The French legal and regulatory framework applicable to medicines and medical devices has been subject to a variety of changes in 2021, with a view to allowing increased access to innovative treatments for French patients and remedying weaknesses in the existing framework, as reaffirmed during the 2021 Strategic Council for Heathcare Industries (Conseil Stratégique des Indutries de Santé or CSIS).
These changes include an overhaul of the early access schemes, the implementation of a new framework agreement applicable to the pricing and financial regulation of healthcare products, and the introduction of a variety of measures through the Social Security Financing Law for 2022.
Other notable developments concerning the substitution of hybrid medicines and the framework applicable to CBD and cannabis-based products are also presented herein.
Overhaul of the French Early Access and Compassionate Use Schemes
The willingness to enhance innovation and accelerate access to innovative medicinal products in France has lead to an overhaul of the derogatory systems of access and reimbursement for medicines not holding a marketing authorisation (MA) – or not in the concerned indication – which was implemented in France in July 2021.
This huge reform was based on Article 78 of the Social Security Financing Law for 2021, which introduced, instead of the temporary authorisations for use (autorisation temporaire d’utilisation or ATU) and temporary recommendations for use (recommendation temporaire d’utilisation or RTU) systems, two new access and reimbursement systems: the “early access” and the “compassionate access” systems. On 30 June 2021, two implementation decrees and four orders were adopted in order for the new systems to come into force on 1 July 2021. A decree of 11 February 2022 inserted additional provisions regarding the compassionate prescription framework.
The main aims of this overhaul were:
- acceleration; and
All these objectives converge towards the same idea of quicker access to innovative medicines for patients, in an easier and safer framework.
Simplifying the framework
In order to simplify the previous legal framework, only two systems of early access and compassionate access have been created instead of the six regimes that previously existed under the ATU and RTU framework.
The conditions of application for each system have been defined by the Social Security Financing Law for 2021. Notably, to obtain the early access authorisation, the new framework adds a new requirement compared to the previous ATU system, namely that the medicine must be presumed to be innovative. This confirms that access to innovation is at the heart of the reform.
However, the announced goal of simplification was not completely achieved since sub-categories in each system, with different criteria for each, were created, which makes the framework more complex. In practice:
- The new early access system is divided in two sub-categories since it may either be implemented prior to the obtaining of the MA, or after, in the waiting of the obtaining of the price and reimbursement. The authorisations are granted by the French High Authority for Health (Haute Autorité de Santé or HAS), after the opinion of the French National Agency for Medicine and healthcare product Safety, (Agence Nationale de Sécurité du Médicament et des produits de santé or ANSM) in the first case.
- The new compassionate access system comprises the compassionate access authorisation, which may be “pre-early” or not, and the compassionate prescription framework. The first system is implemented at the request of prescribing physicians and the second one by the ANSM.
Even if not completely achieved, the goal of simplification of the systems may lead to a more recurrent use of them, and therefore, to easier access to innovative treatments for patients.
Speeding up market access
In order to allow for quicker market access of innovative medicines that comply with the requirements of each system, timelines to obtain the above-mentioned authorisations, and to make the medicines available, have been clearly defined. For instance, the following timelines have been set by the decrees:
- the HAS now has three months (or four in case of a very high number of requests) to grant the early access authorisations to applicants – in the absence of answer, when the ANSM provided a favorable opinion, the HAS silence will constitute agreement;
- the pharmaceutical company that obtains an early access authorisation for a medicine without a MA must have submitted a MA request or undertake to submit one within a maximum of two years;
- early access authorisations are granted for a maximum of one year, which is renewable, and compassionate access authorisations are granted for the duration of treatment of the patient concerned, up to a maximum of one year, which may be renewed; and
- in order to ensure quicker access to innovative treatments, the pharmaceutical companies must make the medicine available within two month of the early access authorisation.
Quicker access to the derogative systems may also be enhanced for the compassionate prescription framework since modalities of electronic reporting to the ANSM of off-label prescribing practices, which can only be made by certain actors, are provided.
