The regulatory regime
The Medicines Act consolidates in a single legal act the regime applicable to, among other things, the marketing authorisation, manufacture, import, export, marketing, labelling, promotion and pharmacovigilance of medicines; it transposes into Portuguese Law several directives, including Directive 2001/83/EC, as amended (the Directive).
Medical devices, in turn, are governed by the Medical Devices Act, which, further to transposing several directives related to the manufacture, marketing and vigilance of medical devices (including Directive 93/42/EEC, as amended), establishes the regime applicable to promotion. With regard to promotion, the Medical Devices Act closely follows the regime set out for medicines. In early 2017, Decree-Law No. 5/2017 introduced general principles applicable to the promotion of medicines and medical devices, and further implemented specific rules for scientific, educational and promotional events that take place in National Health Service entities.i Classification
The definitions of a medicinal product for human use and of a medical device are identical to those arising from EU legislation, with the distinction between them being made on the basis of the intended use and the mechanism through which this is achieved. As is the case under the Directive, where any doubt arises, the classification as a medicinal product prevails.ii Non-clinical studies
Directive 2010/63/EU on the protection of animals used for scientific purposes was transposed into Portuguese law in August 2013. This regime follows closely the one set out in Directive 2010/63/EU, thus establishing several requirements applicable to the use of animals for scientific or educational purposes, namely in what concerns the accommodation, care and use of animals in procedures; the origin, breeding, marking and killing of animals; licensing of breeders, suppliers and users; and the procedures for evaluation and authorisation of scientific or educational projects.
In addition, and similarly to what happens at EU level, the testing of finished cosmetic products and cosmetic ingredients on animals is prohibited, with the same applying to the marketing thereof if animal testing was conducted for cosmetic purposes.iii Clinical trials
In April 2014, a new legal regime for clinical research was approved, consolidating in one legal act the provisions applicable to clinical studies, whether interventional or not, and covering medicines, medical devices and cosmetics. The regime encompasses the provisions of Directive 2001/20/EC regarding the conduct of clinical trials on medicinal products for human use and the provisions of Directive 2007/47/EC on clinical investigation with medical devices.
All clinical studies are subject to a prior favourable opinion from the competent ethics committee. In addition, interventional clinical trials with medicines depend on authorisation from Infarmed, with the same applying to interventional studies with Class III medical devices, implantable medical devices and long-term invasive devices falling within Classes IIa or IIb. For the remaining classes of medical devices, interventional studies depend only on the favourable opinion from the ethics committee and on notification to Infarmed. The conduct of clinical interventional studies with cosmetics should also be notified in advance to Infarmed, with the sponsor being entitled to initiate the study should Infarmed not issue an unfavourable decision within 30 days of the notification.
Both the sponsor and the investigator are jointly and severally liable, regardless of fault, for material and non-material damage suffered by subjects – liability that must be covered by insurance. Should an interventional study be at stake, there is a legal presumption that damage that affects the health of subjects during the study and for a one-year period following its term (which may be extended by the ethics committee) is caused by the study. This reverses the general rule on burden of proof, subject to which whosoever alleges damage should demonstrate the causal relationship between the damage and the act (in this case, the study).iv Named-patient and compassionate-use procedures
Similar to what happens under EU legislation, the general rule is that medicines can only be marketed following the granting of a marketing authorisation. In exceptional circumstances, however, Infarmed may authorise the use of non-approved medicines, such as when the product is, subject to a clinical assessment, considered indispensable for the treatment of a given pathology and there is no therapeutic alternative among authorised products.
Within the context of interventional clinical studies, following the conclusion of a study, the sponsor is under an obligation to supply the investigational medicinal product or device under clinical investigation for free until its marketing should the investigator consider that continuation of its use by the former participant is indispensable and that there are no therapeutic alternatives with an equivalent degree of safety and efficacy.v Pre-market clearance
The Medicines Act reflects EU rules in this regard and thus medicines can only be placed on the market following the granting of a marketing authorisation – Infarmed being the competent authority for authorising medicines that follow national procedures.
The marketing in Portugal of medical devices bearing a CE mark does not require any authorisation from Infarmed. Nonetheless, Infarmed must be notified of all medical devices marketed by a given entity prior to its commercialisation.vi Regulatory incentives
The Medicines Act reflects the regime established in the Directive regarding regulatory data protection and market exclusivity. Generic applications cannot be submitted for a period of eight years following the first authorisation in the European Union. After this eight-year period has elapsed, the generic cannot be launched on the market for an additional two years. This period may be extended for one supplementary year should the innovator, within the data exclusivity period of eight years, obtain a marketing authorisation for one or more indications of significant clinical benefit.
