Medicinal products are regulated differently according to their destination. Articles L5121-1 and seq as well as R5121-1 and seq of the Public Health Code (PHC) set up the legal framework on medicinal products for human use, which incorporated Directive 2001/83. Articles L5141-1 and seq as well as R5141-1 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 applicable on 26 May 2021 (for MD) and on 26 May 2022 (for IVDR).
Medicinal Products for Human Use
Regarding medicinal products for human use, the regulatory bodies are:
Medicinal Products for Veterinary Use
Regarding medicinal products for veterinary use, the competent regulatory bodies are:
Regarding medical devices, the competent regulatory bodies are the EC and the ANSM.
With the exception of preparatory acts, decisions of the regulatory bodies authorising or refusing the marketing of a medicinal product, relating to the coverage by the health insurance or the fixing or modification of the price of a medicinal product are subject to an appeal for excess of power before the competent administrative court.
The same applies for the fixing of the price or tariff of medical devices listed in the LPP.
The Economic Committee for Health Care Products (CEPS) decisions that concern conventional remittances and financial penalties are administrative decisions that might be 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.
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. 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 2021, 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.
In addition, the ANSM can regulate prescriptions that do not comply with the MA, subject to the following conditions:
Early Access and Compassionate Access Schemes
The Social Security Financing Act for 2021 removes these two derogatory benefit regimes and replaces them with the "early access" and "compassionate access" schemes.
The early access scheme provides for the same four conditions as the ATU with an additional criterion: only medicines presumed to be innovative will be eligible for early access.
The compassionate access mechanism is intended for medicines that are not necessarily innovative nor intended to obtain a MA in the indication concerned but which respond satisfactorily to a therapeutic need. Only medicines that are not the subject of research involving the human person for commercial purposes will be eligible for this scheme.
The new provisions should be effective by 1 July 2021 at the latest.
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 concerned medicines to fight against counterfeited and falsified medicines. This means that since 9 February 2019, the packaging of each concerned 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 French order of 26 February 2021 on good practices in the dispensing of medicinal products in retail, mutual and mine rescue pharmacies, fully incorporates in its provisions the role of pharmacists in the fight against the falsification of medicinal products.
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 of Pharmaceuticals and Medical Devices.
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 the Importation of Pharmaceuticals and Medical Devices). 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 medicines 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.
Exemptions apply to:
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.
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 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 and medical devices is regulated and set by a convention between CEPS and the company. The process takes into account various criteria set out in article L162-16-4 and L165-2 of the Social Security Code.
Depending on the price in Germany, Spain, Italy and the UK (defined as reference countries because of their comparable market size), the retail price/insurance tariff 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".
The Economic and Public Health Evaluation Commission (CEESP) assesses the efficiency of a medical device if it claims an improvement of the required level of service (ie, major, significant or moderate) and is likely to have a significant impact on health insurance expenditure.
This evaluation consists of determining the interest for the society in the new product compared to those existing by comparing the means employed (ie, the cost) with the results obtained.
Finally, a specific package allows for the exceptional and temporary coverage of a particularly innovative medical device, subject to the completion of a relevant study aimed at providing missing clinical or medico-economic data. This coverage is decided by the publication of a specific decree by the Minister of Health, following the opinion of the High Authority for Health (HAS).
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. Since 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 for Pharmaceuticals and Medical Devices).
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 L6316-1, 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.
Order No 2020-1408 of 18 November 2020 implementing electronic prescription aims to develop the practice of prescriptions issued in a dematerialised manner.
It authorises healthcare professionals in private practices to prescribe care, products or services in a dematerialised manner and to transmit it through teleservices provided by the health insurance system. After an experiment focusing on medicines’ prescriptions, e-prescription will be widespread step by step by the end of 2024, with a series of tests for each type of prescription and procedure.
Finally, it will make it possible for patients to access such prescriptions from their shared medical record (DMP). See 8.6 Electronic Health Records.
Only non-prescription medicines can be sold on the internet through physician online shops. No specific regulation exists for online sale of MDs. Pursuant to the application of the Treaty on the Functioning of the European Union and Regulation (EU) 2017/745, the principle is the free distribution of medical devices bearing the CE marking, with the exception of those subject to a monopoly (ie, optics, hearing aids, in vitro diagnostic devices, prostheses and orthoses).
