products that would seem to fall within the scope of food, food supplements or cosmetics).
The definition of a medical device is broad and includes products ranging from plasters to advanced diagnostics scanners. The definition in Swedish legislation is based on the applicable EU directives, and the primary national definition is stipulated in Section 2 of the Medical Devices Act, which states that a medical device is a product that, according to the manufacturer, is intended for use, separately or in combination with other products, in human beings for the purpose of:
- diagnosis, prevention, monitoring, treatment or alleviation of disease;
- diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap;
- investigation, replacement or modification of the anatomy or of a physiological process; or
- control of conception.
However, if the product achieves its principal intended action in or on the human body by pharmacological, immunological or metabolic means, it is not a medical device according to the Medical Devices Act.
The Medical Devices Act also stipulates certain requirements of medical devices. For instance, according to Section 5 of the act, a medical device must be suitable for its intended use. A device is suitable if it is delivered and installed in accordance with the manufacturer's directions and if it achieves its purposes according to the manufacturer and caters for the requirements of protection of life, personal safety and the health of patients and users. These safety requirements derive from the EU legislation on medical devices.
In addition, the Product Safety Act applies to medical devices that are intended for consumers, or if it can be assumed that the device will be used by consumers, in areas of product safety that are not covered by the Medical Devices Act.ii Non-clinical studies
A candidate drug must be tested for efficacy and security in a non-clinical study before it is tested on human beings in a clinical trial. The scope and type of experiments and studies that have to be carried out in the non-clinical study are laid down, for example, in guidelines issued by the European Medicines Agency (EMA). The European Commission has also issued guidelines on non-clinical studies, which give detailed information regarding the types of non-clinical studies that need to be carried out prior to conducting a clinical study.
Non-clinical studies sometimes involve animal testing. The Swedish legislation governing animal protection in general and animal testing in particular is strict, and animal testing methods may only be used if the intended results of the research cannot be reached with any other method. All animal testing in Sweden must be in accordance with the Animal Protection Act and before any animal experiment begins, it must be approved by an ethics committee.
A non-clinical study must, throughout the entire process, meet the requirements of good laboratory practice (GLP). The Swedish requirements on GLP are in line with the standards set out in Directives 2004/9/EC and 2004/10/EC. The monitoring authority on GLP in Sweden is the MPA. The authority may, for example, conduct inspections to ensure that non-clinical studies are in compliance with applicable GLP standards.iii Clinical trials
According to the Medicinal Products Act, a clinical trial may be carried out to establish or confirm the safety and effectiveness of a medicinal product. The trial may be conducted either with or without a connection to regular medical treatment. It must be performed by a qualified medical doctor (or dentist or veterinary surgeon, as applicable) with sufficient knowledge and experience of managing clinical trials. As mentioned above, a non-clinical trial must have been carried out prior to conducting the clinical trial.
Before a clinical trial can be conducted, it must be approved by the MPA, in line with the Medical Products Act. For clinical trials involving human beings, there are also applicable rules set out in the Ethical Review Act, including, inter alia, the requirement to obtain approval by an ethics committee. Clinical trials also require explicit consent of the study subject, and the trial subject must have been duly informed about the study, the risks involved and about his or her right to withdraw from the trial at any time.
MPA Regulations LVFS 2011:19 and 2004:6 state that the principles of good clinical practice and the most recent edition of the World Medical Association's Declaration of Helsinki must be observed during a clinical trial. In clinical trials where a substance is tested in human beings for the first time, the EMA Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products should be observed, and any deviation should be justified in the application to perform the trial.
According to the Medical Devices Act, the government or the relevant competent authority may decide what types of medical devices shall be tested clinically and how the clinical trial shall be performed. The MPA has been given the authority to oversee clinical trials of medical devices. A clinical trial shall only be performed when the necessary information about a device's performance, safety and use cannot be established or confirmed without testing in human beings.
Clinical trials in Sweden have to be registered with the European Clinical Trials Register. The personal data of patients collected during clinical trials must be processed in accordance with the EU General Data Protection Regulation and the Patient Data Act, which specifically govern the processing of sensitive, or 'special categories', of personal data, including, for example, personal information about health, biometric data, genetic data or a natural person's sex life.iv Named-patient and compassionate-use procedures
In some cases, certain medical needs are not met by approved medicinal products. In such cases, affected patients are, in addition to participation in clinical trials, able to obtain treatment through named-patient use licensing, a compassionate-use programme (CUP) or through a hospital exemption. The use of unauthorised medicinal products is primarily governed by the Medicinal Products Act, the Medicinal Ordinance and MPA Regulations LVFS 2008:1 and LVFS 2011:3.
