June 08, 2022
Product Launch in the EU: Regulatory Affairs Considerations
The launch of medicinal products in the European Union (EU) is a complicated process. Although in theory, the grant of a marketing authorisation (MA) approval allows the marketing of medicinal products in the EU, in practice, before a medicinal product can be actually launched to market, the Marketing Authorisation Holders (MAHs) need to tackle local requirements and launch-related regulatory process in each EU country.
Unlike the marketing authorisation procedures, which are well-documented in European guidelines and available in English, the product launch related regulatory requirements are highly country-specific and are often available only in the national languages of EU member states, complicating the process even more. Navigating through these requirements may become a challenge. It may be especially burdensome for smaller MAHs having modest size infrastructures in the EU. For example, the majority of the biotechs, producers of orphan or advanced-therapy medicines, all of whom are subject to compulsory centralised authorisation procedure in the EU.
In this blog article, we will summarise the key aspects of the launch of medicinal products in the EU from a regulatory affairs perspective. Consideration of these country-specific requirements could help create and execute successful regional and local product launch plans.
Shared Pack requirements
In the EU, there are 27 different countries with 24 recognised languages, each adding specific product packaging requirements. To minimise stock holding and maximise flexibility, many pharmaceutical companies will choose to group markets into multi-language / country packs and implement regionalisation strategies. However, such regionalisation strategies should be carefully thought through. Aspects such as local regulatory requirements or guidelines for shared packs, common languages, cultural precedents, local market sizes and serialisation requirements must be considered.
Labelling exemptions to supply products in foreign packaging
While shared packs may be a good strategy for larger markets, it may not be the best solution in smaller ones. A solution to this could be to obtain local labelling exemptions to supply the medicinal product in a foreign packaging. However, it is important to keep in mind that not all products will qualify for the exemptions – labelling exemptions are typically aimed at orphan medicinal products with small patient populations. Companies seeking to obtain a labelling exemption for their product will have to meet certain country-specific requirements and will most often have to go through a local exemption approval process with the National Competent Authority.
Artwork review and approval, including ‘blue-box’ requirements and additional information
Once the decisions on shared packs and potential labelling exemptions are made, the companies should initiate, review, and approve initial artworks. During this process, the so-called ‘blue-box’ requirements (the boxed area for information specific to the member state) should be considered. In some of the EU countries, the MAH or its delegated person should request the ‘blue-box’ information from the National Competent Authority. For example, the French health authority (Agence Nationale de Sécurité des médicaments) should provide the MAH with the CIP code (a national code specific to France), local distributor, classification of the list of poisonous substances, level of pictogram for safety instructions (such as use when pregnant or driving warnings).
Promotional materials compliance review and approval
Product launch is often closely connected with the promotion activities and materials (interactions with HCPs, advertisements, brochures, websites, presentations from speakers, and others). Such collateral or activity must not only follow the EU guidelines but also be aligned with the national regulations relating to the promotion of medicines. What is more, it should also adhere to the national pharmaceutical industry codes of ethics. It is highly recommended to seek advice from local regulatory experts to ensure that the promotional materials are compliant with the applicable regulatory requirements and the respective ethical codes in the local country. As well as that all local requirements regarding submission/approval of materials, organization of events or interactions with HCPs are met. Last but not least, some of the EU member states require the MAHs to nominate a local person responsible for the promotion of medicinal products/ Such roles include, for example, the information officer (‘Informationdbeauftragter’) in Germany or the Responsible Pharmacist (‘Pharmacien Responsable’) in France. MAHs should not overlook the responsible person nomination requirements, and if such role cannot be filled internally, one may also seek external support from specialised service companies.
Educational Materials adaptation to local requirements and approval with national authority
If the medicinal product in scope has a requirement for additional risk minimisation measures (aRMM), for example an Educational Material aimed at healthcare professionals or patients, a local regulatory approval for such aRMM will have to be obtained before the product could be launched and distributed in the local market. Even though medicinal products authorised via the Centralised Authorisation Procedure have the contents of the aRMM already aligned with the European Medicines Agency (EMA), the aRMM must again be adapted to local requirements and submitted to the National Competent Authority for their approval. The regulatory processes and timelines vary from one country to another. Additional aspects such as states fees, design of mock-ups, printing of materials and its distribution plans should also be considered.
Local Person for Pharmacovigilance (LPPV) nomination and local PV system set-up
Local Person for Pharmacovigilance (LPPV) requirements should also be considered. The LPPV requirements vary between the EU member states. Some countries will require LPPV nomination upon submission or upon approval of the Marketing Authorisation (MA) application, while some will require the local person to be appointed upon first launch of the product or only when additional risk minimisation materials (aRMM) have to be distributed in the country. We have summarised the strategic considerations for the Local Person for PV (LPPV) Strategy in the EU in one of our previous blog articles.
Pricing application and local price approval
Before the product can be sold its price should be registered in the local market. Depending on the country, it may be a formal price application review and approval process with the National Competent Authority, while in some countries it can be a straightforward product price self-declaration process. What is important to note, that price approval should not be mistaken with reimbursement approval. While in some countries the processes of price approval and reimbursement are closely connected, in others these are completely separate processes.
Product reimbursement is another crucial thing a pharmaceutical company should consider while planning the local product launch. This is especially important if the cost of a medicinal product could barely be borne by end-users (patients or hospitals). Each EU member state has its own reimbursement systems. For example, reimbursement is automatic in Germany for EMA’s centrally approved products, however in most countries the MAHs will need to go through the manual reimbursement application process. The process will again vary from one country to another. Alongside the standard process of local Health Technology Assessment most countries also provide reimbursement on a named-patient basis. The latter may be particularly advantageous and faster to obtain for companies aiming to launch orphan medicinal products.
The EU Falsified Medicine Directive and serialisation requirements should be considered before the product launch. In particular, when it comes to local market launch, the MAH must sign an agreement with the relevant National Medicines Verification Organisation (NMVO), pay the annual fees, and perform the necessary serialisation steps both with the central and national medicines verification organisations. It is important to note, that some of the companies may be eligible for exemptions or discounts on the annual fees of the NMVO, that may particularly be relevant for smaller companies, such as holders of orphan medicinal product licences, where there are only a few patients available in the local market.
National medicinal database updates
Most of EU member state authorities manage national medicinal databases directly. However in few countries, the MAH is expected to update the national medicinal database and upload the product information, e.g. SmPC, Educational Material, to the official medicines listing. It is noteworthy that some countries also have private compendia which need to be updated by MAH or their delegate (mandatory or recommended), for example the FASS in Sweden.
Notification to the National Competent Authority about the start date of commercialisation
Finally, notifying the National Competent Authority about the start date of commercialisation is an easy step, however it should also not be forgotten. Marketing status of centrally authorised products should also be reported to EMA using IRIS database.
Insuvia offers a range of services to help pharmaceutical companies implement successful product launch strategies. We can help you plan the launch of your product, advice on the expected timelines, as well as anticipate potential pitfalls and risks that might cause delays. Our expertise will help you achieve optimal success in bringing your product to market and patients.Contact us to learn more.Back to news