Marketing authorisation

Time frame

How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation?

The ordinary time limit for the Director General of the National Agency for the Safety of Medications and Health Products (ANSM) to grant a marketing authorisation (MA) is, in theory, 210 days, a rule that comes from Directive 2001/83/CE. The application fees depend on the characteristics of the medicinal product and they can vary a lot. The first MA issued will be valid for five years and, once renewed, it will have no more time limit unless circumstances of pharmacovigilance require it to be renewed continuously.

For all medical devices (MDs), except those of Class I other than Class Is, Im and Ir, the CE marking is mandatory and subject to the obtaining of a CE certificate, issued by a body referred to as the notified body, authorised by the competent authorities. Tariffs and file processing time differ from one notified body to another but also depend on a number of criteria, including the class of the MD, the size of the company and associated standards.

Protecting research data

What protection or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms?

There is a regime of data exclusivity and market protection provided to manufacturers of brand name medicinal products that can be found in article L 5121-10-1 of the Public Health Code (PHC), and the principle is often referred to as the ‘8+2+1’ formula. From the date of approval of the brand name medicinal product’s MA, the ANSM must deny all MA applications submitted for generic medicinal products, and this prohibition lasts for eight years. After this period, manufacturers of generics can start to apply for a MA, even though the MA may only be issued 10 years after the launch of the brand-name medicinal product on the market. Furthermore, the exclusivity can be granted for an extra year if, during the initial eight-year period, the originator obtained an extended new therapeutic indication that brings a major advantage.

Freedom of information

To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices?

In France, the Commission on Access to Administrative Documents is required to provide any person who so requests with the administrative documents in its possession, whether drawn up or received by the administration, provided that any information likely to affect confidential information protected by law has been previously concealed, in particular information relating to commercial and industrial confidentiality.

Requests to release documents at the EU level can be made to the European Medicines Agency (EMA) in accordance with the Transparency Regulation, EC Regulation No. 1049/2001.

Be that as it may, the EMA Policy 0070 of 2 October 2014 establishes a transparency policy in the frame of centralised MA procedures based on a proactive approach with the publication of clinical overviews, clinical summaries, the clinical study reports and their appendices (protocol and protocol amendments, sample case report form and documentation of statistical methods). The EMA has been publishing on the publicly accessible basis of European Union Drug Regulating Authorities Clinical Trials concerning clinical trials.

Finally, under Regulation (EU) 536/2014, which will come into force in 2021, the EMA is responsible for setting up a ‘single portal’ allowing the public to access a clinical trials database for all national and multinational interventional research on medicinal products, excluding other health products. In addition, within one year of the end of the clinical trial in all the member states concerned, the sponsor shall, unless it is impossible for justified scientific reasons, submit a summary of the results of the clinical trial together with a written summary and the clinical study report.

Regulation of specific medicinal products

Are there specific rules for approval, and rewards or incentives for approval, of particular types of medicinal products, such as traditional herbal and homeopathic products, biologicals and biosimilars, controlled drugs, orphan drugs and those for paediatric use?

The PHC defines herbal medicinal products in article L 5121-1 as a medicinal product that has its active ingredient extracted from a plant. Despite having unique characteristics, there are no specific rules of entry to the market for herbal products; they should either apply for the MA if considered as a medicinal product or fall under the regime of preparations in some situations. Nevertheless, together with homeopathic products, some traditional herbal medicinal products may avoid the rigorous formalism of MAs and go through the lighter registration, provided that the conditions in articles L 5121-13 and L 5121-14-1 are met. For biosimilar medicinal products, the legal framework is not exactly the same as the rules on generic medicinal products, but the reasoning is comparable.

Manufacturers of biosimilars can submit their application for a MA before the extinction of the originator’s intellectual property rights, but the biosimilars may only be commercialised after the end of the patent. In addition, the ANSM is particularly cautious in assessing biosimilar medications and ensures that they guarantee the same level of effectiveness, quality and security as their reference medication. Last, paediatric medicinal products for minors under 17 are governed by a complex system that encompasses the common rules of MAs, but also an extra step called the paediatric investigation plan (PIP). The purpose of the PIP is to assure the suitability of the product for use on children and the procedure is described in Regulation (EC) 1901/2006 on medicinal products for paediatric use.

Post-marketing surveillance of safety

What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market?

Manufacturers of medicinal products are required to carry out pharmacovigilance and implement a risk-management plan to assess and minimise the risks linked to the medicinal product use. They shall report any suspected drug-related adverse reaction and ensure the collection, recording and processing of such information. Post-marketing obligations, including Phase IV trials, may be imposed as part of the granting of a centralised MA when there is no alternative treatment for the targeted disease and indication, and when the benefit-risk balance of the medicinal product is positive but needs to be reassessed based on complementary data.

As part of the materiovigilance, manufacturers of MDs are required to report any serious incident or risk of serious incident and any recall of a product from the market.

Other authorisations

What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity?

In principle, the manufacturing, importation, exportation or wholesale distribution of medicinal products in France can be done exclusively by ‘pharmaceutical establishments’. The opening of a pharmaceutical establishment must be authorised by the ANSM, regardless its activities. The Director General of the ANSM has 90 days to respond to such a request.

Regulation (EU) 2017/745 on MDs particularly stresses the respective obligations of the manufacturers, authorised representatives, importers and distributors, their good cooperation for the surveillance of MDs and the need to monitor each other and to report post-marketing surveillance information to the manufacturer and (where necessary) to national authorities.

Sanctions

What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities?

The profession of pharmacist is one of the regulated professions in France and every pharmaceutical establishment must have a head pharmacist before opening. The illegal practice of the profession of pharmacist is sanctioned with criminal law provided by article L 4223-1 of the PHC: the offender will be sentenced up to two years of imprisonment and fined up to €30,000. The illegal practice of medical biology is sanctioned with the same penalties according to article L 6242-2 of the same code.

Exemptions

What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market?

Article L 5121-1 of the PHC distinguishes three different non-industrial ways to produce medicinal products: pharmaceutical compounding, preparation in a hospital and preparation in a pharmacy. Despite the divergences in the production process, they share some common conditions to be implemented, such as the mandatory supervision of a pharmacist and the recognised absence of adapted medicinal product on the market.

Parallel trade

Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements?

Various conditions are required for the lawfulness of parallel imports:

  • the exercise of the right to property shall not contribute to the partitioning of the internal market;
  • the repackaging shall not adversely affect the original condition of the product;
  • the packaging shall clearly indicate the person who repackaged the product and the name of the manufacturer of the product;
  • the presentation of the repackaged product must not damage the reputation of the trademark and its owner; and
  • the importer shall notify the right-holder before the repackaged product is offered for sale.

 

The Court of Justice has recently applied the same principles to parallel imports of MDs.