There are mainly three ways in which a patient can get access to an unauthorised medicinal product. First, the MPA can at short notice allow a prescription through a special permission (licence) on a named-patient basis, either for a specific person (individual licence) or to a group of patients being treated at a clinic or another equivalent institution (general licence). The named-patient permission is available for prescribers to facilitate necessary treatment when medical conditions cannot be treated with approved medicinal products. The prescriber may initiate the application process by writing a prescription and handing it in at a pharmacy with their justification for the prescription. If there are no approved treatment options available, the pharmacy shall then submit the application to the MPA for individual assessment. There are certain specific requirements for the reporting of adverse reactions applicable to named-patient sales.
Second, patients are able to access unapproved medicinal products through a CUP that is governed by Regulation (EC) No. 726/2004 on compassionate use of medicinal products. The purpose of a CUP is to complement the named-patient licensing procedure. It is intended for patients with a chronic or seriously debilitating disease, or patients whose disease is considered life-threatening and cannot be treated satisfactorily with an authorised medicinal product. Certain requirements about satisfactory documentation of efficacy and safety apply, as well as specific obligations for the responsible physician to report adverse reactions. The permit holder must also submit annual safety reports to the MPA.
Third, access to an unauthorised medicinal product can be provided through a hospital exemption. This means that, under certain conditions, a healthcare provider can obtain a manufacturing permit from the MPA to use advanced therapy medicinal products that have not been evaluated or approved in the European Union. The product must be customised for a specific patient on a non-routine basis. A qualified person must be appointed to be responsible for the treatment and the treatment is subject to applicable rules on good manufacturing practice (GMP). The MPA may revoke the permit temporarily or permanently.v Pre-market clearance
The MPA grants marketing authorisation for medicinal products in Sweden according to certain procedures. A marketing authorisation is mandatory for manufacturers or importers of medicinal products before they can engage in any sales activity. The MPA grants marketing authorisations under the mutual recognition procedure (MRP), the decentralised procedure (DCP) and the national procedure. The EMA also grants marketing authorisations under the centralised authorisation procedure; these authorisations apply directly in Sweden.
When an application is made for marketing authorisation under the MRP, reference is made to a national marketing authorisation in another EU Member State, which should then be recognised in Sweden unless the MPA finds reason to believe that the medicinal product may pose a serious risk to public health. Under the DCP, an application is made in several EEA Member States with a request that the medicinal products agency in one particular state shall serve as the reference Member State. The medicinal products agency in that reference Member State (e.g., the MPA in Sweden) shall manage the review of the application by preparing the necessary documentation for assessment by the other Member States affected by the application.
When medicinal products are to be granted marketing authorisation in Sweden through the national procedure, the applicant must be able to establish, inter alia, that the medicinal product meets the requirements set out in Chapter 4 of the Medicinal Products Act. To obtain marketing authorisation, the medicinal product must meet the requirements of quality, efficacy and safety and be effective for its intended purpose. An applicant must also show that the medicinal product is not disproportionately harmful in achieving its intended effect. The packaging of the medicinal product needs to meet certain standards too (e.g., the packaging must be functional), and all information about the medicinal product has to be accurate and comprehensible. The MPA may grant a marketing authorisation subject to certain conditions, which should be reviewed annually.
A marketing authorisation is valid for a period of five years, and may thereafter be renewed for another five-year period or without any time limit.
Medical devices are not subject to pre-market approval in Sweden or the European Union. However, all medical devices must meet the requirements of the applicable legislation and it is the responsibility of the manufacturer to ensure compliance. To confirm that a medical device conforms with the applicable legal requirements, it should be provided with a CE mark prior to being placed on the market. The CE mark procedure is dependent on the classification of the medical device. High-risk medical devices must also be assessed by a third person, known as a 'notified body', prior to being placed on the market.vi Regulatory incentives
Patent protection for an invention is typically valid for 20 years from the filing date of the patent application. However, patents for medicinal products can, according to Regulation (EC) No. 469/2009, have the term of protection extended for generally up to five years by a Supplementary Protection Certificate (SPC). The rationale of the supplementary protection springs from the fact that development and authorisation of medicinal products is complex and time-consuming, and that long periods typically pass between the filing date of the patent and when the product may first be placed on the market. The purpose of an SPC is thus to compensate the patent owner for the time when the patent rights cannot be commercialised.