Since 2004, patients can request the creation of a unique and electronic medical record, which is not mandatory. Such electronic medical record has never been able to deploy due to multiple obstacles. The law on the modernisation of the health system of 26 January 2016 and the implementing decree of 4 July 2016 renewed the objective of an introduction of the medical record, renamed "shared medical record" (DMP) whose implementation is carried out by National Health Insurance Fund (CNAM) (Article L1111-14 of the PHC).
In order to protect sensitive data, the law provides a framework for the activity of hosting providers.
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 R1111-11 of the PHC.
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:
The existing legislative framework concerning forced licences includes compulsory licenses (judicial licenses) and ex officio licences (administrative licenses). The ministry in charge of IP can specifically implement such regime for medicinal products and medical devices in the event of health or competition issues. Such procedure, 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).
A counterfeit can trigger civil and criminal liability, 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 to Tackle Counterfeit Pharmaceutical and Medical Devices).
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.
This applies to biological medicinal products.
In response to COVID-19, an emergency law was first adopted in France on 23 March 2020. It introduced a new Chapter in the PHC, entitled State of health emergency.
Such new provisions allow the French government to declare a state of health emergency on all or part of French territory. This state of health emergency enables the Prime Minister to take measures by decree to guarantee public health.
These measures include the requisition of persons, goods and services necessary to preserve public health (see 11.9 Requisition or Conversion of Manufacturing Sites), all necessary measures to ensure appropriate access to medicines needed to face the public health threat (see 11.5 Import/Export Restrictions or Flexibilities as a Result of COVID-19), temporary measures to control the prices of certain necessary products and any other measures restricting the exercise of economic activities.
Such measures must be "strictly proportionate to the health risks involved and appropriate to the circumstances of the time and place" and "shall be terminated without delay when they are no longer necessary". In addition, compensation for requisitions is governed by the Code of Defence.
Successive laws were adopted to extend the state of health emergency. As long as it is maintained in France (as it stands, this will be until 1 June 2021), these provisions will remain applicable.
On 20 March 2020, the ANSM published a communication, further updated following the course of the epidemic, on ongoing clinical trials in France. This communication, addressed to clinical trials sponsors, calls for a re-evaluation of the relevance of ongoing or new clinical trials.
Exceptional measures provided by the ANSM for ongoing medical trials included the possibility to suspend ongoing trials, change of research location, collection of information through teleconsultation and home delivery of experimental treatments.
The intended aim of the ANSM, through these special measures, was to give priority to trials involving patients infected with COVID-19.
To achieve said objective, fast-track procedures before ethical research committees (CPP) and ANSM benefit to COVID-19 researches granted with the label of "national research priority" by an ad hoc committee (CAPNET), which is based in particular on a scientific and methodological evaluation carried out by the scientific council of the REACTing consortium. To support this effort, the EMA offers a fee waiver and a fats-track procedure for scientific advice.
Several measures have been provided for the renewal of medicinal products benefiting from compassionate use (ie, nominative or cohort temporary authorisations for use (ATUs)), not reserved for hospital use and prescribed as part of a chronic treatment. In the same vein, the ANSM has granted a cohort ATU to allow continued access on national territory to the antiviral medicinal product remdesivir indicated for the treatment of the COVID-19 virus.
The new Chapter on the state of health emergency specifies that any measures necessary to enable patients to be provided with appropriate medicines to eradicate the health disaster may be taken.
Regarding medical devices, some of these products have been granted access to the market, prior to obtaining a CE mark (see also 11.4 Flexibility in Manufacturing Certification as a Result of COVID-19).
Through an order dated 18 May 2020, and in the context of COVID-19, the French government has authorised, by way of derogation, the use of in-vitro diagnostic medical devices that do not have a CE mark in order to allow a sufficient number of medical biology examinations to be carried out.
In order to benefit from this derogation, manufacturers must meet several cumulative conditions. These conditions consist of a declaration to the ANSM, a validation by a national reference centre (CNR) and being the subject of a mandatory publication on the site of the Ministry of Health.
More generally, in accordance with European provisions, the ANSM authorises, upon duly justified request, the placing on the market and putting into service within the French territory of a specific device for which the conformity assessment procedures have not been applied, but whose use is in the interest of public health or the safety or health of patients.
