In the previous article, we reviewed in detail some of the proposals of the European Commission for a comprehensive overhaul of European pharmaceutical legislation, contained in the new draft Directive on the Union code relating to medicinal products for human use (the “Directive”) and in the draft Regulation laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency (the “Regulation”), which were not addressed by the Bulgarian media.
The proposals for changes discussed in the article concerned the introduction of new sub-types of medicinal products, changes to the procedure for authorization of medicinal products and measures to ensure easier market for generic medicinal products.
Although numerous, the above changes are far from all changes falling under the scope of the reform planned by the European Commission. In this article we will try to complement the missing pieces of the legal “puzzle” presented to us by the European Commission.
I. Changes to the rules governing advertising of medicinal products
- The draft Directive expands the definition of advertising of medicinal product by adding a new type of activity considered advertising, under the rules of the Directive – advertising related to medicinal products that does not refer to specific medicinal products. At first glance, it appears that the proposed definition is abstract and vague and may be subject to differing interpretations in the Member States. Under the current legal framework, it is very likely that such an activity would not be deemed to constitute advertising of medicinal products within the meaning of the MPHMA and will not be subject to authorization/notification;
- The draft Directive prohibits comparative advertising of medicinal products aimed to negatively highlight another medicinal product. At the same time, the Directive provides that any other comparative advertising claiming that a medicinal product is safer or more effective than another medicinal product is prohibited, unless the claims are supported by the summary of product characteristics. Similar rules are already present in most industry codes of ethics, but this proposal introduces the concept at the legislative level;
- For the first time, the draft Directive states that, in exceptional cases (no criteria are defined), samples of medicinal products that are not subject to medical prescription may also be provided to healthcare professionals. Directive 2001/83/EC previously stated that “free samples shall be provided on an exceptional basis only to persons qualified to prescribe them”, which suggested that these were samples of Rx medicinal products (although Bulgarian legislators have omitted this specific detail in the MPHMA when transposing Directive 2001/83/EC);
- The Directive provides that the scientific service in charge of information on medicinal products may be set up both within the structure of the MAH and in a separate not for-profit legal entity.
II. Environmental protection measures
- The draft Regulation and Directive specify and extend the ERA requirements that should be applied to applications for MA. Moreover, unlike the current framework, should the competent regulatory body find such assessment unsatisfactory, this may serve as a basis for refusal to authorise the medicinal product;
- The draft legislative acts also contain another “unpleasant surprise” for MAHs – a MAH of medicinal products authorised before 30 October 2005, when the requirement to submit ERA to applications for MA was introduced for the first time (albeit in a simpler version than the proposed version) will have to carry out an assessment of these medicinal products and submit environmental risk data to regulatory authorities. Priority “old” medicinal products subject to ERA will be defined in a programme published by the EMA on the basis of the risk-based approach;
- It is also envisaged that regulatory authorities, both in the issued MA and on an ad hoc basis, may include additional post-authorisation obligations for environmental risk assessment by the MAH, including the conduct of a new ERA. Newly identified environmental risks caused by the medicinal product may serve as a legal ground to suspend or revoke the MA.
III. Changes in respect of orphan medicinal products, advanced therapy medicinal products and medicinal products intended for paediatric use
- Regarding orphan medicinal products, the drafts of the Commission contain only a few but important changes:
- While the basic principle for determining which product is considered an orphan medicinal product (for a disease that affects not more than five persons per 10,000 in the Union) is maintained, powers are delegated to the Commission to adopt additional rules to derogate from the above principle with regard to a specific disease – potentially lowering or raising the prevalence criteria;
- The baseline period for commercial exclusivity of an orphan drug is reduced from 10 years to 9 years. It can be increased to 10 years if the medicinal product addresses a “high unmet medical need” (no other medicinal product is available for the disease and the product significantly reduces morbidity or mortality) or reduced to 5 years, if the medicinal product has received MA solely on the basis of bibliographic data, because its active ingredient has a well-established use in the medical practice.