In addition, access to innovative medicines will probably be enhanced through the coverage conditions implemented since an immediate and automatic coverage of the patient is provided for.
Protocol and data collection
Under the new framework, the pharmaceutical company must comply with a protocol for therapeutic use and real-life data collection defined by the HAS and attached to the authorisation decision. It must in that regard, commit to finance the collection of data according to a set of specifications defined jointly by the HAS and the ANSM for the early access authorisation and by the ANSM alone for the compassionate access. It must therefore set up agreements signed between them and the health care institutions to facilitate the collection of data by prescribers. The aim is to ensure more quickly that the medicine is safe and target any potential side effects.
Therefore, this new legal framework should allow for a quicker and safer access to innovative medicines for patients who do not have the time to wait for the usual MA timeline, or access to medicines where there is an uncovered medical need in the indication.
As an example, in the context of the COVID-19 pandemic, where quick access to innovative medicines is crucial, four treatments have been authorised under the “early access” system for the management of people at high risk of severe COVID-19 disease. The safety and efficacy data for these medicines are being closely monitored, through the data shared by the pharmaceutical companies.
Signature of a New Framework Agreement Between LEEM and CEPS
In France, the national trade association for the pharmaceutical industry (Les entreprises du Médicaments or LEEM) and the French Economic Committee for Healthcare Products (Comité économique des produits de santé or CEPS) enter into a framework agreement every few years, which sets out the conventional rules applicable to the pricing of medicines and medical devices.
The existing agreement had been in place since 2015 and was supposed to be reviewed every three years, and. The industry had been calling for a substantial update of the agreement, to better reflect the trends of the sector.
The CEPS and the LEEM finally came to a consensus in 2021, and entered into a new three-year framework agreement on 5 March 2021. The new agreement integrates the ideas evoked during the 2018 CSIS, and is structured based on the following objectives:
accelerate procedural negotiation timelines;
promote patient access to innovation;
stimulate investment and exports in the sector;
promote the adequate supply of medicines which respond to a public health need; and
This new agreement, amongst other things, integrates new mechanisms to favour innovation and access to treatment: for instance, it now guarantees the stability of net prices during the first five years of marketing for the most innovative medicinal products.
It also introduces new schemes to promote local manufacturing and attract foreign investment, following increased concerns over security of supply and the European dependency on third-party countries for the production of medicines, which can lead to shortages. Local manufacturing efforts can now be rewarded by price stability for a fixed period of time, or by credits on the discounts owed every year by pharmaceutical companies to the CEPS.
The new agreement should remain applicable until 5 March 2024 at least, although it can be subject to further amendments during that period.
Novelties Brought by the French Social Security Financing Law for 2022
Another wave of measures to promote patients’ access to innovation was introduced into French law through the passing of the French Social Security Financing Bill for 2022. The law, enacted at the very end of 2021, contains a variety of measures concerning healthcare products, the majority of which aim to facilitate access to treatment in a timely manner – which implies facilitating access to market for innovative products, as well as guaranteeing a good security of supply for French patients. The most emblematic of these measures are presented below.
It should be noted that most of these new provisions will only become applicable after publication of relevant decrees and orders, which will set out the modalities of their implementation.
Reintroduction of biosimilar substitution intro French law (Article 64 of the French Social Security Financing Law)
After a first unsuccessful attempt at introducing the possibility to substitute biological medicines with biosimilars in 2014 (withdrawn in 2020), the French Social Security Financing law for 2022 reintroduces this possibility into French law, with a mind to generate cost savings for French social security, and allow for a diversification of supply.
The new provisions allow pharmacists to deliver a biosimilar to a patient, in substitution to the prescribed biologic medicine. The pharmacist can perform such substitution if the following conditions are met:
- the biosimilar must be in the same biosimilar group as the biologic medicine;
- the biosimilar group must be listed on the substitution list (which can define specific substitution and information conditions);
- the prescribing doctor must not have expressly excluded the substitution in its prescription; and
- the substitution conditions can be complied with (when applicable).
When the pharmacist chooses to perform such a substitution, they must indicate the name of the biosimilar delivered on the doctor’s prescription, and favour large packaging of the biosimilar to the extent possible.
