The complex landscape of French regulatory affairs

Once a product is registered in Europe through the decentralized or mutual recognition procedures, companies must then undergo the national phase for each country.² In France, this can fall to the Exploitant to handle product information translation and submission to ANSM, the French health authority. 

While not highly complex, experience shows that the submission process is laborious and time-consuming. In the case of an initial MA, companies must submit translations using a specific template form on the ANSM website, the “Feuille de style”, which fits the QRD template, with some national requirements.³ 

Once complete and assessed by ANSM, the company receives notification from ANSM with a PDF document and a locked Word document to be used for further submissions (variations, renewals) and further requests for national phases. If there are any errors on the document, changes must be requested in future submissions. 

For products registered through the centralized procedure, the national phase is performed simultaneously for all EU countries, after the CHMP opinion.⁴ However, the blue-box is a purely national step. Indeed, if the wording is strictly identical for SmPC, labels and PIL across the whole EU, each member state can allow the MAH to add some specific and national requirements inside a blue-box that can be found on the outer packaging.^5,6 The MAH has to liaise with ANSM in order to add this specific French information (national registration codes, so-called “CIP codes”, name of the Exploitant for blood-derived products, local prescription and delivery conditions, etc.). 

As the Exploitant status is purely French, Exploitant transfer is also a purely French activity, managed by the MAH. Exploitant transfer is often combined with an MAH transfer, but this is not mandatory. Some activities are managed in all involved countries in the case of EU registration procedures (through a variation) whereas Exploitant transfer remains managed locally in France with ANSM. 

Inevitably, there will be ongoing communication with the ANSM and the Exploitant must be ready to address these questions as part of their regulatory affairs responsibilities. 

Regulatory affairs in France is also responsible for reviewing the artwork and text that is on the inner and outer packaging. These must be implemented in the mock-up and must include, in addition to the approved product information, French-specific requirements with regard to drug classifications (List I products are non-renewable medicines, except if clearly stated otherwise by the prescriber, while List II products are renewable, except if clearly stated otherwise by the prescriber. The label for List I products should have a red frame, while List II products have a green frame⁷). The label must also include information in Braille on the external packaging, using the specific French Braille code.⁸ 

French specific information also has to be included on the packaging for blood-derivative medicines (for traceability purposes).⁹ 

Some pictograms can also be mandatory, depending on the active substance contained.¹⁰ Examples include a pregnancy pictogram warning concerning potential risks with the use of a product during pregnancy; a warning pictogram for use where there might be effects on the patient’s ability to drive and use machines or a warning pictogram for use of a product while the patient is exposed to sunlight. 

Finally, depending on how the medicine is distributed (in other words, to the patient or used in hospital only), some recycling information logos need to be included on the outer packaging. 

As is the case across Europe, all information available to the public must be in the local language, in other words, in French.

Given the many country-specific requirements and the need for good quality French translation of all patient-facing material, companies often choose to work with an outsourcing partner. This ensures access to knowledge of the local regulations and understanding of regulatory trends and developments. Working with an outsourcing partner that has a team of in-country experts gives companies access to area-specific knowledge, for example, to do with a regulatory change or what ANSM will permit with promotional materials or packaging requirements. Given the often very precise requirements set out by the health authority, a slight deviation can result in costly and time-consuming errors by the company. Knowing how best to update the product information if there is a variation in the dossier, what can or can’t be on a label, or even the relevant fees to pay for different variations can be difficult for a company that isn’t steeped in this day-to-day knowledge. 

Communicating with the agency and responding to their queries also requires local knowledge and a relationship with the ANSM. There may be questions raised about an adverse event or a request to provide data regarding a new indication or queries about product stock. The company itself may have queries for the agency, such as whether packaging can include several languages, or how to update clinical trial information or transferring a marketing authorization. 

Having that on-the-ground expertise in France to manage regulatory affairs activities removes the many challenges companies often face, and helps them to ensure a smoother process in marketing and promoting their product in France.