Medicinal product regulation and product liability in Spain: overview
A Q&A guide to medicinal product regulation and product liability law in Spain.
The Q&A gives a high level overview of key issues including pricing and state funding, manufacturing, marketing, clinical trials, advertising, labelling, and product recall and liability.
For information on pharmaceutical patents, trade marks, competition law, patent licensing, generic entry, abuse of dominance and parallel imports, visit Pharmaceutical IP and Competition Law in Spain: overview.
To compare answers across multiple jurisdictions, visit the Medicinal product regulation and product liability Country Q&A tool.
The Q&A is part of the global guide to life sciences law. For a full list of jurisdictional Q&As visit www.practicallaw.com/lifesciences-guide.
The main regulatory framework is set out by:
Royal Legislative Decree 1/2015 (24 July 2015) which approves the refunded text of the Law on guarantees and the rational use of medicinal products and medical devices.
Royal Decrees on particular regulatory issues.
The existing Royal Decrees are being replaced to conform with and develop Royal Legislative Decree 1/2015.
The Agency on Medicinal Products and Medical Devices (Agencia Española de Medicamentos y Productos Sanitarios) (AEMPS) (www.aemps.es) is responsible for the following in relation to medicinal products:
Grant, modification and revocation of manufacturing and marketing authorisations.
Authorisation of clinical trials.
Promotion, control and supervision of medicinal products in the market.
Enforcement of the regulations and entries in the relevant registries.
Guaranteeing the supply of medicinal products.
Medicinal products must be authorised for marketing by either the:
AEMPS, for national marketing authorisations (MAs), decentralised and mutual recognition procedures.
European Medicines Agency (EMA), for the centralised procedure.
At EU level, the centralised procedure is mandatory for:
Medicinal products developed by recombinant DNA technology and/or controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes, including transformed mammalian cells and/or hybridoma and monoclonal antibody methods.
Orphan medicinal products.
Medicinal products which contain a new active ingredient, not as yet authorised in the EU, relating to:
a neurodegenerative disease;
auto-immune diseases and other immune dysfunctions, and viral diseases.
The pricing of medicinal products in the healthcare system is determined by the General Directorate on Basic Services Provision of the National Health System (DGCB) (Dirección General de Cartera Básica de Servicios). The DGCB is responsible for the following in relation to medicinal products:
Direction, development and implementation of national pharmaceutical policy.
Public funding and price setting.
Establishing special conditions for the prescription and sale of medicinal products in the National Healthcare System (NHS).
Biologicals are regulated by Royal Legislative Decree 1/2015 on Guarantees and Rational Use of Medicinal Products and Medical Devices. Biologicals include insulines, hemoderivatives, vaccines and biotechnological products.
Vaccines and biological products used as medicinal products are subject to the regulations applicable to medicinal products with the special features provided by Royal Legislative Decree 1/2015. With regard to biological products, where necessary in the public health interest, the AEMPS can subject to authorisation each manufacturing batch of a terminated product and impose conditions on its marketing.
Hemoderivatives are considered medicinal products when used for therapeutic purposes. Therefore, hemoderivatives are subject to Royal Legislative Decree 1/2015.
There are no specific regulations applicable to vaccines and biological products and hemoderivatives developing the provisions set out in Royal Legislative Decree 1/2015, but the following should be considered.
Biologicals cannot be substituted without the specific authorisation of the doctor who prescribed the product under Order SCO/2874/2007 28 September, which sets out the medicinal products that cannot be substituted by the pharmacist.
There is a lack of specific regulation on combination medicinal products (though in practice, there will be a revision of the price if one of the medicines is affected by the reference pricing system). However:
When a medical device is intended to administer a medicinal product, the product is considered a medical device and the medicinal product must comply with Royal Legislative Decree 1/2015 (Royal Decree 1591/2009 16 October on medical devices).
If a product of this type is put on the market in a manner by which the product and the medicinal product constitute one integrated product, intended to be used solely in this association and which is not reusable, the product is subject to Royal Decree 1345/2007 of 11 October on the procedure for authorisation, registration and conditions of supply of industrially manufactured medicinal products for human use. Regarding the product features related to their safety and benefits, Article 5 of Royal Decree 1591/2009 applies.
On the other hand, where a medical device incorporates as an integral part a substance which, if used separately, can be considered a medicinal product which can act on the human body with an action ancillary to that of the product, the product will be evaluated and authorised as a medical device.
Where a product incorporates as an integral part a substance which, if used separately, can be considered a component of a medicinal product or a medicinal product derived from blood or human plasma which can act on the human body with an action ancillary to that of the product, the product will be evaluated and authorised as a medical device (Royal Decree 1591/2009).
Medical devices are governed by the Royal Decree 1591/2009. Medical devices, other than devices intended for clinical investigation and custom-made devices, can only be placed on the market if they hold the CE marking.
Physical and legal persons who want to manufacture, import, assemble or sterilise medical devices and the premises where such activities are performed must obtain an operating licence in advance from the AEMPS. For the manufacturing of custom-made devices, the operating licence is issued by the authorities of the relevant Autonomous Community.
For all devices of type IIa, IIb or III, a notification must be made to the AEMPS by any physical or legal person that puts them into service for distribution and/or use for the first time in Spain.
The entities responsible for the distribution and sale of medical devices (other than pharmacies, except when they sell products that need to be adapted) must notify initiation of activity to the relevant health authorities, which includes the following:
Identification of the distribution or sale establishment.
Type of products to be distributed or sold.
Identification and qualification of the technical person responsible.
