Promotion of a medicinal product begins usually with the first press release following a Marketing Authorisation (MA). It is the responsibility of each Marketing Authorisation Holer (MAH) to ensure that all promotional materials comply with the Product Information and other specific national requirements. Many EU Member States have Codes of Conduct which specify obligations for different types of promotional material and the media by which they will be distributed; these include presentations, advertisements, websites and all forms of social media.
Educational programmes are additional risk minimisation measures (aRMM) (GVP Module XVI and its addendum) and usually include educational material aimed to minimise an important risk and/or to maximise the benefit‑risk profile of a medicinal product. The content of any educational material must be fully aligned with the currently authorised Product Information.
Educational material is agreed at EU level, often as part of the initial MA, but also subsequently if there are additional safety concerns. It must then be adapted to local requirements and submitted for national approval to local Authorities before product launch in each country (following the initial MA) or for implementation within an agreed timeframe (if required post-authorisation). Additional educational material to those agreed at EU level can also be considered and submitted for review to local Authorities.
Members of the EUDRAC team have been specifically trained in promotional review of pharmaceutical products and we are the Regulatory Representative on review teams for many of our clients. We also have Partners in all EU countries who work with us to ensure national requirements are implemented and appropriate submission of documents to the Regulatory Agencies is undertaken when required.
Labelling and artwork have specific national requirements that must be implemented for the Centralised and Decentralised/MRP Procedures, as well as for National Procedures. Addressing these requirements in a timely manner ensures that the product can be launched without regulatory delays.
EUDRAC has Partners in all EU countries and in other regions. We also have an experienced Labelling team who works with clients on pre-and post-authorisation procedures for products with licences issued via all regulatory routes. We review core labelling and artworks for our clients and also support in implementing specific requirements on national versions; EUDRAC conducts all necessary translations and ensures the different formatting requirements for regulatory submissions are met.
Following the submission of the initial MAA for a medicinal product, the Product Information (PI) continues to evolve throughout its authorisation and marketing. It is reflected in the Packaging, Prescribing information, Educational and Promotional Materials as well as National Formularies and Product Databases.
The EU has strict requirements for both the content and format of the PI, as well as the procedures in which it is updated.
EUDRAC has an experienced Labelling Team who is involved in the development of the PI for new Marketing Authorisations, as well as in the review of mockups and other post-marketing documentation which are based on the PI. We have Partners in all EU countries so we can perform translations and implement national requirements.
Within the EU it is possible, in some cases, for Member States (MS) to authorise the use of medicinal products that have not yet been granted a marketing authorisation (MA) but are undergoing clinical trials or have entered the MA application process. Such cases are exceptional and usually only permissible when other treatment options for the patient have been exhausted, or are not available. The provision of unauthorised medicines in such a manner can be made via different types of “Early Access Programmes”, which require regulatory approval on a national basis. It should be noted that, in many cases, the EAP will be specific to the drug in question and its provision may differ in each MS. Such EAP are regulated as clinical trials in some countries or have specific registration procedures in others.
EUDRAC has worked with clients to secure the provision of unauthorised medicines through different EAPs in different MS. We have Partners in all EU countries so are able to liaise directly with the Regulatory Authorities and Investigators to ensure that the procedure is efficient and complies with national regulations.
Compassionate use allows the use of an unauthorised medicinal product under strict conditions for a group of patients who have a disease with no satisfactory authorised treatments and who cannot be included in clinical trials. Compassionate use should not be confused with Named-Patient-programs which are under the direct responsibility of the investigator and done on an individual basis.
In France, the exceptional use of pharmaceutical products that do not have a MA and are not used in clinical trials is covered by obtaining a Temporary Authorisation for Use (ATU) prior to its use. Such authorisation is delivered by the French National Agency for Medicines and Health Products Safety (ANSM) and is aimed for medicinal products intended to treat serious or rare diseases when no appropriate treatment exists and the initiation of treatment cannot be deferred. Recently, we successfully supported one of our clients in the preparation and submission of an ATU for a group of patients (cohort ATU). Named-patient ATUs are requested directly by doctors to the ANSM via the platform e-Saturne. Finally in specific cases where a marketed medicinal product is used off‑label in a new indication not validated in the MA, the ANSM can also consider authorising the use of that product in that specific indication if it meets specific requirements. The ANSM thus elaborates a ‘Recommendation Temporaire d’Utilisation’ (RTU) for the medicinal product in that indication.
Specific guidance regarding ATU registration in France can be found here.
Recently, there has been significant progress in the collaboration between EU and third countries in the sharing of information on the manufacture and distribution of pharmaceuticals and a number of Mutual Recognition Agreements (MRA) are being reached e.g. MRA between the EU and USA in 2017. A consequence of this is a reduction in the burden on pharmaceutical manufacturers e.g. removal of the requirement for additional testing following importation. National Competent Authorities (NCA) also benefit through a better exchange of information on GMP compliance and a reduced requirement for auditing of sites in third countries.
However, increased globalisation has led to increased complexity and challenges in ensuring the integrity of the supply chain at each stage in the manufacturing process. The NCA are also issuing more regulations and increasing enforcement which further increase the supply chain complexity and compliance burden for manufacturers.
It is anticipated, therefore, that compliance with both existing legislation and recent changes made by both NCAs and the European Commission will be increasingly demanding (e.g. implementation of the Falsified Medicines Directive 2011/62/EU.
Compliance failures by manufacturers can have severe consequences, causing supply chain disruptions and delays as well as product expiry and market recalls. There is understandably, therefore, an increasing need to improve supply chain efficiency.
The EUDRAC team advises clients on regulatory requirements for supply chain rationalisation and review their drug supply chains for regulatory compliance. Recently we have been providing information summarising the local requirements following National implementation of the Falsified Medicines Directive in EU countries.
Our Regulatory Intelligence service ensures that our Consultants are aware of the latest regulatory changes affecting the supply chain from both a wider EU perspective and also local country requirements. We have provided advice to clients who want to expand their operations by establishment of an EU entity to act as the Marketing Authorisation Holder (MAH), and also on national requirements to aid the setup and location of local operating companies (LOCs).
EUDRAC also assists clients with the sales and marketing functions that can be performed by LOCs, and relevant local and EU licenses or authorisations that must be maintained. One example of such specific local expertise that EUDRAC has provided to a client recently was concerned with the requirements for supply and distribution of medicinal products in Germany. In order to begin commercial sale of their product the client was required to obtain a Wholesale Dealers Authorisation (WDA), setup a Quality Management System (QMS) and appoint a Responsible Person (RP). To facilitate this, EUDRAC acted as the Deputy Responsible Person on behalf of the client, provided technical assistance with the setup of the QMS and both prepared and submitted the WDA application. We also provided the client with advice on local compendia and databases to support the sale of the product.