- Regarding advanced therapy medicinal products (such as gene therapy, somatic cell therapy and tissue engineering), the draft Regulation extends the framework for the ‘hospital exemption’ allowing medical institutions to prepare such medicinal products on site. Member States shall adopt a framework and procedure for the approval of such preparations for medicinal products by medical institutions and shall inform the EMA thereof. Where such authorisation is revoked, EMA should also be informed. The aim of the changes is to carefully find a balance between the needs of the medical practice and patients, but also to establish sufficient controls, in order not to convert healthcare institutions, intentionally or unintentionally, to unregistered manufacturers of such medicinal products on an industrial scale;
- The proposals in the Regulation on medicinal products for paediatric use mainly concern an increase in the requirements concerning the paediatric investigation plan, which should be attached to the application for the issuance of MA. As stated above, a new category of MA is also introduced – pediatric MA which may only be issued pursuat to a centralized procedure conducted before the EMA.
IV. Other changes
The proposed new Directive and Regulation contain a number of other amendments that cannot be categorised in any of the above sections, including changes concerning the manufacture, prescription, administration, etc. of medicinal products. Amongst them, some of the most important changes include the following:
- The draft Directive envisages, for the first time, rules for determining the prescription status of medicinal products (with or without medical prescription). In the issued MA, regulatory authorities shall the product to medical prescription if: (i) its use without medical supervision (irrespective whether used correctly or incorrectly) may pose a direct or indirect danger to human health; (ii) the product contains substances or preparations thereof, the activity or adverse reactions of which require further investigation; (iii) the product is normally prescribed by a doctor to be administered parenterally; (iv) is an antimicrobial medicinal product; or (v) contains ingredients and active substance which, by their nature (persistence, bioaccumulation, toxicity), pose a risk to the environment. Medicinal products not subject to medical prescription shall be those that do not meet the above criteria;
- The draft Directive introduces a new type of manufacturing sites – decentralised manufacturing sites, the establishment of which is not subject to authorisation by national regulatory authorities. The Commission’s aim is to introduce more flexibility and accelerate the manufacturing of medicines in the EU (which would also help to alleviate the shortage of medicines in the Union). Each decentralised manufacturing site should be under the supervision of the qualified person at the central (authorised) production site, who has an obligation to monitor compliance with good manufacturing practice in decentralised sites;
- The rights of pharmacies to prepare prescription medicinal products are supplemented. Under the current legal framework, a pharmacy is entitled to compound or prepare a prescription product only when the same product has already been prescribed by a doctor to a particular patient. The proposal lays down that pharmacies shall have the right to prepare products on a prescription in advance – based on the estimated medical prescriptions for the following seven days. Such a change would solve the problem of Bulgarian pharmacists, who protested at the beginning of the year against sanctions imposed by the Bulgarian Drug Agency for the advance preparation of prescription products;
- The draft Directive also provides for increased accountability of pharmaceutical companies. Under the proposed changes, the MAH should make public any funding from a state or publicly funded body received in connection with the development of a medicinal product that has received a MA in a Member State or in the Union as a whole.
All the changes described in this and the previous article are part of a proposal by the European Commission to change pharmaceutical legislation and can be substantially amended during the legislative process before the European Parliament and the Council of the European Union. Depending on the outcome of the complex negotiations between MEPs, governments of Member States and taking into account the concerns raised by the pharmaceutical sector and patients’ rights associations, it is possible that many of the above changes will not find place (or will be significantly modified) in the final text of the new Regulation and Directive.
The European Commission’s ambition is for the final texts to be approved before the term of the European Parliament expires in 2024, but this deadline seems too ambitious and is highly likely to be missed. Even with swift approval of the final text of the legislative acts, they will certainly contain a long transitional period before their entry into force (in view of the current European practice – most likely several years), during which Member States shall transpose the provisions of the Directive into their legislation and the participants in the pharmaceutical market will have to make the necessary preparations to adapt to the numerous changes.
By Philip Kiossev, Senior Associate, and Eleonora Mateina, Managing Associate, Eversheds Sutherland