The emergency law of 23March 2020, taken in response to COVID-19 introduced Article L3131-15 in the PHC.
It allows under paragraph 9 the Government, by regulatory decree and for the purpose of guaranteeing public health, to take all necessary measures to ensure that appropriate medicines are made available for patients in order to eradicate the public health threat.
Under these provisions, the French Government took a regulatory decree on 11 May 2020 that banned exportations of hydroxychloroquine and specialities containing the lopinavir/ritonavir combination by the wholesalers. Such a decree was revoked on 27 May 2020.
As for imports, the ANSM published a list of imported medicines needed to treat patients in intensive care units.
In order to face the emergency of the health situation in France, these products were not labelled in French, as it is usually done.
The “Health Data Hub” has been created by a ministerial order of the 29 November 2019. Its aim is to allow the health sector to use the potential of artificial intelligence by providing researchers with health data from French public health organisations.
Through a ministerial order of 21 April 2020, the French Government has issued an early launch of the Health Data Hub to facilitate the management of health emergencies and improve knowledge on COVID-19.
Only data necessary for the pursuit of a public interest purpose in relation to COVID-19 are allowed and for the duration of the state of health emergency.
In addition to the compulsory licences pronounced by the Judicial Court, the French legislation provides for three types of ex-officio licences that can be granted by decision of the public authorities for general interest reasons: ex-officio licence in the interest of public health, in the interest of economic development or for the needs of national defence.
None of these licences appear to be adapted to the current situation because of their stringent conditions.
It is therefore understandable that the government preferred to resort to the emergency measures of the law of 23 March 2020 and in particular to the new Article L3131-15 of the Public Health Code.
In order to compensate for the high risks taken by manufacturers due to the unprecedented context of vaccines production and limited time to observe side effects, advance purchase agreements provide for member states to indemnify the manufacturer for liabilities incurred under certain conditions.
The emergency law of 23 March 2020 taken in response to COVID-19 introduced Article L3131-15 in the PHC.
Paragraph 7 of this Article allows the government to order by regulatory decree and for the purpose of guaranteeing public health, in territorial constituencies where a state of health emergency has been declared, the requisition of all persons, goods and services needed to face the health emergency.
The government issued an Order No 2020-319 on 25 March 2020 adapting the rules for the award procedure or execution of public procurement contracts in order to deal with the COVID-19.
These measures were implemented to the extent that they were necessary to deal with the consequences of COVID-19 and applied to contracts in progress as of 12 March 2020 until 23 July 2020 included.
In particular, this Order allows:
The Order also provides financial support to companies which have difficulties in executing public contracts due to the health crisis. This is reflected in particular by the possibility to extend the execution period, provided the context allows it, the absence of all or part of the contractual penalties and the possibility of receiving financial support.
In France, changes in attitudes and practices now make it possible to open the market to certain products previously considered contrary to good morals. The arrival on the market of CBD, a product derived from cannabis and experiments on therapeutic cannabis are proof of this. This trend towards openness to novelty is also illustrated by the objective of simplifying exceptional access to medicines. Telehealth is also a topic which, with the lockdown due to COVID-19, has also been simplified under French law.
However, this openness is accompanied by a need for transparency and trust towards pharmaceutical laboratories. The anti-gift law strictly regulates the relations that a laboratory may have with healthcare professionals. Furthermore, the legislator wishes to protect health data access from laboratories.
Paradoxically, this protection may become a hindrance to medical research because of the cumbersome procedures, which is an indirect impediment. In addition, access to and research on genetic is still very conservative under French law as seen in the current debate at the French Parliament.
The Exceptional Access to Medicines Reform (the ATU and RTU Reform)
The Social Security Financing Law for 2021 (the "LFSS 2021") of 14 December 2020, reforms the Temporary Authorization of Use Programme (ATU) and the Temporary Recommendation of Use Programme (RTU). This reform will come into force on a date to be set by decree or no later than 1 July 2021.
The RTU concerns a medicine that has been granted Marketing Authorization (MA) for another therapeutic indication and is already marketed in France. An RTU is issued by the French National Agency for the Safety of Medicines and Health Products (ANSM), when there is a therapeutic need or when the benefit-risk ratio of the medicine is presumed to be favourable. However, the ATU issued by the ANSM allows patients to benefit from pharmaceutical specialities which do not have an MA yet. These pharmaceutical specialities must be intended for the treatment of serious or orphan diseases and in the absence of other appropriate treatment. There are several forms of ATU such as named-patient ATU and cohort ATU, which complicates their application.
