The European Union: Translation of Medication Information

The E.U. takes a far different approach than the U.S. when it comes to the translation of medication information. The E.U. has incorporated the translation of medication information into its centralized drug approval procedure, requiring translated medication information targeted to consumers in the official languages of the E.U. member states.

In 1995, the E.U. established the European Medicines Evaluation Agency and with it, an opportunity for the pharmaceutical industry to consolidate the drug approval process across E.U. member states. The agency, now known as the European Medicines Agency (EMA), is responsible for evaluating drug approval applications, post-market monitoring and pharmacovigilance, and providing scientific advice to companies developing new drugs. Pharmaceutical companies wishing to market their drugs in E.U. countries can choose to use the EMA's centralized drug approval procedure or submit drug approval applications directly to one or more member states. The benefit of using the centralized procedure is that, if successful, the drug approval extends across all E.U. countries. The downside is that the centralized procedure contains requirements that are not necessarily included in an individual country's application process. The centralized procedure must be used for certain drug classes; for example, certain biologicals and medicines for the treatment of AIDS, cancer, diabetes, and orphan medical products can only be approved for sale in the E.U. through the centralized procedure.

Drug Approval Process under the Centralized Procedure

The EMA has very specific requirements concerning the development of medication information as part of its marketing approval process. Materials must be prepared in English for the initial review process. If the drug receives preliminary approval (subject to further review and final approval), the medication information must then be translated by the manufacturer into 24 languages and Braille.

The EMA provides oversight for consumer-directed medication information through its Working Group on Quality Review of Documents, which conducts a detailed review of the English-language version of the medication information. In addition to the content, the review covers the style and layout of the information. The Working Group reviews the labeling and package information leaflet and, if satisfactory, the materials are forwarded to representatives of each member state, who in turn conduct their own review of the English-language versions of the medication information. Some additional back and forth discussion during the review process is common between the applicant and the various national and EMA reviewers. A team of medical writers also conducts a review of the documents and submits a final decision regarding approval of the documents as one component of the overall drug application.

EMA decisions to approve medications are conditional upon the applicant's submission of translations of the approved English-version medication information into 24 other languages plus Braille.

Pharmaceutical Labeling Requirements

An important feature of drug packaging in the E.U. (and most of the industrialized world) is that medicines are not generally shipped in bulk for repackaging in pharmacies, but instead are packaged for individual consumers with tablets generally supplied in blister packaging.

The EMA requires pharmaceutical companies to provide information to consumers on two areas of the drug's package as well as via a leaflet included with or inside the package (see Table l). These are referred to as the outer packaging, the inner packaging, and the patient information leaflet.

Outer Packaging

The box which holds the blister pack, bottle, or other direct container of the drug constitutes the outer packaging. The outer packaging must contain the product's name, strength, active substances, method of administration, and any necessary warning statements (e.g., keep out of reach of children). The outer packaging must also include the expiration date, the production batch number, storage instructions, disposal instructions for unused doses, as well as the name and contact information of the manufacturer. Individual member states may require additional information on outer packaging, such as information regarding the cost of the drug and how it can be accessed through various social service agencies.

Inner Packaging

The inner packaging is the container that directly encloses the pharmaceutical. Inner packaging is required to display the same information as the outer packaging. The majority of prescriptions in the E.U. are distributed through blister packs, which provide too little space to include all of the required information and still meet guidelines for legibility and comprehensibility. For this reason, most inner packaging qualifies for an exemption from this requirement. At a minimum, blister packs must contain the name of the drug and manufacturer, the expiration date and the batch number.

Patient Information Leaflet

The Patient Information Leaflet is provided to consumers separately with each prescription purchased at the pharmacy or included within the outer packaging. It is the most comprehensive information provided with each drug. In addition to many of the items required on the outer packaging, the patient information leaflet includes the approved indications of the drug, contraindications, interactions with drugs, food, or other substances, drug administration instructions, reported side effects, and a detailed list of drug components. Individual member states may require additional information, commonly referred to as a “blue box,” that provides country-specific information such as price, health insurance coverage details, and availability through social service agencies.

The patient information leaflet must be written specifically for and reviewed by consumers. As part of the marketing approval process, the EMA requires manufacturers to undertake targeted patient reviews of the English-language versions of the leaflets to make sure that they are legible, clear, and easily understood. Generally, this takes place through consumer testing of patients' understanding of important components of a draft version of the leaflet. The results of these consumer tests must be included in the initial marketing approval application to the EMA and are taken into account when revising the materials. Consumers are targeted based on the intended users of the drug; for example, leaflets on diabetes medications must be tested by consumers with diabetes.

Translation Process

The outer packaging and patient information leaflet must be available in the official language or, in the case of countries like Belgium that have multiple official languages, the languages of each of the E.U. member states in which a medication is sold. In countries with two official languages, both languages must appear on all medication labels. Additionally, the name of the drug must be printed in Braille on both the outer and inner packaging, and the entire patient information leaflet must be available in Braille on request.

The window for completing the required translations is remarkably short. Pharmaceutical manufacturers must submit translations of their English-language versions of packaging and patient information, in 24 other languages plus Braille, to the EMA no longer than five days after the initial application has been granted conditional approval. In practice, companies begin the translation process long before the English-language versions have received conditional approval. After they have been submitted by applicant companies, the EMA forwards the translations to regulatory agencies in member states for review and comment. France and Germany, for example, review the French and German materials to be used in member states where these languages are spoken. The review process for the translated documents is also quite rapid. Designated E.U. member state pharmaceutical regulatory agencies must complete their language-specific reviews within two weeks of receiving the translated medical information, at which point they provide comments and questions for the applicant. Guidance from the European Commission on requirements for translation of the patient information leaflet states that the translations should be “faithful [to the user-tested English-version,] allowing for regional translation flexibility, whilst maintaining the same core meaning,” rather than a literal translation of the English words, which could be confusing or change the meaning of the original.

The short (five-day) turnaround time between initial approval and submission of translations is considered very onerous by the pharmaceutical industry. The two-week translation review period at the country drug agency level is also considered inadequate. Translation review duties are often in addition to the regular demands of the jobs held by reviewers and deadlines are often missed, delaying the application review. Revised translations indicating how comments by reviewers have been addressed are submitted along with the full drug application.

Pharmaceutical companies use both staff and contractors to prepare translations. Information on the cost of the translation process to manufacturers is proprietary; however, one estimate suggests that the resources necessary to complete the translations correspond to two full time equivalent employees. Despite the burden associated with the translation process, pharmaceutical manufacturers routinely use the centralized procedure to gain access to a drug market of over half a billion people. The efficiencies associated with the centralized procedure greatly offset the relatively small costs associated with translations.