Patent linkage is not permitted. The Medicines Act expressly provides that marketing authorisation applications cannot be dismissed on the grounds of the potential existence of industrial property rights of the reference product. A similar rule exists for pricing and reimbursement decisions.
There are no special provisions to encourage the development or market launch of innovative products. On the other hand, special provisions to encourage the sale of generics exist in a variety of areas; for example, generics benefit from a simplified regime regarding pricing and reimbursement, and prescription is mandatorily made by active substance once a generic is launched in the market, the rule being that of generic substitution, save in very limited circumstances expressly provided for by law.vii Post-approval controls
Pharmacovigilance rules applicable to medicinal products were modified in 2013 with the transposition into Portuguese law of Directive 2010/84/EU and Directive 2012/26/EU. In the same year, the provisions of Directive 2011/62/EU regarding prevention of entry into the supply chain of falsified medicinal products were also transposed, with the Medicines Act currently closely following EU legislation on these matters, such as the placing of safety devices on the packaging of certain medicinal products, to identify and authenticate them. Detailed rules for these safety devices were to be adopted through Delegated Regulation 2016/161, including a repository system containing information on the safety features. These rules were to be implemented by marketing authorisation holders up until 9 February 2019. In 2018, the Medicines Act was amended, to adapt local legislation to Delegated Regulation 2016/161.
A similar regime applies regarding medical devices, with the vigilance requirements stemming from the relevant directives. In addition, a pharmacovigilance system has been implemented that is similar to the system applicable to medicines.viii Manufacturing controls
In line with the Directive, the manufacture of medicinal products is subject to prior authorisation by Infarmed, even if products are intended for export. An authorisation will only be granted if the applicant has adequate premises that comply with the applicable legislation and with the European Commission Guidelines on Good Manufacturing Practice (in 2018, the Medicines Act was amended to transpose Directive 2017/1572) and has a qualified person permanently and continuously at its disposal. The qualified person, who is responsible for all manufacturing activities performed, must be a pharmacist registered with the Portuguese Order of Pharmacists.
Any change to the manufacturing authorisation requires prior authorisation by Infarmed.
In 2013, the Medicines Act was amended, transposing Directive 2011/62/EU and thus requiring that the manufacturers of active substances established in Portugal register their activity with Infarmed.
The manufacture of medical devices, as well as the assembling, packaging, processing, fully refurbishing, labelling or assigning to them a purpose different from that of its original intended use, among others, is subject to prior notification to Infarmed. The engagement in these activities is dependent on the applicant having adequate premises and equipment with capacity to ensure the manufacture, storage and conservation of medical devices and a technician responsible to ensure the quality of the activities performed.
In addition, and in line with what is set out in EU directives, manufacturers or their authorised representatives placing medical devices on the Portuguese market should notify Infarmed, providing in the notification the required level of information depending on the classification or nature of the device concerned.ix Advertising and promotion
The regime applicable to the advertising of medicines closely follows the regime set out in the Directive. The major differences relate to the definition of advertising, to the scope of the prohibition on granting benefits to healthcare professionals and to the prohibition on granting any kind of benefit to patients, matters in respect of which the Medicines Act goes beyond what is established in the Directive.
The definition of advertising is broader than that set out in the Directive, advertising being considered, under the Medicines Act, as any kind of information, canvassing activity or inducement that has as its object or effect the promotion of the prescription, dispensation, sale, purchase or consumption of medicines. Contrary to what is foreseen in the Directive, Portuguese law does not require that the conduct be designed to promote a given product for it to qualify as advertising. It suffices that the conduct at issue has that effect.
Second, the Medicines Act extends the scope of the prohibition on pharmaceutical companies granting gifts, pecuniary advantages or benefits in kind to healthcare professionals to also include bonuses – a notion that is associated with the granting of discounts in kind, such as free products. The broadening of this prohibition is particularly relevant to the relationship between pharmaceutical companies and pharmacies, being hardly in line with the EU legal framework and with the principle that promotion rules do not apply to measures or trade practices related to prices, margins and discounts – provided for in both the Directive and the Medicines Act.