The purpose of this reform is to simplify the categories of exceptional access to medicines and the coverage by health insurance. Indeed, the system needs greater visibility and coherence. It was created in 1994 as part of the fight against AIDS, and since then the system has become more complex with multiples reforms, introduced by different Social Security Financing Laws.
Pursuant to Article 78 of the LFSS 2021 the ATU and RTU systems are now combined under two exceptional regimes: early access and compassionate access.
Early access authorisation
The conditions for granting early access are based on the former ATU's conditions as well as a new condition. These conditions are: the lack of appropriate treatment, the start of the treatment cannot be postponed; the efficacy and safety of these medicines are highly effective, presumed on the basis of therapeutic trials results. The new requirement is that the medicine must be presumed to be innovative.
Another major evolution is that the authority issuing the authorisation will now be the High Authority of Health (HAS), which intervenes after receiving the ANSM's assent and only at the company's request. For faster treatment, the HAS decision sets out both the granting of early access and the coverage by health insurance. The reimbursement indemnity is freely determined by the laboratory.
In line with what was planned before the reform, early access authorisation is conditional on the laboratory's commitment to apply for an MA and a registration for reimbursement for the medicine in question. Furthermore, the laboratory's compliance with a Protocol for Therapeutic Use (PUT) and the collection of real-life data on the medicine is necessary. The data focus on efficacy, side effects, the actual conditions of use as well as the characteristics of the population benefiting from the authorised medicine.
An innovation of the reform is that early access authorisation is granted for a limited period of time set by a decree. Whereas today the validity of the ATU is not limited by any law.
Compassionate access authorisation
Three cumulative conditions must be met. The medicine is not to be the subject of clinical trials for commercial purposes in the indication concerned. There is no appropriate treatment available. The efficacy and safety of the medicine are presumed on the basis of available clinical data and, when the indication concerns a rare disease, work and data collected by health professionals.
Compassionate access authorisation is requested for the treatment of a serious, rare and disabling condition for medicines that are not or no longer marketed. This authorisation concerns medicines that are not necessarily innovative and which are not necessarily intended to obtain an MA in the indication concerned but which respond satisfactorily to a therapeutic need. This new category simplifies the procedures of the named-patient ATU and the RTU. This authorisation is granted only by the ANSM, the HAS does not participate in the process. The coverage by health insurance is automatic when the authorisation is granted. The reimbursement indemnity is freely determined by the laboratory unless there is a published price.
The reform distinguishes the compassionate access authorisation that is solicited by a prescribing physician, from the "compassionate prescribing framework" that is established at the initiative of the ANSM or at the request of Ministers. The ANSM may establish, for a renewable period of three years, a "compassionate prescribing framework" for a medicine subject to a MA for other indications, in order to secure a prescription that does not comply with this authorisation.
Both the "compassionate prescribing framework" and the compassionate access authorisation must be backed up by a PUT that specifies the conditions for collecting information concerning efficacy, adverse reactions, the actual conditions of use of the medicine and the characteristics of the patients benefiting from this exceptional access.
These numerous criteria show that goal of simplification has not really been achieved. The reform only simplified the classification of derogatory authorisations to market a medicine.
Medicinal Cannabis and CBD
In recent years, global interest in cannabis products has increased very sharply, with projections stating that it will be worth over USD75 billion by 2027. Currently, French regulatory framework prohibits the marketing of products derived from the whole hemp plant, with the use of hemp flowers and leaves forbidden in France. Only the use of the plant’s fibre and seeds is authorised in France, so importation is allowed for products made from fibre and seeds but authorised products should not contain more than 0.2% THC (tetrahydrocannabinol, the main psychoactive ingredient in cannabis that gets recreational users “high”). However, synthetically produced CBD is generally permitted. CBD (cannabidiol) is an active but non-psychoactive ingredient in cannabis.
Regarding medicinal cannabis, therapeutic use of cannabis is authorised for certain therapeutic indications or clinical situations such as patients suffering from serious illnesses. Further developments are expected in this area as in October 2020, the Ministry of Health announced that it had authorised the first experimentation of cannabis for therapeutic use in France, in a very controlled and limited framework. According to the announcement, the experiment will last two years, beginning before March 2021 and will involve approximately 3,000 patients.