The Swedish Patent and Registration Office handles applications and grants certificates for supplementary protection. An SPC protects the active substance that is covered by the patent and authorised for sale on the market. The supplementary protection will take effect once the original patent has. In some circumstances, the initial term of protection by the SPC (never longer than five years) may be extended by an additional six months if the patent owner has tested the suitability of the medicinal product in children.
A medicinal product for use in human beings can also be granted a one-year regulatory data exclusivity by the MPA if an application for marketing authorisation has been granted for a new indication for an already established substance and if substantial clinical assessments and studies of the new indication have been made. Data exclusivity protection means a prohibition for generic medicinal products to refer to documentation of the reference medicinal product.vii Post-approval controls
The legal framework for supervision and control of medicinal products is harmonised with applicable EU legislation, including, inter alia, Directive 2010/84/EC and Regulation (EU) 1235/2010. According to the Medicinal Products Act, the MPA is responsible for the supervision of medicinal products in Sweden. The purpose of the supervision is to collect, record, store and scientifically evaluate data on suspected adverse reactions. The MPA regularly controls authorised medicinal products and evaluates whether the authorisations should remain in effect. The MPA may order a marketing authorisation holder to verify that the medicinal product still meets the requirements and, if considered necessary for safety reasons, it may withdraw the marketing authorisation.
Swedish law also requires marketing authorisation holders to maintain an internal system for surveillance of safety and to observe and adjust to developments in the pharmaceutical field, such as new scientific research or new recommendations from the MPA. The marketing authorisation holder shall register, keep, evaluate and report to the MPA any information on all suspected adverse reactions of its medicinal products. If the marketing authorisation holder detects circumstances that may render inaccurate the information and documentation upon which the authorisation is based, it must report this to the MPA. Furthermore, there is an obligation for the marketing authorisation holder to inform the MPA two months in advance if a product is permanently or temporarily taken off the market in Sweden, and to state the reasons for this. For the purpose of its overall safety surveillance, marketing authorisation holders must keep a qualified person with sufficient knowledge and experience at its disposal.viii Manufacturing controls
Manufacturing of medicinal products shall take place in suitable premises and be carried out using appropriate equipment. All manufacturing must be in accordance with GMP and a qualified person with sufficient knowledge and influence shall be responsible for ensuring that the quality and safety standards and the requirements of the medicinal products are met.
According to the Medicinal Products Act and MPA Regulation LVFS 2004:7, professional manufacturing of medicinal products requires a manufacturing authorisation by the MPA. The MPA will regularly perform inspections of the facilities to ensure compliance with the relevant requirements for the manufacturing authorisation. A manufacturing authorisation is valid for the time specified in the permit and may be extended subject to continued compliance with the requirements.
A manufacturing authorisation can be revoked by the MPA if, for instance, if any of the required conditions mentioned above are no longer being met or if the manufacturer has not paid the applicable annual fees to the MPA.
As mentioned in Section II.v, it is the responsibility of the manufacturer of a medical device to ensure compliance with the requirements of the applicable legislation, including the Medical Devices Act and MPA Regulations LVFS 2003:11 and LVFS 2001:7. To facilitate inspections by the MPA, inter alia, Swedish manufacturers and authorised representatives that manufacture or provide certain medical devices are required to register with the MPA. However, registration does not result in approval of the medical device.ix Advertising and promotion
The Marketing Practices Act, which governs advertisements in general, is also applicable to the advertising of medicinal products. Its aim is to protect consumers from misleading advertisement and unethical marketing practice. The Radio and Television Act is also applicable.
The Medicinal Products Act and the MPA's provision published in the MPA's Code of Statutes contains specific rules on the advertising of medicinal products. The Medicinal Products Act stipulates that only medicinal products that have been granted marketing authorisation may be advertised in Sweden. The Act includes requirements that, for example, an advertisement has to be up to date, objective and balanced. It must also be accordance with best practice for the advertising of pharmaceuticals. Advertisements that are misleading, addressed to children or for prescription-only medicinal products are prohibited (with the exception of campaigns for vaccination against human infection diseases). The rules apply both to advertisements aimed at the general public and at healthcare professionals. The Medicinal Products Act stipulates that pharmaceutical companies shall have an in-house function with scientific competence who is responsible for surveillance of the provision of information about their medicinal products.
