Contributed By Intuity
Medicinal products are regulated differently according to their destination: Articles L5121-1 and seq of the Public Health Code (PHC) set up the legal framework on medicinal products for human use, which incorporated Directive 2001/83, and Articles L5141-1 and seq of the PHC govern medicinal products for veterinary use (which transposed Directive 2001/82).
The regulatory framework on medical devices (MD) is set out in Articles L5211-1 and seq of the PHC as well as in Articles R5211-1 and seq of the PHC, which incorporated the Medical Devices Directives 93/42/EC, 90/385/EEC and 98/79/EC. Medical devices can be distinguished from in vitro diagnostic medical devices (IVDR) and active implantable devices, which are regulated differently.
The current regulatory framework went through important changes with the implementation of two new Regulations on MD (2017/745) and IVDR (2017/746) on 25 May 2017, which will be fully applicable on 26 May 2020 (for MD) and on 26 May 2022 (for IVDR).
Regarding medicinal products for human use, the regulatory bodies are the EC, the Committee for Medical Products of Human Use (CHMP) of the European Medicines Agency (EMA) and the French National Agency for the Safety of Medicines and Health Products (ANSM).
Regarding medicinal products for veterinary use, the competent regulatory bodies are the EC, the Committee for Medicinal Products of Veterinary Use (CVMP) of the EMA and the French National Health Security Agency for food, the environment and work (ANSES).
Regarding medical devices, the competent regulatory bodies are the EC and the ANSM.
Decisions of the regulatory bodies (whether for medicines and medical devices) are administrative decisions, subject to an ex gratia/informal appeal that is addressed to the author of the challenged decision. In the event of failure of such an appeal, a judicial appeal can be exercised on grounds of misuse of power to the competent administrative court.
The ex gratia appeal can be submitted in the form of a letter, which shall state the facts and its legal grounds. Regarding the judicial appeal, the applicant shall be represented by a qualified attorney, have an interest in bringing proceedings and the capacity to act. The challenged decision must also be an administrative decision that is prejudicial and have legal effects on the applicant’s legal situation.
These procedures also apply for other regulated products.
Medicines and in vitro medical devices are only distributed by pharmacists, who retain a monopoly on such products through physical and online shops, although few exceptions exist (eg, contact lenses and accessories, Class I MD such as bandage or earplugs). Online shops shall only sell non-prescription medicines.
Clinical trials (whether on medicines or on medical devices) are regulated according to the level of risk the subject is exposed to. Interventional studies involving an intervention on the subject require the sponsor to obtain ANSM’s approval and a positive opinion from an Ethics Committee (CPP), which is composed of a group of scientists and non-scientists. For interventional studies involving low or no risk for the subject and non-interventional studies, although a positive opinion of the CPP is required, the ANSM shall only be informed of the performance of the trial. Should the clinical trial fall within the criteria outlined in one of the baseline methodologies implemented by the CNIL (National Commission for Information Technology and Liberties), the sponsor can go through a simplified procedure and submit a compliance commitment. Otherwise, the sponsor shall be authorised by the CNIL to collect and process data during the performance of the trial.
In 2020, interventional studies on medicinal products for human use are expected to fall within a new EU Regulation under which pre-approval and opinion of the CPP will be co-ordinated with other Member States’ bodies. A unique authorisation and assessment procedure will also be implemented.
Sponsors shall obtain a research registration number. For interventional studies on medicines, sponsors must obtain that number in the EU database of clinical trials (EudraCT). For any other types of studies, they must seek a registration number on the ANSM’s website.
Sponsors shall then send an application file for authorisation and/or opinion, by electronic means or by mail, to the ANSM and/or the CPP, in accordance with the file formats provided for each type of trial. The evaluation process may last from 14 days to 88 days.
All clinical trials must be registered before starting on the register of the World Health Organization (WHO). In addition, all interventional studies conducted in the EU and the European Economic Area (EEA) must be registered on the EMA’s dedicated website no later than 21 days after the recruitment of the first subject. Some institutions also provide a list of clinical trials performed in specific therapeutic areas (cancer, rare diseases, hepatitis). The summary of the trial results is made available on these websites at the end of the study. Requests to release further documents can be made to the EMA in accordance with the "Transparency Regulation"; ie, Regulation (EC) No 1049/2001.
Online tools are not prohibited per se. However, the requirements in terms of information and consent of the subjects and data protection may seriously impair their usefulness. Moreover, all advertisement/communication used to invite subjects to participate in clinical trials and arrangements for information or advice shall be submitted and approved by the CPP. The procedures proposed for handling responses to the advertisement shall also be outlined.
