Cannabinoid drugs, medicinal cannabis and opioid drugs in Spain – a legal guide. 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 GBP 119.

 

Cannabinoid Drugs

For the purposes of this Chapter 8: Cannabinoid Drugs, Cannabinoid Drugs shall mean any industrially produced medicinal product which contains cannabinoids.

 

1. Are Cannabinoid Drugs authorized in your country?

Cannabinoid Drugs may be authorized in Spain on the basis of scientific criteria on its quality, safety and efficacy. The foregoing is provided that applicable regulations on narcotics, such as Law 17/1967 on narcotics, and Royal Decree 2829/1977 on narcotics and its production, distribution, prescription and dispensation are observed.

 

2. What are the regulatory authorities with jurisdiction over Cannabinoid Drugs?

The main Spanish authorities with jurisdiction over Cannabinoid Drugs are the Spanish Ministry of Health and the AEMPS. 

 

3. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Cannabinoid Drugs?

No. The general regulatory framework applicable for the authorization, pricing and reimbursement of medicinal products apply to Cannabinoid Drugs. 

There are, however, specific regulations that may be applicable to other activities related to Cannabinoid derivatives whenever they are considered narcotics, such as manufacturing, distributing, prescribing, dispensing etc. (see, among others, Law 17/1967, Royal Decree 2829/1977 and Royal Decree 1675/2012 on prescribing and dispensing narcotics for both human and veterinary use).

 

4. Which are the cannabinoid drugs that have received market approval to date?

To date, only Sativex 2,7 mg / 2,5 mg Oromucosal spray solution (“Sativex®”) has received market approval in Spain. Sativex® is a Cannabinoid Drug which contains, per each single 100 microlitre spray, 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD) from Cannabis sativa L. The marketing authorization holder of Sativex is GW Pharma Ltd. 

Sativex® has been classified as a hospital diagnosis drug, which means that it shall only be used for the treatment of diseases diagnosed either in hospitals or centres which have appropriate diagnosis means, or by specialized physicians (see art. 24.3.b of Royal Decree 1345/2007 on the procedure for authorization of industrially produced medicinal products for human use). 

Likewise, according to section 4.1 of the technical sheet of Sativex®, Sativex® must only be used “to improve symptoms of adult patients with moderated or serious spasticity due to multiple sclerosis” if “other anti-spasticity medicines have not worked” and “a significant clinical improvement has been observed regarding the symptoms of spasticity after an initial trial period of the treatment”.

 

5. Who can prescribe Cannabinoid Drugs?

Physicians, odontologists and veterinaries, each of them in the field of its competence, can prescribe narcotic drugs.

 

6. Is there a list of doctors authorized to prescribe Cannabinoid Drugs?

There is not a list of doctors authorized to prescribe Cannabinoid Drugs. Doctors, provided that they comply with the applicable requirements and procedures (which include the need to use the appropriate prescription forms), can prescribe Cannabinoid Drugs without need to be previously registered in any official list. It is to be noted that doctors holding prescription forms for narcotic drugs may be controlled (and, therefore, somehow listed) but these are lists relating to the prescription forms (holders of such forms are listed) and not related to the doctors themselves. 

 

7. What approvals or notifications are required to prescribe Cannabinoid Drugs?

Provided that applicable regulations are complied with (including the use of the appropriate prescription forms), doctors themselves do not have to ask for any specific approval or make any specific notification each time they prescribe Cannabinoid Drugs. 

 

8. Which organizations are authorized to sell/distribute Cannabinoid Drugs available?

Cannabinoid Drugs (provided that their dispensation to the public is not specifically restricted in their marketing authorization) can be dispensed to the public by authorized pharmacy offices/services. 

Cannabinoid Drugs can be distributed (that is, sold to either other authorized distribution entities or pharmacy offices/services) by any of the following entities provided that they comply with all applicable regulations on medicinal products and narcotics (such as Law 17/1967, Royal Decree 2829/1977 -and its complementary regulations- and Royal Decree 1675/2012): 

• Pharmaceutical laboratories;
• Distribution entities duly authorized to distribute medicines for human use (see Royal Decree 782/2013 on distribution of medicinal products for human use); and/or
• Distribution entities duly authorized to distribute veterinary medicines (see Royal Decree 109/1995 on veterinary medicinal products). 

 

9. Is there a list of retailers/distributors authorized to sell Cannabinoid Drugs?

• Retailers. The AEMPS, with the cooperation of the regional authorities, publishes lists including all pharmacy offices opened to the public in Spain. Such pharmacy offices can dispense Cannabinoid Drugs if they comply with applicable regulations (please refer to Question 8).
• Distributors. The AEMPS publishes lists including all entities authorized to distribute veterinary medicines and medicines for human use in Spain. All entities authorized to distribute Cannabinoid Drugs must be included in such lists.

 

10. Are there proposals for reform or significant change to the regulation of Cannabinoid Drugs?

We are not aware of any proposal to significantly reform the regulation of Cannabinoid Drugs in Spain. Spanish Law on Medicinal Products, which is the basic regulatory framework for medicinal products, is subject to a process of modification and currently in the phase of public consultation. However, we have not detected, within the objectives pursued by this process of amendment, any reference to the regulatory regime of Cannabinoid Drugs. Please refer to Question 24 for further information regarding Medicinal Cannabis.

 

11. When are they likely to come into force?

N/A.

 

Medicinal Cannabis

For the purposes of this Chapter 8: Medicinal Cannabis, Cannabis shall mean “the flowering or fruiting tops of the cannabis plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted” (see art. 1 of the Single Convention on Narcotic Drugs of 1961); and Medicinal Cannabis shall mean Cannabis used/intended to be used for medicinal purposes. Cannabinoid Drugs (as defined in Chapter 8 above), products formulated by pharmacists containing cannabinoids which qualify as medicines under Spanish law (see art. 8.1.b and c of the Spanish Law on Medicinal Products) and cannabinoid products with very low concentrations of THC fall outside the concept of Medicinal Cannabis for the purposes of this Chapter. 

 

12. Is Medicinal Cannabis authorized in the country?

The use of Cannabis for medicinal purposes is not specifically regulated in Spain; being a legal void in this field which generates significant legal uncertainty. 

Notwithstanding the foregoing, we make the following comments: 

• Cannabis qualifies as a narcotic in accordance with art. 2.1 of Law 17/1967 and List I of the Single Convention on Narcotic Drugs of 1961. Likewise, Cannabis is considered as a “prohibited product” in accordance with art. 2.2 of Law 17/1967 and List IV of the Single Convention on Narcotic Drugs of 1961.
• Art. 22 of Law 17/1967 (which states that the use of narcotic drugs for therapeutic uses may be allowed under certain circumstances), art. 51.3 of the Spanish Law on Medicinal Products (which states that plants traditionally used as medicines and offered without reference to therapeutic, diagnosis or preventive properties may be sold under certain circumstances)and other regulations have been used by certain authors to try to defend Medicinal Cannabis in Spain. Such interpretations, however, shall be read with extreme caution (and be considered as mere opinions) as long as in Spain there is not a clear regulatory framework regarding Medicinal Cannabis and, therefore, no clear and solid conclusions can be reached in this regard.
• From a criminal point of view, self-consumption of Medicinal Cannabis (provided that the corresponding requisites established by case law are complied with) is not criminally punishable. Other activities connected somehow with Medicinal Cannabis shall be carefully analyzed as long as they may trigger legal risks, including criminal ones (see art. 348 of the Spanish Criminal Code which literally states that “those who execute acts of cultivation, processing or trafficking, or otherwise promote, favour or facilitate the illegal consumption of toxic drugs, narcotics or psychotropic substances, or possess them for those purposes, shall be punished…”).
• Rules such as Law 17/1967, Royal Decree 2829/1977 (and its complementary regulations), Royal Decree 1675/2012 and criminal regulations should be considered when reviewing rules applicable to Medicinal Cannabis as long as certain activities connected somehow with Medicinal Cannabis may fall within their scope.
• With regard to the CBD as a cannabinoid derived from cannabis, the question about its legality was put in front of the Court of Justice of the EU (CJEU). On 19 November 2020, the CJEU decided in the “Kannavape case” that the rules on the free movement of goods within the European Union (articles 34 and 36 of the Treaty on the Functioning of the European Union, TFEU) “must be interpreted as precluding national legislation which prohibits the marketing of CBD lawfully produced in another Member State when it is extracted from the Cannabis sativa plant in its entirety and not solely from its fibre and seeds”. According to the CJEU, CBD does not qualify as a narcotic drug in that matter, since it appears that the CBD in that matter (used for e-cigarettes) does not have any psychotropic or harmful effect on human health. This resolution confirming that CBD is not a narcotic is fully applicable in Spain. 

It is to be noted that Medicinal Cannabis is being object of discussion for regulation within the Spanish Congress of Deputies. Please refer to Question 24.

13. What are the regulatory authorities with jurisdiction over Medicinal Cannabis?

The main Spanish authorities with jurisdiction over Medicinal Cannabis are the Spanish Ministry of Health and the AEMPS.

 

14. What is the regulatory framework for the authorization, pricing, and reimbursement of Medicinal Cannabis?

There is no special regime for Medicinal Cannabis and consequently, for its authorization, pricing and reimbursement. With regard to Cannabis Drugs, please refer to  Question 12.

 

15. How is the production and import of Medicinal Cannabis regulated and by which agencies/authorities?

Production/import of Cannabis is mainly regulated in Law 17/1967 and Royal Decree 2829/1977. General foreign trade regulations and international conventions, when applicable, shall also be observed. 

In addition to the foregoing, it is also worth mentioning a ministerial order dated on 7 May 1963 on cultivation of medicinal plants related to narcotics and two informative notes published in the official website of the AEMPS in December 2018 which regulate the matter of the cultivation of Cannabis for medicinal and scientific purposes. According to these notes, cultivation of Cannabis for these purposes requires a previous authorization from the AEMPS. The proceeding for this authorization to be granted has not been laid down in any specific law other than the informative notes and has also been widely criticised for lacking transparency and clarity. 

The Spanish Ministry of Health and the AEMPS have authority regarding the production/import of Cannabis. 

 

16. What approval or notifications are necessary to produce or import Medicinal Cannabis?

The production/import of Cannabis is only permitted for scientific and/or medicinal purposes and it is subject to an authorization to be granted by Spanish regulatory authorities according to the regulations and the informative notes mentioned in  Question 15. 

 

17. What is the regulatory framework for the marketing and distribution of Medicinal Cannabis?

There is no regulation specifically regulating the promotion of Medicinal Cannabis. However we make the following comments:

• If a product (such as Cannabis) is presented for treating or preventing diseases, it may be considered as a medicinal product according to Spanish regulations (see art. 2.a of Spanish Law on Medicinal Products which refers to the definition of medicinal product by presentation);
• In Spain, medicinal products cannot be promoted if they have not received a valid marketing authorization (see art. 2.1 Royal Decree 1416/1994 on marketing of medicinal products for human use).
• Provided that Cannabis, to date, has not received a marketing authorization, the promotion of Medicinal Cannabis is not acceptable.
• It is also worth mentioning the fact that plants that have been traditionally considered as medicinal plants (someone could try to argue that this is the case of cannabis) have a specific regime in Spain (see art. 51.3 of Spanish Law on Medicinal Products and related regulations). Without analyzing such regime (or analyzing if cannabis can be authorized through the same), we note that such “medicinal plants”, even if they are finally authorized, cannot be “offered to the public with reference to its therapeutic properties”.

Regarding the distribution of Medicinal Cannabis, please refer to Question 12.

 

18. How can patients obtain Medicinal Cannabis?

Please refer to Question 12.

 

19. Who can prescribe Medicinal Cannabis?

Please refer to Question 12.

 

20. Is there a list of doctors authorized to prescribe Medicinal Cannabis?

Please refer to Question 12.

 

21. What approvals or notifications are required to prescribe Medicinal Cannabis?

Please refer to Question 12.

 

22. Where is Medicinal Cannabis available?

Please refer to Question 12.

 

23. Is there a list of retailers authorized to sell Medicinal Cannabis?

Please refer to Question 12.

 

24. Are there proposals for reform or significant change to the regulation of Medicinal Cannabis?

The Spanish Parliament (Congreso de los Diputados) has recently created a commission devoted to the analysis of the available scientific evidence in connection with the use of Medicinal Cannabis as well as the results of experiences of use. This commission issued, in June 2022, a report confirming that Medicinal Cannabis could have positive therapeutic effects for certain pathologies. This report also proposed the legal qualification that Medicinal Cannabis products may adopt (i.e. medicinal product, magistral formulas, etc.) or how this resulting products should be commercialized and distributed in Spain. We are not aware of any specific regulation being implemented yet. However, as per the information informally provided by the representatives of this commission, the issuance of this favourable report is the first step for the future regulation of Medicinal Cannabis, which should be expected between 2023-2024. 

 

Opioid Drugs

For the purposes of this Chapter 8: Opioid Drugs, Opioid Drugs shall mean any industrially produced medicinal product which contains opioids.

 

25. Are Opioid Drugs authorized in your country?

Opioid Drugs may be authorized in Spain on the basis of scientific criteria on its quality, safety and efficacy. The foregoing is provided that applicable regulations on narcotics, such as Law 17/1967 on narcotics, and Royal Decree 2829/1977 on narcotics and its production, distribution, prescription and dispensation, are observed.

 

26. What are the regulatory authorities with jurisdiction over Opioid Drugs?

The main Spanish authorities with jurisdiction over Opioid Drugs are the Spanish Ministry of Health and the AEMPS.

 

27. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Opioid Drugs?

No. The general regulatory framework applicable for the authorization, pricing and reimbursement of medicinal products apply to Opioid Drugs. 

There are, however, specific regulations that may be applicable to other activities related to Opioid Drugs such as manufacturing, distributing, prescribing, dispensing etc. (see, among others, Law 17/1967, Royal Decree 2829/1977 and Royal Decree 1675/2012 on prescribing and dispensing narcotics for both human and veterinary use).

 

28. Which are the Opioid drugs that have received market approval to date?

There are many medicinal products containing opioids that have received market approval to date in Spain. 

An updated and complete list of all medicinal products authorized in Spain classified by active ingredient (as well as by trademark, registration number, etc) can be found in CIMA, and online data base held by the AEMPS and available in the official website of the AEMPS. All medicinal products containing opioids that have received market approval in Spain are included in such list. 

 

29. Who can prescribe Opioid Drugs?

Doctors, odontologists and veterinaries, each of them in the field of its competence, can prescribe Opioid Drugs.

 

30. Is there a list of doctors authorized to prescribe Opioid Drugs?

There is not a list of doctors authorized to prescribe Opioid Drugs. Doctors, provided that they comply with the applicable requirements and procedures (which include the need to use the appropriate prescription forms), can prescribe Opioid Drugs without need to be previously registered in any official list. It is to be noted that doctors holding prescription forms for narcotic drugs may be controlled (and therefore somehow listed), but these are lists relating to the prescription forms (holders of such forms are listed) and not related to the doctors themselves.

