Why some peptides are prescription medicines in the EU

A peptide does not become a prescription medicine because it is a peptide. It becomes a medicinal product because it satisfies the legal definition in Article 1(2) of Directive 2001/83/EC — either because it is presented as having properties for treating or preventing disease, or because it may be used to restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action ^[1]. And it becomes prescription-only because, at the moment the marketing authorisation is granted, the competent authority classifies it as subject to medical prescription by applying the criteria in Article 71 ^[1]. The regulated object is never the molecule; it is the product.

That distinction explains something that looks contradictory. The same amino acid sequence can exist at the same time as an authorised medicine with a marketing authorisation, as an active substance being manufactured in a licensed facility, and as laboratory material with no pharmaceutical status in law at all. These are not three grades of the same thing. They are three different legal objects, carrying different documentation duties and supervised by different authorities.

When a substance counts as a medicinal product under EU law

Directive 2001/83/EC gives two alternative definitions, and meeting either one is enough. The first is the definition by presentation: any substance or combination of substances presented as having properties for treating or preventing disease in human beings. The second is the definition by function: any substance that may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis ^[1].

• By presentation: judged from how the product is offered — label, leaflet, product page, spoken claim. A single therapeutic claim is enough to trigger the definition, whatever the composition happens to be ^[1].
• By function: judged from pharmacological properties as scientifically established for that specific product and under its conditions of use ^[1].
• The doubt clause (Article 2(2)): where a product may fall within the definition of a medicinal product and also within the scope of other EU legislation, the pharmaceutical legislation prevails ^[1].

The Court of Justice of the European Union has drawn the boundaries of the function limb. In Case C-140/07 (Hecht-Pharma) it held that the Directive does not apply to a product where it has not been scientifically established that the product is a medicinal product by function, even though that possibility cannot be excluded; and that a product cannot be regarded as a medicinal product by function where, having regard to its composition — including its content of active substances — and under normal conditions of use, it is incapable of appreciably restoring, correcting or modifying physiological functions ^[3]. That case law is precisely why classification is done product by product rather than molecule by molecule.

Marketing authorisation: who issues it and what it certifies

No medicinal product may be placed on the market in a Member State without a marketing authorisation — either a national one issued by that Member State's competent authority, or a Union one granted centrally ^[1]. For certain categories the centralised procedure is compulsory: the Annex to Regulation (EC) No 726/2004 provides that medicines made by biotechnological processes — recombinant DNA technology, controlled expression of genes coding for biologically active proteins, hybridoma and monoclonal antibody methods — are assessed by the European Medicines Agency and authorised by the European Commission ^[2]. Therapeutic peptide-hormone analogues such as semaglutide and tirzepatide sit in that group.

In Greece, national marketing authorisations are granted by the National Organisation for Medicines (EOF), a public-law body established by Law 1316/1983 and supervised by the Minister of Health ^[5]. The Directive was transposed into Greek law by joint ministerial decision D.YG3a/G.P. 32221/2013, which restates the definitions, the authorisation procedure and the classification of a product's supply status ^[4]. EOF is also the national authority that assesses and authorises clinical trials in Greece, within the framework of Regulation (EU) No 536/2014 ^[11].

A marketing authorisation does not certify that a molecule works; approval is a decision taken on one product, not a verdict on a substance. It certifies that one specific dossier — quality, non-clinical and clinical — was assessed for one specific indication, strength, pharmaceutical form, route of administration and manufacturing process, and that the benefit-risk balance was judged positive for a defined population. Changing any of those elements requires a formal variation to the dossier, not a revised label.

Why most therapeutic peptides end up prescription-only

Supply classification is decided at the moment of authorisation. Title VI of the Directive sets out four criteria, and where even one of them applies the product is made subject to medical prescription ^[1]. Therapeutic peptides usually meet more than one, and the last criterion — parenteral administration — is on its own sufficient for the great majority of them, because the reasons a peptide swallowed as a tablet never survives to be absorbed leave the injectable route as the only workable one for the product.

The Directive also allows sub-categories within the prescription class: products on renewable or non-renewable prescription, products on special medical prescription, and products on restricted medical prescription reserved for use in a specialised environment ^[1]. Anything meeting none of the criteria is classified as not subject to medical prescription — in Greek practice, MI.SY.FA. There is no third category. Pharmaceutical law recognises either an authorised medicine with a defined supply status, or a product that falls outside its scope entirely.

