In a regulatory context, labelling refers to the entirety of all written, printed or graphic information that is affixed to or accompanies a medicinal product or medical device. This includes the Summary of Product Characteristics (SmPC), the patient information leaflet, the outer and immediate container labelling of the packaging, and any other product information that contributes to identification, traceability and safe use. Labelling is one of the most heavily regulated elements of the marketing authorisation process and is subject to specific requirements in the EU, the US and other markets, some of which differ considerably. Errors or gaps in labelling are among the most common causes of objections to marketing authorisation applications and of product recalls in the post-market setting.
Regulatory requirements in the EU
In the EU, Directive 2001/83/EC governs labelling requirements for human medicinal products. Articles 54 to 65 specify what must appear on the outer packaging, the immediate packaging and in the package leaflet—including the name of the medicinal product, composition, pharmaceutical form, marketing authorisation number and the name of the marketing authorisation holder. The European Medicines Agency has issued additional guidance on format, readability and language requirements. In all EU Member States, labelling must be provided in the respective national language, which requires extensive translation and layout processes for multinational authorisations. The EMA provides standardised templates via the so-called QRD template (Quality Review of Documents), which must be used for the preparation of the SmPC and package leaflet. Deviations from the prescribed format require justification and are critically assessed by authorities during dossier review.
For medical devices, the requirements of the EU MDR (Regulation 2017/745) and the EU IVDR (Regulation 2017/746) have applied since 2021. These regulations impose significantly expanded labelling requirements compared with the predecessor directives, including the obligation to use harmonised symbols and to include the UDI carrier (Unique Device Identifier) on all labels.
Labelling for investigational medicinal products in clinical trials
In clinical trials, specific provisions apply to the labelling of investigational medicinal products, as set out in Annex 13 of the EU GMP Guide and in EU Regulation 536/2014. At a minimum, the labelling must include the following information: name or code of the sponsor, protocol number, pharmaceutical form, contents and dosing instructions, batch number, expiry date, as well as a statement that the product is for clinical trial use only and storage instructions.
In blinded studies, labelling must be designed so that the investigational medicinal product and placebo are not distinguishable in appearance, without compromising blinding. At the same time, emergency unblinding must be possible at any time. The logistical challenge is to deliver correct, country-specific and linguistically appropriate labelled units to the trial sites in a timely manner for all study participants. Labelling errors can lead to trial interruptions, regulatory reporting obligations and, in the worst case, jeopardise patient safety. Even minor deviations—such as an incorrect expiry date or missing storage statement—may require immediate notification to the authority and relabelling of the affected units.
Post-approval labelling and lifecycle management
After initial approval, labelling is not a static document. New findings from pharmacovigilance, such as new contraindications or warnings, must be incorporated into the product information in a timely manner. Authorities may require labelling changes, for example following the assessment of Periodic Safety Update Reports or as a result of regulatory review procedures. Depending on the category, each labelling change must be submitted to the competent regulator as a minor, moderate or major variation. Lifecycle labelling management is therefore an ongoing regulatory task that requires close coordination between Regulatory Affairs, Medical Affairs and the Pharmacovigilance team. In the EU, labelling changes must be submitted via a clearly defined variation process and approved by the authorities before the updated product information may be implemented on the market. Compliance with these timelines is mandatory for the marketing authorisation holder and is verified during inspections.
Relevance for Regulatory Affairs and CROs
The preparation, review and updating of labelling documents is a core responsibility of the Regulatory Affairs team. Substantive errors, outdated information or missing mandatory statements can delay marketing authorisation applications, trigger authority questions or lead to recalls in the post-market setting. Full-service CROs such as mediconomics support sponsors in preparing EU-compliant labelling documents, coordinating country-specific translations, and preparing and submitting labelling variations as part of ongoing marketing authorisation lifecycle management. In addition, experienced Regulatory Affairs teams support sponsors in implementing authority requirements arising from PSUR assessments, European referrals or authority-initiated labelling revisions.
Frequently Asked Questions (FAQ)
Does the labelling of an investigational medicinal product have to be in the local language of the trial site?
Yes, as a rule, the labelling of investigational medicinal products must be in the language of the country in which the study is conducted. Exceptions are possible if the competent ethics committee and authority have explicitly accepted English-language labelling. This must be clarified in advance with the competent authorities.
What is the difference between labelling and packaging?
Labelling refers to the textual and graphic information on or accompanying the packaging. Packaging refers to the physical packaging itself (primary and secondary packaging). In a regulatory context, the two terms are strictly distinguished, even though they are closely linked in practice. Packaging requirements are anchored in the GMP context, while labelling requirements are anchored in the regulatory marketing authorisation context.
What happens if a labelling error is discovered after approval?
Depending on the severity of the error, the marketing authorisation holder must submit a variation, inform the competent authorities and, if necessary, decide on a batch recall. In the case of safety-relevant errors, the authority may order an immediate recall. The entire process must be documented in the pharmacovigilance system.