Finally, pharmaceutical companies are prevented from granting any kind of benefit to patients. Similarly to what happens in relation to healthcare professionals, companies cannot grant or promise to grant, directly or indirectly, gifts, prizes, bonuses, pecuniary advantages or benefits in kind to patients.
Although companies are under an obligation to provide Infarmed with a summary description of all advertising materials, no prior-approval requirement exists. In addition, companies must notify Infarmed in advance of the sponsorship of any congress, symposium or event of an educational or promotional nature.
The regime applicable to advertising and promotion of medical devices is very similar to that applicable to medicines. There is, however, no prohibition on granting gifts or benefits to the public. The advertising of medical devices, the use of which requires the intervention of healthcare professionals, such as implantable medical devices, cannot be promoted to the public.
Medical device companies are also required to notify Infarmed in advance of the sponsorship of any congress, symposium or event of an educational or promotional nature.x Distributors and wholesalers
Wholesale distribution of medicines is subject to prior authorisation from Infarmed, the only exception being for holders of manufacturing authorisations in relation to the products covered by those authorisations (similarly to what happens under the Directive).
The granting of such an authorisation is dependent on the applicant having adequate equipment and premises, located in Portugal, to ensure proper conservation and distribution of medicines and a technical director, who must ensure, effectively and permanently, the quality of the activities carried out in the distribution premises. The technical director must be a pharmacist registered with the Portuguese Order of Pharmacists and personally fulfil his or her responsibilities in the wholesale premises. Until 2013, the technical director had to exercise the functions of this role exclusively and could not perform those functions for more than one company, even if the wholesale distribution premises were the same. Currently a technical director may cumulate functions within the same wholesale premises, up to a limit of five wholesale distribution authorisations. In 2015, a new regulation on good distribution practices applicable to the wholesale distribution of medicines was approved, closely following Commission Guideline 2013/C 343/01.
In addition, wholesalers are under a legal obligation to have medicines permanently available in sufficient quantity and variety to ensure the appropriate and continued supply of medicinal products with a view to guaranteeing the satisfaction of patients' needs. The minimum quantities of products that wholesalers must keep at all times to comply with this public service obligation were set out in a regulation issued by Infarmed.
In 2013, to address shortages of medicinal products on the Portuguese market, mainly resulting from parallel exports to other EU Member States, the Medicines Act was amended, granting Infarmed powers to list the medicines of which it requires notification prior to exportation (within and outside the European Union). In 2015, Infarmed published a regulation setting out the terms applicable to the notification and to the medicines covered (a list that has been regularly updated), and wholesalers are currently under an obligation to notify in advance all sales of medicines included on this list made to countries outside Portugal. In addition, marketing authorisation holders, wholesalers and pharmacies must notify Infarmed, once a month, of the quantities of certain listed medicinal products that are sold, dispensed, exported or subject to intra-community commerce. The compatibility of this regime with principles of EU law has always been far from clear. In 2016, the European Commission initiated a procedure against Portugal, determining, in its reasoned opinion, that Portugal should suppress unjustified and disproportionate notification obligations because they constitute an obstacle to the free movement of goods within the European Union. To comply with the terms of the reasoned opinion, Infarmed revised its rules in 2017. Although the regime of prior notification was maintained, clear and transparent criteria for the inclusion of medicines on the list in question, and for the list's revision, were implemented. Finally, Infarmed has the power to prevent the exportation of medicines – be it inside or outside the European Union – on the grounds of protection of public health or to ensure patient access to a given medicinal product.
The regime governing the brokering of medicinal products under the Medicines Act follows closely that of Directive 2011/62/EU, thus engagement in the activity of brokering does not require prior authorisation from Infarmed; neither is it dependent on the existence of premises or a permanent address in Portugal. Persons brokering medicines with a permanent address in Portugal must register their activity with Infarmed.
