The Community Code on Medicinal Products

EU medicines law for human use rests on two complementary instruments. Regulation (EC) No 726/2004 governs products authorised centrally via the EMA: one application, one CHMP opinion, one Commission decision valid EEA-wide. Directive 2001/83/EC is the other pillar: the harmonised national baseline that governs every medicine authorised at Member State level through the national, mutual-recognition or decentralised procedure. Where 726/2004 is the centralised spine, 2001/83 is the horizontal rulebook underpinning the decentralised system.

Even centrally authorised products are not free of the Code: its definitions (Title I), labelling requirements (Title V), classification provisions (Title VI), wholesale distribution obligations (Title VII), advertising rules (Title VIII) and pharmacovigilance framework (Title IX) apply across all authorisation routes. The Code thus touches every medicine that reaches EU patients.

The directive was adopted under Article 95 TEC (now Art 114 TFEU), the internal market approximation provision, via the co-decision procedure of Art 251 TEC. The legal basis reflects the directive's core purpose: eliminating distortions caused by divergent national rules on the conditions under which medicinal products are placed on the market. It was signed in Brussels on 6 November 2001 by EP President Nicole Fontaine and Belgian Council Presidency Minister Didier Reynders, and published in OJ L 311 on 28 November 2001.

The directive entered into force on the 20th day after its publication in the OJ (Art 129), but as a codification it set no fresh transposition deadline for Member States: Annex II Part B preserved the original transposition deadlines of the eleven directives it repealed.

The directive is structured into 61 recitals explaining the legislative purposes and 14 Titles containing 130 articles. Three Annexes complete the instrument: Annex I sets the standards for analytical, pharmacotoxicological and clinical dossiers; Annex II lists the repealed directives and their transposition deadlines; Annex III is a correlation table mapping each article of the Code to its predecessor in the eleven repealed directives. The directive has subsequently been amended by five further directives (2004/24, 2004/27, 2010/84, 2011/62, 2012/26) and is now the subject of a proposed replacement under the 2023 pharma reform (as amended).

Article 1 contains the full lexicon of the Community Code: 28 numbered definitions used throughout EU medicines law. Définitions clés include:

• Medicinal product (no. 2): any substance or combination of substances presented as having properties for treating or preventing disease in human beings, or any substance administered with a view to restoring, correcting or modifying physiological functions by pharmacological, immunological or metabolic action. The dual test - "presentation" and "function" - was established by Court of Justice case law and incorporated here.
• Immunological medicinal product (no. 4): vaccines, toxins, serums and allergen products
• Homeopathic medicinal product (no. 5): prepared from homeopathic stocks in accordance with a homeopathic manufacturing procedure
• Radiopharmaceutical (no. 6): a medicinal product which, when ready for use, contains one or more radionuclides
• Adverse reaction (no. 11): a harmful and unintended response to a medicinal product
• Serious adverse reaction (no. 12): one that results in death, is life-threatening, requires hospitalisation, results in disability, or causes a congenital anomaly
• Unexpected adverse reaction (no. 13): one whose nature or severity is not consistent with the summary of product characteristics
• Periodic safety update report (PSUR) (no. 15): the periodic report submitted by MA holders on benefit-risk balance
• Post-authorisation safety study (no. 15a): any study carried out after authorisation aiming to identify, characterise or quantify a safety hazard
• Wholesale distribution (no. 17): all activities consisting of procuring, holding, supplying or exporting medicinal products to persons other than end-users
• Public service obligation (no. 18): the obligation for wholesale distributors to maintain an appropriate range of medicines for their territory at all times

Article 6 states the fundamental rule: no medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authority of that Member State in accordance with the directive, or an authorisation has been granted in accordance with Regulation 726/2004. There are no exceptions to this principle within the industrial scope of the directive.

The MA holder must be established in the Community (Art 8). Where the MA holder is not the manufacturer, the holder must designate a person within the Community responsible for pharmacovigilance.

An application for MA must include: details of the applicant, the name of the product, qualitative and quantitative particulars of all active substances and excipients, description of manufacturing method, therapeutic indications, contraindications and adverse reactions, posology and method of administration, precautions and safety measures, particulars of shelf life and storage conditions, and the analytical, pharmacotoxicological and clinical tests in accordance with Annex I.