In vitro diagnostic medical devices are regulated by Royal Decree 1662/2000 29 September on in vitro diagnostic medical devices. The manufacturing, assembly or sterilisation of in vitro diagnostic medical devices in Spain also requires a prior operating licence for the establishment from the AEMPS. As medical devices, in vitro diagnostic medical devices can only be placed on the market if they hold the CE marking.
In relation to health IT issues and mobile medical applications, there are no specific regulations on mobile medical applications besides the provisions in Law 29/2006, in conjunction with Royal Decree 1591/2009. However, Law 15/1999 of 13 December on the Protection of Personal Data and Law 34/2002 of 11 July on Information Society Services and Electronic Commerce also apply on a general basis.
Pricing, state funding and reimbursement
The Ministry of Health, Social Services and Equality (Ministry of Health) has competence to rule on all healthcare issues, including funding and the inclusion of medicinal products in the NHS.
Attached to the Ministry of Health are several organisations with responsibility over specific areas of health and welfare regulation, including:
The regional governments of the Autonomous Communities, which implement measures on medicinal products in their territories.
The prices of medicinal products are regulated under Article 94 of Royal Legislative Decree 1/2015.
DGCB regulates the industrial price of medicinal products sold in Spain and financed by social security funds or state funds allocated to healthcare (that is, included in the NHS), as follows.
Laboratory selling price. This is fixed by the Interministerial Medicinal Products Price Commission, dependent on the Ministry of Health. The level of the laboratory selling price is also determined by objective and verifiable criteria, particularly the:
Manufacturing costs (including administrative and marketing costs).
Research and development costs.
The resulting price must be adjusted by the therapeutic importance of the medicinal product (based on reports on the therapeutic use of the medicinal product developed by the AEMPS) and by the proportionality principle, to ensure the price accords with existing alternatives.
In practice the cost criterion has been replaced by correcting mechanisms such as the:
Cost of financing for similar therapeutic medicinal products.
Modulating factor of the lowest price of the medicinal product which is being financed in Europe.
The most commonly used criterion is European reference prices (based on an unofficial list of selected countries, or on the lowest price in Europe) although it is not referred to in regulations. The government is working on a draft Royal Decree on Pricing and Funding of Medicinal Products which is expected in the next few months, and which will probably deal with the above mechanisms for fixing prices. The pricing and reimbursement reform will probably need to adapt regulatory requirements to new criteria set out by recent amendments to Law 29/2006 and the practice of the health authorities. However, the health authorities will probably continue to have very wide discretionary powers to weigh the relevant circumstances.
Public retail price. This is calculated by adding to the laboratory selling price the annually updated commercial margins (fixed by resolution of the Ministry of Health) for wholesalers and pharmacies, and value added tax (VAT).
In the case of over the counter (OTC) medicinal products excluded from financing by the NHS and/or non-financed indications, the laboratory notifies its selling price to the Ministry of Health. The health authorities can object to the notified price for public interest reasons. The expected Royal Decree on Pricing and Funding of Medicinal Products will review and develop this notification process.
As a general rule, the law states that the funding price will be lower than the laboratory selling price when the medicinal product is dispensed outside the NHS.
Once a medicinal product has been authorised, the DGCB must decide, before it is marketed, whether it should be included in the NHS and therefore publicly funded. When making that decision, the DGCB takes into account criteria of a general and objective nature, which include the (Article 92, Royal Legislative Decree 1/2015):
Seriousness, duration and after effects of the various pathologies for which the product was approved.
Requirements of certain groups.
Product's therapeutic and social use and the relationship between its additional clinical benefit versus its cost benefit.
Limits of public healthcare expenditure allocated to pharmaceutical benefits and budgetary impact within the NHS.
Availability of medicinal products or other alternatives that treat the same illnesses at a lower price or inferior treatment costs.
Level of innovation of the medicinal product.
Certain groups, subgroups, categories or classes of medicinal products are excluded from public financing, as decided by the government considering the criteria set out above and both:
The price or cost of treatment of comparable medicinal products existing in the market.
The guidelines provided by the Interterritorial Counsel of the NHS.
The level of reimbursement is capped by a system of reference pricing. Reference prices are the maximum amount the NHS will fund for each medicinal product in a group. For this purpose, a group of medicinal products is the total of the financed medicinal product's presentations that have the same active ingredient and identical administration route (at least one of those must be a generic or biosimilar medicinal product or have been authorised within the EU for a term of ten years). Paediatric presentations and hospital medicinal products make up independent groups.
According to Royal Decree 177/2014 21 March 2014 governing the system of reference prices and homogenous groups of medicinal products in the NHS, there must be at least a presentation of a generic or biosimilar medicinal product in each group of medicinal products. If there is no generic or biosimilar medicinal product, a group must be created when the medicinal product or its main active ingredient has been authorised for at least ten years in Spain or in another EU member state, provided there is a medicinal product different from the innovator and its licensed products.
Royal Decree 177/2014 also provides that reference pricing orders must be drafted in April of each year, which gives more certainty to the system.
The reference price for each group, updated every year, is the lowest cost per treatment per day within the presentations of the group. The availability of lower-priced medicinal products in pharmacies must be guaranteed. Royal Decree 177/2014 also provides:
In certain cases (presentations of medicinal products with special dosages of active ingredient, of use in serious pathologies or when prices have been revised by lack of profitability) where the price adjusted by the reference price system does not guarantee its economic viability, a weighted reference price will apply.
A minimum threshold of EUR1.60 as the reference price.
The presentation in Spain will be marketed at the lowest price in an EU member state if:
The minimum threshold or the weighted reference price has been applied.
