On 14 December 2020, the French Social Security Financing Act for 20211 (article 78) reformed early market access mechanisms in France and simplified the former systems of derogatory reimbursement for medicines, which included the temporary authorisation for use (ATU) and temporary recommendation for use (RTU) regimes.
Two new regimes have been created: early access authorisation (AAP – exceptional use of certain drugs for specific therapeutic indications, intended to treat serious, rare, or disabling diseases) and compassionate use (exceptional use of certain medicines in specific therapeutic indications).
On 1 July 2021, two Decrees dated 30 June 20212 have come into force, allowing the immediate application of the new early access regime in France. Four ministerial decisions dated 1 July 2021 have completed those decrees and have been published on 2 July 2021. The French High Health Authority (HAS) also published online its doctrine on the interpretation of these new mechanisms and a related online submission portal has been made available as well.
1. Early access authorisation (AAP)
Newly created article L.5121-12 of the French public health code (FPHC) provides that early access (former ATUc) can be granted to certain medicines, under specific therapeutic indications, which aim at treating severe, rare or disabling diseases, provided that (i) there is no current appropriate treatment, (ii) the implementation of the treatment cannot be postponed, (iii) the safety and efficacy of the treatment are strongly presumed based on clinical trials and (iv) the medicine is presumed to be innovative, notably in consideration of a potential clinically relevant comparator.
The early access regime applies to:
i. medicines which have not been granted a marketing authorisation (MA) in the concerned indication and for which the Company (ie the company which holds the exploitation rights for the product) already submitted, or undertakes to submit within a specific delay fixed by the HAS, a request for MA (pre-MA AAP);
ii. and medicines which have been granted a MA in the concerned indication without being registered on the reimbursement lists and for which the Company already submitted or undertakes to submit within one month from the day the MA has been granted, a request for registration on such lists (post-MA AAP).
Alongside the applicable regulation, the authorities have put in place a ‘pre-deposit’ meeting for pre-MA AAPs, aiming at assisting the industrials and discussing the conditions for eligibility of the AAP request for a specific product. This pre-deposit meeting is not mandatory but highly recommended. According to the HAS recommendations, it should occur within a two or three month delay prior to the anticipated date of the submission of the AAP request.
The request for AAP is submitted by the owner of the exploitation rights for the product or their representative, on a dematerialised platform (SESAME) hosted by the HAS. Should the request involve a medicine without any MA in the concerned indication, the French National agency of medicines safety (ANSM) will be requested to deliver an opinion on the benefit-risk balance of the medicine.
Once the request has been submitted, the HAS will have ten days to confirm whether the file can be considered complete or not. Should the HAS need additional information, the Company will then have to provide the requested documents within 20 days from the request. Should the Company not comply with this delay, the AAP request will be deemed waived3.
Once the file is complete, HAS’ decision on the AAP will occur within three months4 from the receipt of the complete file. Should no decision occur after this three-month period, the request is deemed granted, unless the ANSM issued an unfavourable opinion5.
The Company which holds the exploitation rights for the product will have to provide the product within two months from the early access authorisation.
The HAS and ANSM are entitled, at any time, to request the Company to transmit additional data to appreciate whether the conditions for early access are still met6. On its own initiative, or under the French ministries of Health or Social Security request, the HAS may amend an AAP or the therapeutic use or data collection protocol, or even suspend or withdraw an AAP, should one of the conditions for early access be no longer fulfilled.
2. Compassionate use
Under new article L.5121-12-1 of the FPHC, compassionate use applies to products that are not necessarily innovative, initially not intended to obtain a MA, but that satisfactorily address a specific therapeutic need, provided that (i) the product is not under any research involving human beings for business purposes, (ii) there is no current appropriate treatment in the concerned indication and (iii) the efficacy and safety of the product are presumed in consideration of the available clinical data.
Compassionate use applies to two different situations:
i. Compassionate use authorisation (AAC) for a product which has not been granted a MA (former ATUn). In such a case, the request must be filled by a healthcare professional for a specific patient, and the authorisation can be granted by the ANSM. The authorisation, if granted, will be valid for one year and can be renewed, and the product will be provided to the Patient(s) via the internal pharmacy of a healthcare facility.
ii. Compassionate prescription frame (CPC) for a product which has been granted a MA but not in the required indication (former RTU). In such a case, the request can be submitted by the French ministry of Health and will have to be approved by the ANSM, or the decision can proactively occur on the ANSM’s initiative, notably to secure off-label use and prescription. The decision, if granted, will be valid for three years and can be renewed.
In both cases, ANSM will request from the Company which holds the exploitation rights for the product to establish a therapeutic utilisation protocol and regularly monitor patients’ data.
1 Law No 2020-1576 of 14 December 2020, of Social Security Financing for 2021.
2 Decree No 2021-869 of 30 June 2021, relating to early access authorisations and compassionate use for certain medicines, and Decree No 2021-870, 30 June 2021, fixing delays mentioned in articles L.5121-12 and L.5121-12-1 of the French public health code and article L.162-16-5-4 of the French social security code.
3 Article R.5121-69 of the FPHC.
4 By exception, the delay can be extended to four months – article R.5121-69 of the FPHC.
5 In such a situation, the request will be deemed rejected – article R.5121-59 of the FPHC.
6 Article R.5121-71 of the FPHC.