The 29 October 2020 order laid down the technical terms and conditions for the national electronic register for the experimentation of the medical use of cannabis. This order stated that a national register will be set up by the French National Agency for Medicines and Health Products Safety (ANSM). Its purpose is to ensure the proper monitoring of patients during the pilot program and the compensation of volunteer pharmacists who take part in the implementation of the program.
Patients participating in the program will be listed in the register and will obtain certificates allowing them to obtain cannabis-based medicines. Similarly, each pharmacist or physician taking part in the program will have to register in order to be able to prescribe/dispense cannabis-based medicines, and ensure the traceability of medicines used during the programme.
Progress of the medicinal cannabis agenda
While this is still in the very initial stages, it does show that the use of medicinal cannabis is firmly on the French agenda and strides are being taken to explore the possibilities in this area.
However, this medical cannabis experiment does not meet with the unanimous approval of health professionals. The French National Pharmaceutical Academy (Académie Nationale de Pharmacie) expressed, on 24 November 2020, its "greatest reservations" concerning the forthcoming medical cannabis experiment, voicing concern about its lack of scientific rigour.
When it comes to vaping products containing CBD, the recent final decision by the Court of Justice of the European Union (CJEU), Case C663/18 – KanaVape has broken new ground.
The case concerned an electronic cigarette with CBD oil but also looked at the general ban on natural CBD in France. The 19 November 2020 decision was clear that a general ban, based on CBD being a narcotic/psychotropic was not sustainable and was contrary to EU law on free trade and the European Single Market.
This case was the first time that the highest European Court had been requested to take a position on the legality of the commercialisation of CBD and CBD-based products in Europe, and has potentially extensive implications. French (and other) national authorities have been given the possibility of still imposing a national ban, but only if the real risk alleged for public health appears sufficiently established on the basis of the latest scientific data available at the date of the adoption of such a decision.
In this decision, the Court gives its interpretation on the nature of CBD (and how it should be regulated by Member States). The CJEU considers that the COM (Common Organisation of Markets) regulations, applicable to agricultural products, are not applicable to CBD. Furthermore, in the current state of scientific knowledge, it is not established that CBD has psychotropic or otherwise harmful effects on human health. Therefore, CBD cannot be considered a medicine within the meaning of the Single Convention on Narcotic Drugs, and the principle of free movement of goods within the European Union is applicable to CBD.
The case is referred back to French courts, who will have to decide whether the French general ban on the marketing of natural CBD is appropriate and does not go beyond what is necessary to attain the objective of public health protection alleged by the French government (in which case it would justify the restriction on the free movement of goods within the EU).
Observations for the national court against a general ban
However, the Court does give two observations for the national court to take into account. It does not appear as through the risk to human health allegedly presented by CBD is sufficiently established, especially as the marketing of synthetic CBD (which has the same properties and effects as natural CBD) is generally allowed under this framework. Therefore, a general ban on the marketing of natural CBD may not be appropriate to attain the public health objective alleged by the French government as a justification for such ban.
Furthermore, a general ban on marketing is the most restrictive measure on the free movement of goods, and although the French government is not obligated to prove that CBD is as dangerous as other narcotics, the French court will have to consider currently available scientific data to determine whether such a restrictive measure is indeed appropriate does not go beyond what is necessary to protect public health.
Based on these elements, it does appear as though the CJEU considers that the French ban is indeed contrary to EU law – although it will be left for French courts to definitively rule on the matter.
New Anti-gift Provisions in the Health Sector
The French healthcare anti-gift regime was amended on 19 January 2017 and creates an obligation to use a remote electronic procedure. The anti-gift regime prohibits any company manufacturing or marketing healthcare products reimbursed by social security from offering or providing direct or indirect benefits to healthcare professionals who prescribe and dispense these products.
Precisions were necessary for a clear application of the system. From June to September 2020 five implementing texts (a decree on June 15th, two ministerial orders on August 7th and two ministerial orders on 24 September) were published to provide technical details on the reinforcement of the "anti-gift" regime. Pursuant to these new texts, the complete anti-gift system came into force on 1 October 2020, and introduced major constraints.