The same presentation is commercialised in that EU member state.
The presentation has a lowest price than that in Spain.
In addition to the reference pricing system, there are "homogenous groups" which include the presentations of financed medicinal products with the same:
Route of administration.
Such products have to be interchangeable when dispatched. There are monthly updates of the price financed for each homogenous group.
Additionally, Article 92.5 of Royal Legislative Decree 1/2015 provides that the government must periodically review the list of the reimbursed medicinal products and medical devices according to:
The criteria of rational use.
The appearance of new medicinal products with a higher therapeutic use.
The appearance of side effects.
Reimbursement is normally paid by the NHS to the pharmacist (through the Official Association of Pharmacists of each region).
Also, Article 99 of Royal Legislative Decree 1/2015 establishes that certain groups of medicinal products may be included in a new system of selected prices. For financed medicinal products, this system can apply for medicines subject to reference prices, depending on:
The level of consumption of such products.
The impact on the NHS' budget.
The existence of a minimum of three medicinal products within the group.
The absence of a risk of non-availability.
The pharmacist must dispense the lowest priced medicinal product in each homogenous group. There is no specific compensation for the pharmacist for his dispensing services. The remuneration of the pharmacist consists of a margin established by law (currently Royal Decree 823/2008 16 May establishing the margins, deduction and discounts corresponding to the distribution and dispensing of medicinal products).
The above provisions are likely to be reformed in the forthcoming Royal Decree on Pricing and Reimbursement.
Legislation and regulatory authorities
Clinical trials with medicinal products are regulated by Royal Decree 1090/2015 on clinical trials. The AEMPS is the authority responsible for approval of clinical trials.
Trials can be submitted to the AEMPS for authorisation once a favourable opinion from the relevant ethics committee on clinical investigation has been received. The ethics committees are independent organisations that must be accredited by health authorities of the Autonomous Communities and the AEMPS. The approval of the centres where the clinical trial is to be carried out must also be provided. The following time limits apply to the process:
10 days from application. The AEMPS must decide whether the application meets legal requirements. If it does, the AEMPS informs the applicant that the application is admitted and the application process starts.
60 days from admission of the application. Authorisation is considered to have been granted if the AEMPS does not oppose it, provided the applicant has previously notified the AEMPS of the favourable opinion of the relevant ethics committee and the centre's approval. An express response is not usually given.
15 days from refusal. If the AEMPS refuses to authorise the application, the applicant has this period to modify its application or make any necessary statements. The AEMPS makes an express decision on the revised application, which is final.
The following trials require the AEMPS' prior written authorisation, and are subject to special procedural rules:
Trials where the AEMPS has notified objections to the sponsor.
Trials that refer to products that require qualification as products under clinical investigation. These products are pharmaceutical forms of active ingredients that are investigated or used as a reference in a clinical trial (including products with MA), which are:
used or combined differently from the authorised form;
used to treat an unauthorised symptom; or
gain more information on the authorised use.
Trials that are undertaken with medicinal products relating to:
somatic cell therapy; and
medicinal products containing genetically modified organisms.
These authorisations have the same time limits as the ordinary applications but if the applicant receives no response to the application from the AEMPS within 60 days, the application is deemed refused. The time limit is 90 days for trials with medicinal products relating to gene therapy, somatic cell therapy and containing genetically modified organisms. For medicinal products relating to xenogeneic cell therapy, the AEMPS is not under any time limit to either authorise or reject the clinical trial.
A participant in a clinical trial must consent to participation after having understood, in an interview with an investigator working for the hospital where the trial is to be carried out, the following (Article 4, Royal Decree 1090/2015):
The trial's objectives.
Its risks and inconveniences.
The conditions under which it will be undertaken.
The participant's right to withdraw the consent at any time without expressing the real reason for the withdrawal.
The participant's consent must be documented in a specific form. The requirements under Article 4 of Law 14/2007 on biomedical investigation must be met if biological samples are involved in the clinical trial.
Sponsors are responsible for obtaining insurance to cover any harm that could arise to trial subjects as a consequence of the trial (Article 9, Royal Decree 1090/2015 on clinical trials). The insurance must provide liability cover for the sponsor, the principal investigator, its collaborators and the centre.
The minimum amount of the insurance cover is EUR250,000 per patient participating in the clinical trial. The maximum amount is limited to EUR2.5 million per year and per clinical trial.
The trial starts once:
The sponsor has obtained the relevant authorisation and consent (see above Authorisations and Consent).
Obtained the insurance cover.
The agreement between the parties for performing the clinical trial has been signed.
The trial must be performed according to the trial protocol, legal and ethical regulations, and good clinical practices. In particular:
The principal investigator must regularly inform the ethics committee of the progress of the clinical trial (Article 41, Royal Decree 1090/2015).
The sponsor must notify the health authorities, the investigators and the ethics committees involved of any serious and unexpected adverse reaction (Article 39, Royal Decree 1090/2015).
The sponsor must immediately inform the investigators and the ethics committee of any relevant information that emerges during the conduct of the trial.
Once the clinical trial has finished, the sponsor must notify this to the AEMPS and the ethics committees involved, within 90 days of the end of the study. Within one year of the trial termination, the sponsor must send the AEMPS a final report on the study's results. Additionally, if the term of the clinical trial is longer than one year, the sponsor must send the AEMPS and the ethics committees involved an annual report on the development of the study.
Applications are made to the AEMPS in Spanish through the online application set out by the AEMPS. However, the AEMPS may authorise one or certain parts of the scientific-technical documentation to be filed in another language. Certain information and documents must be provided with the application (Article 7.2, Royal Decree 824/2010).