A key deliverable is the Summary of Product Characteristics (SmPC) (Art 11), which sets out the product's approved properties: name, composition, pharmaceutical form, clinical particulars (indications, dosage, contraindications, warnings, interactions, adverse effects, overdose), pharmacological and pharmaceutical properties, and regulatory information. The SmPC is the authoritative scientific reference document for healthcare professionals and forms the basis for the package leaflet.

Once the competent authority of a Member State receives a valid application, it must take a decision within 210 days (Art 17). During the assessment, the authority may require the applicant to supply additional information; the clock stops until the information is received. The authority may also consult the EMA's scientific committees. The 210-day standard national clock mirrors the CHMP procedure of 726/2004, creating procedural parity across authorisation routes.

If the competent authority considers that the application raises issues of public or animal health of general Community interest, it may refer the matter to the Committee for Proprietary Medicinal Products (CPMP, now CHMP) before a decision is taken (Art 29, referral procedure).

In the original 2001 text, Art 24 set MA validity at 5 years, renewable for further 5-year periods. Directive 2004/27/EC amended Art 24 so that after the first 5-year renewal, the MA becomes unlimited in duration unless the competent authority decides, on justified grounds relating to pharmacovigilance, that a further 5-year renewal is necessary. The sunset clause (Art 24(4)-(5)) provides that an MA lapses if not exercised within 3 years of grant, or if the authorised product is absent from the market for 3 consecutive years (as amended).

Article 10, as substantially amended by Directive 2004/27, is the legal basis for generic medicines in the decentralised system. An applicant for a generic medicine need not provide the results of pre-clinical and clinical tests if it can demonstrate that the medicine is a generic of a reference medicinal product that has been authorised for at least 8 years in a Member State or the Community.

The art 10 abridged route also covers: the "well-established medicinal use" bibliographic route (Art 10a) for substances in use in the Community for at least 10 years; the fixed-dose combination route (Art 10b); and the informed consent route where a previous dossier holder consents to use of their data (Art 10c). Each of these routes was reorganised and clarified by Directive 2004/27 to reduce fragmentation across Member States.

In the original 2001 text, Art 10 provided data protection of 6 years (10 years for high-technology/biotechnology products) before generic applicants could rely on the innovator's data. Directive 2004/27/EC replaced this with the harmonised 8+2+1 formula applicable across all routes:

• 8 years of data exclusivity: generic applicants may not file an abridged application relying on the reference product's data
• 2 additional years of market protection: even if a generic dossier has been compiled, the generic may not be placed on the EU market for 10 years from the initial authorisation of the reference product
• +1 further year of market protection if, within the first 8 years, the MA holder obtains an authorisation for one or more new therapeutic indications bringing a significant clinical benefit compared with existing therapies

The maximum combined protection period is 11 years. The 8+2+1 formula applies equally under the centralised procedure (via Art 14(11) of 726/2004) and the national/decentralised routes governed by 2001/83 Art 10.

Where an applicant has already obtained a national MA in one Member State (the Reference Member State, RMS) and wishes to extend it to one or more other Member States (Concerned Member States, CMS), they may apply through the mutual-recognition procedure. The CMS must normally recognise the existing RMS authorisation within 90 days of receiving the assessment report, SmPC, labelling and package leaflet from the RMS. If the CMS raises no objection, the MA is granted on the same terms as in the RMS.

If a CMS raises a serious potential risk to public health that cannot be resolved between the RMS and CMS, the matter is referred to the CPMP (now CHMP) under the referral procedure of Arts 29 to 34 for a binding Community-level resolution.

Where an applicant seeks MAs in several Member States simultaneously for a product not yet authorised anywhere in the EU, they may use the decentralised procedure (added to Art 28 by Dir 2004/27). One Member State acts as RMS and prepares the draft assessment report, draft SmPC, labelling and package leaflet. The CMS then have 210 days to agree. At the end of the procedure, each participating Member State grants a national MA with an identical SmPC, labelling and package leaflet.

The decentralised procedure therefore produces a set of nationally granted MAs (not a single Community authorisation) but with identical product information across all participating Member States, giving the commercial coverage of a near-Community authorisation while respecting national competences.

Where a Member State considers that there are grounds for considering that a medicinal product authorised by another MS presents a risk to public health, or where there is disagreement in the mutual-recognition procedure, the matter is referred to the CPMP for arbitration under Arts 29 to 34. The CPMP must deliver an opinion within 60 days (extendable to 90 days in complex cases). The Commission then adopts a decision in the Standing Committee (comitology) that is binding on all Member States. This referral mechanism was the central tool for resolving cross-border disagreements on risk-benefit assessments before CHMP opinions became binding via 726/2004 for centralised products.

