Bridging Chemistry and Biology: EU Court Clarifies Generic Pathways for Synthetic Peptides Referencing Originator Biological Medicines?

On 23 April 2026, the Court of Justice of the European Union (CJEU), in Case C-118/24 EG Labo Laboratoires Eurogenerics SAS, Theramex France SAS v ANSM et al., provided important clarification on the regulatory treatment of chemically synthesised peptides that reference originator biological medicines under Directive 2001/83/EC. The Court addressed two key issues: (a) the competence of national courts to judicially review the legality of national marketing authorisations granted through the Decentralised procedure; and (b) whether a chemically synthesised peptide can be properly considered a generic medicinal product of a reference biological product developed using recombinant DNA technology, which, under EU law, is classified as a biological process.

Summary of Ruling:

The CJEU has confirmed that, where generic criteria are met—same qualitative and quantitative composition in active substances, same pharmaceutical form, and demonstrated bioequivalence— a chemically synthesised peptide can be authorised as a generic of a biological reference product made by recombinant DNA technology, and that Member States may allow judicial review of such authorisations to ensure compliance with Directive 2001/83/EC and the protection of public health.

Key Issues and Legal Principles:

The case concerned Teriparatide Biogaran, a peptide produced by chemical synthesis, for which authorisation was sought as a generic of the biological reference product developed via recombinant DNA technology. In this case, the originator’s product was approved through the EU Centralised procedure, whereas the follow-on chemically synthesised peptide was approved through the Decentralised procedure and the Reference Member State was Germany, and France was a Concerned Member State. The central question was whether a chemically synthesised peptide could be authorised as a generic of a biological reference product using the abridged procedure for a generic medicinal product instead of a biosimilar product, and whether national courts could review such authorisations.

1. National Courts’ Competence to Review Marketing Authorisations Granted Through Decentralised Procedure

The CJEU confirmed that Directive 2001/83/EC does not govern or restrict the judicial review of national marketing authorisations (MAs) granted at the conclusion of a Decentralised procedure, leaving it to Member States to determine the scope and existence of such review under their own laws. National courts are therefore competent to review whether a medicinal product has been correctly classified as a ‘generic medicinal product’ under Article 10(2)(b) of the Directive and may annul a national MA if that classification is found to be incorrect. However, such annulment only affects the MA in the reviewing Member State and does not impact MAs granted in other Member States or the reference Member State. This judicial oversight supports the Directive’s primary objective of safeguarding public health by ensuring that only products meeting the strict criteria for generics benefit from the abridged approval process, while also recognising the procedural autonomy of Member States within the Decentralised system.

1. Recognition of Chemically Synthesised Peptides as Generics of Reference Biological Medicinal Products

The Court reasoned that Directive 2001/83/EC does not distinguish between chemically synthesised and biological medicinal products when designating a reference product for the purposes of the abridged (generic) procedure under Article 10(1). A biological medicinal product can serve as a reference for a generic application, provided the follow-on product meets the three cumulative criteria: same qualitative and quantitative composition in active substances, same pharmaceutical form, and demonstrated bioequivalence. The Directive’s definition of a generic medicinal product is sufficiently broad and does not require exact molecular identity or identical manufacturing processes—only that there are no significant differences in safety or efficacy.

Consequently, a chemically synthesised peptide may be authorised as a generic of a biological reference product, rather than being subject to the more demanding biosimilar pathway, as long as it fulfils the generic criteria. The assessment of whether these criteria are met is left to the competent health authorities on a case-by-case basis. Only if significant differences in the properties of the active substances are identified would additional data be required. This approach supports regulatory flexibility and avoids unnecessary duplication of preclinical and clinical trials, provided patient safety and efficacy are not compromised.

Alignment with Advocate General¹’s Opinion:

The Court’s decision closely followed the Advocate General’s Opinion that:

• Judicial review by national courts is important for public health and is not limited to the Reference Member State.
• The definition of a generic medicinal product focuses on equivalence in active substance properties, not production method.
• The manufacturing process (chemical vs biological) does not, by itself, preclude use of the abridged procedure if generic criteria are met.

Regulatory and Scientific Context:

Recent advances in peptide synthesis now make it possible to produce small peptides using chemical methods with greater purity and efficiency. This development offers an alternative to recombinant DNA-based biological manufacturing processes. If these peptides are regulated as generic chemical medicines rather than as biosimilars, they may be subject to a lower evidentiary threshold for approval. Typically, approval would require only proof of chemical equivalence and bioequivalence, rather than the more extensive bridging preclinical and clinical data required for demonstrating ‘biosimilarity’ and the absence of clinically meaningful differences.

While this regulatory approach could expedite market entry, it prompts questions as to whether such standards fully address potential safety and/or efficacy differences that could arise from distinct manufacturing processes or the multifunctional nature of therapeutic peptides. Where relevant, consideration should nonetheless be given to whether supplementary evidence is needed to assess if any differences could impact the safety and/or efficacy profile, with the nature and extent of such evidence determined by regulators on a case-by-case basis.

If you have any questions regarding the new regime, please contact any member of Ropes & Gray’s life sciences regulatory and compliance practice or your usual Ropes & Gray advisor.