The conditions are as follows (Article 6, 15 and 16, Royal Decree 824/2010):
Personnel requirements. The manufacturer must have sufficient technically qualified personnel, under the management of a technical director, to guarantee the product's quality and perform the required controls. Manufacturing laboratories must also have an employee responsible for quality control and for the manufacturing process. Although, under very specific circumstances, the technical director can perform the duties of quality control, a separate person must always be responsible for the manufacturing process.
Material and technical requirements. A manufacturing laboratory must have suitable and sufficient premises and technical and control equipment for the manufacturing activity.
Quality requirements. Laboratory processes must comply with the Good Manufacturing Practices and the MA conditions (see Question 9).
Restrictions on foreign applicants
There are no restrictions on foreign applicants.
Key stages and timing
The AEMPS verifies the information and documents provided, and must make a reasoned decision within 90 days of the application. If all requirements are met, the AEMPS grants the authorisation, which must be immediately communicated to the Autonomous Communities. This authorisation is then entered in the Registry of Pharmaceutical Laboratories. If an applicant fails to meet these requirements, the AEMPS informs the applicant of its unfavourable decision and provides the applicant with 15 days to provide the relevant information. If the AEMPS does not communicate a decision within three months of the application's submission, the application is dismissed. There is a right of appeal to the AEMPS. If that appeal is unsuccessful, an administrative appeal can be made to a court. During the application, the AEMPS:
Inspects the premises.
Informs the applicant on remediable defects and gives the applicant a period in which to remedy those defects.
The AEMPS can also:
Require pending information for the validity of the application to be provided within ten days (the application is set aside if the information is not provided).
Hear statements from the applicant.
For current details on payable fees, see the Tasas section in the Industria division of the AEMPS' website (www.aemps.es). For 2015, the fee payable for an authorisation to begin activity as a pharmaceutical laboratory is EUR5,916.36.
Period of authorisation and renewals
Authorisations are granted for an indefinite period.
Monitoring compliance and imposing penalties
The health authorities of the Autonomous Communities periodically monitor compliance with manufacturing authorisations. They have powers to inspect, supervise and fine.
If there exists or there are reasonable grounds to suspect an imminent and serious risk to health, the AEMPS and the health authorities of the Autonomous Communities can impose:
Fines. The level of the fine depends on whether the infringement is classed as minor, serious or very serious.
Interim measures. These are used if there is reasonable suspicion of an imminent and serious risk to health, and can be imposed by both the AEMPS and the Autonomous Communities. They include a number of measures, such as:
putting into quarantine;
suspending medicinal products from manufacturing, import, marketing, export, advertising and use;
provisionally closing establishments, centres and services; and
suspending the elaboration, prescription, dispensing or supply of medicinal products under research.
Additionally, the AEMPS can suspend or revoke the manufacturing authorisation if the pharmaceutical laboratory ceases to meet the requirements to obtain such authorisation under Article 6 of Royal Decree 824/2010. The maximum term to notify the decision on the suspension or revocation of the authorisation is six months from the date of the AEMPS' agreement to initiate the procedure, or from the date the application is filed.
If the AEMPS decides to suspend or revoke the manufacturing authorisation, the manufacturing laboratory must cease its activities from the date of notification of the decision. The AEMPS will immediately notify the Autonomous Communities of the decision adopted.
Authorisation and abridged procedure
An application for a MA must be made in Spanish to the AEMPS, and signed by the applicant and the laboratory's technical director. In some circumstances, an application must be made to the EMA.
To receive a MA, a medicinal product must (Article 10, Royal Legislative Decree 1/2015):
Achieve the established quality requirements.
Be safe (that is, in normal conditions of use it does not produce toxic or unwanted effects disproportionate to the benefit obtained).
Have shown its efficacy for the therapeutic purposes for which it is offered.
Be correctly identified and accompanied by the required information (accessible and comprehensive for the patient).
Key stages and timing
The AEMPS must decide whether to grant or refuse the application within 210 days from the application date (Royal Decree 1345/2007). The following are the key stages:
The AEMPS receives the application and ensures it is complete. If not, it gives the applicant ten days to provide the required documentation (for example, the results of pharmacological or toxicological tests or clinical trials). Once the application is considered valid, the AEMPS evaluates the documentation and makes an assessment report. To this purpose, the AEMPS can request additional documentation to be filed within a term of three months. This interrupts the 210-day period. If this information is not provided, the AEMPS informs the applicant and, after three months, if the information is still not provided the application expires.
On the AEMPS' request, the Committee of Medicinal Products for Human Use (Committee), an official body of the AEMPS, issues a non-binding report during the 210-day period.
The AEMPS makes a final decision on the application within ten days of the Committee's report (if provided).
The AEMPS' decision sets out the medicinal product's marketing conditions, including the text, labelling and packaging requirements to comply with the Summary of Product Characteristics (Technical Deed). At the same time, the product is also entered into the Registry of Medicinal Products (Registry).
The following fees apply:
EUR20,734.46 for MA and entry in the Registry for medicinal products.
EUR8,434.22 for MA and entry in the Registry for a generic medicinal product.
EUR2,342.71 for renewal fees (see below).
For further details on fees payable, see the section Tasas within the division Industria of the AEMPS' website (www.aemps.es).
Period of authorisation and renewals
MAs are granted for an initial period of five years. The authorisation can be renewed after five years following a re-evaluation of the risk-benefit relation. Renewal is for an indefinite period unless pharmacovigilance reasons justify it being submitted to a new renewal procedure. Additionally, the MA holder must annually declare to the AEMPS its intention to market the medicinal product (Article 21.3, Royal Legislative Decree 1/2015). The MA expires (sunset clause) if either:
Its holder does not effectively market the medicinal product within three years.