Under Regulation 2016/679, the resulting data from clinical trials falls within the definition of sensitive data, which is considered as a specific category of personal data.
The resulting data may be transferred to a third party or an affiliate if the baseline procedure or the CNIL’s authorisation to collect and process such data allows it. In addition, the sponsor shall ensure that such affiliate or third party complies with the legal framework set out in Regulation 2016/679 (Article 44 and seq).
The creation of a database containing personal or sensitive data may be authorised without further requirements if the database is not intended for a different purpose than the one under which the initial data collection was performed and the database should comply with the data retention period as agreed in the simplified procedures or in the CNIL’s authorisation.
In most cases, it will involve a modification of the initial authorisation or a new authorisation.
EU legislation provides a definition of medicinal products and medical devices. Guidelines tend to distinguish such products based on their principal intended actions. Hence, the medicinal product will have a pharmacological, metabolic or immunological action, whereas the principal intended action of a medical device will be physical or mechanical.
Biological medicinal products have specific MAs dossiers and requirements; eg, application files for vaccines shall include a Vaccine Antigen Master File containing all relevant information concerning each of the active substances.
The initial period of validity of an MA is five years. The CE marking has a period of validity limited from one to five years.
Application for renewal must be filed at least nine months before the expiry date of the initial MA. A renewal has no time limit unless there are post-marketing surveillance issues. Guidelines are available for the different procedures on EMA and ANSM’s websites.
The MA can be revoked if the medicinal product is not commercialised within three years of its granting or if the product is not commercialised in France for three consecutive years.
In the case of risks to human health, safety or quality concerns, the regulatory bodies may modify, restrict or impose specific requirements in order for the product to be put on the market. They may also suspend or withdraw the product from the market.
The MA may be granted through four main procedures. MAs issued only allow the product in question to be marketed in the EU Member State(s) concerned, unless the product has been authorised via the centralised procedure. The CE marking can be obtained at a national level by a Notified Body and is valid within the EEA.
Applicants must submit data on the use of a medicinal product in children obtained in accordance with an agreed paediatric investigation plan. If the requirements of Regulation 1901/2006 are fulfilled, applicants may be then eligible for a reward.
Procedures for variation of MAs are classified according to the extent of the modification and their consequences on quality, safety and efficacy. Although minor modifications (type IA and IB) shall only be notified, major modifications (type II) and extensions shall be approved by the regulatory bodies.
A change of the MA holder shall be authorised by the ANSM on supporting documents. The transfer should be deemed accepted 60 days after the request has been made.
Patients may have access to medicines that are not yet authorised but have entered the authorisation application process provided that:
Temporary authorisations (ATU) may be delivered for a group of patients upon request of the manufacturer (compassionate use programmes) or on a named-patient basis upon request of a healthcare professional. Such possibility does not exist for medical devices outside clinical trials.
Manufacturers of medicines are required to carry out pharmacovigilance and implement a risk-management plan to assess and minimise the risks linked to the medicine use. They should report any suspected drug-related adverse reaction and ensure the collection, recording and processing of such information. As part of the technovigilance, manufacturers of medical devices are required to report any incident or risk of serious incident and any recall of a product from the market.
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 medicine is positive but needs to be reassessed based on complementary data.
The list of medicines under evaluation by the CHMP is available on the EMA’s website and includes international non-proprietary names and therapeutic areas. Pending applications for medical devices are not available publicly.
Following a positive opinion, a public assessment report is made public on the ANSM and EMA’s websites. Following a negative opinion, a refusal question and answer document and the refusal public assessment report are published.
There is no publication of any information of a commercially confidential nature or of sensitive information.
Directive 2011/62/UE and Delegated Regulation 2016/161 supplementing Directive 2001/83/EC set the safety features that shall appear on the packaging of medicines to fight against counterfeited and falsified medicines. This means that since 9 February 2019, the packaging of each medicine newly put into circulation shall have a data matrix with a unique identifier and an anti-tampering device for the purposes of allowing its identification and authentication. In France the non-profit organisation France MVO is in charge of the IT interoperability of the verification system.
The Ministry of Economy is specialised at the borders in the control of the flow of goods and shall verify all points of entry and exit of the territory and all the vectors of fraud. It also operates on storage sites and after customs clearance. Customs powers in the area of counterfeiting have been strengthened at the European level with the adoption of Regulation 2015/2424 and Directive 2015/2436 on counterfeit goods from and to third countries. As a precautionary measure, withholding of goods suspected of infringing an IP right can be carried out by customs services, upon prior filing of a request for intervention by the right-holder. A request can be filed for monitoring goods on the national territory and at the borders of another Member State.
