On 1 July 2021, the early access and compassionate use reform entered into force. A medical treatment is generally only available to patients after being granted a market authorisation (“MA”). However, certain conditions call for a medicinal product not yet approved. In recent years, different derogatory procedures have been designed and implemented in France to give patients who are suffering from rare, serious or disabling conditions access to medicinal product where there is no appropriate and available treatment previously authorised.
The French Social Security Financing Law 2021 reviews the entire framework in France and provides a new simplified and harmonised framework for early access and compassionate use of medicinal products.
Overview of the previous frameworks in France
Previously, the exceptional use of medicinal product not covered by MA, or clinical trial, was authorised or established by the French National Agency for Medicines and Health Products Safety (Agence de sécurité sanitaire du médicament et des produits de santé – “ANSM”). The main systems in force were:
- Temporary Authorisations for Use (“ATU”) (Cohort ATU or Nominative ATU);
- Post-ATU scheme;
- ATU for extension of indication;
- Recommendations for Temporary Use (RTU); and
- off-label recommendations.
These systems were the result of ad hoc developments. Over time they were no longer easy to implement, as they all had specific conditions of access, reimbursement and their scope partly overlapped. The new framework aims to overcome these issues and provide better visibility for access to medical treatment.
New early access and compassionate use schemes
The previous framework has been entirely replaced and divided into two new systems. These systems are “early access” (accès précoce) and “compassionate access” (accès compassionnel). Besides, off-label prescription remains possible under strict conditions.
Early access – specifically intended for innovative medicinal products
Early access authorisation (autorisation d’accès précoce – “AAP”) is dedicated to medicines that are either still under development and are intended to be placed on the market or for medicines for which MA has been granted but the registration on the “reimbursable list” is still pending. The request for AAP is made by the company exploiting the product (the “exploitant”). For AAP approval, the exploiting company must commit to requesting MA or registration on the “reimbursable list” promptly.
Several criteria must be met to obtain an early access authorisation:
- There must be no appropriate treatment currently on the French market;
- Prescription of this medicinal product cannot be delayed;
- Efficacy and safety of the medicinal product are strongly presumed based on the results of
- clinical trials; and
- The treatment is presumed to be innovative.
The reform extends the remit of the High Health Authority (Haute Autorité de Santé – “HAS”) which is now the competent authority to grant early access authorisations (subject to the ANSM giving its prior approval of the efficacy and safety of the treatment, in circumstances where MA is yet to be granted).
The HAS issued its “Doctrine of evaluation for early access” that provides guidelines on how evaluations are to be carried out to ensure enhanced visibility, transparency and consistency of decisions. Besides, the exploiting company will have to draw up a Protocol for Therapeutic Use and collection of data (“Protocole d’utilisation thérapeutique et de recueil des données” – “PUT-RD”) subject to HAS approval (and ANSM approval when relevant) which will be binding for the industry.
Compassionate access – intended to satisfy specific therapeutic needs
Compassionate access is designed for exceptional use of a medicinal product that is not necessarily innovative, covered by MA in France or when the pharmaceutical company does not intend to apply for a French MA.
Conditions to be eligible to this system are:
- The medicinal product must not be subject to a clinical trial;
- There must be no appropriate treatment for this specific indication; and
- Efficacity and safety are presumed based on available data.use
The ANSM remains the competent authority regarding compassionate access. This framework includes two different mechanisms: the compassionate access authorisation and the compassionate prescription framework.
Compassionate access authorisation (authorisation de l’accès compassionnel – « AAC »)
Compassionate access permits a patient suffering from a serious, rare or disabling condition, to access a medicinal product that is not covered by MA or that has been withdrawn from the market where the therapeutic indication requested differs from the one that was authorised.
“Very early” compassionate access authorisation: By way of derogation, AAC can also apply where the medicinal product is subject to an ongoing clinical trial which the patient could not take part in and their treatment could be differed. In these cases, the exploiting company has to commit to requesting early access authorisation within a period determined by decree.
The AAC is issued by the ANSM, for a named individual, at the request of the physician prescribing the medicinal product. The authorisation must be accompanied by a Protocol for Therapeutic Use and patient monitoring (“Protocole d’utilisation thérapeutique et de suivi des patients” – “PUT”) established by the ANSM.
Compassionate prescription framework (cadre de prescription compassionnelle – « CPC »)
This framework aims to secure off-label prescriptions, where medicinal products are prescribed for indications which do not comply with their MA.
The ANSM may issue a framework that sets out specific conditions for use of the medicinal product. This then applies for a period three years, during which the physician will be able to prescribe the treatment in question in accordance with its compassionate prescription framework.
By way of derogation, the existence, in the indication concerned, of a treatment with a marketing authorisation does not prevent the establishment of a CPC for a medicinal product when it is not a medicinal product with the same active ingredient, the same strength and the same pharmaceutical form as the authorised one. Such a medicinal product may be subject to a compassionate prescription, provided that the prescriber considers that it meets the patient’s needs at least as well as the medicinal product that has been granted marketing authorisation for that indication.
Entry into force of the new derogatory access framework
This new framework is effective as of 1 July 2021.
The new regime is a welcome change and clarifies the derogatory access to medicinal products in France. The law and its implementing decree provide guidance on the formalities surrounding issuing requests, financial regulation, application time limits and time limits to request a MA or registration on the “reimbursable list” after having been granted an AAP.
A report on the early access and compassionate use reform should be published by the Government after three years, reporting the – hopefully positive – impacts of this new harmonised framework, indicating that it has successfully simplified early access to innovative medicines for patients who need them, without bypassing the classical scheme (MA and registration on the “reimbursable lists”), and facilitated compassionate access, while always ensuring social security coverage.