 

31. What approvals or notifications are required to prescribe Opioid Drugs?

Provided that applicable regulations are complied with (including the use of the appropriate prescription forms), doctors themselves do not have to ask for any specific approval or make any specific notification each time they prescribe Opioid Drugs.

Treatments with Opioid Drugs for patients addicted to Opioid Drugs have their specific regulations (such as Royal Decree 75/1990 on treatments with opiates for people addicted to opioids, and the circular of the AEMPS 6/2003 regarding the conditions to distribute narcotics for the treatment of people addicted to opioids.

 

32. Which organizations are authorized to sell/distribute Opioid Drugs available?

Opioid Drugs can be dispensed to the public by authorized pharmacy offices/services.

Opioid Drugs can be distributed (that is, sold to either other authorized distribution entities or pharmacy offices/services) by any of the following entities provided that they comply with all applicable regulations on medicinal products and narcotics (such as Law 17/1967, Royal Decree 2829/1977 -and its complementary regulations- and Royal Decree 1675/2012):

• Pharmaceutical laboratories;
• Distribution entities duly authorized to distribute medicines for human use (see Royal Decree 782/2013); and/or
• Distribution entities duly authorized to distribute veterinary medicines (see Royal Decree 109/1995).

 

33. Is there a list of retailers/distributors authorized to sell Opioid Drugs?

Retailers. The AEMPS, with the cooperation of the regional authorities, publishes lists including all pharmacy offices opened to the public in Spain. Such pharmacy offices can dispense Opioid Drugs if they comply with applicable regulations (please refer to Question 32).

Distributors. The AEMPS publishes lists including all entities authorized to distribute veterinary medicines and medicines for human use in Spain. All entities authorized to distribute Opioid Drugs must be included in such lists. 

 

34. Are there proposals for reform or significant change to the regulation of Opioid Drugs?

We are not aware of any proposal to significantly reform the regulation of Opioid Drugs in Spain.

 

35. When are they likely to come into force

N/A.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

Want to know more about regulatory reforms in Spain? Read on! 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 GBP 119.

 

1. Are there proposals for reform or significant change to the healthcare system?

In July 2022, the Ministry of Health opened a public consultation on the first draft of the law that will amend the current Spanish Law on Medicinal Products. The document published by the Ministry of Health shows that the reform that is being considered will have three principal axes:

a) Public financing of medicines

The document of the Ministry of Health refers to adopting new measures to rationalize pharmaceutical expenditure and promote rational use of public funds. In this regard, it is proposed to modify the Reference Price System by introducing elements that increase competition and value the contributions that represent an incremental benefit in the use of medicines. The document contemplates modifying the system of co-payment of medicines with the purpose of protecting the persons that are more in need. The document does not refer to whether the co-payment system may also be used as an instrument that may help modulating the demand of certain products. The document also announces measures of additional pressure to the industry by stating that quarterly contributions may also apply to medicines dispensed in healthcare centres.

b) The experience of the pandemic and the impact of new technologies

The pandemic has created important challenges related to the availability of medicinal products and medical devices. In this sense, the Ministry of Health aims to consolidate the non-presential dispensing of medicines for hospital dispensing and telepharmacy in the National Health System.

c)  Implementation of the European Union Law

The text published by the Ministry of Health proposes to make the necessary amendments to incorporate the amendments and definitions of the Regulation (EU) 2017/745 on medical devices and Regulation (EU) 2017/746 on in vitro medical devices into Spanish law.

d) Clarify competences regarding the control of advertising of medicinal products and medical devices.

The aim of this reform is to undertake a comprehensive regulation of the advertising of medicinal products for human use and medical devices for both the general public and healthcare professionals. It also aims to better define the competences of the State and the Autonomous Communities in the different areas of action in the field of advertising. Finally, the aim is to adapt the regulations to technological advances, in particular to the predominance of digital and audiovisual media. 

e) Modify and update the sanctioning procedure and the infringements provided for in Royal Legislative Decree 1/2015.

On the other hand, it is also proposed to reform Royal Decree 1015/2009. The aim of this reform is to better delimit the different existing cases of access to medicines in special situations and the different categories included in each of them, as well as the healthcare setting in which they can be used. It also aims to improve the procedure for accessing them. On the other hand, the aim is to introduce elements that guarantee that the use of medicinal products in special situations does not become routine, establishing measures that encourage the marketing and use of medicinal products through the channels established in ordinary legislation without the exceptional becoming habitual. 

A draft of this new Royal Decree has not yet been published.

 

2. When are they likely to come into force?

The process for approval of the abovementioned proposals is still ongoing. Considering the current political situation in Spain (near elections at a national and local level), it is difficult to predict when such proposals will be approved and how the final texts of the same will be.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

The legal framework for patents and trademarks 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 GBP 119.

 

1. What are the basic requirements to obtain patent and trademark protection?

Pursuant to Law 24/2015 on patents, the basic legal requirements to obtain a patent are: (i) to have a new invention in any field of technology; (ii) that such invention involves an inventive step; and (iii) that such invention is susceptible of industrial application.

Pursuant to Law 17/2001 on trademarks, the basic legal requirement to obtain a trademark is to have a sign subject of graphic representation which has a distinctive character and which is not identical with or similar to earlier trademarks, in order to avoid likelihood of confusion on the part of the public.

 

2. What agencies or bodies regulate patents and trademarks?

The Spanish Patent and Trademark Office (www.oepm.es).

 

3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?

The products, substances, and processes that can be protected by patents are those which can be considered as ‘inventions’, meeting the basic legal requirements referred to in Chapter 6, Question 1, which are not subject to any of the following exceptions to patentability:

• inventions the commercial exploitation of which would be contrary to public order or morality principles, including but not limited to processes for cloning human beings, processes for modifying the germ line genetic identity of human beings, uses of human embryos for industrial or commercial purposes, or processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes;
• plant or animal varieties; however, it is possible to patent plant or animal varieties if the technical feasibility of the invention is not confined to a particular plant or animal variety;
• essentially biological processes for the production of plants or animals, meaning those processes which consist entirely of natural phenomena such as crossing or selection; however, it is possible to protect by patent inventions consisting in microbiological or other technical process, or a product obtained by means of such processes;
• methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body; however, it is possible to patent products, in particular, substances or compositions, for use in any of these methods;
• the human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or -partial sequence of a gene; however, it is possible to patent an element isolated from the human body or otherwise produced by means of a technical pro-cess, including the sequence or partial sequence of a gene, even if the structure of such element is identical to that of a natural element; or
• a mere DNA sequence, without indicating any biological function.

The law does not define the term ‘invention’ but it states what cannot be considered as such. To such effect, the following cannot be regarded as inventions:

• discoveries, scientific theories and mathematical methods;
• literary, artistic or scientific works or any other aesthetic creations;
• schemes, rules and methods for performing mental acts, playing games or doing business, and programs for computers; or
• ways to present information.

On the other hand, trademark protection is possible for any signs meeting the basic legal requirements referred to in Question 1, provided that such signs do not fall within any of the following prohibitions:

• those consisting exclusively of signs or indications which may serve, in trade, to designate the kind, quality, quantity, intended purpose, value, geographical origin, or the time of production of the goods or of rendering of the service, or other characteristics of the goods or services;
• those consisting exclusively of signs or indications which have become customary in the current language or in the bona fide and established practices of the trade;
• signs consisting exclusively of: (i) the shape, or another characteristic, which results from the nature of the goods themselves; (ii) the shape, or another characteristic, of goods which is necessary to obtain a technical result; (iii) the shape, or another characteristic, which gives substantial value to the goods;
• signs which are contrary to public order or morality principles;
• signs which are deceiving the public, e.g. to the nature, quality or geographical origin of the goods or service;
• signs which have not been authorized by the competent authorities and are to be refused or invalidated;
• signs copying or imitating the armorial bearings, flag, insignias and other emblems of Spain, its Autonomous Regions, municipalities, etc.  

 

4. How can patents and trademarks be revoked?

Pursuant to article 102 of the Law 24/2015, a patent can be invalidated based on any of the following grounds:

• if the subject matter of the patent is not patentable, (please refer to Questions 1 and 3);
• if the invention is not disclosed in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art;
• if its subject-matter exceeds beyond the content of the application as filed, or, if the patent was granted on a divisional application or on a new application filed by a non-entitled person, beyond the content of the earlier application as filed;
• if the protection of the patent was extended after its grant; or
• if the holder of the patent is not its rightful owner as provided in the law.

Pursuant to the provisions contained in article 105 of Law 24/2015, the holder of a patent can request the Spanish Patent and Trademark Office to revoke the patent at any time during its validity. To such effect, an official form must be filled-out, and the corresponding fees paid. The authorities can deny such request in certain cases, for example, if the patent is subject to certain type of rights (such as rights in rem or call options) or licenses dully recorded in the Patent Registry. 

On the other hand, a trademark can be revoked due to failure to renew it, withdrawal by the owner or failure to pay the maintenance fees. Also, according to article 54 of Law 17/2001, a trademark can be revoked pursuant to a request filed before the Spanish Patent and Trademark Office or a counterclaim in trademark infringement proceedings, based on any of the following grounds:

• if during a five-year period the trademark has not been put to genuine use in Spain for the products or services for which it has been registered;
• if, due to acts or inactivity of the proprietor, the trademark has become the common name in the trade for a product or service in respect of which it is registered; or
• if, due to the use of the trademark by the proprietor or with the proprietor’s consent in respect of the goods or services for which such trademark is registered, if can mislead the public, particularly as to the nature, quality or geographical origin of those goods or services.

 

5. Are foreign patents and trademarks recognized and under what circumstances?

Both patents and trademarks are territorial rights, meaning that they are only applicable and enforceable in the country in which they have been filed and granted. Therefore, in order to be recognized in Spain, patents and trademarks must be validated / registered before the Spanish Patent and Trademark Office. In this regard, pursuant to the European Patent Convention, a European patent validated in Spain has the same effect of and is subject to the same conditions as a Spanish national patent. Regarding Unitary Patents, Spain is one of the few EU member states who did not ratify the Unified Patent Court Agreement. Therefore, neither Unitary Patents nor Unitary Patent Court decisions will have effects in Spain.

As regards trademarks, it is possible to fill a request for an EU trademark before European Union Intellectual Property Office. The EU trademark has a unitary character and, thus, is effective throughout the entire territory of the European Union. 

Also, according to the so-called Madrid System, which includes two international treaties: the Madrid Agreement and the Madrid Protocol, it is possible to fill an international trademark request. Such request can be filed before the Spanish Patent and Trademark Office, in case the applicant is Spanish or based in Spain. The protection granted will be applicable in countries belonging to the Madrid System (currently 119 countries, including Spain).

 

6. Are there any non-patent/trademark barriers to competition to protect medicines or devices?

Yes, there are non-patent/trademark barriers to competition when it comes to protecting medicinal products in Spain. 

On the one hand, there is the data exclusivity period regulated under Spanish Law on Medicinal Products. The data exclusivity period is the one during which the applicant of a generic medicinal product cannot cross-reference the clinical data (i.e. results of pre-clinical tests and clinical trials) of the reference medicinal product. This period lasts 8 years from the approval of the first marketing authorization of the reference medicinal product by the authorities of any Member State (not necessarily Spain) or the European Union. Once this 8-year period has expired, the applicant of a marketing authorization for a generic medicinal product is not required to provide the results of pre-clinical tests and clinical trials. 

On the other hand, there is another barrier to competition related to medicinal products known as the market exclusivity period. Once a generic medicinal product is authorized using the results of pre-clinical tests and clinical trials of the reference medicinal product, it cannot be launched until the expiry of the marketing exclusivity period of 10 years counted from the first marketing authorization of the reference medicinal product in the EU. The exclusivity period of 10 years may be extended for 1 additional year, i.e. up to 11 years maximum, if, during the first 8 of those 10 years, the holder of the marketing authorization of the reference medicinal product obtains an approval for new indication(s) having significant clinical benefit in comparison with existing therapies. 

As regards orphan medicinal products, there is a market exclusivity period conferred by Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products, which is directly applicable in Spain. Pursuant to the provisions contained in article 8 of this Regulation, when there is a marketing authorization granted in Europe for an orphan drug, the authorities in Europe and in all Member States must refrain during a 10-year period from accepting another marketing authorization application or from granting another marketing authorization, when there is an existing marketing authorization for a similar medicinal product having the same therapeutic indication. Such 10-year market exclusivity period may be shortened to 6 years if, at the end of year 5, it is established that the product no longer meets the criteria laid down for granting the orphan designation in the first place, and it is proven that such product is sufficiently profitable not to justify maintenance of market exclusivity. However, the market exclusivity period for orphan drugs will not apply, and therefore another marketing authorization may be granted for a similar medicinal product having the same therapeutic indication if:

• the holder of the marketing authorization for the original orphan medicinal product has given his consent to the second applicant, or
• the holder of the marketing authorization for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product, or
• the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorized, is safer, more effective or otherwise clinically superior.

 

7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?

Not specifically. Please refer to Question 3.

 

8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?

No, Spanish government or regulatory bodies do not need to approve or accept patent/trademark license agreements.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

The low-down on the situation regarding product liability 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 GBP 119.

 

1. What types of liability are recognized in your jurisdiction?

The Spanish regime for product liability is a strict liability regime.  Such regime imposes strict liability to the “producer” of a defective product. The producer will be liable for personal injury or death or damage to property caused by the defective product, provided that such defective product was objectively intended for private use or consumption and was utilized mainly as such by the injured party. It is on the claimant to prove that (i) the product was defective, (ii) the damage occurred and (iii) there was a causal link between the defective product and the damage suffered.

This strict liability system does not preclude other liability systems providing the injured party with a greater protection neither affects any other right to compensate damages, including moral damages, that the injured party may have as a consequence of contractual liability, based on the lack of conformity of the goods or any other cause of non-performance or defective performance of the contract, or of any non-contractual liability that may apply.

 

2. How do these types of liabilities apply to the manufacturers of medicines and devices?

Under the Spanish product liability regime only the “producer” bears responsibility for the fault of the product.

It is considered as “producer”, depending on the case, any or all of the followings: (i) the manufacturer or the importer in the European Union of a finished product, raw material or component of the product; and (ii) the apparent producer of the product (i.e. any person presenting itself as the producer of the product by providing its name, trademark or other identifying features along with the product, whether on the container, wrapping or other any protective or presentational component). 

In the event that the “producer” cannot be identified, the supplier of the product (i.e. the distributor or the “retail” supplier) shall be considered as such, unless it informs the injured party about the identity of the manufacturer or of the person who supplied the product to it, within a term of three months before it is requested to give such information. This same rule applies in the case of imported products in the European Union, if the product does not indicate the name of the importer, even if it indicates the name of the manufacturer.

