Biological medicinal products are used in the treatment of numerous pathologies, such as diabetes, cancer and autoimmune diseases. Any biological medicinal product whose patent has fallen into the public domain can be copied: this is known as a “biosimilar”. A biosimilar is a medicinal product which, like any biological medicinal product, is produced from or derived from a cell or living organism, and whose efficacy and side effects are equivalent to those of its reference biological medicinal product. By February 2022, 67 biosimilar medicinal products had been authorized in the European Union.
The marketing authorization of a biosimilar medicinal product
The marketing authorization of a biosimilar medicinal product must meet strict regulatory requirements to demonstrate that its pharmaceutical quality, efficacy and safety are clinically equivalent to those of the reference biologic medicinal product. The ANSM maintains the reference list of similar biological groups registered in France. It is presented by common name of the active substance. It includes all the medicines registered in France with the legal basis of a “similar biological” marketing authorization file within the meaning of b of 15° of article L5121-1.
Since biosimilar medicinal products are derived from living organisms, they cannot be strictly identical to reference products. Consequently, the substitution principle, which applies to chemical medicinal products and their generics, cannot be applied automatically.
However, in the light of advances in knowledge, interchangeability and substitution during initial prescription or treatment can now be envisaged under strict conditions and within the framework of the indications, dosage regimens and routes of administration common to the reference product.
In order to guarantee proper use and safety during substitution, this substitution is introduced gradually in France. The right of substitution for biosimilars is decided at national level by each member state. In France, the order of April 12, 2022 first sets out the first two groups of biosimilars that can be substituted in pharmacies within a specific framework: filgrastim and pegfilgrastim (immunostimulant-cytokine agents).
More recently
More recently, the decree of October 31 and the decree of February 20, 2025 have expanded the list of similar biological groups that can be substituted by the community pharmacist and specified the conditions of substitution and information for the prescriber and the patient:
- Filgrastim (2022)
- Pegfilgrastim (2022)
- Ranibizumab (2024)
- Adalimumab NEW
- Enoxaparine NEW
- Epoétine NEW
- Etanercept NEW
- Follitropine alfa NEW
- Teriparatide NEW
What’s the latest on biosimilar substitution in France?
> Prescription
The prescriber must inform the patient of the possibility of substitution by the pharmacist of the prescribed biological medicine. He can also indicate on the prescription which type of medical administration device is to be preferred for a given patient (adalimumab, etanercep, teriparatide).
> Dispensing
When dispensing, the pharmacist must inform the patient of the actual substitution and the associated useful information, in particular by recalling the rules for storing the specialty. He – mentions on the prescription the name of the medicine actually dispensed and informs the prescriber about the medicine dispensed. He records the name of the medicine dispensed by substitution and its batch number by all appropriate means in order to implement the traceability required for all biological medicines. Finally, he ensures the continuity of dispensing of the same medicine during subsequent dispensations.
For the following specialties, the pharmacist must also:
– substitute specialties with the same active substance dosage: Etanercept, adalimumab, enoxaparin, epoetin
– not substitute with a biosimilar that would have a higher injection volume than the prescribed medication: Adalimumab
For follitropin αlfa, the pharmacist:
– dispense a specialty that allows the administration of the exact dosage prescribed in the event of substitution of multi-dose pens by single-dose pens and vice versa,
– ensure that the patient has the appropriate pen in the event of dispensing of cartridges and support the patient in learning the new device,
– in the context of ovarian stimulation, ensures understanding of the protocol implemented including the prescribed dosage regimen and the administration methods of the specialty dispensed. ;
– supports the patient in learning the new device,
> The patient has the possibility of returning to the specialty initially dispensed if necessary, “based on their feedback” (adalimumab, enoxaparin, epoetin, etanercep, follitropin alfa, teriparatide).
> Finally, the laboratory provides dummy administration devices to healthcare professionals and patients (adalimumab, enoxaparin, epoetin, etanercep, follitropin alfa, teriparatide).
Atessia is monitoring this evolving subject on a daily basis.
Glossary :
– Biological medicinal product (article L.5121-1, paragraph 14 of the French Public Health Code): “any medicinal product whose active substance is produced from or extracted from a biological source and whose characterization and quality determination require a combination of physical, chemical and biological tests as well as knowledge of its manufacturing process and control”.
– Biosimilar” medicinal product (article L.5121-1, paragraph 15 of the French Public Health Code) “any biological medicinal product with the same qualitative and quantitative composition in active substance and the same pharmaceutical form as a reference biological medicinal product, but which does not meet the conditions laid down in 5° of this article to be considered as a generic, due to differences linked in particular to the variability of the raw material or the manufacturing processes, and requiring the production of additional preclinical and clinical data under conditions determined by regulation”.
– Reference medicinal product: biological medicinal product approved in the EU that a company developing a biosimilar medicinal product chooses as a reference point for direct comparison of quality, safety and efficacy.
– Interchangeability: refers to the possibility of replacing one medicinal product with another that is intended to have the same clinical effect. Interchangeability can be achieved in two ways:
– Permutation: when a prescriber substitutes one medicinal product for another with the same therapeutic intent.
– Substitution: the practice of dispensing a medicinal product in place of another equivalent and interchangeable medicinal product, without reference to the prescriber.
This article was written by Estelle ICARD