Once on the market, the medicinal product is not available for three years (that is, the medicinal product is no longer available or being produced).
Monitoring compliance and imposing penalties
The powers of the AEMPS and the health authorities of the Autonomous Communities in their territories to monitor compliance with and enforce MAs are similar to those that can be used if there is a breach of a manufacturing authorisation (see Question 8).
Post-marketing commitments and pharmacovigilance obligations
The MA holder must (Article 62, Royal Decree 1345/2007):
Maintain the conditions of the MA.
Observe the principle of continuity in the provision of the service.
Maintain an updated dossier of the product.
Contribute to the knowledge of the medicinal product and to promote its rational use.
Collaborate on control programmes and notify of any product's withdrawal from the market.
Guarantee waste collection of medicinal products at particular addresses of patients.
Comply with any other obligation provided by the applicable laws and regulations.
In accordance with pharmacovigilance good practices, MA holders must advise the health authorities of the Autonomous Communities where the informing healthcare professional is located of any suspected adverse reactions they become aware of, and which might have been caused by the medicinal products they manufacture or market.
Also, under national (Royal Decree 577/2013 on the pharmacovigilance of medicinal products and Article 53.4 of Royal Legislative Decree 1/2015) and European guidelines, MA holders must:
Continually update the information relating to the safety of the product.
Execute pharmacovigilance plans and risk management programmes.
Carry out continuing assessments of the risk-benefit relation of the medicinal product.
The obligations of MA holders are set out under Article 62 of Royal Decree 1345/2007. The authorisation can be refused on the following grounds (Article 20, Royal Legislative Decree 1/2015 and Article 19, Royal Decree 1345/2007):
When the risk-benefit relation is not favourable.
When the therapeutic efficacy is not sufficiently demonstrated.
When the medicinal product does not have the declared qualitative and quantitative composition or lacks the appropriate quality standard.
When the data and information contained in the documentation of the application for authorisation submitted are erroneous or do not comply with the applicable regulations.
The distribution of authorised medicinal products must be carried out through distribution entities or directly by the laboratory holder of their MA (Article 67, Royal Legislative Decree 1/2015). The distribution activity must ensure a quality service having as its priority and essential function the supply of pharmacy offices and pharmacy services legally authorised in Spain.
Distribution entities and, if applicable, pharmaceutical laboratories distributing their products directly, must ensure (Royal Legislative Decree 1/2015):
Minimum stocks of medicinal products to guarantee adequate continuity of the supply.
Delivery time limits are met.
A minimum delivery frequency.
Permanent technical pharmaceutical advice.
A means of support to pharmacy offices and services.
As a recent development, Royal Decree 782/2013 11 October on distribution of medicinal products for human use regulates the activity of brokering medicinal products. This consists of all activities that do not include physical handling and that consist in negotiating independently and on behalf of another legal or natural person. Brokers must be registered in a register held by the AEMPS.
An abridged procedure, where the applicant is not required to provide the results of pharmacological or toxicological tests or clinical trials, is available when one of the following applies:
The application is made with the consent of an MA holder of a medicinal product with the same qualitative and quantitative composition and identical pharmaceutical form.
The active ingredient of the relevant medicinal product has a clearly established medicinal use of at least ten years in the EU, with known efficacy and an acceptable level of security established by a detailed scientific bibliography.
The medicinal product is a generic of a reference medicinal product authorised under EU regulations for a minimum period of eight years. The generic medicinal product, however, cannot be marketed in Spain until ten years have elapsed since the initial MA was granted (or 11 years if a relevant new indication is subsequently authorised).
EU regulations provide for mandatory mutual recognition of MAs granted by EU member states. If an application is filed for MA of a medicinal product that has already been examined by another member state's health authority, the AEMPS suspends examination of the application until it receives a report from that health authority. Within the following 30 days, the AEMPS must either:
Grant the authorisation.
Start a consultation period (if, on public health grounds, the medicinal product cannot be authorised), in which representations of the applicant and the relevant member states are obtained. If the AEMPS still refuses to accept the application, a European Commission conciliation procedure starts, following which the Commission issues a final decision.
The AEMPS has a similar intervening role in the decentralised procedure, which was also introduced by EU regulations. (The decentralised procedure differs in that medicinal products have not been examined or received MA at the time of application.)
Royal Decree 1785/2000 (as modified by Royal Decree 11/2005) regulates parallel imports of medicinal products in the EU. The following requirements must be met before a member state's medicinal product can be authorised in Spain.
Technical requirements. The following requirements must be met:
The medicinal product must have MA in the member state of origin and be entered in the AEMPS' Registry of Medicinal Products.
The labelling and packaging of the medicinal product must meet requirements set out in Royal Decree 1345/2007 (see Question 18).
The conditioning material (that is, the label and the leaflet with the product) must contain information required under Royal Decree 1785/2000 and specify that the medicinal product has been the object of parallel trade.
Any repackaging must be carried out according to applicable Spanish law and must not affect the medicinal product's original contents.
Qualification requirements. If the parallel importer carries out the conditioning, repackaging or relabelling of the medicinal product in Spain, it needs to be qualified as a manufacturer (Articles 6, 7 and 15, Royal Decree 824/2010). Otherwise, the parallel importer must be qualified as a distribution entity (Articles 13 to 19, Royal Decree 782/2013).