The supplier of a defective product shall also be liable towards the injured party as if it was the producer if it supplied the product knowing that the defect existed.

Therefore, according to Spanish law not only the final manufacturer, or the importer in EU, of a medicinal product or a medical device will be subject the Spanish product liability regime. Such regime will also apply to the manufacturer, or importer in the EU, of raw material or component of said product as well as to the apparent producer of said medicinal product or medical device and to the supplier under certain circumstances. 

 

3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?

Under the Spanish regime on liability for defective products, the responsibility for damages caused by a defective product is only borne by the “producer” [i.e. (i) the manufacturer or the importer who introduces the product into the European Union; (ii) the apparent producer and; (iii) the supplier only under certain circumstance]. Therefore, as the corporate executives, employees, and representatives are not the producer, they will not be responsible under this regime.

 

4. How can a liability claim be brought?

A liability claim shall be brought by filing a claim before the Courts, by every injured party. When the injured party is a group of consumers, then the claim can be brought by associations of consumers, a group of consumers or by the Public Prosecutor’s Office.

 

5. What defenses are available?

The producer shall not be liable if they can prove that the product is not defective because it provides the safety which could legitimately be expected from it, taking all circumstances into account, including the time when the product was put into circulation, the presentation of the product and the reasonable use of the product.

Additionally, the producer shall not be liable if it can prove that:

• it did not put the product into circulation;
• given the circumstances of the case, it may be presumed that the defect did not exist when the product was put into circulation;
• the product had not been manufactured for sale or for any other form of distribution with an economic purpose, nor that it was manufactured, imported, supplied or distributed within the context of a professional or entrepreneurial activity;
• the defect is due to the fact that the product was manufactured in accor-dance with existing mandatory rules; and
• the state of scientific and technical knowledge existing at the time the product was put into circulation did not allow for the discovery of the existence of the defect.

The producer of a part that is integrated into a finished product shall not be liable if it proves that the defect is attributable to the design of the product into which the part was integrated, or to the instructions provided by the manufacturer of the finished product.

Additionally, the doctrine points out that the apparent producer shall not be liable if it can prove that it was not the one who placed the sign, brand, logo or stamp that identifies it as apparent producer in the defective product or its packaging. 

In the case of medicinal products, foods or foodstuffs intended for human consumption, the persons liable shall not be able to invoke the state of scientific and technical knowledge defence set out before in this answer.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

A brief overview of the situation regarding traditional medicines and OTC products 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 GBP 119.

 

1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?

Plants traditionally used in Spain for medicinal purposes can be sold to the public without the need for a marketing authorization issued by the AEMPS or the European Medicines Agency. These plants must be offered to the consumer without mentioning any properties for treating or preventing diseases.

Besides, herbal medicines, homeopathic medicines, vaccines and medicinal gases are considered medicinal products, and can only be sold to the public if they have a marketing authorization issued by the AEMPS or the European Medicines Agency. Herbal medicines traditionally used in Spain for medicinal purposes, as well as non-injectable homeopathic medicines that are offered to the public without claiming their value in one or more therapeutic indications, can benefit from a simplified authorization procedure.

The marketing of other alternative products, such as food supplements based on vitamins, minerals and other substances, may be subject to the obligation to communicate their placing on the market to the Spanish competent authorities.

 

2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?

Traditional, herbal, complementary or alternative products which are not a medicinal product and/or a medical device may be advertised directly to the public provided the requirements described in Question 3 are met.

 

3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?

Plants traditionally used in Spain for medicinal purposes must be offered to the consumer without mentioning any properties for treating or preventing diseases.

Regarding other traditional, herbal, complementary, or alternative products, Royal Decree 1907/1996 states that such products cannot be advertised in Spain if they:

• Claim properties for preventing, treating or curing diseases.
• Claim slimming properties or against obesity.
• Offer relief or healing certainties.
• Claim to have authorizations, homologations or certificates issued by health authorities of any country.
• Claim their use in healthcare centers or their distribution through pharmacies.
• Are accompanied by healthcare professionals, famous people, or real or suspected patients’ testimonials.
• Suggest that their use or consumption enhance physical, mental, sports or sexual performance.
• Use the term “natural” as a characteristic linked to intended preventive or therapeutic effects.
• Attribute a superfluous nature to medicinal products or medical devices or that are presented as an alternative to such products.
• Attribute a superfluous nature to the intervention of healthcare professionals or that are presented as an alternative to the intervention of said professionals.

These prohibitions do not apply to medicinal products and medical devices that are governed by their specific regulations. Likewise, food products may also claim healthy properties and properties for the prevention of diseases under the terms and with the limitations provided in the European Regulation (EC) No 1924/2006 on nutrition and health claims made on foods.

 

4. What are the regulatory requirements for over-the-counter (non-prescription) medications?

Over the counter (OTC) medicinal products are governed by the rules of Spanish Law on Medicinal Products as well as Royal Decree 1345/2007, which regulates the authorization and registration procedure for medicinal products industrially manufactured. 

Advertising to the public of OTC medicinal products which are not reimbursed in Spain is allowed. Advertisements shall include the following claim: “This product is a medicinal product. Refer to the leaflet. If in doubt, consult your pharmacist”.

In addition, such advertisements shall not include any information that:

• leads to the conclusion that no medical appointment or surgical procedure is necessary and that induces a certain diagnosis, or treatment by correspondence;
• suggests that the effect of the medicinal product is guaranteed, with no adverse reactions or side effects, with results greater or equivalent to those of another treatment or medicinal product;
• suggests that the person’s normal health condition may be improved by the use of the medicinal product;
• suggests that the person’s normal health condition may be impaired in case the medicinal product is not used (except for vaccination campaigns approved);
• is exclusively or mainly targeted at children;
• refers to a recommendation from scientists, healthcare professional or other persons, who because of their celebrity may encourage the consumption of medicinal products;
• suggests that the medicinal product is food, a cosmetic or personal hygiene product, or any other consumption product;
• suggests that the safety or efficacy of the medicinal product is due to the fact that it is a natural product;
• may lead to an erroneous self-diagnosis through a detailed description or representation of patient history;
• suggests that its use enhances sports performance;
• refers to alarming, abusing or misleading healing testimonials;
• uses abusively, alarmingly or misleadingly images of alternations of the human body produced by disease injuries, or of the action of the consequences of a medicinal product to the human body; or
• mentions that the medicinal product has obtained the health authority or any other authority.

As regards the advertising of medical devices to the public, the prior authorization from the Spanish regional authorities must be previously obtained. Spanish Law on Medicinal Products expressly prohibits to advertise to the public medical devices which are publicly financed and/or medical devices which are intended to be used or applied exclusively by HCP. Also, according to Royal Decree 1591/2009, it is prohibited to advertise to the public (i) medical devices for self-diagnosis (except for fertility, pregnancy or HIV diagnosis devices), and/or (ii) genetic diagnosis devices.

 

5. Are there any limitations on locations or channels through which OTC products may be sold?

OTC medicinal products must be sold and delivered by pharmacies only. OTC medical devices may also be sold and delivered to consumers in other stores, such as supermarkets or cosmetic shops. As regards distance selling to the public (e.g. via post) of medicinal products and medical devices, please refer to Chapter 3, Questions 18 and 19 .There are no restrictions in terms of places of sale or distance selling of other OTC products, except for limitations indicated in Question 3.

 

6. What health, advertising, and marketing claims may be made for OTC products?

Please refer to Chapter 4, Question 3 and 4.

 

7. Can OTC products be marketed or advertised directly to the public?

Please refer to Question 3 and 4.

 

8. What is the mechanism by which a prescription-only product can be converted to an OTC product?

Medicinal products shall be subject to medical prescription when: (i) they are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision, (ii) they are used frequently, and in a very considerable way, under abnormal conditions of use and this may involve, directly or indirectly, a danger to health; (iii) contain substances or preparations based on these substances whose activity or adverse reactions need to be studied in more detail, or (iv) they are administered parenterally, except in exceptional cases, by medical prescription.

The AEMPS may modify the classification granted to a medicinal product (from prescription-only to OTC and vice versa), when new information is obtained that justifies the re-evaluation of the file. When this happens, a period of one year of data exclusivity is granted from the date in which the authorization of modification is granted. 

 

9. What are the requirements for the importation of either traditional medicines or OTC products?

OTC medicinal products may be imported by the marketing authorization holder in Spain or by a legal entity authorized as importer of medicinal products by the AEMPS. In the event that OTC medicinal products come from EU countries, parallel imports requirements must be followed (please refer to Chapter 3, Question7).

Besides, to import OTC medical devices from non-EU countries, a specific authorization from the AEMPS is required. Medical devices acquired from other EU countries can freely circulate in Spain. To import cosmetics, it is necessary the previous presentation of an affidavit before the AEMPS indicating the contact qualified person details.

As regards importation of OTC products different from the above mentioned, there are no specific rules and general rules on importation and intracommunity trade of goods apply.

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

All about marketing, manufacturing, packaging & labeling, advertising 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 GBP 119.

 

1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?

The AEMPS is the authority in charge of granting marketing authorizations in Spain, whether they result from a national procedure or from a mutual-recognition or decentralized procedure. Marketing authorizations granted by the AEMPS are regulated by Royal Decree 1345/2007. Some provisions of such Royal Decree also affect medicines authorized by the European Commission pursuant to the centralized procedure.

The AEMPS shall grant an authorization if the product:

• fulfils the established quality requirements;
• is safe under normal conditions of use;
• is effective in the therapeutic indications;
• is correctly identified; and
• provides the patient with the necessary information.

The positive therapeutic effects of the medicinal product shall be assessed in relation to any risk for the patient’s health or public health, viewed under a risk-benefit perspective.

The key stages of the procedure are the following:

•  submission of the application to the AEMPS;
• validation and acceptance of the submission;
• issuance of the evaluation report; and
• resolution of the application, and issuance, where appropriate, of the marketing authorization of the product.

The maximum period to notify to the applicant the resolution of the authorization procedure is 210 calendar days.

As regards marketing of medical devices, except for custom-made devices, all medical devices must bear the CE marking of conformity when they are placed in the Spanish market (please refer to Chapter 1, Question 3). Likewise, 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 in the Spanish market for its distribution or use.

 

2. What is the authorization process for the marketing of generic versions of these products?

As regards the authorization process for the marketing of generic versions of medicinal products, such process is simpler than the one foreseen for brand-name medicinal products because the applicant  shall not be required to provide the results of pre-clinical and clinical trials if it can demonstrate that the medicinal product is a generic medicinal product of a reference medicinal product which is or has been authorized for not less than eight years in a Member State of the European Union or in the Community. 

The applicant may also replace the pre-clinical and clinical trial results with appropriate scientific literature, if he can demonstrate that the active substances of the medicinal product have been in well-established medical use within the Community for at least ten years, with recognized efficacy and an acceptable level of safety.

Finally, where the medicinal product possesses the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form as another medicinal product that has already been authorized, the applicant may rely on the pre-clinical and clinical documentation of the authorized medicinal product, with the permission of the holder thereof.

In the case of biological medicinal products which are similar to a reference biological medicinal product but do not meet the conditions in the definition of generic medicinal products, the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. 

 

3. What are the typical fees for marketing approval?

Please refer to Chapter 1, Question 4.

 

4. What is the period of authorization and the renewal process?

Please refer to Chapter 1, Question 5.

 

5. What are the requirements, if any, for post-approval pharmacovigilance?

Royal Decree 577/2013 imposes the following post-approval pharmacovigilance obligations to the marketing authorization holder:

• respecting the Good Practices on Pharmacovigilance for the pharmaceutical industry published by the AEMPS;
• having an adequate pharmacovigilance system, including a master file of the system and undertake periodic audits;
• having a suitably qualified person responsible for pharmacovigilance in the European Union;
• having a contact person for pharmacovigilance in Spain;
• submitting periodic safety reports to the European Medicines Agency;
• having a risk management system for each medicinal product;
• notifying and recording in the Eudravigilance database suspected adverse reactions to the medicinal product;
• monitoring worldwide scientific literature related to the medicinal product;
• carrying out post-authorization studies of efficacy and/or safety required by the competent authorities; and
• performing a continuous evaluation of the benefit-risk parameters of the medicinal product.

Furthermore, products subject to additional monitoring requirements must include a black inverted triangle in their package leaflet and data sheet, accompanied by the phrase “this medicine is subject to additional monitoring”.

 

6. Are foreign marketing authorizations recognized?

Under Royal Decree 1015/2009, the recognition of a medicinal product that has a foreign marketing authorization requires prior approval from the AEMPS. Approval is subject to the following requirements:

•  there is no other adequate medicinal product authorized in Spain;
• a physician must justify in writing the prescription; and
• the patient must consent in writing to the prescription, after having been duly informed.

 

7. Are parallel imports of medicines or devices allowed?

According to Royal Decree 1785/2000, parallel imports are allowed in Spain, but the following requirements must be met:

•  the medicinal product in question needs to have a marketing authorization both in the country of origin as well as in Spain;
• the company responsible for the parallel import must obtain the prior authorization from the AEMPS;
• the labelling and leaflet of the product must comply with the provisions of Royal Decree 1345/2007; and
• the parallel importer must have an authorization as manufacturer of medicinal products in Spain if it carries out in Spain any repackaging and relabeling of the imported product (otherwise, the importer must have an authorization in Spain to perform the activities of a wholesaler).

Intellectual property rights cannot be used to oppose parallel imports. However, before beginning the marketing of a product that has been introduced in Spain through parallel import, the importer must notify the marketing authorization holder of the medicinal product in Spain of its intention to carry out such marketing in Spain (providing, if requested, a sample of the reconditioned product to be marketed by the importer).

 

8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?

Under the Code of Farmaindustria (Farmaindustria is the Spanish innovative medicinal products industry association) providing gifts to healthcare organizations is subject to certain restrictions. The main restrictions are: that gift must  not constitute an inducement to prescribe, recommend, purchase, supply, sell, administer or use any particular product; the gift must be for the internal use of the institution in general and not for the use of an individual; and the provision of the gift must be formalized in writing and the receiving company shall retain a copy of such document.

