EMA: Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance
Summary
Provides the core scientific and regulatory guidance for biosimilar development in the EU, complementing the legislative framework for authorizing biosimilars—biological medicines shown to be highly similar to an approved reference product, with no clinically meaningful differences in quality, safety, or efficacy. Approval relies on a totality-of-evidence assessment.
Key Principles & Scope
Provides general principles for biosimilar development and assessment. It must be read with product-class and modality-specific guidelines, notably the two for biotechnology-derived proteins (quality; non-clinical/clinical) and class guidelines (e.g., mAbs, insulin).
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Quality foundation: Extensive head-to-head analytical and functional comparison (structure, PTMs/glycosylation, impurities; biological activity) using state-of-the-art methods.
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Non-clinical: In vitro / in vivo studies targeted to residual uncertainties from quality.
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Clinical: PK/PD comparisons are generally required; additional efficacy and safety studies may be conducted where needed to resolve residual uncertainty. Immunogenicity assessment is always essential.
- Extrapolation to other approved indications of the reference product is possible if biosimilarity is convincingly demonstrated and scientifically justified, considering mechanism of action, immunogenicity, and safety/efficacy across indications.
- Notable Rev.1 features. Clarifies reference product use (including when a non-EEA reference can support certain studies) and reinforces reliance on sensitive analytical/clinical models.