Manufacturing plants of medicinal products shall be authorised by the ANSM, whereas manufacturers of medical devices or their representatives shall declare their activities and the medical devices they manufacture to the ANSM.
The declaration for medical devices and the application for authorisation to manufacture medicinal products can be sent by registered mail or by electronic means, with acknowledgement of receipt. Application for an authorisation shall be made at least 60 days before any operation.
The scope of the declaration and the authorisation will be determined by the manufacturer’s application or by its declaration. However, any modification of the scope of the activities shall be reported to the ANSM.
There is no period of validity of such authorisation.
As manufacturers, wholesalers of medicines shall be authorised, while establishments engaged in wholesales of medical devices must report their activities and the products they distribute. Distributors shall comply with the Good Distribution Practices. The process for the authorisation or declaration is the same as for manufacturers (see 4 Manufacturing of Pharmaceutical and Medical Devices).
See 1.3 Different Categories.
Articles L5121-8 and seq, and R5121-108 and seq of the PHC govern the import and export of medicinal products.
Articles L5211-3 and seq as well as Articles R5211-12 and seq of the PHC regulate imports and exports of medical devices, while Articles L5221-2 and seq as well as Articles R5221-8 and seq of the PHC govern imports and exports of in vitro diagnostic medical devices.
Only pharmaceutical establishments can act as the importer of record, provided that they are authorised by the ANSM (with some exemptions – see 6.3 Prior Authorisations). For certain controlled substances (eg, toxins, narcotics), an additional authorisation may be required.
Such establishments can act as importers of record, provided that they report their activities and the products they import to the ANSM.
Imports of pharmaceuticals require import permits, which are delivered by the ANSM. Import permits may be delivered for an import within three months or for several imports within a year for a predefined quantity.
Medical devices can only be imported if they are CE marked and importers shall report to the ANSM their activities and the products they import.
Exemptions apply to:
Specific restrictions may be imposed for well-defined therapeutic categories of products (eg, vaccines, narcotics, psychotropic drugs, gene and cell therapy products, clinical trial products and medicinal products used in biomedical researches). The EU product classification system provides a classification for all products under a tariff code that includes information on the duty rates, applicable protective measures, external trade statistics, import and export formalities, and other non-tariff requirements. The classification includes:
The Council Regulation (EEC) No 2658/87 of 23 July 1987 and the Commission Implementing Regulation (EU) 2018/1602 of 11 October 2018 set up the EU product classification system.
A new type of trade agreement (ie, bilateral or regional agreements) that tend to reduce non-tariff barriers are currently signed between the EU and industrialised third countries; for example, the CETA (EU-Canada), the TAFTA/TTIP (EU-US) and the JEFTA (EU-Japan).
For the hospital market, prices are freely set through bids. For the private market, the price is free on the non-reimbursable market. On the contrary, on the reimbursable market, the retail price is regulated and set by an agreement between the Economic Committee for Health Care Products (CEPS) and the company, or in the absence of an agreement, by the CEPS alone. Prices for OTC products are free. The maximum margins that can be applied by wholesalers and pharmacists are set out by law (order dated 4 August 1987 as amended). The price to be applied by the pharmaceutical company is calculated as a result of the application of these maximum margins to the retail price.
Most medical devices used in hospitals should be covered through the cost of the hospital stay related group (GHS). Price is freely negotiated between the company and the hospital-purchasing group.
Medical devices for personal use outside hospital can be reimbursed if the company requested to enter the reimbursable market through registration within the List of Reimbursed Products and Services (LPPR). The price is then determined the same way as for medicines.
Price and reimbursement are governed by the Security Social Code (Articles L162-16 and seq for medicines, and L165-1 and seq for medical devices).
The pricing of reimbursable medicinal products is regulated and set by a convention between CEPS and the firm. The process takes into account various criteria set out in article L162-16-4 of the Social Security Code, including the improvement of clinical benefit evaluated through the Transparency Commission of the French National Authority for Health, prices of other medicinal products within the same therapeutic class, the expected or recorded sales volume and the actual and foreseeable use of the medicinal product.
Depending on the medicine’s price in Germany, Spain, Italy and the UK (defined as reference countries because of their comparable market size), the retail price may be adjusted or revised by the CEPS.
If the clinical benefit of a medicine or the service expected of a medical device is judged sufficient, the product may be included in a reimbursement list. The National Union of Health Insurance Funds (UNCAM) determines the reimbursement rate for medicines and an order of the Ministry of Health shall enforce the inclusion of the product on the list. The Pharmaceutical Innovation Funding Fund (FFIP) created by the Social Security Financing Act (LFSS) for 2017 outlining the expenses associated with the management of innovative medicines was abolished by the LFSS for 2019.
