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 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 availability of biosimilar medicinal products has a dual benefit:
– Public health, by facilitating access to care: increasing the number of biologics available helps to limit supply tensions and prevent stock-outs and/or production accidents. This guarantees patients continued access to their treatments.
– Economic: stimulating competition and lowering the price of biological medicinal products, while guaranteeing the safety and quality of treatments.
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 must be introduced gradually, initially for a limited number of medicines. The right of substitution for biosimilars is decided at national level by each member state. In France, the order of April 12, 2022 sets out the first two groups of biosimilars that can be substituted in pharmacies within a specific framework: filgrastim and pegfilgrastim (immunostimulant-cytokine agents). To date, only these two active substances are eligible for substitution in pharmacies.
What’s the latest on biosimilar substitution in France?
Pharmacists may substitute biologics under certain conditions:
– The similar biological medicinal product dispensed belongs to the same similar biological group as the biological medicinal product prescribed, within the reference list of similar biological groups published by ANSM,
– This similar biological group is included in a list established by a joint order of the ministers responsible for health and social security, issued after consultation with the ANSM (the consolidated order of April 12, 2022),
– The prescriber has not excluded the possibility of this substitution by expressly stating so on the prescription,
– The pharmacist must indicate the name of the medicinal product dispensed on the prescription and inform the prescriber and patient of the substitution.
The gradual introduction of substitution will make it possible to :
– evaluate in real-life situations the prescribing and dispensing circuit following substitution of biologics by the pharmacist;
– guarantee the proper use of biosimilar medicinal products and appropriate clinical monitoring of patients (traceability, reporting and assessment of adverse events) in the same way as the reference medicinal product,
– and to improve information and support for patients and healthcare professionals.
The reference list of similar biological groups is automatically completed when a new biosimilar MA is granted. It is regularly updated on the ANSM website. It should be noted that this list is not intended to present substitutable or interchangeable biological medicinal products. In this respect, ANSM will make available the list of substitutable biological medicinal products on its website.
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 Leslie Gorge.