Information requirements. Before the medicinal product is marketed in Spain, the parallel importer must:
Notify the Spanish holder of the MA of its intention to market the product in its territory and, on the holder's request, provide a sample of the repackaged product, to verify that the product does not damage the trade mark's reputation.
Keep, for at least two years following the expiry date of the imported product, data on every product batch for the health authorities.
Inform the AEMPS when it stops importation activities.
Give prior notice to the AEMPS when it intends to send certain medicinal products to other EU member states (Circular 2/2012). These are listed on its website (www.aemps.gob.es), and are medicinal products considered to be at risk of non-availability. If the AEMPS considers there is a supply problem, it will refuse authorisation to export. In addition to the parallel importer, the AEMPS must inform the health authority of the relevant Autonomous Community which has the duty to enforce the export ban.
For information on pharmaceutical patents, trade marks, competition law, patent licensing, generic entry, abuse of dominance and parallel imports, see Pharmaceutical IP and Competition Law in Spain: overview ( www.practicallaw.com/0-569-3265) .
Restrictions on dealings with healthcare professionals
It is prohibited to (directly or indirectly) give, offer or promise, to professionals authorised to prescribe or dispatch medicinal products, their relatives or co-habiting people any bonus, pecuniary advantage or benefit-in-kind, discount or gift. Early payment discounts or discounts on account of sales volumes are allowed to the extent they are not made to the detriment of competitors and are included in the corresponding invoice. The same conditions apply in the case of reimbursed medicinal products with the limit that discounts must not exceed 10%.
However, hospitality for events of an exclusive professional or scientific character is allowed, provided it is secondary to the main purpose of the event and is not extended to non-healthcare professionals. Gifts, scholarships and sponsorship made to meetings, congresses and similar events involving doctors must exclusively benefit the event's scientific purpose.
From 1 January 2015, companies subject to the Farmaindustria's Code of Conduct for the Promotion of Medicinal Products (Code) must document and disclose the following transfers of value made directly or indirectly to (Article 18, Code):
A health organisation in Spain:
contributions to costs related to events (including registration fees, sponsorship agreements, travel and accommodation expenses);
fees for services.
A healthcare professional whose primary place of practice is Spain:
contribution to costs related to events (including registration fees and travel and accommodation expenses);
fees for services.
Farmaindustria is the main Spanish association gathering research-based pharmaceutical companies.
Sales and marketing
Prescription medicinal products and OTC medicinal products must be sold in pharmacies. Retail outlets are only allowed to sell products which are not medicinal products such as food supplements and some types of medical devices subject to certain conditions.
The sale of prescription-only medicines by post and by telematic procedures is prohibited (Article 3.5, Royal Legislative Decree 1/2015). The door-to-door sale of medicinal products and any type of indirect sales to the general public is prohibited.
Royal Decree 879/2013 8 November, approved on 9 November 2013, permits the telematic sale of non-prescription medicinal products, provided the sale is made both:
Through the website of a legally authorised pharmacy, which has made a prior notification to the Health Authorities of the Autonomous Community where it is located.
With a prior personalised assessment by a pharmacist from the pharmacy.
Since the approval of Royal Decree 879/2013, various steps have been taken to make the telematic sale of non-prescription medicinal products available to the public. In July 2015, Regulation 699/2014 on the design of the common logo to identify persons offering medicinal products for sale at distance to the public has been implemented in Spain. The AEMPS has set up a website named distafarma.aemps.es, where pharmacies must register online and be approved by the AEMPS to start their online sales, and put the EU logo on their website to verify they are operating legally. Currently over 200 pharmacies in Spain have registered and are operating as online pharmacies.
Legislation and regulatory authority
Advertising of medicinal products for human use is regulated by:
Royal Legislative Decree 1/2015.
Royal Decree 1416/1994.
DGFPS Circular 6/95.
Some of the Autonomous Communities have adopted regional codes that apply in their territories. Restrictions on advertising a medicinal product differ depending on if it is addressed to the general public or to healthcare professionals.
The Ministry of Health and the health authorities of the Autonomous Communities can enforce legislation on the advertising of medicinal products.
General public. Only medicinal products that have been authorised as publicity medicinal products (medicamentos publicitarios) can be advertised to the general public. From 25 July 2013, no prior administrative authorisation is required for advertising of non-prescription medicinal products (Article 80.3, Royal Legislative Decree 1/2015.).
Public medicinal products are usually OTC products.
Healthcare professionals. A notification must be made to the competent health authority of the relevant Autonomous Community where the laboratory is located. The advert must satisfy the requirements set out in:
Article 78 of Royal Legislative Decree 1/2015.
Royal Decree 1416/1994.
The applicable regional guidelines.
Pharmaceutical companies associated with Farmaindustria (the main Spanish association of research-based pharmaceutical companies) also need to comply with the Code of Conduct for the Promotion of Medicinal Products (Code).
The Code has been recently updated to include, among others, the:
Codes of the European Federation of Pharmaceutical Industries and Associations (EFPIA) on Interaction with Healthcare Professionals and on Interaction with Patient Organisations and Transparency.
Code of the International Federation of Pharmaceutical Manufacturers.
The update to the Code also involves changes to the system of self-regulation in the pharmaceutical industry. The Code covers not only promotion of prescription medicinal products but also interaction of company members of Farmaindustria with health professionals, health institutions and patient associations. Consequently, the Code also applies to OTC medicinal products in relation to incentives, hospitality and interaction with health professionals, health institutions and patient associations.
The update to the Code also introduces obligations on the digital promotion of medicinal products. It obliges company members of Farmaindustria to establish:
Usage and style guidelines.