As regards gifts to healthcare professionals (‘HCP’), the following restrictions contained in Royal Decree 1416/1994 apply: the gift must be relevant for the practice of medicine or pharmacy and the cost of the gift must be insignificant. Moreover, according to the Code of Farmaindustria gifts to HCP are subject -among others- to the following general restrictions: (i) the gift must have stationery or professional use, (ii) it must not be related to a prescription-only medicinal product, and (iii) its market price must not exceed EUR 10. Informational or educational materials and items of medical utility can be given to HCP as a gift subject to certain restrictions: (i) such materials must be directly relevant to the practice of medicine or pharmacy, (ii) they must directly benefit patient care, (iii) they must not affect the routine practice of the HCP, and (iv) their market price must not exceed EUR 60. In addition, the Code of Farmaindustria prohibits the offering or provision of gifts for stationery or professional use within the framework of (i) medical visits mainly related to prescription-only medicines, and (ii) scientific and professional meetings organized by a third party, where promotion mainly pertains to prescription-only medicines, with the exception of pens or pads included in the congress bag, that shall not include any kind of corporate/institutional advertising or product advertising. Within the framework of scientific and professional meetings organized by a company, only pens and pads may be offered or provided; as long as that they are not related to a prescription-only medicine and their market price does not exceed EUR 10 (tax included).

Sponsorship of scientific meetings or congresses for HCP, as well as organizing informative, professional and/or scientific meetings is allowed but subject to restrictions. Such sponsorship must be stated in all documents related to the event, as well as in any published derivative work. It is also possible to pay for the necessary travel, accommodation and enrolment costs to HCP attending such congresses or meetings. According to Royal Decree 1416/1994, such hospitality must be reasonable, meaning that it must not exceed what recipients would normally be prepared to pay for themselves, and such hospitality must remain secondary to the main scientific objective of the event. There are additional restrictions contained in the Code of Farmaindustria, for example: hospitality cannot be extended to accompanying persons, hospitality may be granted only for the duration of the event and one additional day, scientific activities must cover at least 60% of an eight-hour working day, there is a limit of EUR 60 Euros per meal per guest, etc.

As regards entertainment, the hospitality offered to HCP cannot include the organization of social, entertaining or cultural events, except for reasonable welcome cocktails, working meals and gala dinners. The new Code of Farmaindustria, which is in force since 1 January 2021 prohibits any kind of hospitality for training activities or scientific-professional meetings held virtually / by telematic means. 

 

9. How is the manufacturing of medicines and devices regulated and by which agencies?

Performing the industrial manufacturing of medicinal products in Spain requires obtaining an authorization from the AEMPS. The application shall normally be electronically submitted directly to the AEMPS and must be at least in Spanish (although scientific-technical documentation may be submitted in another language). However, non-industrial preparation of compounded medicinal products at hospital and community pharmacies do not require the authorization of the AEMPS.

The key stages in the process to obtain a manufacturing authorization are:

• compilation of the documentation to be submitted to the AEMPS; 
• receipt and review of the documentation by the AEMPS; 
• compilation and submission of additional information requested by the AEMPS;
• inspection of the manufacturing sites by the AEMPS;
• submission of allegations and additional information as regards objections raised by the AEMPS as a result of the inspection of the manufacturing premises; and
• issuance by the AEMPS of a resolution granting or denying the authorization.

Although the law foresees a period of 90 days for the issuance of the decision regarding the grant of the manufacturing authorization, in practice such decision is issued by the AEMPS around 180 to 270 days after the submission of the application.

The manufacturing of medical devices requires a prior authorization granted by the AEMPS (for custom-made devices an authorization may also be required from the competent regional authorities). 

 

10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?

The local manufacturing practices are in accordance with the guidelines issued by the European Medicines Agency.

 

11. What is the inspection regime for manufacturing facilities?

The health administrations, whenever deemed necessary, are entitled to undertake periodic inspections to the manufacturing facilities. The AEMPS may also inspect the manufacturing facilities whenever it deems necessary, by itself or through the health departments of the relevant Autonomous Regions.

 

12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?

No. The inspections shall be conducted by the AEMPS and any other Spanish competent health administrations. However, there may be inspections undertaken at the request of other agencies, including EMA and FDA.

 

13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?

The storage, packaging and handling of medicinal products shall comply with the provisions set forth in Royal Decree 824/2010, Royal Decree 782/2013 and the EU Good Distribution Practices of medicinal products for human use.

The storage, packaging and handling of medical devices shall comply with the provisions set forth in Royal Decree 1591/2009.

 

14. What information must be included in medicine and device labelling?

According to Royal Decree 1345/2007, the labelling of medicinal products must contain the following information:

• name of the medicinal product including the dosage and the pharmaceutical form. Where appropriate, the mention of baby, children or adults. When the product contains up to three active ingredients, the Spanish Official Denomination (DOE) shall be included, otherwise, the International Common Denomination (ICD) or, in its absence, its common name;
• name of the medicinal product in Braille alphabet, considering the particularities of each medicinal product;
• active substances expressed qualitative and quantitative per dosage unit or according to the form of administration for a given volume or weight, using the Spanish DOEs or the ICDs, or, failing that, their common or scientific names;
• list of those excipients known to have a recognized action or effect whose knowledge is necessary for the use of the product and if the product is injectable, or a topical or eye preparation, all excipients must be stated;
• the pharmaceutical form and the contents by weight, volume or number of doses of the product;
• the method and the route of administration;
• a special warning that the medicinal product must be stored out of reach of children;
• any special warning, when the medicinal product requires so;
• In the case of medicinal products containing radionuclides, the dangerous goods transport conditions must be included;
• in case of medicinal gases, the technical specifications they must comply with, the conditions of supply and transport, and, where appropriate, the corresponding symbols must be included;
• expiry date including month and year. In addition, in case of medicinal products with reduced stability after reconstitution, dilution or opening, the shelf life of the reconstituted preparation, diluted or after opening shall be included and they shall also include a box for consignment by users. In case of medicinal products containing radionuclides, the day/ month/year shall be included, and, where appropriate, time: minutes and country of the time reference will be expressed;
• special storage precautions, if any;
• special precautions for disposal of unused medicinal products or waste materials from medicinal products, if appropriate; and if applicable, the symbols authorized by the AEMPS, in order to facilitate the application and development of medicinal products collection systems and to favor the protection of the environment;
• the name and address of the holder of the marketing authorization and, where appropriate, the name of the local representative designated by the holder;
• the National Code of the Medicinal Product;
• the manufacturer’s batch number;
• the number of the authorization for placing the medicinal product on the market;
• in case of medicinal products not subject to medical prescription, the indication of use;
• prescription and dispensation conditions;
• box or blank space to indicate the dosage, duration of treatment and frequency of use or intakes, except in those cases determined by the AEMPS, taking into account the particularities of each medication;
• symbols, acronyms and legends described in Annex IV to Royal Decree 1345/2007; and
• seal of the NHS, when applicable. 

According to Royal Decree 1591/2009, the labelling of medical devices shall contain the following information:

• the name or business name and address of the manufacturer. In case of products imported into the EU territory and intended to be distributed in the EU, the label, the name and address of the authorized representative must be included, where the manufacturer does not have a registered office in the EU;
• the information strictly necessary for the user to be able to identify the device and contents of the packaging;
• if applicable, the expression “sterile”;
• if applicable, the batch number;
• if applicable, the deadline for safe use of the device, expressed in the year and month;
• if applicable, indication that the device is for single use;
• if applicable, the expression “custom made device”;
• for devices intended for clinical investigations, the expression “exclusively for clinical investigation”;
• special storage or handling conditions;
• instructions for use;
• any warning and cautions;
• manufacturing year; and
• if applicable, sterilization process.

 

15. What additional information may be included in labeling and packaging?

Please refer to Questions 14.

 

16. What items may not be included in labeling and packaging?

Generally speaking, any item that may lead to an irrational use of the medicinal products or medical devices shall not be included in the labelling and or packaging of a medicinal product.

 

17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?

Advertising of prescription medicinal products or publicly financed medicinal products directed to the general public is strictly prohibited under Royal Decree 1416/1994 and the Code of Farmaindustria. Also, according to Royal Decree 1416/1994, mentioning certain therapeutic indications (i.e. sexually transmitted diseases, other serious infectious diseases, cancer, chronic insomnia, diabetes or other metabolic illnesses) in the advertisement directed to the public of medicinal products is prohibited.

The advertising of non-financed OTC medicinal products must comply with the following requirements: (i) it must clearly indicate that it is an advertisement and that the product advertised is a medicinal product; (ii) it must provide certain information (e.g. the complete name of the product, an invitation to read the instructions of the leaflet and to consult a pharmacist, etc.); and (iii) it must not contain claims or statements that are prohibited (e.g. claims or statements exclusively or mainly targeted at children , claims or statements suggesting that the effect of the medicinal product is guaranteed, with no adverse reactions or side effects, , etc.). Please refer to Chapter 4, Question 4.

According to Royal Decree 1416/1994, advertising of prescription medicinal products is allowed only to HCP. Among the requirements to be complied with, certain information must be provided to the HCP, such as: the dosages and pharmaceutical forms in which the product is available, the prescription and dispensation regime, the retail price and conditions under which the product is publicly financed and the estimated cost of treatment (if possible). 

As regards the advertising of medical devices to the public, the prior authorization from the Spanish regional authorities must be previously obtained. On the restrictions, Spanish Law on Medicinal Products expressly prohibits to advertise to the public medical devices which are publicly financed and/or medical devices which are intended to be used or applied exclusively by HCP. Also, according to Royal Decree 1591/2009, it is prohibited to advertise to the public (i) medical devices for self-diagnosis (except for fertility, pregnancy or HIV diagnosis devices), and/or (ii) genetic diagnosis devices.

 

18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?

Medicinal products must be dispensed to the public by pharmacies or pharmacy services only. Medical devices may also be sold and delivered to the public by pharmacies. However, there are non-prescription medical devices which may also be sold and delivered to consumers in other stores, such as supermarkets or cosmetic shops.

As regards the distance selling to the public (e.g., via post) of medicinal products and medical devices, there are certain restrictions. According to article 3.5 of Spanish Law on Medicinal Products, it is strictly prohibited to sell medicinal products and medical devices which are subject to prescription via post. 

Distance selling of non-prescription medicinal products and medical devices to the public is not entirely regulated in Spain. There is one specific regulation issued in this regard in connection with medicinal products for human use. We refer to Royal Decree 870/2013 regulating the distance selling of non-prescription medicinal products to the public. According to the conditions contained therein, pharmacies are entitled to have their own official website to sell OTC medicinal products to the public. 

However, certain Spanish Regions have passed regional regulations which allow other forms of home delivery in exceptional cases (such as home delivery in isolated rural areas or to people who are dependent).

 

19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?

The same restrictions and requirements applicable for non-electronic marketing and advertising apply to the electronic marketing and advertising (please refer to Question 17).

 

20. May medicines and devices be advertised or sold directly to consumers?

Please refer to Questions 17 and 18.

 

21. How is compliance monitored?

Compliance monitorization is exercised by the Spanish regional authorities via prior authorization and/or control ex-post. 

Advertising of medical devices to the public is monitored via prior authorization. 

Advertising of medical devices to HCP or  advertising of medicinal products to the public or to HCP is monitored via control ex post. Monitorization ex-post means that the authorities can inspect and review the advertising activities carried out by the company to ensure compliance with the applicable legal requirements. In case of advertising materials addressed to HCPs, the company must send a copy of such materials to the competent authority of the Autonomous Region where said company is located at the time of their distribution in order to facilitate the monitoring tasks of these authorities.

 

22. What are the potential penalties for noncompliance?

Please refer to Chapter 1, Question 9.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

Preclinical & clinical trial requirements in Spain – a comprehensive legal overview. 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 GBP 119.

 

1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?

No, clinical trial may be conducted abroad. For those cases whenever clinical trials are conducted outside the European Union, the applicant of the marketing authorization shall submit a declaration stating that the clinical trials carried out outside the European Union meet the ethical requirements set forth in the Spanish legislation.

 

2. How are clinical trials funded?

Most clinical trials conducted in Spain are sponsored by the pharmaceutical industry, being funded by the sponsoring companies. Clinical trials in Spain might be sponsored also by individuals, institutions or organizations, either private or public.

 

3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?

The clinical trials protocols shall describe the reasons, objectives, design, methodology, statistical considerations and organization of a clinical trial. The authorizing of clinical trials in Spain by the AEMPS requires prior assessment of the protocol, done jointly, by the AEMPS and the Ethics Committee for research with medicinal products.

 

4. What are the requirements for consent by participants in clinical trials?

Trial participants must freely give their consent before being included in a clinical trial. Consent must be given after having been informed of all aspects of the clinical trial that are relevant to the participant’s decision to participate. Minors or incapacitated persons’ consent must be given through their legal representatives. Consent must be given in writing. The principal investigator is normally in charge for obtaining informed consent from trial subjects.

The Ethics Committee shall approve the process for obtaining consent from trial subjects and the patient information sheet / informed consent form. Such documents must be at least in Spanish.

 

5. May participants in clinical trials be compensated?

According to Spanish law participants may only be reimbursed for any expenses or losses related to their participation in trials. However, in special situations, the Ethics Committee may report favourably the compensation to participants for the inconveniences derived from their participation in the clinical trial, provided that said compensation does not influence the decision of the participant to participate in the clinical trial.

 

6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?

Participants will be compensated against any personal damage caused as a result of their participation in the clinical trial, as well as the economic damages that derived from said personal damage, provided that this damage is not inherent either: (i) to the pathology under study or (ii) to the natarual course of the disease of the participant as a result of the ineffectiveness of the treatment.

Under Spanish law, one of the conditions for conducting a clinical trial is the contracting, by the sponsor, of a civil liability insurance covering the civil liability the sponsor, the principal investigator and the investigator’s team, and the site against any claim brought by participants for damages suffered due to the clinical trial. The minimum guaranteed amount shall be EUR 250,000 per trial subject. A maximum insured capital per trial and per year of EUR 2,500,000 may be established.

 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

Also from this Legal Handbook

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.

 

The guide is available to purchase here for GBP 119.

 

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 (‘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, is responsible, among others, for granting marketing authorizations for medicinal products 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 patients 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:

1. national procedure, mutual-recognition procedure, or decentralized procedure at the AEMPS; or
2. centralized procedure at the European Medicines Agency (‘EMA’).

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?

Fees for services provided by the AEMPS are approved on an annual basis. Current fees were approved by Law 22/2021 on the budget for 2022. A list of the services provided by the AEMPS and the corresponding fees may be found at: https://www.aemps.gob.es/industria-farmaceutica/tasas/relaciontasas/?lang=en 

AEMPS’s services/fees include, among others, the following: 

• Fee for the evaluation, authorisation and registration of a new medicine for human use (no generic): 21,576.3 Eur
• Fee for the evaluation, authorisation and registration of a new generic medicine for human use: 8,776.68 Eur
• Authorisation of a new pharmaceutical laboratory: 6.156,58 Eur
• Authorisation and/or certification for medicines warehouses under customs control or supervision: 1,366,31 Eur
• Individual inspection activities in Spain, unless a complaint has been made or it is requested by a representative association of consumers: 5,208.19 Eur

 

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 an initial period of 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 2,437.84) 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 Chapter 1, Question 4) 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 clinical trials results (bioequivalence studies must be provided instead of).