The engagement in the activity of wholesale distribution of medical devices, although not subject to express authorisation from Infarmed, must be notified in advance to that authority, and is only permitted if (as is the case for medicines) the applicant has adequate premises and equipment with capacity to ensure good storage, conservation and distribution of medical devices and a responsible technical director is appointed to the wholesale premises to ensure the quality of the activities performed. In contrast to the regime applicable to medicines, the technical director does not have to be a pharmacist but must have an adequate technical qualification to ensure the quality of the distribution activity, as well as adequate knowledge of the legislation and regulations applicable to medical devices. Also, differently from the regime applicable to medicines, the wholesale premises do not have to be located in Portugal. Nonetheless, should the premises be located abroad, the applicant must comply with the Portuguese legal provisions applicable to the wholesale distribution of medical devices. In 2016, good distribution practices applicable to the wholesale distribution of medical devices were approved (although initially legally set out in 2009). This regime is extremely demanding and, in many aspects, follows the good distribution practices for medicines.xi Classification of products
The criteria laid down in the Medicines Act for classifying a medicine for medical prescription are very similar to those set out in the Directive.
The classification has related consequences for the regime applicable to advertising, pricing, reimbursement and point of sale or dispensing. Only non-prescription products may be promoted to the general public, which is the same under the Directive. In addition, while there is no price control for non-prescription drugs (unless these are reimbursed – the general rule, however, is that non-prescription products are not subject to reimbursement), prescription products have their maximum sale prices approved, regardless of whether they are reimbursed or not. Finally, whereas the dispensing of prescription drugs is restricted to pharmacies – unless subject to restricted medical prescription, in which case they can only be dispensed or administered in hospitals – over-the-counter products (OTCs) may be sold at points of sale duly authorised by Infarmed.xii Imports and exports
In line with the regime laid down in the Directive, the importation of medicines is subject to prior authorisation from Infarmed, with requirements very similar to those applicable to the manufacture of medicines (see Section II.viii). The importation of active substances is also subject to registration with Infarmed. The export of medicinal products does not require any authorisation from Infarmed, nor does it require registration with Infarmed.
As regards medical devices, there are no additional requirements related to imports and exports other than those applicable to the manufacture, placing on the market and wholesale distribution, analysed above.xiii Controlled substances
The manufacture, use, marketing, distribution, importation, exportation and possession of narcotics and psychotropic substances are subject to a specific regime. Narcotics and psychotropic substances are divided into several categories, each identifying the relevant substances. Infarmed is the entity responsible for authorising engagement in these activities in relation to certain categories of substances. Specific requirements also exist for prescribing, dispensing and keeping records when such substances are included in medicinal products.
Further to constituting a misdemeanour punishable with a fine, engagement in any of the above-mentioned activities without the relevant authorisation may be considered a criminal offence.
In addition, the use of cannabis-based medicines, preparations and substances for medicinal purposes, was authorised under Law No. 33/2018, which came into force on 1 August 2018. 'Cannabis-based medicines, preparations and substances' are defined as the leaves, flowers and fruits of the cannabis plant, as well as oil and other standard extracts or preparations obtained from the plant.
Physicians are only allowed to prescribe cannabis-based products if conventional treatments with authorised medicines are not having the expected effects or they are generating relevant adverse effects; also, cannabis-based products can only be prescribed for use in indications authorised by Infarmed.
Law No. 33/2018 further indicates that these products must be prescribed by a physician, pursuant to a special medical prescription, which must be approved by the Ministry of Health. The prescription must mention the names of the physician and the patient, and it must identify the cannabis-based medicine, preparation or substance, as well as the relevant quantity, dosage and form of administration.
Since they are considered medicinal products, they will, generally, require a marketing authorisation from Infarmed before being placed on the market.
Cannabis-based products can only be sold in pharmacies. The buyer is required to provide identification, or evidence of being the legal guardian of the patient, together with the prescription. Each prescription can only be used once (i.e., the law does not provide for a renewable prescription, or for a prescription that can be used several times).xiv Enforcement
Infarmed is entrusted with the supervision and enforcement of regulatory provisions applicable to medicines and medical devices.
A breach of these provisions is considered a misdemeanour punishable with a fine calculated according to the infringer's annual turnover, or a fine of a predetermined fixed amount (whichever is lower). In addition to this penalty, a breach of the provisions of the Medicines Act, including advertising, may also give rise to ancillary sanctions to be applied by Infarmed, such as a prohibition on exercising the activity, exclusion from participation in public tenders and the suspension of any authorisations and permits – all up to a maximum of two years.
Should the infringement of promotion rules be at stake, both regarding medicines and medical devices, Infarmed may order that the condemnatory decision be published in the media as well as the suspension of advertising of the product concerned for a period of up to two years. Medicinal products may further be delisted as a result of infringement of promotion rules.