Interchangeability and substitution of biosimilars

Interchangeability refers to the possibility of replacing a reference biological medicinal product with a biosimilar, or one biosimilar with another, with the expectation of the same clinical effect. It differs from substitution, which is replacement by the pharmacist without the prescriber’s involvement, and from switching, which is decided by the doctor. The authorisation of a biosimilar is governed by EU law, whereas the rules on prescription and substitution are a matter for the Member States.

The position of the European authorities

In 2022, the European Medicines Agency and the Heads of Medicines Agencies network stated that biosimilars approved in the Union are interchangeable, from a scientific standpoint, with their reference product and with one another. This position rests on the demonstration of similarity required at the authorisation stage and on the experience gained since the first biosimilars were placed on the market. It does not create any particular legal status, unlike US law, which provides for a specific interchangeability designation, and it does not settle the question of substitution in retail pharmacies.

Substitution of biosimilars in France

The French Public Health Code defines the similar biological medicinal product in Article L. 5121-1 and provides for a reference list of similar biological groups drawn up by the national agency. Substitution by the pharmacist, long excluded in practice, is now permitted for similar biological groups included on a list set by ministerial order after consulting the agency. This list, initially limited to a few molecules, has been gradually extended. The pharmacist must comply with any exclusion by the prescriber and inform both the patient and the prescriber, so as to ensure traceability of the product dispensed.

Issues for litigation

Opening up substitution changes the economics of the market for biological medicinal products. The entry of a substitutable biosimilar has effects close to those of a generic, which increases the value of provisional measures for the holder of patents still in force, particularly process or formulation patents, and the cost of a launch at risk for the manufacturer. Communications about switching are also sensitive, since unsubstantiated doubts cast on interchangeability may amount to disparagement.

Key points

Interchangeability, substitution and switching are distinct concepts that should not be confused in contracts, communications and pleadings. For each molecule, it should be checked whether the similar biological group appears on the list of authorised substitutions, as the pace of biosimilar uptake depends on it. For the patent holder, inclusion on that list should be anticipated as a signal of market entry.

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This glossary entry is general in scope and does not constitute legal advice.

Dhenne Avocats acts in pharmaceutical patent disputes and on the medicines regulatory questions that accompany them, from the marketing authorisation to the supplementary protection certificate.

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