The law does not contemplate any difference for local manufacturers vs foreign-owned manufacturers when it comes to the authorization procedure for medicinal products.

 

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. The NHS 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 (the “CIPM”).

 

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?

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/CIPM. Also, in case that there are legitimate public reasons, the Ministry of Health/CIPM may control the price of medicinal products that are excluded from the reimbursement.

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. This is regulated in Royal Decree-Law 8/2010.

Prices of reimbursed medical devices dispensed to non-hospitalized patients are also regulated (see Spanish Law on Medicinal Products and Royal Decree 9/1996) and fixed by the Ministry of Health/CIPM. 

 

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?

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 dispensing 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 treatments established by the competent health authorities. The conditions and requirements of such personalized dosing systems shall also be established by health authorities. 

 

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Click the following links to read more legal articles from Spain:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reform
8. Cannabinoid Drugs, Medicinal Cannabis and Opioid Drugs

1.  Please make a general introduction to the public health sector in your country and its organization

The National Health System (“NHS”) is based on the principles of universal coverage and solidarity. Art. 43 of the Spanish Constitution establishes the right to healthcare as one of the basic principles that must inspire action by all public administrations, and this has been interpreted to recognise universal access to healthcare. The NHS is mainly funded from taxes.

Spain has a decentralized political system, with a central government and 17 regions, so-called Autonomous Communities. This has a relevant impact on the organization of the NHS because many healthcare competences have been transferred to the Autonomous Communities.

The central government is responsible for establishing the bases and general coordination of healthcare throughout the state, as well as for establishing legislation on pharmaceutical products. The Interterritorial Council of the National Health System (“CISNS”), which comprises the national health minister and the 17 regional ministers of health of each Autonomous Community (except for the two Autonomous Cities of Ceuta and Melilla), is responsible for high-level coordination of actions across the regional health system.

The central government, through the Ministry of Health, is also responsible for approving pricing and reimbursement of medicinal products. However, since the public funds that may be used to finance such reimbursement come out the budget of the 17 Autonomous Communities, such Autonomous Communities participate in the committee of the Ministry of Health (Inter-Ministerial Commission of Prices of Medicinal Products) responsible for assessing applications for price and reimbursement of medicinal products.

Regional governments, for their part, have broad powers on health matters, including the provision of public healthcare services and related funding.

 

2.  Please provide any infographics including, the actors involved in the market access process (market authorization, pricing decisions, reimbursement decisions); and the process and flow.

Also from this Market Access & Health Technology Assessment

1. Which are the administrations, bodies and institutions in charge of public health in your country and what are their respective responsibilities?

The main administrations in charge of public health and reimbursement of medicinal products in Spain are: the Spanish Agency of Medicines and Medical Devices (“AEMPS”), the Ministry of Health (“MOH”), particularly the General Directorate of Pharmacy (“DGCC”), the Inter-Ministerial Commission of Prices of Medicinal Products (“CIPM”), the Advisory Committee for the Pharmaceutical Provision of the NHS, REVALMED (which is a net of different bodies in charge of HTA as we will discussed below)[1], and the health departments of the regional governments.

We will discuss the role of each of such bodies in the following questions.

 

2. Which are the administrations, bodies and institutions in charge of drug approvals in your country and what are their respective responsibilities?

The AEMPS is responsible for the evaluation and, where appropriate, authorization of medicinal products by national, decentralized (“DCP”) or mutual recognition procedures (“MRP”). Its legal regime and functions are contemplated in Royal Decree 1275/2011 which created the AEMPS and approved its Statute.

In addition, the AEMPS plays an important role in the process of preparing the Therapeutic Positioning Report (“TPR”) to which we will refer below.

3. Which are the administrations, bodies and institutions in charge of Health Technology Assessment in your countries and what are their respective responsibilities?

There is some confusion in Spain on this issue; especially after the recent Judgement of 26 June 2023 by the Spanish National High Court that has annulled the Plan to consolidate TPRs that the MOH had approved to regulate the preparation of TPRs (the main HTA instrument in Spain for medicinal products). The European HTA Regulation also adds uncertainty to this scenario insofar as it is still unclear how the evaluation reports foreseen therein will affect Spanish TPRs.

Be it as it may, as things stand, the main bodies in charge of HTA in Spain are the AEMPS, the MOH and the regional governments; all of such bodies acting in coordination through REVALMED. This statement, however, needs to be qualified and contextualized. We do so below.

First, the main HTA instrument for medicinal products in Spain is the TPR. TPRs were created in 2013 with the objective “to provide, beyond the authorization of the medicinal product, relevant information, based on scientific evidence of the position that the new product occupies in the market in comparison with other drugs or health measures already in existence”[2]. The legal basis for such TPRs is Third Additional Provision of Law 10/2013 which establishes that the position of a medicinal product in the pharmaceutical provision and its comparison with other therapeutic alternatives will be carried out through TPRs, which are binding, and have to be elaborated and approved by the AEMPS, having a common scientific-technical basis for the entire NHS.

Second, notwithstanding what is said in Law 10/2023, in 2020 it was approved the so called “Plan to Consolidate TPRs”, which created REVALMED[3], a network under which other agencies, in addition to the AEMPS, have a relevant role in the preparation and approval of the TPRs. REVALMED has been responsible for the coordination of the TPR process in Spain since 2020, and is composed of:

• Therapeutic Evaluation Group. Its function is to prepare the first draft of the TPR with regard to the therapeutic sections. It is led by the AEMPS, although it also includes members of the DGCC.
• Pharmaco-Economic Evaluation Group. Its function is to prepare the first draft of the TPR with regard to pharmacoeconomic aspects. It is led by the DGCC, although it can also include members appointed by the Autonomous Communities.
• Evaluation Nodes. Their function is to review the draft of the TPR and make contributions. They are made up of expert management and clinical professionals appointed by the Autonomous Communities.
• Coordinating Group. Its function is to identify the TPRs to be developed, prioritize them (according to certain pre-defined criteria) and, finally, approve them. It is made up of members of the DGCC, the AEMPS, coordinators of the Evaluation Nodes and representatives of the Autonomous Communities.

 

Third, since approval of the Plan to Consolidate TPRs in 2020, some TPRs also include pharmaco-economic evaluation assessments. This inclusion has created some tension and discrepancies among relevant stakeholders who question whether TPRs are the appropriate instrument for incorporating this type of evaluation.

Fourth, Farmaindustria (the National Trade Association of the Spanish based pharmaceutical industry) appealed the Plan to Consolidate TPRs. The legal basis of the appeal was based on two arguments. First, the Plan to Consolidate TPRs is in the nature of a general provision. It is not a mere internal organizational instrument, as the MOH defended. This being so, Farmaindustria requested the nullity of the Plan as it was approved by a manifestly incompetent body (the Committee on Pharmacy of the CISNS) with absolute omission of the legally established procedure. Second, the Plan to Consolidate TPRs must be annulled because it is contrary to the principle of hierarchy of norms. The Plan to Consolidate TPRs provides that TPRs will have a “scientific and economic basis”, and that they will be approved by the REVALMED Coordination Group. However, Law 10/2013, the only legal basis for the TPRs, provides that TPRs “shall have a scientific basis” (without any mention of the economic issue) and must be approved by the AEMPS.

The Spanish National High Court upheld the appeal in its entirety. The Judgement (as per the information available at the time of publication) was not appealed.

As stated above, the impact of this Judgement to the Spanish HTA process is still unclear but it is likely that it will imply profound changes in that process over the coming months. Close follow-up of the topic will be necessary.

 

4. Which are the administrations, bodies and institutions that qualify as “payers” in your country and what are their respective responsibilities?

Spain’s regional governments pay for all healthcare services from their own budgets. They enjoy a large degree of autonomy to decide how they purchase the goods and services they may require to provide healthcare services to patients.

The MOH is the department of the central government responsible for approving the reimbursement of medicinal products. As explained, the public funds that may be used to finance this reimbursement come out of the budgets of the 17 Autonomous Communities into which Spain is divided. Because of this, the Autonomous Communities participate in the CIPM, the specific committee within the MOH responsible for assessing applications and deciding on the maximum ex-factory price (so called “PVL”, which stands for “Precio Venta Laboratorio”) for reimbursed medicinal products.

This generates a complex situation where the basic content of the pharmaceutical provision is set forth at the state level (because the MOH makes the decision on pricing and reimbursement, as explained below) but regional governments are responsible for financing it out of their budgets.

 

5. Which are the administrations, bodies and institutions in charge of reimbursement decisions in your countries and what are their respective responsibilities?

The MOH, particularly the DGCC, is the department of the central Spanish government in charge of pricing decisions of medicinal products. The DGCC’s functions are contemplated in Royal Decree 735/2020. Such functions include deciding on whether a medicinal product shall be reimbursed or not by the NHS and providing technical and administrative support to the CIPM.

The CIPM is a collegiate body formed by representatives of the MOH, the Ministry of Economic Affairs and Digital Transformation, the Ministry of Treasury and representatives of the Autonomous Communities. The CIPM is responsible for deciding on the maximum ex-factory price for reimbursed medicinal products (PVL). Its specific legal regime is contemplated in Law on Rationale Use of Medicines and Medical Devices (Royal Legislative Decree 1/2015) and in Law on Legal Regime of the Public Sector (Law 40/2015).

The MOH, through the DGCC, and the CIPM, decide on reimbursement and then on price. In theory, the DGCC is the first to decide whether the product is reimbursed, and the CIPM then decides on the maximum reimbursed price. In practice, however, the two procedures run in parallel and overlap because the decision of the DGCC regarding reimbursement is also based on the price that the CIPM would set for the product. The DGCC, on the other hand, takes care of process management, preparing the rulings that the CIPM shall adopt. It is also the de facto leader of the negotiations with the Marketing Authorization Holder (“MAH”) and coordinates the work carried out by evaluation groups who handle the dossiers prior to the meeting of the CIPM.

6. Which are the administrations, bodies and institutions in charge of reimbursement decisions in your countries and what are their respective responsibilities?

See Q5 (Section II).

7. Which are the administrations, bodies and institutions in charge of public procurement and tendering in your country and what are their respective responsibilities?

Regional governments and public hospitals are in charge of public procurement and tendering in Spain. See Section IX below.

 

8. What are the other actors of significance with regards to market access in your country and what are their respective responsibilities?

The Autonomous Communities play a large role in market access. This is because even though the MOH decides which therapies are financed, the Autonomous Communities allocate the budget for financing such therapies. This means that in the case of high budgetary-impact products, companies may expect access to the market to be subject to agreements with regional authorities (or sometimes with local hospitals) regarding the conditions under which the product will be available in such a region or hospital.

The role of the Autonomous Communities become even more relevant for non-reimbursed products, that is products that the MOH has decided not to reimburse. The purchase of such products by the Autonomous Communities is subject to the approval of the relevant Therapeutic Commission of each Autonomous Community. Such Commission may decide whether such non-reimbursed product may be purchased by hospitals of the Autonomous Community or not.

 

 

[1] REVALMED has been recently questioned by a Court Judgement as we indicate in different sections of this publication.

[2] Collaboration proposal for the elaboration of Therapeutic Positioning Reports of medicinal products, accessible at: https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/propuesta-colaboracion-informes-posicionamiento-terapeutico.pdf.

[3] Plan to consolidate the Therapeutic Positioning Report in the National Health System, accessible here: https://www.sanidad.gob.es/profesionales/farmacia/IPT/docs/20200708.Plan_de_accion_para_la_consolidacion_de_los_IPT.actCPF8Julio.pdf.

Also from this Market Access & Health Technology Assessment

1. What are the pricing models, processes and principles for originator drugs?

Originator medicinal products must go through price and reimbursement proceedings (P&R Procedure) where it is decided if they are to be reimbursed or not. If reimbursed, the PVL is also fixed.

To determine whether a medicinal product is reimbursed or not, the DGCC/CIPM must take into account the following criteria (art. 92 and 94 of Royal Legislative Decree 1/2015):

1. the seriousness, duration and sequels of the pathologies for which the product is approved;
2. the needs of special groups of people;
3. the therapeutic and social utility of the product as well as its incremental clinical benefit, taking into account its cost and effectiveness;
4. the need to limit and rationalise public pharmaceutical expenditure and the impact of the medicinal product on the NHS;
5. the existence of medicines already available and the existence of other alternatives for the same illnesses, which have a lower price;
6. budget impact and cost-effective analysis;
7. The contribution of the product to Spain’s gross domestic product;
8. the degree of innovation of the product: whether it provides an indisputable therapeutic advance for altering the course of an illness or easing the course of such illness; and its results or contribution to the NHS;
9. The return mechanisms that may be proposed by the MAH (discounts, price reviews). This is the result of the increasing relevance that risk-sharing schemes are currently having in Spanish practice; many companies, especially for high-budgetary-impact products, are required to offer specific arrangements to obtain reimbursement.

From a procedural standpoint, the typical P&R Procedure (there may be particularities/changes on a case-by-case basis) incorporates the following phases: (i) initiation: the P&R Proceeding starts ex-officio; the DGCC shall send a letter to the MAH or to its local representative (“LR”), informing it that the process has begun and granting the MAH a period between 10 and 15 working days to make any submission it deems convenient on the reimbursement of the product, (ii) negotiation between the MAH/LR and the DGCC, and preparation by the DGCC of a report for the CIPM in which the DGCC performs a therapeutic (and sometimes economic) evaluation of the new drug/new indication (this report is commonly referred to as the “Associate Report for the CIPM” or “Associate Report”), (iii) evaluation of the new medicinal product/new indication by the CIPM, (iv) issuance by the DGCC of a draft resolution on the reimbursement/non reimbursement of the new medicinal product/new indication as resolved by the CIPM, (iv) submission of allegations by the MAH/LR (if any), (v) assessment of the allegations by the CIPM/DGCC (if any) and (vi) final ruling of the DGCC.

Under the law, the whole P&R Proceeding may take up to 180 days. However, authorities usually request additional information, and these requests may stop the clock on the procedure. In practice, companies may well expect the reimbursement approval to run for a minimum of six months. Occasionally, procedures have taken longer.

 

2. What are the pricing models, processes and principles for generics and biosimilars drugs?

Theoretically, generics and biosimilar drugs must go through the same P&R Procedure explained in Q1 (Section III) above. However, in practice, what usually happens is that such products go through a sort of “simplified” P&R Procedure which, in essence, means that generics/biosimilar products are reimbursed with an approximate 40% (generics) or 20-30% (biosimilars) discount with respect the originator.

 

3. What are the reimbursement approval processes and principles for originator drugs?

Please refer to Q1 (Section III) above.

 

4. What are the reimbursement approval processes and principles for generics and biosimilar drugs?

Please refer to Q2 (Section III) above.

 

5. Are there any other special processes to be considered for certain types of drugs?

Non-industrially manufactured advanced therapy medicinal products (“ATMPs”) are subject to a special P&R Procedure.

