La entrada Retos y oportunidades del Anteproyecto de Ley de Medicamentos y Productos Sanitarios aparece primero en Faus Moliner.

La entrada Retos y oportunidades del Anteproyecto de Ley de medicamentos y productos sanitarios aparece primero en Faus Moliner.

La entrada Faus Moliner participates in “Chambers Global Practices Guides Medical Cannabis & Cannabinoid Regulation 2024” aparece primero en Faus Moliner.

La entrada Faus Moliner participates in “Chambers Global Practices Guides Medical Cannabis & Cannabinoid Regulation 2023” aparece primero en Faus Moliner.

La entrada The Pharma Legal Handbook: Spain aparece primero en Faus Moliner.

The precise and unambiguous definitions of “active substance” and “similar active substance” is essential in the field of medicinal products for rare diseases: the so-called “orphan medicinal products”.

Regulation (EC) 847/2000, where the definitions of “active substance” and “similar active substance” are contemplated, was recently amended by Regulation (EU) 2018/781, effective as of  19 June. Changes introduced by this new Regulation (mainly referring to the definition of “similar active substance” as opposed to “same active substance”) are theoretically limited to the field of rare diseases. However, it is to be noted that the content of such changes may be useful in other fields in which a calm reflection on the terms and scope of the terms “active substance” and “similar active substance” is also necessary. This is the case, for example, of the new reference price system for medicines of the National Health System announced by the MoH earlier this year.

Regulation (EU) 2018/781

Two are the main amendments introduced by the new European Regulation which deserve special attention. The first of them is the deletion of the “active substance” definition contained in Regulation (EC) 847/2000 which differed from the same term defined in Directive 2001/83/EC. Such deletion is due to the fact that the Commission was not empowered to modify, through implementing regulations (such as Regulation (EC) 847/2000), the legal term of “active substance” already defined in the above-mentioned Directive. The second relevant amendment is the development and clarification of the term “similar active substance”. In this regard, the new Regulation accurately determines what “principal molecular structural features” should mean, which has been the only criterion used so far for the similarity assessment between two active substances.

Additionally, the new Regulation incorporates an additional criterion to assess similarity between certain kinds of medicines such as advanced therapy medicinal products. This criterion refers to the evaluation of the active substances to be compared on the basis of their biological and functional characteristics.

New rules regarding the reference price system

Several considerations arise from the new Regulation, which may be useful in connection with the announced amendment of the reference price system in Spain. First, we consider that changes must be addressed carefully to prevent them from altering the current definition of “active substance” which, as this new Regulation reminds us, is a well-established definition of in the Community legislation. Second, the precise definition provided by Regulation (EU) 2018/781 of “similar active substance”, as opposed to “identical active substance”, is something that, in our opinion, should be considered by Spanish authorities when defining the term of “same active substance” in the context of the Spanish reference price system.

La entrada Changes on European regulations on orphan drugs aparece primero en Faus Moliner.

The former Royal Decree 2208/1994, which was repeated, introduced a transitory provision, according to which companies marketing homeopathic medicinal products in Spain could continue marketing such products as long as they had submitted an application to obtain a marketing authorization within 6 months following the entry into force of such Royal Decree. Later on, such provision was regulated by the sixth transitory provision of Royal Decree 1345/2007, which provided that companies marketing these medicinal products must submit a communication to the AEMPS indicating their intention to follow the registration procedure foreseen for these products in said Royal Decree 1345/2007. The period for sending such communication was 3 months from the entry into force of the order of the MOH, establishing the minimum requirements and the procedure to be followed in order to make such communication.

The order SSI/425/2018 has come to implement these provisions, providing that those companies which are marketing these medicinal products and which are interested in continuing doing so, must send a communication through the website enabled by the AEMPS within the  corresponding period, providing the information required and, in particular, informing whether or not the product in question will claim certain therapeutic indications. If such period elapses without sending any such communication, the company will not be able to continue marketing these medicinal products, which must be withdrawn from the market.

Once the period for the submission of communications has ended, the AEMPS will have a maximum period of 3 months to set a timetable so that companies that communicated their intention to register their products may submit the corresponding marketing authorization applications.

According to the provisions of Royal Decree 1345/2007, the ordinary registration procedure must be followed, attending to the specific characteristics of this type of medicinal products. However, there is a simplified procedure available for products having an oral or external administration route, provided that no specific therapeutic indications are claimed and that the degree of dilution of such product ensures its safety. If the application is not submitted in accordance with the established timetable, companies must proceed to withdraw the product from the market.

La entrada How does the future for homeopathic medicinal products in Spain looks like? aparece primero en Faus Moliner.

This case refers to the position taken by the European Medicines Agency (“EMA”) in relation to an application filed by Shire to obtain orphan designation for Idursulfase-IT. The EMA rejected to validate such application on the grounds that Idursulfase-IT contained the same active substance (“API”) as that of Elaprase®, another medicinal product for which Shire had previously obtained orphan designation and a marketing authorization.

The EMA did not give value to the fact that Idursulfase-IT had been developed so that it would be possible to deliver its API directly into the cerebrospinal fluid through intrathecal administration. This new route of administration, according to Shire, met an unsatisfied clinical need for treatment of some patients with Hunter Syndrome: the ones suffering from a severe form of that disease with cognitive disorders. Shire considered that the medical condition that Idursulfase-IT could treat was different from the common Hunter Syndrome.

Court’s position and local consideration

In its judgement, the Court departs from the idea that the sole fact that both Idursulfase IT and Elaprase® contain the same API does not necessarily mean that they are the same medicinal product. The API, the Court says, is the main constituent of a medicinal product but it must not be confused with the medicinal product itself.