In terms of pricing and reimbursement, as the measure aims to generate savings for the French social security, the new provisions expressly state that the price of the delivered medicine (ie, the biosimilar) must not go higher than that of the priciest medicine of the relevant biosimilar group.
The law also introduces incentive mechanisms targeting both prescribing doctors and pharmacists, in order to ensure a high penetration rate for biosimilar, as soon as possible, in a similar manner to what was done to promote generic substitution a few years ago.
Creation of a pilot programme for early, direct access to medicines in hospitals (Article 62 of the French Social Security Financing law for 2022)
Article 62 of the French Social Security Financing law for 2022 creates a pilot programme to allow even faster access to innovative medicines in hospitals, when they are not yet listed as reimbursed products.
Under the programme, eligible medicines used in hospitals will be reimbursed by the French Social Security for up to year. Medicines will be considered eligible if:
- they have obtained a MA;
- they have been assessed as innovative by the HAS (the necessary levels of actual clinical benefit and clinical added value will be defined in an order yet to be published); and/or
- they have not yet obtained reimbursed status nor benefit from other early access mechanisms.
As regards medicines that are eligible to more than one of these derogative mechanisms, early access mechanisms above-mentioned must prevail over direct access, ie, a company must first request inclusion of eligible medicines to the two other early access mechanisms and have their request be denied before inclusion in the direct access scheme can be considered.
The beneficiary (ie, the pharmaceutical company commercialising the medicine) will be able to set freely the price of the eligible medicine, which will be fully reimbursed by the French Social Security.
In return, the beneficiary will have to comply with a series of obligations, during and after the reimbursement period, which includes having to file for the medicine to be registered on the list of reimbursed products before the end of the one-year early reimbursement period, as well as ensuring security of supply to patients once the one-year reimbursement period expires.
The aim of the programme is not to replace but rather to complement the new early access and compassionate use schemes – in particular, as some medicines are not considered eligible to these, to ensure better and faster access to medical innovation for French patients.
The programme, expected to last four years, will begin on 1 July 2022 at the latest.
Creation of anticipated access to reimbursement scheme for innovative digital solutions (Article 58 of the French Social Security Financing law for 2022)
The French Social Security Financing law for 2022 has also introduced a new mechanism allowing innovative digital medical devices to obtain anticipated access to reimbursement, in line with the overarching objective to ensure better and faster access to medical innovation for French patients
The mechanism targets digital medical devices, which either have a therapeutic purpose, or are used for medical remote monitoring activities (tele-surveillance).
In order to benefit from the mechanism, the device must:
- have obtained a CE marking;
- be compliant with the applicable personal data regulatory framework;
- allow for data exports and use in interoperable format; and
- be presumed innovative.
A digital medical device that will be considered as meeting those criteria will benefit from early reimbursement for one year, subject to the effective use of the device, and the beneficiary’s compliance with their obligations (which are quite similar to the direct access mechanism presented above).
Introduction of new criterion for the pricing of medicines and medical devices (Article 65 of the French Social Security Financing law for 2022)
Under the existing French legal framework applicable to pricing and reimbursement, the price of a medical device or a medicine is be set through a negotiation process between the CEPS and the relevant company, based on a number of criteria which includes (Article L. 162-16-4 of the French social security code):
- the clinical added value of the relevant, as evaluated by the HAS;
- where applicable, the results of a medico-economic assessment;
- the price of products with a similar therapeutic purpose;
- the forecast or actual sales volume; and
- foreseeable and actual conditions of use of the medicine/medical device.
The French Social Security Financing law for 2022 introduces a new criterion to that list: the geographic location of manufacturing activities. Under the amended framework, competent authorities – in particular the CEPS – will be able, but not obligated, to take into account the “security of supply of the French market guaranteed by the location of production sites”.
It ought to be noted that, during parliamentary works, the proponents of the change indicated that such criterion should be interpreted not as aiming to favour local production in France, but rather as promoting the reinforcement and development of a European supply chain for medicines and medical devices alike. This should be confirmed through the publication, in 2022, of a decree detailing the modalities through which the criterion will be applied in pricing negotiations between the CEPS and relevant companies.