In October 2019, the CISNS issued an agreement on the general conditions for planning, coordination, contracting, procurement and supply of ATMPs for the publicly owned structures and services integrated in the NHS (the “2019 Agreement”).

In the 2019 Agreement, the CISNS confirmed that for the reimbursement of medicinal products, their inclusion in the pharmaceutical provision of the NHS is necessary because this is contemplated in art. 92.1 of Royal Legislative Decree 1/2015. However, in contrast to industrially manufactured medicinal products where the DGCC and CIPM are competent (see Q5 Section II), the 2019 Agreement determined that CISNS is the competent body to decide on the reimbursement of non-industrially manufactured ATMPs.

The 2019 Agreement was based on the opinion of the State Attorney who relied on art. 91.6 of Royal Legislative Decree 1/2015 that expressly states that “[T]he Interterritorial Council of the National Health System may agree on the general conditions for planning, coordination, contracting, procurement and supply of medicines and medical devices of the publicly owned structures and services integrated in the National Health System”.

 

Also from this Market Access & Health Technology Assessment

1. Price Control

1. How does price control at ex-factory prices work in your country?

This question may be broken down in two parts: (i) situations in which a medicinal product may be in connection with its reimbursement status/price; and (ii) criteria to determine PVL.

 

Situations in which a medicinal product may be in connection with its reimbursement status/price:

• Medicinal products that have been granted a MA but for which a reimbursement/price ruling has not been issued.

They may be available in Spain ex art. 17 in fine of Royal Decree 1015/2009 regulating the availability of medicines in special situations. Their use must be authorized by the AEMPS, either for an individual patient or for a specific subpopulation of patients (protocol for use).

Their price is free (not regulated), and it is set by the supplier, usually after negotiation with the hospital pharmacy service. It is not uncommon for hospitals to pressure the company to supply the product free of charge, especially for those patients who were being treated with the medicinal product in the context of a clinical trial. The company has no legal obligation to supply the product free of charge except if the company obtains some information from the administration of the medicinal product (art. 31 and 39.1.f of Royal Decree 1090/2015).

• Medicinal products that have been granted a MA and for which a reimbursement/price ruling has already been issued.

Their commercialization is carried out at the following maximum prices.

For units dispensed in Spain at the expense of the NHS, the maximum reimbursement price is the PVL set by the CIPM.

For units dispensed outside the NHS (that is not reimbursed units), the maximum price at which they can be marketed is the “notified price”. The notified price is free although the DGCC can object to it for reasons of public interest ex art. 94.4 of Royal Legislative Decree 1/2015. Since there is no specific term for the DGCC to express this objection, we understand that the general term of 3 months applies.

• Medicinal products that have a MA and an express non-reimbursement ruling of the DGCC.

According to a Report issued by the DGCC in 2019, the managing entities of the NHS and/or public hospitals cannot acquire medicinal products in this situation. In our opinion, this conclusion of the Report has no legal support and, therefore, lacks any legal validity. Among other issues, the DGCC has no authority to issue such a report. Moreover, there is no regulation that prohibits public hospitals from acquiring these medicinal products; in fact, this possibility is specifically contemplated in Royal Decree 1718/2010 on medical prescriptions and dispensing orders. Be that as it may, the reality is that in practice some Autonomous Communities follow the criteria of the Report and do not purchase medicinal products with an express non-reimbursement ruling.

In our opinion, medicinal products with an express non-reimbursement ruling of the DGCC can be marketed outside the NHS at free price.

• Medicinal products that have a MA but have never been reimbursed and have never been the object of an express non-reimbursement ruling of the DGCC.

They can be marketed at free price.

• Medicinal products that had been reimbursed but have been subsequently excluded from reimbursement.

They can be marketed at free price. However, this price must be communicated to the MOH so that, within a period of one month, it can decide on its conformity (art. 93.3 of Royal Legislative Decree 1/2015). In case of disagreement, the file is submitted to the CIPM, which must decide on the basis of “reasons of protection of public health, equal access to medicines for patients or actual or potential harm to the interests of disadvantaged groups”. As long as the disagreement is maintained, the maximum industrial price that the product had when it was reimbursed remains in force (art. 93.5 of Royal Legislative Decree 1/2015).

• Non-prescription medicinal products.

They can be marketed at free price unless the Government regulates them “following a general objective and transparent regime” (art. 94.3 par 1 of the Royal Legislative Decree 1/2015) or unless the CIPM, when there is an exceptional health situation, and in order to protect public health, fixes the maximum retail price (“PVP”) for the duration of such exceptional situation (art. 94.3 par 2 of Royal Legislative Decree 1/2015).

 

PVL:

As discussed above, units of medicinal products for which a reimbursement/price ruling has already been issued by the DGCC and that are dispensed in Spain at the expense of the NHS [point (ii) above] cannot be commercialized at a price above the PVL set by the CIPM.

 

How is this PVL set?

As regards setting the price of medicinal products, Spain has always been said to follow a “cost plus” system, under which the maximum PVL should respond to the cost of the product plus a given profit margin. This is what Royal Decree 271/1990 contemplates in accordance with the provisions of Directive EC 89/105.

As a matter of practice, it has always been known that the price-approval process entails a negotiation with the authorities where the cost and the profit margin are not really the variables that are considered. Companies should be prepared for prices mainly to be determined by the following two issues: a) a comparative pharmaco-economic evaluation of the medicine in which the advantages of the new product should be quantified; or b) the price of the product in other EU Member States.

Other than these, companies must be ready for the authorities to consider other issues such as the activities performed by the company in Spain (R&D, manufacturing, etc.) and the relationship with a local company through a co-marketing or licensing arrangement.

 

2. How does price control at the wholesale level work in your country?

Please refer to the question above.

 

3. How does price control at the retail pharmacy level work in your country?

The margin of retail pharmacies (“Pharmacy Margin”) is regulated in art. 2 of Royal Decree 823/2008.

Pharmacy Margin is: (i) for those medicines whose PVL is equal to or less than €91.63, 27.9% of the retail price excluding taxes (“Retail Price”); (ii) for those medicines whose PVL is higher than € 91.63 and equal or lower than €200, €38.37 per package; (iii) for those medicines whose PVL is higher than €200 and equal or lower than €500, €43.37 per package; and (iv) for those medicinal products whose PVL is higher than €500, € 48.37 per package.

 

2. External Reference Pricing (ERP)

1. Is there a system of external reference pricing (ERP) in place in your country?

As per written Spanish law, the MOH is not allowed to reference prices internationally. International referencing was contemplated in the Law on Medicinal Products before 2012, but Royal Decree-Law 16/2012 of 20 of April revoked any reference to this practice in 2012 and from then on, international referencing has no legal basis in Spain. The Judgements of the Supreme Court of 28 October 2015 and 11 November 2015 confirmed this understanding.

With respect ERP, however, the theory substantially differs from the practice. While it is clear that the law does not allow the MOH to reference prices internationally, the truth is that ERP is, indeed, a quite relevant factor influencing price rulings in Spain (with respect both the PVL and the Notified Price). The fact that this practice has no legal basis, makes it quite difficult to identify how the MOH exactly factors in international prices and from which sources these prices are obtained. In any case, as per our experience dealing with the MOH, it has become clear that, on the one hand, the MOH requests the MAH to provide information about how the medicine has been priced in other EU countries; and, on the other hand, that EU prices operate as a cap for Spanish prices, meaning that prices in Spain are rarely fixed above the price of the same medicinal product in other EU countries.

 

2. When and/or how often is ERP activated?

Please refer to Q2.1 (Section IV) above.

 

3. What is the legal framework of the ERP in place in your country?

Please refer to Q2.1 (Section IV) above.

 

4. What is the composition of the country basket?

Please refer to Q2.1 (Section IV) above.

 

5. Describe the price calculation and selection for reference products.

Please refer to Q2.1 (Section IV) above.

 

6. How often does the price need to be updated?

Please refer to Q2.1 (Section IV) above.

 

7. How do the “price List”/catalogues from references countries work in your country?

Please refer to Q2.1 (Section IV) above.

 

3. Internal Reference Pricing (IRP) (Note, this is not applicable in some market, develop if is applicable to your country)

1. Is there an internal reference pricing (IRP) system in your country?

Yes. Once a generic or biosimilar version of a medicinal product is approved, or even if no generic or biosimilar exists in Spain but the main active ingredient of a product has been authorised in the EU for the last 10 years (and there exists at least one medicinal product different than the original product and its licences), the MOH may make such ATC5 substance subject to a reference price, which will apply to all reimbursed product presentations having the same ATC5 classification and identical administration route.

The reference price is the maximum price which the Spanish authorities will pay for these products. Such price is fixed on the value represented by the lowest cost of treatment per day of the presentations of the medicinal products included in each group.

 

2. What is the legal framework of the IRP in place in your country?

Spanish IPR is regulated in the Royal Legislative Decree 1/2015 and in the Royal Decree 177/2014 on the reference price system.

 

3. When and/or how often is IRP activated?

The MOH approves a reference price list every year based on the information in the database for reimbursed and marketed products (Nomenclator) as of April 1^st. The list published by the MOH is called Reference Price Order (“RPO”). A draft of the RPO (to which companies may submit allegations) is usually published in Q2-Q3 of each year. The final RPO is usually published in Q3-Q4 of each year.

 

Also from this Market Access & Health Technology Assessment

1. Which are the health technology assessment (HTA) evaluation bodies and their responsibilities in your country?

The main bodies in charge of HTA in Spain are the AEMPS, the MOH (particularly the DGCC) and the regional governments; all of such bodies acting in coordination through REVALMED.[1] Also note that, as mentioned above, a recent Court Judgment (26 June 2023) annulled the documents that served as the basis for REVALMED and that, therefore, it is foreseeable that there will be important changes in this matter (including key players and bodies in charge of HTA in Spain) in the near future. For further details, see Q3 Section II above.

 

2. Do regulators require HTA studies in your country?

Regulators do no requite HTA studies for the application/obtention of MAs of medicinal products in Spain. To obtain a MA in Spain (following a national authorization procedure), medicinal products developers need to submit specific data on their medicinal product (dossier) that does not include HTA reports nor other type of studies comparing the assessed medicine with other medicinal products/therapies. The AEMPS then carries out a thorough assessment of such dossier to decide whether or not the particular medicinal product is safe, effective and of good quality and is therefore suitable for use in patients.

 

3. Do payers require HTA studies in your country?

Generally speaking, yes. Although it depends on the specific medicinal product or new indication assessed for P&R purposes.

According to Law 10/2013, TPRs have been interpreted as compulsory for pricing decisions, although the wording of Law 10/2013 is not entirely clear and may be interpreted otherwise.

The Plan to Consolidate TPRs (recently annulled by a the Spanish National High Court, as discussed above) also seemed to indicate that TPRs are compulsory for P&R purposes in the following cases: medicinal products and new indications authorized by the European Commission through a centralized procedure, new medicinal products authorized through a national procedure that contain new molecules, and all other medicinal products that the Permanent Commission of Pharmacy so considers considering its budget and sanitary impact.

In practice (and until now, this may change in the future due to the profound changes that the Judgment annulling the Plan to Consolidate TPRs may bring), TPRs have been mandatory for P&R Procedures in the cases outlined above. The DGCC (saved from very rare occasions) does not elevate a P&R dossier of new medicinal products/new indications to the CIPM until the TPR is ready and available.

4. How are HTA assessments translated into pricing conditions in your country?

In accordance with Royal Decree 271/1990 (still in force and fully applicable), Spanish authorities should follow a “cost plus” system under which the maximum PVL should respond to the cost of the product plus a given profit margin. Therefore, at least theoretically under Spanish written laws, HTA assessment should have no impact into pricing conditions.

However, as already discussed, the reality is different, and comparative pharmaco-economic assessments are often used to determine pricing conditions. In this respect, whenever a TPR has been approved, it heavily influences reimbursement and pricing decisions. How exactly the results of the TPR are factored in a pricing decision is hard to say, to the extent there is no legally mandatory guidance to be followed in this respect. In Spain, there are not mandatory cost-effectiveness thresholds either (although GENESIS’s guidelines[2] include some non-binding references). Be it is at may, we think is fair to say that whenever a TPR has been approved it is well taken into account by the authorities in charge of pricing decisions (DGCC/CIPM).

Finally, it is also relevant to note that Royal Legislative Decree 1/2015 (arts. 92.1.c and 92.8) contemplates that cost-effectiveness assessments may affect reimbursement decisions. Strictly, Royal Legislative Decree 1/2015 refers to “reimbursement” decisions (i.e., whether to reimburse or not) but not pricing ones (fixing the maximum ex-factory price in case a given product is reimbursed). Anyway, this reference, the fact that the reimbursement decision and the pricing decision overlap to certain extent (because the decision of the DGCC regarding reimbursement is also based on the price that the CIPM would set for the product), and the usual practice described in the preceding paragraph, allow us to conclude that HTA assessments have, indeed, a relevant impact in pricing conditions.

 

5. How are HTA assessments translated into reimbursement conditions in your country?

Please refer to Q4 (Section V) above.

 

6. Which are the evaluation criteria, processes or models and analyses framework used for HTA in your country?

There are no ex lege mandatory criteria, processes or models that must be followed in Spain to perform HTA assessments. Anyway, it is worth noting the existence of a standard operating procedure (SOP) to perform TPRs[3] approved by the Permanent Commission on Pharmacy of the CISNS and some guidelines developed by the GENESIS group[4]. Such documents, although not binding, have had a relevant impact on criteria, processes and models used in HTA assessments during the last years. The SOP, in any case, derives from the Plan to Consolidate TPRs which, as indicated above, has been declared null and void. This means that the legal validity of the SOP could also be questioned.

 

7. What is the methodology used in your country for HTA assessment?

There is no ex lege mandatory methodology that must be used in Spain for HTA assessments. The guidelines mentioned in the prior question (SOP to perform TPR[5] and GENESIS’s guidelines[6]) have also had some impact on the methodology used in Spanish HTA assessments over the last years.

8. Which are the other decisions impacted by the assessed outcome in your country?

The objective of the Spanish HTA assessments (included in the TPRs) is to provide a comparative therapeutic and economic evaluation of medicinal products in order to have relevant information, based on scientific evidence, on the position of the new product or its new indication compared to existing therapeutic alternatives, pharmacological or otherwise.

Such HTA assessments have an impact in several areas (apart from P&R decisions) including the selection, prescription and use of medicinal products. The Autonomous Communities and hospitals may also perform local HTA assessments, and such assessments may sometimes be influenced by the content of the TPRs (nationwide HTA assessment).

 

9. Does your HTA review or inquire other international HTAs during the assessment process? If so, which ones are the usual partners?