The research-based pharmaceutical industry in Sweden has, through its trade organisation, the Swedish Association of the Pharmaceutical Industry (LIF), developed a system of self-regulation in the pharmaceutical sector. LIF has adopted ethical rules and a self-regulation system concerning, inter alia, the advertising of medicinal products to the public sector and healthcare professionals in 'The Ethical Rules for the Pharmaceutical Industry' (the LIF Ethical Rules), which came into force on 1 October 2007; the most recent revision is valid as of 12 February 2018.
Compliance with the LIF Ethical Rules is kept under constant scrutiny by the LIF Information Examiner Committee (IGN). The IGN is responsible for investigating cases and imposing sanctions, both on its own initiative and in response to complaints. IGN's decisions may be appealed to the Information Practices Committee (NBL).
The LIF Ethical Rules have a very important role in the marketing and promotion of medicinal products. Even though they are based on contractual obligations and are not legally binding, the Rules are widely respected and adhered to by the pharmaceutical industry. They are also often considered by the courts as an expression of fair and ethical marketing.x Distributors and wholesalers
Distribution, including the wholesale and retail of medicinal products, is governed primarily by the Act on Trading in Medicinal Products, the Ordinance on Trading in Medicinal Products and MPA Regulation LVFS 2014:8. In addition, there are guidelines issued by the MPA on the interpretation of these rules, as well as guidelines on good distribution practice (GDP) issued by the European Commission.
According to the Act on Trading in Medicinal Products, all distribution of medicinal products shall be conducted in such a way that the products do not harm human beings, property or the environment, and that the quality of the products is not impaired.
The wholesale of medicinal products includes all handling of a medicinal product from the moment it is released from the manufacturer until it reaches the retail level, and is defined in the Act on Trading in Medicinal Products as activities that include acquisition, possession, export, delivery and sale (but excluding retail sale). Retail sale is defined as the sale of medicinal products to consumers, county councils, municipalities, hospitals or other healthcare facilities and to entities authorised to prescribe medicinal products.
A permit from any country within the European Economic Area (EEA) is required to engage in distribution of medicinal products. In Sweden, the MPA may grant such permits.
Permits for the wholesale or retail of medicinal products may be granted only to applicants that are proven capable of meeting certain specific requirements in the Act on Trading in Medicinal Products, including requirements regarding, inter alia, the suitability of the facilities being used and the competence of personnel involved in conducting the distribution activities. Specifically, a wholesaler must also be able to ensure, inter alia, a reliable supply to pharmacies of the medicinal products covered by its permit, must document the handling of medicinal products in such a way as to ensure traceability, must maintain active surveillance to discover and report any suspected forfeited pharmaceuticals, and must adhere to accepted standards of GDP. Retailers must, inter alia, ensure availability of at least one pharmacist in the retail facility during opening hours if supplying medicinal products to consumers (e.g., pharmacies) and have an obligation to supply all prescription pharmaceuticals as well as all medicinal products included in the Swedish pharmaceutical benefits system.
Distribution of medical devices is generally not subject to any specific rules and therefore no particular authorisation is required. However, the trading and importation of syringes and needles are governed by a specific act, an ordinance by the government and a regulation by the MPA.xi Classification of products
Pursuant to Chapter 4 of the Medicinal Products Act, a medicinal product will, in connection with the granting of marketing authorisation, be classified either as a prescription-only or a non-prescription medical product. The MPA will decide the classification for the medicinal product depending on its intended use and characteristics. A prescription-only medical product may be classified into other categories, with limitations for how it can be prescribed and dispensed.
The MPA shall reconsider and, if necessary, change the classification of the medicinal product if new information or circumstances of significant importance for the classification of the medicinal product comes to its attention or if the marketing authorisation holder applies for a change of classification.
Classification of medical devices is governed by Directives 93/42/EEC and 98/79/EC, the Medical Devices Act, the Medical Devices Ordinance and MPA Regulations LVFS 2001:7 and LVFS 2003:11 (see also Section II regarding new EU regulations on medical devices). There are six groups of classification for general medical devices and four groups for in vitro diagnostic medical devices, which reflect the risks associated with the devices. Active medical devices for implantation are considered to be consistently associated with very high risks and these devices are therefore not divided into risk classes. The classification will also determine what type of procedures the manufacturer must apply to ensure that the products comply with legal requirements (see Section II.v).xii Imports and exports
According to the Medicinal Products Act, medicinal products can only be imported into Sweden from a country outside the EEA by someone holding a manufacturing authorisation or a specific authorisation for importation. The latter may be granted by the MPA if: (1) the medicinal product is imported to ensure that the demand for that medicinal product is met; (2) the medicinal product is intended to be used for purposes other than healthcare; or (3) the medicinal product is an investigational medicinal product. The importer of a medicinal product from a third country is responsible for the release of that product within the EEA.