Rules of conduct and consequences for non-compliance.
A procedure for monitoring the content that they provide access to, host, temporarily copy, or link to.
In general, no exaggerated or general statements are permitted in medicinal product adverts. In this sense, claims such as excellent, maximum, perfect, total, or similar, linked to the quality, efficacy, safety or purity of a medicinal product, are not permitted.
General regulations apply to advertising over the internet. However, the following must also be taken into account:
Promotional material of prescription medicinal products on the internet can be addressed to healthcare professionals, as long as it is provided in a technical and/or scientific or professional context, and in websites exclusively targeted to healthcare professionals. Websites must allow access to healthcare professionals only (through technical and/or legal mechanisms) and contain clear and legible warnings stating that the information contained in the website is exclusively addressed to healthcare professionals entitled to prescribe or dispense medicinal products. The updated Code requires healthcare professionals who access such websites to declare they are healthcare professionals entitled to prescribe or dispense medicinal products.
No website targeted to healthcare professionals can include in its domain name the name or brand of a prescription-only medicinal product (as this would be considered as promotion aimed to the general public).
Websites, banners, digital press, social networking sites, blogs and audiovisual materials on the internet are considered suitable ways of promotion, as long as they comply with the legal provisions of promotion of medicinal products and the Code (see above, Restrictions).
The Data Protection Regulations have a substantial impact on pharmaceutical regulations, to the extent pharmaceutical companies process any personal data from data subjects (patients, consumers or website users). The impact is higher when the types of data processed by laboratories qualify as health-related data (for example, clinical history records), as additional care must be taken when collecting, processing, communicating and securing these data.
For example, the Data Protection Regulations impact generally when collecting, processing and communicating patient data in a clinical trial, a biomedical research project or when reporting an adverse drug reaction (ADR). In these scenarios, the Data Protection Principles enshrined by the Data Protection Regulations (for example, the principles of information, quality of data and consent from data subjects) are key, as the previous and informed express consent from patients must be collected.
Packaging and labelling
Legislation and regulatory authority
The information that labels and leaflets must contain to guarantee proper identification and correct use of medicinal products is set out in:
Royal Legislative Decree 1/2015.
Royal Decree 1345/2007.
DGCB' Circular 29/1994.
AEMPS' Circular 2/2000 (as modified by Circular 1/2002).
The regulatory authority is the AEMPS.
The text and other features of the packaging and leaflet form part of the MA and must:
Be authorised by the AEMPS.
Reduce the technical terminology to a minimum and be legible and clear to ensure it is understood by the patient.
Comply with the Summary of Product Characteristics.
Identify the holder of the MA and the manufacturer of the product.
Include instructions for the administration, use and conservation of the product.
Include the adverse effects, interactions and contraindications.
Include the measures to be adopted in case of intoxication.
Provide the complete quality composition and the pharmaceutical form.
Include the expiry date of the product.
Include the date of the last review of the leaflet.
The text and other features of the packaging and leaflet must be written in Spanish.
See also Question 9.
The Pharmacovigilance Spanish System for medicinal products for human use is set out in:
Royal Legislative Decree 1/2015.
Royal Decree 577/2013 26 July governing pharmacovigilance of medicinal products for human use.
The regulatory authority is the AEMPS and 17 regional pharmacovigilance centres.
For the reporting of defects, the notification system and information varies, depending on the notifier and the risk to health associated with the incidents detected.
For notification by the marketing authorisation holder (MAH):
If an imminent and serious danger to health is suspected, the MAH must notify the AEMPS within 48 hours.
For other quality defects, the MAH must notify the AEMPS within seven to 15 calendar days of the MAH becoming aware of an adverse reaction.
Notification must be made to the AEMPS by e-mail (email@example.com).
For notification by the competent health departments of the Autonomous Communities:
If an imminent and serious danger to health is suspected, the Autonomous Communities must notify the AEMPS by e-mail.
For other quality defects, the Autonomous Communities must notify the AEMPS through LABOFAR or by e-mail (firstname.lastname@example.org).
For notification by individuals or other entities (health professionals, hospitals, pharmacies, distribution entities, official college of pharmacists, and so on):
If an imminent and serious danger to health is suspected, notification must be made directly to the AEMPS by e-mail.
For other quality defects, notification must be made to the competent health departments of the Autonomous Communities.
The information regarding quality defects is addressed, as a general rule, to the distribution and dispensing chain (distribution entities, pharmacies and pharmaceutical services of hospitals).
A product recall is a precautionary measure and will normally refer to a specific batch. The AEMPS can:
Order a product recall if it detects either:
any quality problem with a medicinal product and there is a health risk; or
an illegal medicinal product.
Agree on a provisional and urgent modification of the medicinal product information.
Temporally suspend or definitively revoke an MA when certain safety or risks to health arise.
For traceability obligations, Article 90 of Royal Legislative Decree 1/2015 has been modified as follows:
Pharmaceutical laboratories must communicate to the Ministry of Health the units of presentations, identified by batches of medicinal products and recipient, sold in Spain, as well as those that have been returned. They must also guarantee the identification of every unit throughout its circulation.
Distribution entities (a pharmacy or pharmacy service or other distribution entity) must notify the following to the Autonomous Community where they have their registered office and the Ministry of Health, independently of the Autonomous Community where they are located:
the number of units supplied and returned; and
an indication of the batch to which they belong and the recipient.
Pharmacies must communicate to the competent body of the Autonomous Community where they carry on their activities the number of units of medicinal products dispensed. The competent bodies of the Autonomous Communities must send this information to the Ministry of Health.