The Qualified Person (QP) is a cornerstone of EU medicines manufacturing law. Every holder of a manufacturing authorisation must have at their disposal at least one QP (Art 48), and the QP may not be replaced without the prior authorisation of the competent authority (Art 50). The QP must be a person of good standing, possess a university diploma in pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry, biology or equivalent, and have at least two years of practical experience in activities including qualitative analysis, quantitative analysis of active substances, and testing to ensure compliance with GMP.

The QP's core legal duty is set out in Art 51: each batch of medicinal product manufactured within the Community must have been certified by a QP as meeting the requirements of the MA and the applicable GMP standards. For products imported from third countries, the QP must certify that each batch has undergone a full qualitative analysis, a quantitative analysis of active substances, and all other tests or checks necessary to ensure quality, in accordance with MA requirements. No batch may be released for sale or supply unless certified by the QP. The QP is personally responsible for this certification.

Article 54 lists the particulars that must appear on the outer packaging (and where there is no outer packaging, on the immediate packaging) of every medicinal product placed on the EU market. They include: the name of the product; the qualitative and quantitative composition in active substances; the pharmaceutical form and the contents by weight, volume or number of doses; the list of excipients that have a recognised action or effect; the method of administration and, if necessary, the route of administration; a special warning that the product must be stored out of the reach of children; a special warning, if necessary, for the product; the expiry date; the special storage precautions; the special precautions relating to the disposal of unused products; the name and address of the MA holder; the MA number; the manufacturer's batch number; and the patient information leaflet reference.

When granting an MA, competent authorities must classify the product as either subject to medical prescription or not subject to medical prescription (Art 70). Medicines must be subject to medical prescription if they are likely to present a danger, directly or indirectly, if used without medical supervision; are frequently and widely used incorrectly so as to present a direct or indirect danger; contain substances whose activity or adverse reactions require further investigation; or are normally prescribed by a doctor for parenteral administration (Art 71).

Within prescription-only medicines, Art 71 also defines sub-categories: those renewable only once, those indicating "restricted medical prescription" (due to dangerous pharmacological effects), and those subject to "special medical prescription" (for conditions requiring specific supervision, e.g. cytotoxics, immunosuppressants, hormones with potential abuse, or radiopharmaceuticals). Non-prescription medicines sold only in pharmacies form a further sub-category in some Member States.

Article 86 defines advertising broadly: all informational, canvassing or inducement activities intended to promote the prescription, supply, sale or consumption of medicinal products. The definition covers advertising to the general public, advertising to persons qualified to prescribe or supply medicines, visits by medical representatives, the supply of samples, sponsorship of promotional meetings, and scientific congresses.

Article 87 imposes the prohibition on advertising prescription-only medicines to the general public, and Art 87(2) extends the prohibition to medicines reimbursed by Member State health insurance schemes. Article 88 lists permitted disease-awareness campaigns (conducted by competent authorities), and Art 88(2) permits vaccination campaigns where the responsible competent authority approves the advertising materials. The ban on DTC (direct-to-consumer) advertising of prescription medicines is one of the most debated provisions of the Community Code.

Each Member State must establish a pharmacovigilance system to collect information on suspected adverse reactions, monitor the benefit-risk balance of authorised medicines, and take any regulatory action warranted. The competent authority must ensure that such reports are made accessible to the EMA and to the European pharmacovigilance data network (EudraVigilance). Member States must also encourage healthcare professionals and patients to report suspected adverse reactions through spontaneous reporting schemes (Art 102, as amended by Dir 2010/84).

MA holders must submit Periodic Safety Update Reports (PSURs) to competent authorities and EudraVigilance at regular intervals reflecting the product's age: six-monthly for the first two years after initial authorisation, annually for the following two years (as amended by Dir 2010/84), and then five-yearly in line with the MA renewal cycle. PSURs contain a critical scientific evaluation of the benefit-risk balance, a listing of all adverse reactions, the current status of the SmPC, and the QPPV's assessment of whether changes to the authorisation terms are needed. The PRAC (added by Reg 1235/2010 + Dir 2010/84) leads the PSUR evaluation at Community level for medicines on the harmonised PSUR list.