Regulatory, Pricing and Reimbursement
Key legal info on regulatory, pricing and reimbursement in Spain. Prepared in association with Faus & Moliner Abogados, a leading law firm in Spain, this is an extract from The Pharma Legal Handbook: Spain, available to purchase here for USD 99.
1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?
The main regulatory authorities in Spain are:
- The Spanish Ministry of Health, Consumption and Welfare (‘Spanish Ministry of Health’), which is the department of the central Spanish government responsible, among others, for drafting and implementing the rules on pricing and reimbursement of medicinal products that are financed through public funds in Spain.
- The Spanish Medicines Agency of Medicinal Products and Medical Devices (i.e. Agencia Española de Medicamentos y Productos Sanitarios – ‘AEMPS’), which is also part of the central Spanish government and is responsible, among others, for granting marketing authorizations for medicinal products (drugs and biologicals) in Spain through the national, mutual-recognition, or decentralized procedures foreseen in the European regulations and with jurisdiction over medical devices and cosmetics as well.
2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?
The Spanish current regulatory framework regarding authorization, pricing and reimbursement of medicinal products, including biologicals, and medical devices includes (i) Royal Decree-Legislative 1/2015, approving the revised text of the Law on Guarantees and Rational Use of Medicinal Products and Medical Devices (‘Spanish Law on Medicinal Products’), (ii) Royal Decree 1345/2007 on authorization of industrially manufactured medicinal products, (iii) Royal Decree 271/1990, Royal Decree 83/1993, Order of 17 December 1990 and Order of 6 April 1993 on price and reimbursement, and (iv) Royal Decree 177/2014 establishing the Reference Price System. Likewise, Royal Decree-Law 8/2010 (amended by Royal Decree-Law 9/2011), established different mandatory discounts on the ex-factory price of the medicinal product when such medicinal product is dispensed or administered to patient through public funding.
The Spanish current regulatory framework regarding authorization, pricing and reimbursement of medical devices includes (i) Spanish Law on Medicinal Products, (ii) Royal Decree 1591/2009, on medical devices, (iii) Royal Decree 1616/2009, on active implant medical devices, and (iv) Royal Decree 1662/2000, on “in vitro” diagnostic medical devices.
3. What are the steps to obtain authorization to develop, test, and market a product?
Any person or entity that wishes to manufacture medicinal products or medical devices in Spain, must be previously authorized as manufacturer by the AEMPS, in compliance with the provisions contained in Royal Decree 824/2010 or Royal Decree 1591/2009, as the case may be.
A medicinal product can be placed in the Spanish market if it previously holds a marketing authorization obtained by one of the following procedures:
- national procedure, mutual-recognition procedure, or decentralized procedure at the AEMPS; or
- centralized procedure at the European Medicines Agency.
As regards medical devices, please note that they are divided in four classes (III, IIb, IIa and I), ranked mainly considering the level of invasiveness of the device, the part of the body it is in contact with and the duration of such contact. Except for custom-made devices, all medical devices must bear a CE marking of conformity when they are placed in the market in Spain. The CE marking evidences conformity of the device with the requirements of the applicable laws. For class I devices, such conformity shall be evaluated and declared under the exclusive responsibility of the manufacturer. For class IIa, IIb and III devices, the declaration of conformity requires an evaluation of the device by a notified body (the AEMPS in Spain or any other notified body of another European Union member state). Additionally, for class IIa, IIb and III devices, a communication must be made to the AEMPS the first time that a person places a medical device for distribution or use in the Spanish market.
Furthermore, testing of medicinal products or medical devices must be carried out in accordance with clinical investigation rules, which are mainly contained in Royal Decree 1090/2015 regulating clinical trials.
4. What are the approximate fees for each authorization?
The fees due to the AEMPS to be authorized as manufacturer of medicinal products are EUR 6,035.28. Also, in order to carry out clinical investigation with medicinal products, there are fees due to the AEMPS ranging from EUR 412.12 to EUR 4,327.22.