There is no list of international HTAs assessments that Spanish authorities must review before carrying out its own assessment. The SOP to perform TPR[7] and GENESIS’s guidelines[8] include some instructions on how to consider and assess the results of international evaluations, but do not refer to any specific international HTAs for that purpose.

Finally, it is relevant to mention that the DGCC almost always includes a section called “conclusions of other evaluation bodies” in the Associate Report for the CIPM (this is a report that includes the results of the TPR, some other therapeutic and economic evaluations, and a recommendation to the CIPM on whether or not to reimburse the medicinal product). In this section it is common to see references to evaluations made by NICE or French HTA evaluation bodies.

 

[1] As discussed, REVALMED has been recently questioned by a Court Judgement.

[2] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

[3] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[4] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

[5] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[6] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

[7] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[8] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

 

Also from this Market Access & Health Technology Assessment

Before answering the questions in this Section VI, it is appropriate to make an important consideration. In Spain, at least up to the date of this publication, the HTA evaluation is carried out by public authorities, without the industry having to provide a specific HTA dossier with pharmacoeconomic studies of its product.

Once the process has started (which we will detail in the following questions), the company that owns the product (and other relevant stakeholders) have the right to present “allegations” to the TPR draft. And at this point, they can provide studies to support their position. But there is no HTA dossier submission at the very beginning of the HTA process.

The Advisory Board of the NHS (“CAPF”) has issued several reports in favour of changing the current model and increasing the role of the industry in the HTA process (always preserving, the public authorities right to review the work done by the industry and to perform its own HTA assessments)[1].

 

1. Have local authorities published recommendations surrounding value assessment dossiers? (If yes please add link)

The most relevant non-binding recommendations for performing pharmacoeconomic evaluation and budget impact analysis are the GENESIS’s guidelines[2] mentioned in the prior Section. The SOP for TPRs[3], and a Q&A prepared by the MOH[4] may also be useful for such purposes.

 

2. Have local Authorities published guidelines surrounding value assessment dossiers? (If yes please add link)

The most relevant non-binding guidelines for performing pharmacoeconomic evaluation and budget impact analysis are the GENESIS’s guidelines[5] mentioned in the prior Section. The SOP for TPRs[6], and a Q&A prepared by the MOH[7] may also be useful for such purposes.

 

3. Have local authorities published official guidelines surrounding the submission of value assessment dossiers? (If yes please add a link)

Two considerations shall be made prior to answering this question. First, as discussed in the beginning of this Section, there is no formal HTA dossier submission in Spain. Second, as pointed out in Question 3 (Section II), the main document governing HTA in Spain (i.e., the Plan to Consolidate TPRs) have been annulled by the Spanish National High Court. This means that, as of today, there is a lot of uncertainty as to how HTA assessments will be done in the future.

Be it as it may, until the date of publication of this guide, the main steps of the HTA process in Spain were as follows:

• Positive opinion of the Committee for Medicinal Products for Human Use (CHMP).
• The Coordination Group of REVALMED establishes a priority order of the medicinal products with a positive CHMP opinion. The prioritization criteria include, among others, covering an unmet therapeutic need or having a better clinical benefit or safety profile with respect to therapeutic alternatives.
• First draft of the TPR. The different groups (including the Therapeutic and the Pharmacoeconomic groups and the Evaluation Nodes) (see Question 3, Section II) prepare the first draft of the TPR. This first draft is approved by the Coordinating Group.
• Allegations of relevant stakeholders (including scientific societies, patients’ associations and the MAH) to the first draft of the TPR.
• Review of the allegations by the relevant groups and approval of the so-called Phase II TPR which may or may not include the proposals of the relevant stakeholders. The Phase II TPR is disclosed and published at the AEMPS’ website. The Phase II TPR is the one that is used for the DGCC to prepare the Associated Report for the CIPM. It is, therefore, the HTA report that has an impact on P&R decisions.
• After the P&R ruling, the TPR should be adapted including the price of the medicinal product. This is the Phase III TPR.

 

4. Describe the overall process of preparing and submitting a HTA dossier in your country.

As discussed, the nationwide HTA assessment for medicinal products in Spain is included in the TPR. Until the date of publication of this guide, TPRs include all or part of the following content:

• The title of the TPR shall include the name of the medicinal product and the clinical indication evaluated.
• The introduction shall clearly and precisely state the indication for which the product has been authorized and shall contain two parts: description of the health problem and current treatment. The introduction section also includes information about the following very relevant aspects: patient groups that may benefit the most from the treatment, comparators, treatment objective, relevant clinical variables as well as the threshold of clinical relevance in those cases in which a commonly accepted threshold is available.
• Description of the medicinal product. It should include the name of the active ingredient (trade name) and a brief introduction of the new product (therapeutic indication, presentation, dosage and pharmaceutical forms). It may also include aspects of the administration or duration of the treatment and relevant aspects of the authorization (for example, if it is a new medicinal product or a new indication, if the medicinal product has been designated orphan, if it has conditional or exceptional authorization, if it is conditioned to the results of new studies, etc.).
• Data from studies, including pivotal studies with active comparator, mainly the reference standard in clinical practice, and variables suitable for positioning the product will be prioritized for establishing the therapeutic position of the medicinal product.
• This section should follow a similar approach than the “Efficacy” section.
• Clinical benefit assessment and relevance for clinical practice. The objective is to assess whether the magnitude of the treatment effect is of clinical relevance, whether equivalent therapeutic alternatives exist, etc.
• Economic evaluation. The inclusion of this section in the TPRs has been questioned by the Spanish National High Court Judgment. Please refer to Q3 Section II for further information.
• The discussion section should lay the foundations for the conclusion of the report, establishing the argumentative thread that leads to the positioning of the medicinal product.
• Based on the discussion section, this section should establish the contribution of the product for the entire indication or for different subpopulations of the indication. The objective is to position the product as precisely as possible, based on the criteria of efficacy, safety and efficiency and its comparison with available alternatives.
• Therapeutic positioning. This is established after the P&R ruling.
• Bibliography.
• Expert group. The TPR should be signed by the different bodies that have taken part in the evaluation. The MAH, Scientific Societies and Patient Associations that have been contacted during the procedure shall be mentioned as well.

Finally, please note that the above structure of the TPR is included in the SOP for TPRs[8], and that the legal status of such SOP has been indirectly questioned since it represents a direct development of the Plan to Consolidate TPRs, which is currently under legal dispute. Please refer to Q3 (Section II) above for further reference.

 

5. Which are the questions to focus on when preparing a HTA dossier in your country?

TPRs usually follow the so-called “PICO” Process. PICO is a mnemonic used to describe the four main elements of the process which are: Population/patients (P): health problem and patient population to which it is to be applied; Intervention (I): medicinal product/therapy assessed; Comparators (C); and Outcome (O): relevant clinical variables.

 

6. Which are the questions to focus on when preparing a HTA dossier in your country?

In our experience, the key elements of the HTA assessment usually revolve around the selection of comparators, the relevant clinical variables and the thresholds of clinical relevance. Such issues should be carefully assessed by companies in order to be able to provide clear studies and documentation to the authorities supporting its view.

 

 

[1] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/Comite_Asesor_PFSNS.htm

[2] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

[3] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[4] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[5] Accessible at: https://gruposdetrabajo.sefh.es/genesis/genesis/Documents/GUIA_EE_IP_GENESIS-SEFH_19_01_2017.pdf

[6] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[7] Accessible at: https://www.sanidad.gob.es/profesionales/farmacia/IPT/home.htm

[8] See Section 2 of the SOP for TPRs available at: https://www.sanidad.gob.es/en/profesionales/farmacia/IPT/home.htm

Also from this Market Access & Health Technology Assessment

1. In addition to the clinical data obtained through clinical studies please list the data required for:

a. Market approval

Generally speaking, for getting a marketing authorization of a medicinal product, the applicant needs to provide sufficient information to demonstrate that the relevant product fulfills the established quality requirements, is safe under normal conditions of use, is effective in the therapeutic indications, is correctly identified, and provides the patient with the necessary information.

 

b. Pricing Decisions

As discussed above (see Question 1, Section III), reimbursement decisions in Spain are based on the criteria listed in art. 92 of Royal Legislative Decree 1/2015. On the basis of that, and to specifically answer this question, it can be said that the data required for reimbursement decisions are those that allow the company to prove that its product complies with art. 92 requirements. Spanish law does not provide further criteria as how these data should be, which means that companies are free to prepare such data as they deem convenient.

 

c. Reimbursement Decisions

As discussed above (see Question 1, Section IV), Spanish law contemplates a “cost plus” system to determine the PVL of medicinal products. Under such “cost plus” system the maximum PVL should respond to the cost of the product plus a given profit margin. This is what Royal Decree 271/1990 contemplates in accordance with the provisions of Directive EC 89/105. Considering this, companies should submit technical accounting and financial documentation necessary to determine the “full cost” of the medicinal product.

As a matter of practice, this is not the criteria actually used by the DGCC/CIPM to set the price of medicinal products (for further details see Question 1 Section III). The documents that really need to be provided and may have a true impact on the P&R Procedure include comparative pharmaco-economic evaluations, list of prices of the product in other EU Member States, or list of activities performed by the company in Spain (R&D, manufacturing, etc.).

Also from this Market Access & Health Technology Assessment

1. Are there any Managed entry agreements in place in your country? (If so, please list them)

Yes, there are managed entry agreements in Spain. The most frequent Managed Entry Agreements (MEAs) are financial and performance-based agreements (both at patient and population level).

 

2. Describe the fundamentals of the Managed entry Agreement, its rationale and the process for implementing it. When should each Managed Entry Agreement be considered? Which are the specific requirements to implement each Managed Entry Agreement? What are the potential challenges associated with each Managed Entry Agreement?

Financial MEAs

In our experience, the most frequent financial MEAs in Spain are the following[1]:

• confidential discount: an unconditional reduction of the PVL is agreed in a confidential contract, taking the form of an up-front discount or an ex-post rebate refunded by the firm.
• patient-level treatment or expenditure cap: a patient-level treatment (number of products, dosage or duration) or expenditure ceiling is agreed on, and the firm provides products exceeding the cap free of charge.
• population level expenditure cap: an aggregate expenditure ceiling for all patients/ a defined number of patients treated is agreed on, and the firm provides products exceeding the cap free of charge.
• population level price-volume agreement: tiered prices are agreed on, which decrease with increasing aggregate volume purchased for all patients treated.

 

The main objective of these financial MEAs is to tackle financial uncertainty. This implies that financial MEAs are usually used when the demand of the product is difficult to predict or it is expected to experience a sustained growth over time.

All such agreements may be negotiated and concluded at a national or regional/hospital level. The design of such schemes is easier than performance-based schemes to the extent it is not needed in financial MEAs to define clinical variables or relevant thresholds. The implementation of financial EMAs is also simpler because it does not require the continuous evaluation of patients to categorize them as “respondent” or “not respondent”.

Financial MEAs do not have mandatory specific requirements that they must comply with. A case-by-case negotiation takes place every time a company or the public administration suggests there is a need for this type of arrangement.

With respect to the challenges, one of the most relevant is the incentivization of opportunistic behaviors of the Autonomous Communities and/or hospitals, such as waiting until the cap or the next discount tranche is reached before purchasing products. Financial MEAs can alter consumption trends, which poses a risk to companies and also healthcare systems by increasing the risk of stock-outs caused by peaks in demand. Generally speaking, however, financial MEAs are implemented satisfactorily, and they are regarded as a relevant tool to lower the price of medicinal products and to contribute to the sustainability of the NHS.

 

Performance-based MEAs

In our experience, the most frequent performance based MEAs in Spain are the following[2]:

• Patient-level payment by results: payment to the firm for treatment provided is contingent on the achievement of pre-specified response to treatment in each patient. Payers may withhold payment partially or entirely for each patient until the result is achieved, receive full or partial refunds for patients who do not achieve the response, or receive free additional products with which to treat subsequent patients.
• Patient-level conditional treatment continuation: coverage of the treatment is continued only for patients who achieve a pre-specified response to treatment; firms provide products free of charge or discounted for patients who do not achieve results.

 

The main objective of these financial MEAs is to tackle therapeutic uncertainty. This implies that performance based MEAs are usually used when clinical evidence is not entirely satisfactory and, therefore, a scheme were payors only pay when the product actually works makes more sense.

Performance based MEAs may be negotiated and concluded at a national or regional/hospital level. The design of these schemes normally contemplates the creation of a “monitoring committee” made up of the company and representatives of the Autonomous Community and the MOH. This committee has the task of monitoring the agreement and contributing to the resolution of disputes as to whether or not a patient is a “responder” according to the agreed criteria.

A major challenge for this type of arrangement is related to the fact that some hospitals are not yet very accustomed to performance-based schemes, which results in implementation difficulties. The reporting of follow-up data (which ultimately allows to classify patients into responders and non-responders and to determine payer’s payment obligations) is also a challenge.

On the design side, it is often difficult to determine the relevant clinical variables and cut-off values that dictate into which category each patient falls into.

 

 

[1] Reference is made to an OECD report on MEAs where the different types of MEAs are classified and defined. Report accessible at: https://dx.doi.org/10.1787/6e5e4c0f-en

[2] Reference is made to an OECD report on MEAs where the different types of MEAs are classified and defined. Report accessible at: https://dx.doi.org/10.1787/6e5e4c0f-en

Also from this Market Access & Health Technology Assessment

1. Please describe the main cost containment policies in place in your country and their fundamental principles:

a. Pricing and impact of generic/biosimilar approval

The entry of generics/biosimilars into the market affects the price of original drugs by three main mechanisms: (i) homogeneous groups (“HG”), (ii) reference groups (“RG”), (iii) market pressure.

Products subject to generic competition are affected by HG, RG and market pressure. Products subject to biosimilar competition are only affected by RG and market pressure to the extent HG only includes, as we will see, products that are totally interchangeable (and biological products are not).

As a preliminary comment, it is relevant to note that in Spain generics are usually reimbursed with an approximate 40% discount vs the originator; compared to a 20-30% discount for biosimilars.

 

Homogeneous Associations

As soon reimbursement is approved for a generic, it will be included in a HG with the reference product. Each HG comprises all products that are identical (same SKU).

The prices of each HG are fixed for the first time on day 1 of any month (“M”) on the basis of the information included in the Nomenclator as of day 20 of month M-1. Once so fixed, they are updated monthly and then quarterly.

During month M, once each HG includes the original and its generic versions, unless the MAH of the original lowers the price of the original product to the level of the generics, it will lose all reimbursed prescriptions where the product is identified by its active principle because the pharmacist, in such case, must dispense the product with the lowest price in the HG.

 

Reference Groups

Reference groups also affect the price of originators. The effect of the launch of a biosimilar/generic on the originator’s price through reference groups, however, is not immediate. Originator’s price will not have to be reduced until a reference group for the medicinal product is created, and this may take some time after the launch of the biosimilar/generic.