Liability can arise under the following provisions:
The Civil Code, which applies to contractual or extra-contractual (that is, tortious) liability.
Royal Decree 1/2007 of 16 November 2007, which harmonises product liability rules for defective products.
Manufacturers and/or importers are liable if the claimant proves all of the following:
That the product is defective.
A causal relationship between the defect and the damage.
The following may be liable:
The manufacturer and importer are liable for damage caused by a defect in a product that they have manufactured or imported (Article 135, Royal Decree 1/2007). If neither the manufacturer nor the importer can be identified, the supplier of the product will be considered liable unless, within three months, he discloses the identity of the manufacturer and/or importer or the person who he identifies as the person who supplied the product (Article 138.2, Royal Decree 1/2007).
Other persons involved in the manufacture, import or sale of the defective product (or other operation relating to the marketing of the defective product) can be liable for damage attributable to them (Articles 1088 et seq (in relation to contractual liability) and Articles 1902 et seq (in relation to non-contractual liability), Civil Code).
Other persons can be liable for non-contractual liability under the Civil Code if the injured person can prove, in addition to the damage, an act or omission caused by fault or negligence which is causally related to the damage.
Under contractual liability, any person involved in the manufacture or sale of the defective product can be held liable if the injured person proves, in addition to the damage, breach of contract by fault, negligence, or a delay in complying with a contractual obligation, which is causally related to the damage.
The manufacturer or importer is not liable if it can prove one or more of the following:
It did not put the product into circulation.
The defect that caused the damage did not exist at the time when the product was put into circulation.
The product was not manufactured for sale or any form of distribution with an economic purpose, or it was not manufactured, imported or distributed by the manufacturer or importer in the course of its business.
The defect is due to the product complying with existing mandatory regulations.
In the case of a manufacturer or importer of a component, the defect is attributable to the design of the product in which the component has been fitted or to the instructions given by the manufacturer of the product.
Fault on the claimant's part can diminish or extinguish the manufacturer's or importer's liability. If proceedings are brought against other persons under the Civil Code, the claimant must prove that the defendant is liable for the damage through fault, negligence or breach of contract.
A limitation period of three years runs from the day on which the claimant suffers the damage, provided the identity of the person liable for the damage was known (Article 143, Royal Decree 1/2007). The right to bring proceedings ends on the expiry of ten years from the date on which the product which caused the damage was put into circulation (Article 144, Royal Decree 1/2007).
For actions brought under the Civil Code, the limitation periods are 15 years for contractual liability and one year for extra-contractual liability (Articles 1964 (contractual liability) and 1968, section 2 (non-contractual liability), Civil Code).
Class actions for product liability claims filed by associations of consumers and users are permitted (Articles 6.1.7 and 6.1.8, Law 1/2000). However, there is no relevant case law, as class actions for product liability claims are relatively new and uncommon.
The following remedies are available, depending on the relevant law:
An action for damages is available for contractual and extra-contractual liability under the Civil Code and Royal Decree 1/2007.
An action for damages on the basis of product liability under Royal Decree 1/2007, where the product defect caused death, physical injuries or material damage in other goods used by the claimant for private consumption.
Punitive damages are not allowed for product liability claims. In Spain, damages are always intended to compensate for the damage suffered.
Royal Legislative Decree 1/2015 still requires development through a number of Royal Decrees. Many provisions of Royal Legislative Decree 1/2015 do not appear to be enforceable until such legislation is enacted. Specific legislation is currently being developed, in particular with regard to the regulation of prices and reimbursement procedures. There is a new Royal Decree, Royal Decree 1090/2015 on clinical trials, which replaces the prior Royal Decree 223/2004. The new regulation improves the authorisation procedure and the transparency of clinical trials.
For information on pharmaceutical patents, trade marks, competition law, patent licensing, generic entry, abuse of dominance and parallel imports, see Pharmaceutical IP and Competition Law in Spain: overview ( www.practicallaw.com/0-569-3265) .
Agency on Medicinal Products and Medical Devices (AEMPS)
W www.aemps.gob.es/legislacion/portada/home.htm (The English translation is for guidance only.)
Description. The AEMPS is the state agency responsible for the quality, safety, efficacy and accuracy of information in respect of medicinal products and medical devices.
W www.farmaindustria.es/Farma_Public/Codigo/index.htm (The English translation is for guidance only.)
Description. Farmaindustria is the Spanish Association for the Pharmaceutical Industry in Spain. A vast majority of research-based pharmaceutical companies in Spain are members of Farmaindustria.
Description. Fenin is a Spanish association that gathers together manufacturers, importers and distributors of medical devices and medical technologies in Spain.
Héctor Jausàs, Partner
Professional qualifications. Spain, Solicitor, 1995
Areas of practice. Pharmaceutical and healthcare law; EU law; competition law.
Languages. Spanish, Catalan, English, French.
Professional associations/memberships. Member of Conferénce Bleue (European Lawyers' Conference on Pharmaceutical and Health Care Affairs) since 1997 and Co-Managing Partner since 2012.
Publications. Author of the International Encyclopedia of Agency and Distribution Agreements, Kluwer Law International, 1997. Since 1996, he has been a regular contributor to influential magazines and newspapers, including JANO Medical Journal.
Maria Cedó, Senior Associate
Professional qualifications. Spain, Solicitor, 2001
Areas of practice. Pharmaceutical and healthcare law; EU law; competition law.
Languages. Spanish, Catalan, English, French, Russian.
Publications. Maria usually collaborates with several Spanish specialised magazines, such as Economist and Jurist.