An importation authorisation holder must appoint a qualified person with sufficient competence and influence to be responsible for the control of the imported medicinal product.
Repackaging and relabelling of medicinal products is also subject to a manufacturing authorisation by the MPA; the new package and label must comply with the requirements set out in MPA Regulation LVFS 2005:11 (which has been supplemented and amended by MPA Regulation HSLF-FS 2018:62, which enters into force on 9 February 2019).
There are exceptions to the requirement for importation authorisation for products from outside the EEA. For example, natural persons may bring medicinal products to Sweden if they have a medical purpose and will be used personally by the importer. Second, veterinarians may under certain circumstances bring smaller amounts of medicinal products for animals into Sweden without an importation authorisation.
No specific importation authorisation is required to import medical devices into the EEA. In general, the manufacturer is responsible for ensuring that medical devices released on the EEA market comply with applicable rules and regulations. If an importer of a medical device from outside the EEA releases a product on the EEA market in its own name, the same requirements apply to the importer as would have applied to the manufacturer. Furthermore, as stated in Section II.xi, specific requirements apply to the importation of syringes and needles.
It should also be noted that the requirements applicable to manufacturers according to the definition in the Product Safety Act also apply to importers.xiii Controlled substances
Controlled substances particularly include narcotic substances. Narcotic drugs are defined in the Penal Law on Narcotics as medicinal products and hazardous goods with addictive properties or euphoric effects, or goods that can be readily converted into products with those properties or effects, and (1) on these grounds are included in an international agreement to which Sweden is a part (including the 1961 UN Convention on Narcotic Drugs) or (2) the Swedish government has declared that the substance shall be considered a narcotic. The MPA has listed all substances classified as narcotics in Regulation LVFS 2011:10.
According to the Act on the Control of Narcotic Drugs, medicinal products classified as narcotics are under the supervision and control of the MPA. A general permit issued by the MPA is required to import, export, transport, produce, trade or possess narcotic medicinal products. Furthermore, certain narcotic substances require an additional permit for each individual occasion when the substance is brought into or out of Sweden. However, there are some exceptions; for instance, governmental or municipal institutions do not need a permit to possess narcotics if used for scientific research, studies or education.
Other categories of substances subject to special control include, for example, psychotropic substances, doping substances and certain hazardous goods.xiv Enforcement
The MPA is responsible for the supervision and enforcement of compliance with Swedish legislation and a number of EU Regulations and Directives on medicinal products and medical devices. The EMA is responsible for the supervision of compliance with certain requirements relating to centrally approved medicinal products.
The MPA is authorised to demand any information needed during its supervision, both oral and in writing. The MPA has authority to access areas, premises and other facilities used for the manufacturing or handling of medicinal products and medical devices, active substances, auxiliary substances and packaging materials for medicinal products, and to obtain samples of medicinal products and medical devices. It may also gain access to facilities where testing of medicinal products takes place. However, the MPA does not have the right to access private homes.
If the MPA finds it necessary, it may issue injunctions and prohibitions for compliance with the relevant legislation. An injunction or prohibition may be combined with a fine. A fine may also be imposed if the MPA is denied access or assistance when conducting its supervision.
The MPA may decide to recall medicinal products from the market and to temporarily or permanently revoke marketing authorisations.
Certain violations of regulatory requirements relating to medicinal products and medical devices may be considered criminal and be punished pursuant to the Medicinal Products Act and the Medical Devices Act; punishments range from fines to imprisonment for up to one year. Offences may also be punishable under the Swedish Penal Code.
Pursuant to the Marketing Practices Act, in the event of a breach of regulatory requirements, prohibitions and constraints can be imposed by a competent court. A prohibition for a company to continue with a measure contrary to the Marketing Practices Act may be combined with a fine. Disruption of marketing practices may also lead to fines and liability.
The LIF Ethical Rules, while not legally binding, impose sanctions such as fines on non-complying organisations that have not contractually adhered to the rules. The IGN and NBL are responsible for enforcement of the LIF Ethical Rules.