The anti-gift regime could be seen as a French-style Sunshine Act. Its purpose is to guarantee healthcare professionals' independence. The new provisions expand the scope and set very strictly the conditions under which healthcare companies (HCC) can provide advantages to healthcare professionals (HCP), in cash or in kind.
Most of the health sector players are now subject to this regime. The definition of HCP has been progressively extended and now includes a wide range of doctors whose profession is regulated by the CSP and chiropractors, osteopaths and psychotherapists. In addition, medical students, medical associations and civil servants involved in the public health policy are subject to these provisions.
Benefits excluded from the scope of prohibition
Although prohibition is the principle, Article L1453-6 of the French Public Health Code (CSP) excludes certain benefits from the scope of prohibition, stating, for example, that remunerations paid for an employment contract are not included into the meaning of benefits used in the Article L1453-3 of the CSP. Moreover, benefits in kind or cash "of negligible value" are not prohibited.
A recent important change is that the ministerial order of August 7th, sets the amounts below which benefits in kind or cash are considered of "negligible value". Hereafter a few examples of the thresholds chosen by the legislators:
Pursuant to Article L1453-4 of the CSP, three categories of advantages can be authorised: benefits related to research, consulting and services agreements, benefits related to donations and gift and benefits related to hospitality. However, these exemptions do not apply to the civil servants involved in the public health policy.
Therefore, the granting of benefits is possible but is conditional on the signing of an agreement between the HCC and the HCP, which, depending on the amount of the advantage, must be the subject of a declaration or an authorisation procedure with the Professional Order concerned or the Regional Health Authority (ARS) when there is no competent Professional Order. The details and course of these two procedures are provided for by the decree of 15 June. By regulating relations between HCC and HCP with a desire for transparency, the legislators have also created a particularly complicated and cumbersome system with two different procedures, which may become counterproductive.
If the convention needs to follow the declaration procedure, the submission must be filed eight days before the grant of the benefit and the Professional Order or the ARS can make recommendations. However, if the convention needs an authorisation, the competent authority shall take a decision within the two months from the date of receipt of the complete file. The decree also explains the strict procedure in case of a file refusal.
As stated above, the submission procedure depends on the amount of the advantage set by the ministerial order of 7 August. This text distinguishes whether the benefit is granted to a healthcare professional (such as doctor or medical auxiliaries), a medical student or a medical association. These differences according to the status of the beneficiaries bring in more constraints than before.
The anti-gift regime, which is already very strict in its application, is even stricter in its sanctions. HCC who are forbidden to offer advantages are liable to two years' imprisonment and a fine of EUR150,000. HCO who are forbidden to receive benefits, expose themselves to one year of imprisonment and a fine of EUR75,000. Additional penalties are also provided for natural persons. However, based on our experience sanctions are quite rare, because pharmaceutical companies as an example are very rigorous in order to comply with these provisions.
Developments in Health Data Management
The National Health Data System (SNDS) was created in 2016 and is one of the largest health databases in the world, it gathers and makes available the main national health databases. Access to the SNDS is allowed only to public or private structures conducting research in the public interest.
It is extremely useful for laboratories to have access to this data, for example to know the state of the market and the needs of patients before developing a medicine. However, access to this database is very long and complicated. The procedure is divided into many steps in order to obtain, at the end, an access authorisation from the French data protection Authority, la Commission National de l'Informatique et des Libertés (CNIL), the French data protection authority. Furthermore, companies wishing to access the SNDS cannot obtain the health data directly, the process is cumbersome since companies must go through an intermediary who will in practice provide them with an analytical report on the information obtained on the basis of the SNDS data to which he has had access.
Draft decree to enlarge the National Health Data System
A draft decree, plans to open the SNDS to new health databases. Currently, there are three databases in the SNDS: the health insurance database, the hospital database and a statistical database on causes of death. Opening up to new databases, that are currently freely accessible, would make these data much more difficult and complex for the pharmaceutical industry to access. The decree is therefore eagerly awaited to clarify the SNDS shadow zones and its scope.
In the same vein of increasing complexity of the regulations relating to health data, on 28 July 2020 the CNIL published two guidelines on the retention period of health data. These guidelines list the legal or regulatory retention periods applicable to the health sector, and in the absence of regulations in force, the CNIL's recommendations on these data retention periods. This publication testifies to the complexity of the regulations and the need for tools to make the regulations more readable.