On December 14, 2020, the Social Security financing law for 20211 (article 78) reformed the mechanisms for early market access in France and simplified the old systems of derogatory reimbursement of drugs, which included the temporary authorization of use (ATU) and temporary recommendation for use. (RTU).
Two new regimes have been created: early access authorization (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 drugs in specific therapeutic indications).
On July 1, 2021, two decrees of June 30, 20212 entered into force, allowing the immediate application of the new early access regime in France. Four ministerial decrees dated July 1, 2021 supplemented these decrees and were published on July 2, 2021. The Haute Autorité de Santé (HAS) has also posted its doctrine on the interpretation of these new mechanisms and a portal for Associate online submission was made available. also.
1. Early Access Authorization (AAP)
Article L.5121-12 of the newly created Public Health Code (CSP) provides that early access (ex ATUc) may be granted to certain drugs, in specific therapeutic indications, which aim to treat serious illnesses, rare or disabling, provided that (i) there is currently no suitable treatment, (ii) the initiation of treatment cannot be postponed, (iii) the safety and effectiveness of the treatment is strongly presumed based on clinical trials and (iv) the medicinal product is presumed to be innovative, in particular in consideration of a possible clinically relevant comparator.
The early access regime applies:
I. medicinal products that have not obtained Marketing Authorization in the indication concerned and for which the Company (i.e. the company which holds the rights to use the product) has already filed, or undertakes to file within a determined period set by the HAS, a request for MA (pre-MA AAP);
ii. and medicinal products which have obtained Marketing Authorization in the indication concerned without being registered on the reimbursement lists and for which the Company has already submitted or undertakes to submit within one month of the granting of the authorization. Marketing Authorization, a request for registration on these lists (post-Marketing Authorization PAA).
In addition to the applicable regulations, the authorities have set up a “pre-filing” meeting for pre-MA PDAs, aimed at assisting manufacturers and discussing the eligibility conditions of the PDA request for a specific product. This pre-deposit meeting is not compulsory but highly recommended. According to the recommendations of the HAS, it must take place within two or three months before the scheduled date of filing of the request for PAA.
The AAP request is made by the holder of the product exploitation rights or his agent, on a dematerialized platform (SESAME) hosted by HAS. If the request concerns a medicinal product without Marketing Authorization in the indication concerned, the National Medicines Safety Agency (ANSM) will be asked to issue an opinion on the benefit / risk ratio of the medicinal product.
Once the request is filed, HAS will have ten days to confirm whether the file can be considered complete or not. If HAS needs additional information, the Company must then provide the requested documents within 20 days of the request. If the Company does not meet this deadline, the AAP request will be deemed abandoned3.
Once the file is complete, the HAS decision on the PAA will be made within three months4 from receipt of the complete file. If no decision is made after this three-month period, the request is deemed to be accepted, unless the ANSM5 advises against it.
The Company holding the rights to use the product must provide the product within two months of the early access authorization.
HAS and ANSM may, at any time, ask the Company to transmit additional data to assess whether the conditions for early access are still met6. On its own initiative, or at the request of the Ministries of Health or Social Security, the HAS can modify an AAP or the protocol for therapeutic use or data collection, or even suspend or withdraw an AAP, if one of the conditions for early access is not fulfilled.
2. Compassionate use
Under the terms of the new article L.5121-12-1 of the FPHC, compassionate use applies to products which are not necessarily innovative, initially not intended to obtain an MA, but which satisfactorily meet a specific therapeutic need, provided that (i) the product is not the subject of research involving humans for commercial purposes, (ii) there is currently no appropriate treatment in the indication concerned and (iii) the efficacy and safety of the product are presumed taking into account the available clinical data.
Compassionate use applies to two different situations:
I. Compassionate use authorization (AAC) for a product that has not obtained a Marketing Authorization (former ATUn). In such a case, the request must be completed by a healthcare professional for a specific patient, and the authorization may be granted by the ANSM. The authorization, if granted, will be valid for one year and may be renewed, and the product will be supplied to the Patient (s) via the internal pharmacy of a healthcare establishment.
ii. Compassionate prescription framework (CPC) for a product that has obtained Marketing Authorization but not in the required indication (former RTU). In such a case, the request may be introduced by the Ministry of Health and must be validated by the ANSM, or the decision may be taken proactively at the initiative of the ANSM, in particular to secure uses and prescriptions outside AMM. The decision, if granted, will be valid for three years and may be renewed.
In both cases, the ANSM will ask the Company holding the product exploitation rights to establish a protocol for therapeutic use and to regularly monitor patient data.
1 Law n ° 2020-1576 of December 14, 2020, on the financing of social security for 2021.
2 Decree n ° 2021-869 of June 30, 2021, relating to early access authorizations and compassionate use of certain drugs, and decree n ° 2021-870 of June 30, 2021, setting the deadlines mentioned in articles L.5121 -12 and L.5121-12 -1 of the public health code and article L.162-16-5-4 of the social security code.
3 Article R.5121-69 of the FPHC.
4 As an exception, the period may 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.