The fees due to the AEMPS to obtain a marketing authorization for a new medicinal product vary depending on whether such medicinal product is a generic or not:
|Marketing Authorization for a medicinal product (other than a generic)||EUR 21,151.22|
|Marketing Authorization for a generic medicinal product||EUR 8,603.75|
Besides, the fees due to the AEMPS to be authorized as manufacturer of medical devices are EUR 731.49 plus EUR 103.03. The fees in order to carry out clinical investigation with medical devices are EUR 824.24. No fees are due to the AEMPS in order to place a medical device in the Spanish market; however, if declaration of CE marking of conformity of the device is assessed by the AEMPS as a notified body, then there are fees due to the AEMPS that start in a range of EUR 754.13 to EUR 2,509.81, but may be higher depending on the complexity and scope of the assessment.
Kindly note that these fees are updated yearly according to the Spanish Budget Law. The Spanish Budget Law currently in force is the one for 2018, as the one for 2019 has not been officially approved and published yet.
5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?
The marketing authorization of a medicinal product is valid for five years. At least nine months before expiration of period, the marketing authorization holder may apply for a marketing authorization renewal, pursuant to article 27 of Royal Decree 1345/2007. Together with the renewal application, the applicant must pay the relevant fees (EUR 2,389.80) and provide a consolidated version of the registration dossier including evaluation data contained in suspected adverse reactions reports and periodic safety update reports, as well as all the variations introduced since the marketing authorization was granted.
Once renewed, the marketing authorization will be valid for an unlimited period, unless the AEMPS requires an additional five-year renewal based on duly justified pharmacovigilance-related reasons.
6. How does the authorization process differ between brand-name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?
The authorization of both a brand-name medicinal product and a generic medicinal product follow the same legal process. There are only minor differences as regards the fees to be paid to the AEMPS (as explained in Question 4 above) and as regards the application documentation since the authorization procedure of a generic medicinal product does not require the applicant to provide pre-clinical tests and of clinical trials results (bioequivalence studies must be provided instead of).
7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug +biologic + device) regulated?
There is no specific regulation for combination products in Spain. Please note that biologics are considered as medicinal products and, thus, subject to the same rules.
A combination product comprising both a medicinal product and medical device may be authorized as a medicinal product. E.g. an injectable medicinal product that comes in a pre-filled syringe; such product may be authorized as a medicinal product (although the syringe itself may be authorized as a medical device). It is also possible that a combination product comprising both a medicinal product and medical device is authorized as medical device. E.g. a medical device incorporating as an integral part a substance which, used separately, may be considered as a medicinal product (Judgement of the European Court of Justice in the Case C-527/17 Boston Scientific v Deutsches Patent).
The AEMPS has the final decision on the classification of any such combination product.
8. How is compliance with regulation monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?
The AEMPS as well as the Health Authorities of the Autonomous Regions (Spain is divided in 17 Autonomous Regions) are in charge of monitoring compliance with the applicable regulations in Spain. As the regulatory regime applicable in Spain is based in EU legislation and guidelines, it is aligned with the European Medicines Agency expectations and requirements.
9. What is the potential range of penalties for noncompliance?
The potential penalties for noncompliance of the regulatory regime range from EUR 30,000 to EUR 1,000,000. The amount of the penalty may exceed up to five times the value of the products or services subject to the infringement in case of very serious infringements. Examples of noncompliance include elaborating, manufacturing, importing, exporting, dispensing or distributing medicines without authorization to do so; modifying any of the conditions of the authorization without having the consent of the authorities; or marketing medicinal products without having obtained the authorization to do so.
Additional sanctions may also be agreed, such as confiscation of the illicit profit that has been obtained or shutting down the activities of the company during a period up to five years, in case of very serious infringements (Article 114.2 of the Spanish Law on Medicinal Products). Furthermore, sanctions for the commission of serious and very serious infringements will be published in the corresponding official journal.
