Biosimilar: similar biological medicinal product under Article 10(4)

Article 10(4) of Directive 2001/83/EC covers biological medicinal products that are similar to a reference biological product but do not meet the generic definition because of differences in raw materials or manufacturing processes. The applicant must provide the results of the appropriate pre-clinical tests and clinical trials, with the type and quantity of data set out in Annex I and in EMA's guidelines. Biosimilars of products developed by biotechnological processes fall within the mandatory scope of the centralised procedure, so most are assessed by the CHMP and authorised by the Commission.

The dossier is built around a comparability exercise: an extensive analytical and functional comparison with the reference product in Module 3, then pharmacokinetic and pharmacodynamic studies and, where still needed, a comparative clinical study in a sensitive population. EMA's overarching guideline on similar biological medicinal products and the product-class guidelines set the expectations, and EMA has moved towards a tailored clinical approach in which comparative efficacy trials are not needed by default when analytical and pharmacokinetic comparability is convincing. Extrapolation to other indications of the reference product is accepted when the mechanism of action and the data justify it.

Biosimilars follow the same exclusivity rules as generics. The reference product must be authorised in the EEA, although comparator batches sourced outside the EEA can be used for some studies if bridged to the EEA reference. The product information largely mirrors the reference product's SmPC. In September 2022 EMA and the Heads of Medicines Agencies stated that biosimilars approved in the EU are interchangeable with their reference product and with each other; whether a pharmacist may substitute remains a national decision. Biosimilar applicants also need a reference product authorised on a full dossier, which rules out comparators that are themselves biosimilars or were authorised on the basis of informed consent.

What goes wrong: a comparability package that shows difference without explaining why it is not clinically relevant; immunogenicity data too thin for the authority; a reference product whose own manufacturing changed during development, so the comparator batches no longer match; and launch planning that ignores national substitution and tendering rules, which decide uptake far more than the authorisation itself.