Early access and compassionate use: making a drug available when not authorized in France

When a patient has a serious, rare, or debilitating disease, or has no other treatment options, waiting for marketing authorization (MA) of an innovative drug can be particularly long. In France, Early and Compassionate Access programs provide a solution to therapeutic deadlocks by offering a secure framework for the prescription and reimbursement of drugs that are not authorized for the indication in question or before they are included on the standard reimbursement lists.

 

 

Understanding exceptional access mechanisms

The 2021 Social Security Financing Act has radically reformed the former ATU (temporary authorization for use), PEC-T (temporary coverage), and RTU (temporary recommendation for use) mechanisms.

Two new, more structured procedures have been introduced:

1. Early Access (EA) for innovative drugs, either before obtaining marketing authorization or after marketing authorization but before reimbursement.
2. Compassionate Access (CA), which combines named authorizations (formerly named ATUs) and compassionate prescription frameworks (formerly RTUs).

The roles of the two main authorities have also been clarified: the HAS (Haute Autorité de Santé) rules on applications for Early Access authorization (AAP), after consulting the ANSM where necessary. The ANSM is the competent authority for Compassionate Access Authorizations (AAC).

 

 

Early Access, a framework subject to strict conditions

Early Access authorization is based on a highly structured regulatory framework, defined by Article L.5121-12 of the Public Health Code.

This mechanism allows a drug to be made available, with immediate coverage by social security, for one or more indications, provided that the following five criteria are met:

1. The drug is presumed to be effective and safe based on the results of available clinical trials when the drug does not have marketing authorization for the indication in question.
2. It is intended for a serious, rare, or debilitating disease.
3. There is no appropriate treatment available.
4. The treatment cannot be delayed.
5. The drug is presumed to be innovative, particularly in relation to a clinically relevant comparator.

It should be noted that an Early Access application may be submitted before or after marketing authorization, depending on the drug’s development strategy. This depends on parameters such as the expected timeline for submitting the application and the identified medical need.

To read: Challenges and solutions in the development of rare drugs

 

A regulated procedure, overseen by the HAS

The Early Access application is initiated by the laboratory, which must be able to:

• Provide evidence of data collection on efficacy, safety, and therapeutic use;
• Provide a therapeutic use protocol;
• In the context of Early Access prior to MA, commit to submitting a MA application within a defined timeframe;
• In the context of post-MA Early Access, commit to submitting an application for reimbursement on one of the lists of reimbursable specialties, for the indication in question, within one month of obtaining MA;
• Finance and monitor patients and submit a periodic summary report to the authorities.

This system is both medically safe and financially supported, thanks to automatic coverage by the French national health insurance system, with no out-of-pocket costs for patients.

 

 

Compassionate Access: a temporary solution for exceptional situations

Compassionate Access applies to drugs that do not have marketing authorization for the indication in question, when the patient’s condition requires it.

There are two types of Compassionate Access:

• Compassionate use authorization is nominative, prescribed by a doctor for a specific patient, and relates to a drug that is not the subject of research involving human subjects for commercial purposes and is not, in principle, intended to obtain marketing authorization.
• The compassionate prescription framework, established by the ANSM for a group of patients suffering from the same condition, relating to a drug that has marketing authorization for other indications, in order to ensure that prescriptions that do not comply with this authorization are safe.

 

Eligibility criteria for Compassionate Access authorization

The ANSM grants Compassionate Access authorization in the following cases:

• The patient has a serious, rare, or debilitating condition.
• There is no alternative treatment available for this condition.
• Based on the available clinical data, the drug is presumed to be effective and safe.
• The prescription complies with a safety framework validated by the authorities.

Unlike Early Access, Compassionate is not automatically covered by social security. Coverage remains subject to the assessment of the French national health insurance system and depends on the urgency of access to treatment, the medical context, and the recognized public health interest.

Read also: What are the EMA’s requirements for clinical trials?

 

 

The central role of the “exploitant”*

*The “exploitant” is a pharmaceutical company regularly inspected by ANSM, whose activities are governed by an Opening Authorisation delivered by the ANSM. This status is specific to France.

In Early Access, it is mandatory to declare an “exploitant”. The latter ensures:

• The availability of the drug under the conditions set by the HAS.
• The structured collection of usage and tolerance data.
• Pharmacovigilance monitoring and transmission of information to ANSM.
• Submission of a marketing authorization application within the legal deadlines.

The “exploitant” is also responsible for compliance with the established protocol and may be required to collaborate with ANSM in the context of extended Compassionate Access authorization (compassionate use frameworks).

 

 

A strategic issue for manufacturers

These various mechanisms are major assets for laboratories, enabling them to:

• Use their product in real-world conditions while finalizing regulatory development.
• Accelerate market access through the early collection of clinical and economic data.
• Strengthen their scientific and ethical credibility with prescribers and patients.

Early Access can also facilitate subsequent reimbursement procedures through the accumulation of evidence of therapeutic benefit.

Read also: Strategies to reduce drug development time

 

 

Conclusion

In France, Early Access and Compassionate Use play an essential role in public health. These mechanisms ensure therapeutic continuity for patients who have reached a dead end, while strictly regulating prescription, data collection, and safety of use. For manufacturers, they represent a strategic step in the marketing authorization process, upstream of the commercialization phases.

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