10. Is there a national healthcare system? If so, how is it administered and funded?
Yes, there is a national healthcare system. It is administered by the Spanish Ministry of Health and also by the Health Departments of the Autonomous Regions. It is funded by tax of the contributors. The Ministry of Health is the department of the Spanish central government responsible for approving pricing and reimbursement of medicinal products. However, since the public funds that may be used to finance the reimbursement of medicines come out of the budget of the 17 Autonomous Regions in which Spain is divided, such regions participate in the committee of the Ministry of Health responsible for assessing applications for price and reimbursement of medicinal products.
11. How does the government (or public) healthcare system function with private sector healthcare?
Hospitals belonging to the National Health System (‘NHS’) are in the public sector, under the jurisdiction of the Spanish Ministry of Health as well as under the jurisdiction of the Health Authorities of the Autonomous Regions. Private sector hospitals, both profit-making and non-profit-making, have their own management arrangements.
The Ministry of Health and regional health administrations may contract with private hospitals to provide healthcare services to the users of the NHS whenever this is advantageous, especially considering the quality-cost binomial, and provided that the right of access is guaranteed.
12. Are prices of drugs and devices regulated and, if so, how?
Yes. Prices of medicinal products that are reimbursed may not be freely set by the marketer as they require the prior approval from the Ministry of Health. Also, in case that there are legitimate public reasons, the Ministry of Health may control the price of medicinal products that are not reimbursed.
Royal Decree 271/1990 states that the maximum ex-factory price of a reimbursed medicinal product should be equal to the cost of the product plus a given margin (12 – 18 per cent on capitals allocated to exploitation). As a matter of practice, however, the process of setting the price of a reimbursed medicinal product entails a negotiation of the price with public authorities. Additionally, companies are legally obliged to grant a discount on the maximum ex-factory price approved by the authorities.
With regard to reimbursed medical devices, the Spanish competent authorities are currently drafting a new Royal Decree that will regulate in detail the procedure of pricing and reimbursement of medical devices.
13. How are drugs and devices used by patients paid for? What roles do public and private payers play?
Autonomous Regions are the ones who pay for all healthcare services, including drugs and devices, out from their own budgets, and, subject to certain conditions which may derive from European and Spanish rules on public procurement, they enjoy a large degree of autonomy to decide how they purchase goods and services which they may require in order to provide healthcare services to patients.
The NHS pays for all those drugs and devices which are dispensed in hospitals. On the other hand, products that patients obtain at retail pharmacies are subject to copayment rules under which the patient has to pay part of the price of the product. The copayment percentage depends on the type of product and also on the type of patient.
14. Who dispenses drugs and devices to patients and how are those dispensers compensated?
The medicinal products can only be dispensed by the pharmacists. The patient withdraws the medicinal product from the pharmacy and, if applicable, pays to the pharmacist the amount of the copayment established by the law. Subsequently, pharmacy invoices the government of the Autonomous Region where it is established the selling price of the medicinal product (the maximum ex-factory price approved by the Ministry of Health), plus the margin set forth in the law for the wholesaler and for the pharmacy, less the amount paid by the patient. In the case of the medicinal products that are administered to patients in public healthcare centres and hospitals, such products are not paid by the patients but financed from the budget of the centre itself.
15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?
Pharmacists, as responsible for the dispensing of drugs and devices to the citizens, will ensure compliance of the guidelines established by the physician responsible for the patient in the prescription and will cooperate in the follow-up of the treatment by checking their effectiveness and safety.
Likewise, they will participate in activities aimed at the rational use of drugs, in particular through the information they provide to the patient. Once the drug has been dispensed, they will be able to provide personalized dosing systems to patients who request it, in order to improve adherence to the treatment, in the treatments and with the conditions and requirements established by the competent health administrations.