As to when and how a reference price group is created, this will depend on the date on which the biosimilar/generic is launched. Under the current legislation (Royal Decree 177/2014), the MOH approves a reference price list every year on the basis of the information in the database for reimbursed and marketed products as of April 1st. If the biosimilar/generic is launched before 15^th March of any year (“N”), then it will appear as reimbursed and marketed on April 1 of such year N, and the reference price group will be created and will apply sometime in Q3 or Q4 of year N. If the generic/biosimilar is launched after 15 March of year N, then it will not appear as reimbursed and marketed on April 1 of such year N, and the reference price group will not be created until Q3 or Q4 of year N+1.

As per the magnitude of the price decrease, we note that, upon biosimilar/generic inclusion in the reference price system, originator’s PVL per DDD (which is the assumed average maintenance dose per day) will be reduced to the level of the “reference price” of the group. Such reference price is fixed on the value presented by the lowest cost of the treatment per day of the presentations of the medicinal products included in the group.

As long as the lowest cost of the treatment per day will most likely be set by the new biosimilar/generic, the practical effect of the application of the reference price system will be the reduction of originators’ PVL per DDD to the level of the PVL per DDD of the biosimilar or generic medicinal product.

 

Market Pressure

Leaving aside the compulsory price reduction that may apply via HG and/or RG, it is important to mention that the launch of generics or biosimilars usually result in substantial market pressure to reduce prices as of the day of launch.

 

b. Clawback/Payback/Discounts/Rebates

Royal Decree-Law 8/2010 contemplates the following mandatory deductions on medicinal products:

• Reimbursed retail products are subject to a compulsory 7.5% discount. Pharmacies apply a deduction of 7.5% on the retail price. For the purposes of the application and distribution of this deduction among all agents of the pharmaceutical chain, distributors apply the same deduction (7.5%) on the distributor’s selling price (i.e., price at which the distributor sells the product to the pharmacy), and manufacturers also apply a deduction of 7.5 % on the maximum industrial price (i.e., price at which manufacturer sells the product to the distributor).
• Hospital-use products are also subject to a 7.5% compulsory discount on the “purchase price”.

The above-mentioned deductions do not apply to generic medicinal products or those subject to the reference price system.

The 7.5% discount shall be reduced to 4% in case of orphan drugs; and increased to 15% for products that have no generic/biosimilar competition and that have been reimbursed with public funds for a minimum of ten years (or eleven years in the case a new indication for the very same product was authorized). The mandatory 15% discount does not apply to medicinal products protected by product patents in all EU Member States.

 

c. Existence of Price/Volume agreements in the frame of public tendering

Price/volume arrangements are not unusual in public tendering. They are used to reduce the average price of the contract and to contribute to the overall sustainability of the system. The terms of each arrangement depend on the particularities of each case and the relevant contracting body.

 

d. Existence of price freezes and cuts

It is uncommon to freeze or drastically reduce the prices of medicinal products. However, there have been instances where such actions have been taken. This was the case in 2010 and 2012.

In 2010, amid the economic and financial crisis in Spain, Royal Decree-Law 4/2010 was enacted to rationalize pharmaceutical expenditure by the NHS. This Royal Decree-Law introduced a reduction in the price of all generic medicinal products included in the pharmaceutical provision of the NHS.

In 2012, a total of 417 medicinal products were excluded from the pharmaceutical provision, citing reasons such as their indication for the treatment of minor symptoms.

Apart from such exceptional measures, the MOH regularly oversees the pharmaceutical expenditure in those therapeutic areas that pose a significant cost to the NHS. If the expenditure in these areas exceeds the expected levels, the MOH may implement monitoring measures.

 

e. Post-launch monitoring of prescriptions/sales

Prescriptions may be subject to a “Visa” if healthcare or economic reasons justify such measure. Art. 92.1 of Royal Legislative Decree 1/2015 states that in order to guarantee the rational use of medicines, the MOH may subject medicinal products to special reservations and specific conditions for their prescription, dispensing and use.

Visas may only be imposed under the terms contemplated in c which contemplates that the MOH may only impose a Visa in three scenarios: (i) If the product is classified as a restricted prescription product (i.e., hospital use products, hospital diagnosis products or products requiring a specialist prescription and special monitoring), (ii) if the AEMPS decides that the product must be subject to special reservations for reasons of safety or limitation for certain population groups at risk; or (iii) if only some therapeutic indications are reimbursed or if a reduced contribution is applied depending on the type of patient.

The Supreme Court has validated Visas as a valid tool to control the prescription and use of medicinal products in the scenarios and for the objectives laid down above.

On some occasions, some Autonomous Communities have implemented prescription control programs with effects similar to those of a Visa. This type of measure is only possible with the prior agreement of the CISNS.

 

f. Existence of Generic Substitution Policies

Generic and biosimilar have different substitution regimes. Biological medicinal products are non-eligible for substitution. In this regard, art. 1 of MOH Order SCO/2874/2007 states that biological products “shall not be substituted when dispensed without the express authorization of the prescribing doctor”. Because of this, biological products are not included by the MOH in the so called “Homogeneous Groups”, which are lists of products that may be substituted.

Generics are, indeed, eligible for substitution at a pharmacy level.

 

g. At prescriber level

It is not unusual for Autonomous Communities and hospitals to put in place systems aiming to promote the prescription of generic and biosimilar medicinal products. Some of such systems were declared illegal by the Courts because they affected in an unacceptable way the freedom of prescription of physicians.

As a matter of practice, it is known that some regional authorities or hospitals stimulate the use of biosimilars and generics through mechanisms that are not totally transparent, and which may include the following: informal recommendations and informative actions, include biosimilars and generics as first option in Clinical Guides, request to prescribers to select patients eligible for switching, setting up minimum quotas for biosimilars for naive patients, setting up minimum quotas for biosimilars and generics on a global basis, considering the level of consumption of generics and biosimilars as a KPI when measuring efficiency of a hospital or fixing a maximum budget per hospital in connection with a given therapy.

 

h. At retail level

Reimbursed medicinal products that patients obtain at retail pharmacies are subject to co-payment rules, under which the patient must pay part of the price of the medicinal product. The co-payment percentage depends on the type of product and the type of patient.

 

2. Are there any other policies in place aiming at cost control via incentive programs targeting the different actors (pharma companies, wholesalers, retailers, prescribers etc.)?

In late 2015, Farmaindustria (the association of the innovative Spanish pharmaceutical industry) reached an agreement with the Spanish Government (the “Farmaindustria Agreement”) under which pharmaceutical expenditure was not to grow more than real GDP growth.

The agreement contemplated chargebacks to be paid by pharmaceutical companies in the event that the expenditure exceeded the agreed ratio. The agreement also contemplated that in the situation that the expenditure exceeded said ratio, special measures to rationalize the use of medicinal products may be adopted. These measures, in essence, would imply barriers for prescription of high-budgetary-impact drugs.

The Farmaindustria Agreement was fully effective until 30 June 2020. Since then, Farmaindustria and the Spanish Government have been negotiating a new agreement. No agreement has been reached so far. In 2022, the agreement was included in the agenda for the Stability Plan from 2022 to 2025 presented by the Spanish Government to the European Commission.

Also from this Market Access & Health Technology Assessment

1. Has an essential or priority drug list been published in your country? (If so provide the link)

Yes. Three types of lists have been published by the AEMPS:

• “Essential medicinal products”: according to the WHO definition, these are the necessary medicinal products for a basic health system.
• “Critical medicinal products”: a subgroup of essential medicinal products for which there should never be supply problems in the health system.
• “Strategic medicinal products”: a subgroup of critical medicinal products for which additional measures, whether regulatory, economic or otherwise, are considered necessary to ensure their maintenance in the market both because of their need for basic health care and because of the vulnerability of their supply chain.

Such lists are published at the AEMPS’s official website.[1]

 

2. If so what is the impact/consequences of a drug being published on the EDL/PDL:

a. In terms of market approval

Three main consequences are worth mentioning in this area.

First, AEMPS has put in place the necessary mechanisms to speed up the administrative procedures and the evaluation of changes to the MA of these medicinal products. To this end, it has established shorter deadlines for the validation of applications and a prioritized evaluation of the variations requested.

Second, AEMPS offers scientific and regulatory advice to laboratories. This advice can be provided throughout the application process or facilitating the submission of the registration dossier. The evaluation of authorization applications for medicinal products submitted through the national route will be expedited as a matter of preference in order to favor the availability of these medicinal products on the market in the shortest possible time.

Third, the AEMPS will prioritize the granting of Spanish slots as a reference member state (RMS) for authorization applications through European procedures in order to favor the internationalization of these strategic medicinal products.

 

b. In terms of reimbursement

The inclusion of a product in such lists does not have a direct impact on reimbursement decisions. Being included in such lists, however, may facilitate product’s compliance with art. 92 of Royal Legislative Decree 1/2015 and, therefore, may indirectly facilitate reimbursement. Please refer to Question 1, Section III above.

 

c. In terms of pricing

Essential products may have preferential treatment in the context of reference pricing. As discussed, the inclusion of a medicinal product into a reference group implies the reduction of the PVL of the originator per DDD to the level of the PVL per DDD of the biosimilar/generic. Such reduction may be effective immediately (general rule) or gradually during several years in accordance with specific rules contemplated in art. 4 of Royal Decree 177/2014 (“Weighted Average”). Under the Weighted Average regime, the price of the original product is gradually lowered year by year in a staircase fashion.

The preferential treatment of essential medicinal products consists of freezing their price if they are subject to the “Weighted average” regime. For such special regime to apply, companies must demonstrate that the price freeze is necessary to ensure the availability of the medicinal product and that the essential medicinal product has no reimbursed alternatives.

 

d. In terms of value assessment and pharmacoeconomic requirements

As far as we are aware, being in the abovementioned lists does not have any direct impact on value assessments or pharmacoeconomic requirements. Indirectly, it may have some impact to the extent that being in such lists necessarily means that the product is considered critical and indispensable for the proper functioning of the system, which implicitly implies a recognition of value.

 

3. Do value assessment and pharmacoeconomic data play a role in terms of access to the list?

No. Inclusion in the mentioned lists is based on criticality and vulnerability criteria, not economic assessments.

 

[1] Accessible at: https://www.aemps.gob.es/medicamentos-de-uso-humano/medicamentos-estrategicos/

Also from this Market Access & Health Technology Assessment

1. What is the definition of an orphan drug in your country?

In Spain there is no particularity in relation to the definition of “orphan drug” derived from the Regulation (EC) No 141/2000.

Under Regulation (EC) No 141/2000 a medicinal product shall be designated as an orphan medicinal product if its sponsor can establish: (i) that it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10 thousand persons in the Community when the application is made, or that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the Community and that without incentives it is unlikely that the marketing of the medicinal product in the Community would generate sufficient return to justify the necessary investment; and (ii) that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Community or, if such method exists, that the medicinal product will be of significant benefit to those affected by that condition.

 

2. Describe the pricing process of orphan drugs in your country.

There are no particularities for orphan drugs when it comes to pricing. The same P&R Procedure for non-orphan drugs apply. Please refer to Question 1, Section III above.

Further, it is relevant to note that certain orphan drugs are exempt for being included in the reference price system, which means that they have a preferential treatment in this respect. Four elements are relevant for such purposes.

First. On 3 March 2020, a Resolution of the Council of Ministers excluded orphan medicinal products from the reference price system under the following conditions: that no “therapeutic alternative” exists or, otherwise, that the relevant orphan medicinal product provides a “significant clinical benefit”.

Second. On 2 December 2021, the Spanish National High Court issued an important judgment stating, in essence, that orphan products shall be unconditionally excluded from the reference price system. According to such judgement, subjecting orphan drugs to the reference price system goes against the spirit/objectives of Regulation 141/2000 on orphan drugs. This Judgment was not appealed and, therefore, became final.

Third. In February 2022, the Spanish Supreme Court issued two judgements that concluded that it is incorrect to argue that the principle of primacy of EU law and Regulation 141/2000 enable the unconditional non-application of the reference price system to orphan drugs. According to the Supreme Court, orphan drugs are, indeed, subject to the reference price system by virtue of article 98(2) of RDL 1/2015, which does not contravene Regulation 141/2000. As per the Supreme Court, if orphan drugs are to be excluded from the reference price system, this should be done under the terms of the Resolution of the Council of Ministers of 3 March 2020 mentioned above.

Fourth. The RPO updating the reference price system for 2022 originally included some orphan medicinal products but this was identified as an error, and they were later on excluded. The RPO draft updating the reference price system for 2023 does not include orphan drugs.

 

3. Describe the reimbursement process of orphan drugs in your country.

There are no particularities for orphan drugs when it comes to reimbursement decisions. The same P&R Procedure for non-orphan drugs apply. Please refer to Question 1, Section III above.

 

4. Other than the clinical studies required, do the data and studies required for the pricing and reimbursement of orphan drugs differ from that of other drugs?

No.

Also from this Market Access & Health Technology Assessment

1. What is the definition of a vaccine in your country?

The AEMPS defines a vaccine as an antigen-containing preparation capable of inducing specific and active immunity in humans against an infecting agent or the toxin or antigen elaborated by it. Immune responses include the induction of innate and adaptive (cellular and humoral) mechanisms of the immune system.[1]

2. What are the classifications of vaccines in your country?

The AEMPS distinguishes three types of vaccines[2]:

• Uncombined vaccines: vaccines containing antigens from a single pathogen or a single strain of the infectious agent. Uncombined vaccines can be “non-combination bacterial”, or “non-combination viral”.
• Combined vaccines: vaccines containing, in the same product, antigens from different pathogens or different serogroups, serotypes or strains of the same infectious agent that are administered simultaneously. Combined vaccines can be classified as: “bacterial”, “viral” or “bacterial-viral”.
• Conjugated vaccines, or “flat vaccines”: inactivated bacterial vaccines that contain only a fraction of the microorganism, the polysaccharides, bound to a carrier protein that helps to enhance and increase the immune response, switching from thymus-independent (humoral) to thymus-dependent (cells, leading to immunological memory) immunity.

 

3. Describe the pricing process for vaccines in your country (based on their classifications).

There are no particularities for vaccines when it comes to pricing. The same P&R Procedure for non-vaccine products apply. Please refer to Question 1, Section III above.

 

4. Describe the reimbursement approval process for vaccines in your country (based on their classifications).

There are no particularities for vaccines when it comes to pricing. The same P&R Procedure for non-vaccine products apply. Please refer to Question 1, Section III above.

 

5. Other than the clinical studies required, do the data and studies required for the pricing and reimbursement of vaccines differ from that of other drugs?

No.

 

[1] Accessible at: https://www.aemps.gob.es/medicamentos-de-uso-humano/medicamentos-biologicos/vacunas/

[2] Accessible at: https://www.aemps.gob.es/medicamentos-de-uso-humano/medicamentos-biologicos/vacunas/