The greater the level of improvement in medical benefit of the medicine, the higher the cost treatment granted with regard to its "comparators". A medico-economic assessment shall also be taken into consideration to determine the price of certain products that are judged innovative and have a significant impact on the health budget. In any case, when the level of improvement is considered non-existent, the reimbursement is possible only in the case of "a saving in the cost of treatment".
Pharmacists are able to replace prescribed brand-name medicines with their generic equivalent. To facilitate such a replacement, general practitioners have been required since 2009 to write their prescriptions according to the international non-proprietary names, with a common name for each active substance. In addition, it is now mandatory to justify the mention of "non-substitutable" with medical criteria. From 1 January 2020, patients who refuse, without medical justification, the generic equivalent will see their reimbursement limited to the price of that generic.
Medical apps fall within Regulation 2016/679 on data protection. Depending on their intended purposes, some of them may be considered as medical devices or in vitro diagnostic medical devices. They shall then be regulated by the Medical Devices Directives, at least until the Medical Devices Regulations are fully applicable (See 1.1 Legislation and Regulation).
According to recent case law, a medical app shall be considered as MD or IVDR under three cumulative conditions:
Apps ensuring the patient treatment is taken adequately or used in sports practice do not fall in this scope.
Telemedicine is governed by Articles L63116-1, R6316-1 and seq of the PHC, which apply alongside common principles (eg, deontology). With some exceptions, the physician should be the primary care physician. The free and informed consent of the patient shall be obtained for any act of telemedicine.
Although the use of a mobile device is not prohibited, it shall meet the regulatory requirements, which are the use of a video exchange (ensuring the identity of physicians and patients) and the connection to a secure solution (eg, a link) that may be only accessible via a laptop or a tablet (securing the consultation and data processing).
Online websites promoting medicines or medical devices shall comply with the general principles of advertising (see above). Provided that companies comply with these rules (which entails in practice access restriction and content adapted to the public), advertising or promotion shall be clearly identified as such. The editor (eg, the companies) shall also be clearly identified. The content shall not be misleading and respect certain file formats. With some restrictive exceptions and under specific conditions, advertising on social networks is prohibited. Guidelines are available on the ANSM website.
Electronic prescription is allowed by Law No 2004-810 under some conditions. The prescriber must be identified, the e-prescription must have been established, transferred and stored under conditions that guarantee its integrity and confidentiality, and a clinical examination of the patient should have been carried out beforehand, except in exceptional emergency cases. Furthermore, an experimental project called PEM2D is under way in several departments.
Only non-prescription medicines can be sold on the internet through physician online shops. Very few exceptions to pharmacists’ monopoly exist (eg, anti-parasitic for animals, some class I medical devices such as bandages or contact lenses). See 1.3 Different Categories.
Since 2004, patients can request the creation of a unique and electronic medical record, which is not mandatory. Articles L1111-8 and seq and R1111-9 and seq of the PHC regulate the hosting of health data by electronic means. The data host requires a certificate of conformity, which is delivered by a certification body. The data hosting contract must contain some mandatory provisions, as set up in Article R1111-1 of the PHC.
Several licensing are possible: "co-licensing" agreements for a shared license are to be distinguished from "in-licensing" which consist on the one hand, in acquiring the marketing rights of a product and "out-licensing" which consist on the other hand, in selling the marketing rights of a product.
The Parties are usually expected to use reasonable efforts to resolve in good faith any dispute arising in connection with the agreement. If the dispute cannot be amicably settled, the dispute is finally settled by arbitration or litigation.
In any case, the consequences of the end of the agreement must be duly specified regarding approvals, orders, documentation, remaining stock, property rights, etc.
Specific timelines and tasks are outlined for each party’s diligence obligations. This is the case for example for the consideration for license, the registration/reimbursement of the product, the supply of products.
Some legal provisions are also customary to define each party’s diligence obligations in terms of “reasonable efforts”. Usually, if any assistance is required by the licensee from the licensor, then the licensor shall use commercially reasonable efforts to provide such assistance (eg, in case of litigation in the territory concerning the product). The licensee is also usually expected to provide reasonable assistance regarding the performance of the contract on the territory, this can be the case of the performance of medical information request activities made directly or through sales representatives or partners by external bodies (healthcare providers, patients key opinion leaders, general public, etc).
In any event, the parties shall conclude and perform the contract in good faith and in a loyal manner.