The same molecule, two different legal objects

The Directive itself expressly excludes from its scope medicinal products intended for research and development trials, without prejudice to the clinical trials legislation ^[1][11]. That exclusion is the legal basis of the distinction: material intended for laboratory research, neither presented nor intended for administration to people, is not an unlicensed medicine — it is a product outside the pharmaceutical code. The exclusion depends entirely on intended purpose and presentation, however, not on purity or provenance. The moment the communication around the material attributes therapeutic properties to it, the presentation limb is triggered and the whole authorisation obligation comes with it ^[1].

An authorised medicine carries duties that research material does not have and does not pretend to have: manufacture under a licence and good manufacturing practice, batch release by a qualified person, an approved summary of product characteristics and package leaflet, a pharmacovigilance system, traceability through the supply chain, and a recall obligation. For synthetic peptides specifically, the European Medicines Agency has issued a guideline on their development and manufacture (EMA/CHMP/CVMP/QWP/367182/2025), coming into effect on 1 June 2026, covering characterisation, specifications and the control of synthesis-related impurities ^[6].

What a certificate of analysis proves, and what it does not

A certificate of analysis is a quality document, not a status document. USP General Chapter 1503 sets out the quality attributes expected of synthetic peptide drug substances — identification, content and assay, impurities and related compounds, microbiological contamination, bacterial endotoxins — and supplies the vocabulary needed to read an analytical report properly ^[8]. The credibility of the report itself depends on the laboratory that signs it: ELOT EN ISO/IEC 17025 sets the general competence requirements for testing laboratories, and in Greece conformity with it is accredited by the national accreditation body, ESYD ^[10].

• What it can establish: the identity of the substance, chromatographic purity by the stated method, molecular mass, residual solvents and endotoxins — for one named batch and no other ^[8].
• What it cannot establish: that the material has been assessed by a regulator, that a marketing authorisation exists, or that the product holds medicinal status of any class ^[1].
• What to check before treating it as useful: whether it covers the batch actually received, whether it names the testing laboratory and the test date, and whether that laboratory is accredited for the specific method ^[10].

Where the evidence is thin or contested

This is worth stating plainly, because the internet does not. For a large share of the peptides circulating as research material, the available data come from in vitro systems or rodent models, not from controlled clinical trials in people. Those three categories of evidence are not interchangeable, and the species differences that stop a rodent finding from carrying over to people are the substance of that gap. ICH M3(R2) describes exactly that sequence: which non-clinical studies, at what scope and duration, are expected before each phase of clinical research and before authorisation ^[7]. A finding in a cell line is not a non-clinical package, and a non-clinical package is not clinical proof.

It is equally honest to say that the borders are not always clean. Borderline cases — products that could be characterised as medicines, cosmetics, foods or medical devices — are decided case by case, and national authorities do not always reach the same conclusion about the same product. The doubt clause in Article 2(2) exists precisely because that divergence was expected ^[1], and the Court's case law is still being built one judgment at a time ^[3]. Anyone invoking a single definitive list of permitted and prohibited peptides covering the whole EU is describing something that does not exist.

A separate regime entirely: anti-doping lists

Pharmaceutical classification is often confused with anti-doping lists. They are different systems, with different purposes and different scope. The World Anti-Doping Agency publishes an annual Prohibited List whose section S2 covers peptide hormones, growth factors, related substances and mimetics, and which binds athletes both in and out of competition ^[9]. A substance can appear there while holding no marketing authorisation anywhere in the EU, and the reverse is equally possible. Presence on that list says nothing about whether something is a medicinal product within the meaning of the Directive, nor about how it may be supplied.

What this means in practice for handling laboratory material

Classification is not an abstract question. It determines what the label must say, what has to be kept on file, and what must never be written on an accompanying document.

• Labelling states the material's intended purpose as laboratory material and names no indications, routes of administration or therapeutic properties: the presentation limb is triggered by wording, not by intention ^[1].
• The certificate of analysis is filed alongside the batch number and the receiving date, so that every analytical statement maps to a specific physical material ^[8].
• Analytical methods and acceptance criteria are recorded by reference to a recognised standard and an accredited laboratory, not to an in-house quality claim ^[10].
• Repackaging, decanting into other containers or relabelling changes the product and the liability attached to it; where it happens, it is documented with a date and a responsible person.
• The regulatory picture is reviewed periodically, as guidelines and lists are revised — the EU guideline on synthetic peptides taking effect during 2026 being the current example ^[6].

The conclusion is simple and uncomfortably precise: the question is this peptide a medicine has no answer at the level of the molecule. It has an answer at the level of the product — who supplies it, with what presentation, for what declared purpose, and with what dossier behind it. Those four things determine whether a marketing authorisation is required, whether the product is supplied on prescription, and which authority is competent when something goes wrong.