Competent authorities should therefore take into account both efforts to produce at French level, but also at European level more generally.
Suspension of the Possibility for New Hybrid Medicines to be Registered on the Generic Repertoire to Allow for their Substitution with Reference Medicines
In France, once a generic or hybrid medicine obtains the necessary MA, it must be included in a repertoire which sets out the conditions for its substitution with the reference medicine. Only then can it be considered substitutable. If there is no such inclusion, the hybrid medicine can only be delivered to patients if the prescribing doctor actually prescribes the hybrid medicine itself, and not its reference medicine (ie, the originator).
Although a repertoire of generic groups exists, the repertoire for hybrids was never created. To remedy its absence, medicines authorised through the hybrid procedure have been included in the repertoire of generics, to make their substitution possible.
However, in a decision dated 7 July 2021 (No 440747), the French Administrative Supreme Court (Conseil d’Etat) has declared this system illegal. It pointed out that in order for a medicine to be registered on the repertoire of generic groups, it must fulfil the definition of a generic product. As such, only generic medicines can be registered on this repertoire, and hybrids cannot be listed on it as they do not fulfil the definition of a generic product.
The creation of a French specific repertoire for hybrids is therefore expected in the coming year, in order for their substitution to be made possible.
Multiple Twists in the Evolution of the Regulation of CBD-based Products and Medical Use of Cannabis
Following the landmark 2020 Kanavape decision (case C 663/18) from the European Court of Justice (ECJ), 2021 marked the beginning of much-awaited changes to the French regulatory framework applicable to CBD and CBD-based products.
On 23 June 2021, the French Supreme Court (Cour de cassation) issued a ruling expressly invalidating the French general ban on natural CBD, in application of the Kanavape ruling (Cour de Cassation, criminal division, 23 June 2021, No 20-84.21).
The French Supreme court directly applied the ECJ’s ruling and stated that CBD which had been legally produced in another member state of the European Union could not be banned from being marketed in France.
Other courts then followed the French Supreme Court’s ruling, thus opening the possibility for CBD businesses to legally commercialise in France products containing natural CBD (whatever the part of the plant) legally produced in the EU, to the extent that they does not contain THC to a level higher than 0.2%.
The applicable framework, however, remained the same – thus creating legal uncertainty for actors in the sector – until the publication of a new order in the French Official Journal of 31 December 2021, replacing that of 22 August 1990, which had been invalidated by the Kanavape decision.
The order sets out the new regulatory framework applicable to CBD, and in essence:
- authorises the cultivation, import, export and industrial and commercial use of all parts of hemp (including flowers and leaves), provided that the THC levels does not exceed 0.30% and the variety in question is listed in the Common Catalogue of Varieties of Agricultural Plant Species or in the Official Catalogue of Plant Species and Varieties grown in France; and
- limits the use that can be made of hemp flowers and leaves: they can only be used for the industrial production of hemp extracts, the sale of raw hemp flowers and leaves to consumers remaining prohibited.
This limitation, introduced for public health and public order reasons, has now been temporarily suspended by the French Administrative Supreme Court on 24 January 2021, in summary proceedings. The court considered that there was a serious doubt on the legality of the decree, concerning the disproportionate character of the ban on the sale of hemp flowers and leaves, which justified its temporary suspension pending a decision on the merits. The framework is therefore expected to evolve again in 2022.
In related news, the French experiment on medical cannabis was officially launched on 26 March 2021 with the inclusion of its first patient, in the presence of the French Minister of Health. The experiment will include 3,000 patients in France, and will last two years. It allows cannabis-based products to be given as oils, or products to be inhaled to patients suffering from specific, serious pathologies such as multiple sclerosis.
The French legal framework applicable to the life sciences sector was substantially amended in 2021 in order to introduce several measures intended to promote patients’ access to treatment and medical innovation. Many of these measures will be subject to further orders and decrees, which will specify the way in which they will be implemented.