The licensee and licensor are both protected under corporate law in the event of a change in control of the other party. This solution is based on the autonomy of the legal entity of the company over that of the directors and as such, on the intuitu personae nature of the contractual relationship (Court of Cassation of 29 January 2013 No 11-23676).
Therefore, unless otherwise provided, the agreement entered into before a change of control must be respected by the new directors given the independent legal personality of the company.
In the event of non-compliance with the agreement entered into before the change of control, the new directors may be held liable.
The general consequences of termination relate to the possible transfer of approvals, orders, documentation, remaining stock, property rights from the licensee to the licensor.
However, under French law, the licensor does not have ownership of the discoveries generated by the licensee prior to termination. Indeed, by giving the licence, the licensor only retains the nu-property and therefore would not be likely to claim ownership of the licensee's clinical data and IP.
Article L611-1 and seq of the Intellectual Property Code (IPC) set up the legal framework on patents.
Most issues regarding patent law concern illicit agreements or disputes between generic and originator companies.
There are no patentability requirements specific to medicines or medical devices. However, some features may apply to life sciences (eg, methods of surgical or therapeutic treatment and diagnostic methods cannot be patentable as well as a number of other biological processes).
Second and subsequent medical uses of a known product are recognised as patentable, provided that said use is novel and inventive.
The principle of the patentability of second medical uses was also extended for claims drawing their novelty from a method of administration, a new class of patients, as well as from new dosage regimes, provided that the patentability requirements are met.
The scope of protection of a second patent for a new therapeutic use will be limited to the said use of the product. Therefore, an infringement would be demonstrated if the product is manufactured or offered for this particular medical use.
A supplementary protection certificate (SCP) can be requested from the Patent Offices, which will extend the duration of the protection granted by the initial patent up to five years plus six months in the case of studies with a view to paediatric use.
SCP shall be granted if:
A third party may bring an action for a declaration of invalidity of the certificate before the competent tribunal.
Patent infringements consist of:
Threat of infringement is actionable if there is an imminent infringement of IP rights.
Defences to patent infringement include:
Compulsory licences are available to manufacture and export pharmaceutical products to countries in need of such products. The ministry in charge of IP can also implement such regime for medicinal products and medical devices in the event of health or competition issues. Such provision, whose rationale lies essentially in its deterrent effect, has never been applied.
The right-holder or the exclusive licensee can bring proceedings for patent infringement, unless the licence agreement says otherwise.
Such dispute falls within the exclusive competence of the president of the Tribunal de grande instance of Paris and of the Paris Court of Appeal. An appeal before the Supreme Court is possible in accordance with ordinary law.
A request for seizure for counterfeiting usually precedes most patent infringement actions as it enables the finding of solid evidence before any proceedings. The interlocutory proceedings, which are faster and allow interim measures, are usually favoured. Substantive proceedings can be brought later but are necessary to obtain compensatory damages.
Invalidity of the patent is an available defence and can be raised by a counterclaim.
Prelaunch declaratory action is available for bona fide companies that wish to ensure their activities will not infringe a patent under Article L615-9 of the IPC.
Prelaunch declaratory action remains optional for generic companies.
The authorisation procedure does not directly address patent linkage. When the period of data exclusivity expires (ie, eight years following the granting of the MA) generic companies can apply for an MA. However, the generics cannot be launched on the market before the period of marketing exclusivity (ie, ten or 11 years) and prior to the expiry of the patent(s) without the consent of the proprietary rights (Article L5121-10, PHC). Be that as it may, in the Lundbeck case of 8 September 2016, the General Court ruled that the presumption of a patent validity "cannot be equated with a presumption of illegality of generic products validly placed on the market which the patent holder deems to be infringing the patent".
A counterfeit can trigger the civil and criminal liability of the counterfeiter, which can expose the counterfeiter to a fine of EUR7,500 up to EUR750,000. Customs withholding may also be applicable (see also 3.9 Border Measures).
Trade marks used for medicines must avoid any confusion with the International non-proprietary names or with other medicines. They should not mislead the consumer about the qualities or properties of the product. The ANSM will assess medicines trade marks on the basis of restrictive recommendations.
The trade dress or design of medicines or medical devices can benefit from the protection of designs and models, unless:
Design rights are a useful and relatively inexpensive way to protect life sciences products, especially medical devices.
Data exclusivity, which prohibits the application for a generic MA, shall last eight years following the granting of the originator MA.
The marketing exclusivity that prevents the placing on the market of the generic product lasts ten or eleven years (ie, the originator obtained during the eight years following the granting of its MA a new therapeutic indication that brings a major advantage) following such granting.