In order to assess the differences between two medicinal products, the Court understands it is necessary and reasonable to take into account their methods of administration and the therapeutic effects that may be achieved using one or the other. In this case, the Court argues that the intrathecal administration of Idursulfase-IT allows the API to be delivered directly into the cerebrospinal fluid, and this results in the possibility of treating the cognitive disorders exhibited by some of the patients suffering from Hunter Syndrome. Considering this, the Court concludes that the EMA should not have refused to validate the application for the orphan designation because at least in respect of the route of administration it does not seem that Idursulfase-IT should be considered the same medicinal product as Elaprase ®.

As a local consideration, in our opinion these ideas of the Court should inspire new rules on reference prices in Spain. At present, products containing the same API are included in the same reference price group and their price is determined only taking into account the unitary price of the API of the product having the lowest price in the group. This is known as the reference price system.

The products for which a new route of administration has been developed that may result in a significant clinical benefit for the patient deserve special treatment, and their price should not be determined only taking into account the unitary price of the API of the product having the lowest price in the group.

Otherwise, companies may be bound not to market some of the products, and research on improvements which may be beneficial to patients may be unfairly harmed.

La entrada Some medicines containing the same active substance may not be the same medicinal product (… in terms of reference price) aparece primero en Faus Moliner.

This judgment derives from a previous judgment set down by the High Court of Justice of Andalusia (TSJA) on 29 September 2014, resulting from an appeal filed by the Association for Animal Health against a range of provisions in Decree 79/2011, which established rules on the distribution, prescription, dispensation and use of medicinal products for veterinary use and created the register of Veterinary Medicinal Product Establishments of Andalusia.

The TSJA judgment annulled, amongst others, the provisions of the decree that made it possible for veterinary clinics and pet animal establishments to request authorisation to have a special stock of medicinal products for human use for use on animals in their veterinary medical supplies. The Andalusian court ruled that said provisions infringed the state regulations, which establish that pharmacy services and outlets are responsible for the custody and dispensation of medicinal products for human use. In turn, the Regional Government of Andalusia, which considered that said judgment was in violation of the law, appealed before the Supreme Court.

Conclusions of the Supreme Court

The Supreme Court started its analysis with a reminder that the Spanish legal system allows veterinarians to purchase the medicinal products required to perform their professional activities, which will be supplied by pharmacies and retail establishments. On the other hand, said healthcare professionals are also allowed to employ “the prescribing cascade”, in other words, the one-off prescription of medicinal products for human use to certain animals when no appropriate veterinary medicinal product is available.

The Andalusian Decree, in turn, regulates the so-called “veterinary medical supplies”, as part of which veterinarians store medicinal products supplied by pharmacies and retail establishments for their administration to animals they attend in their veterinary establishments. The Court asserted that the legality of the stocks in question must be analysed according to the logic of veterinary medical supplies and the capacity of veterinary professionals to prescribe medicinal products for human use on an exceptional basis. As a result, the Supreme Court concluded that the regulation on special stocks of medicinal products for human use in veterinary establishments wholly complies with the basic State regulations, as it provides for the use of these medicines as part of veterinary practice pursuant to the aforementioned state regulations and does not address their commercial dispensation, which remains reserved to pharmacy outlets, services and retail establishments. The Supreme Court therefore annulled the TSJA judgment on this matter and ruled that the provisions of Decree 79/2011 regulating these special deposits were legal.

La entrada Veterinary centres in Andalusia may have a stock of medicinal products for human use aparece primero en Faus Moliner.

Hohenzollern Apotheke (HA), a German pharmacy, produces medicinal products without having a marketing authorisation (MA) under the German law, which excludes medicinal products frequently prescribed by doctors and dentists from requiring said authorisation, when the essential manufacturing steps for such products are carried out in a pharmacy and are to be dispensed to the pharmacy’s users, and up to 100 packages per day.

Hecht-Pharma asked the German Courts to order HA to refrain from promoting the aforementioned activities in Germany, alleging that Directive 2001/83/EC prohibits the promotion of medicinal products that do not have a MA pursuant to Community law.

In Germany, the ban on promotion of magistral and officinal formulae is not absolute, as it is in Spain, and only affects products that are required to have a MA on a mandatory basis and yet do not have one. In this context, the German Court referred the case to the CJEU for a preliminary ruling to clarify whether the medicinal products produced by HA required a MA.

Conclusions of the CJEU

The CJEU started by reiterating that only medicinal products manufactured industrially or whose production involves an industrial process, characterised as a succession of mechanical or chemical operations designed to produce a significant quantity of a standardised product, are subject to the Directive, and therefore require a MA. Although these criteria should be assessed by the local Court, the CJEU ruled that in the present case, it would appear that the medicinal products are not produced industrially by an entity operating on a large scale.

The CJEU went on to add that, even if the local Court has a different interpretation of the circumstances of the case, the medicinal products produced by HA would be classified as officinal formulae, which, along with magistral formulae, are excluded from the Directive’s scope of application. The CJEU did not question the correctness of the German law that allows that a pharmacy, such as HA, takes charge of the essential phases of the production of a medicinal product and; therefore, seemingly permitting that other phases of such production are outsourced by the pharmacy to third parties.

It is also interesting that the CJEU did not dispute the German legislation restricting the prohibition on advertising merely to medicinal products required to have a MA on a mandatory basis and yet do not have one. The foregoing would seem to suggest that the CJEU believes that national legislations providing for the promotion of magistral and officinal formulae is compatible with Community law.

La entrada The CJEU provides additional context regarding what should be considered as an industrially manufactured medicinal product according to Directive 2001/83/EC aparece primero en Faus Moliner.