Positive approach: An index gives a user-friendly structure to any booklet label and high compliance has a positive impact on the validity of the studies
Deciding which label is best for a particular trial project is not always easy. Labels have become multifunctional tools which are able to convey variable data in different languages indicate first opening, support ease of use or blind study drugs. They are no longer used as mere carriers of specified contents.
Every clinical trial has its own specific requirements concerning the labelling of investigational products. However, they have one in common: trials taking place within the European Union have to comply with the EU Guidelines to Good Manufacturing Practice while those conducted in the US have to meet the requirements of the Code of Federal Regulations. In the European Union, label contents are still specified in Annex 13. Other aspects such as structure, layout, font size and symbols are defined in the Guideline on Readability.
Several countries, different languages
Clinical trials are not usually limited to a single participating country but conducted in several countries. The labelling of investigational medicinal products has to accommodate an increasing number of languages. Labels may have to be printed in up to 40 different versions. Another option is to integrate several languages into a single product. This can be achieved by using booklet labels, now available in up to 113 pages. These provide an all-purpose solution that can be applied in every participating country. In addition to tables of contents, thumb indexes can help users find their way through booklets. Direct access to user-specific data is to be facilitated by intuitive handling, which enhances patient compliance durably.
Regardless of whether complete marking is achieved by means of one-layer, multilayer or booklet labels, labels should always match the shape of primary packaging. Unusual shapes or additional functions like an integrated hoop for hanging a bottle tend to require a high level of creativity, know-how and experience from label manufacturers. Labels are developed individually and tested for criteria such as adhesion and adaptability as well as user-friendliness. Label performance during application can be simulated at label supplier or tested at the investigational drug manufacturer's facilities.
Security features and material properties
In order for trial subjects and staff to be able to assess the integrity of investigational products, it is advisable to choose labels with tamper-evident features. The area around the mouth of the container is fully or partly covered by the label. Opening the product will damage the label badly and make tampering clearly visible. So staff or customers are able to assess the integrity of trial products.
Often investigational products are stored in cool places or even temporarily frozen. As a result, product labelling must be capable of withstanding temperatures as low as -196°C. To exclude label deterioration caused by water, grease or chemicals right from the start, it is recommended that synthetic materials be used to manufacture labels.
Printing variable data and blinding clinical trials
Personalised data is, however, not specified until very shortly before drug labelling takes place. This is why some label manufacturers tend to offer variable data printing at short notice.
Furthermore, pharmaceutical manufacturers sometimes face the challenge of having to blind their study drugs adequately to make sure that trial investigators, nursing staff, participating patients as well as the persons in charge of handling the data are unaware of the treatment administered to individual patients. Unwanted biases can only be avoided in this manner. Some blinding solutions can only be used for single-blind trials, some others for double-blind trials.
For example, vials can be blinded by using boxes made of opaque and robust cardboard. As a result, the volume and the height of the containers as well as the colour of the contents are entirely masked and therefore unidentifiable. Habitually pharmacists and contract packagers use labels to blind tubes, jars or pots. If trial-specific data needs additional masking, printable laser fields, scratch areas and sections with code-break function can be subsequently incorporated into the secondary packaging.
Custom-made solutions
Labels traditionally used as secondary packaging for trial products have changed into flexible, though compact, multifunctional tools. Increasing demands on quality and user friendliness, shorter lead times in development and production describe the significantly general conditions of clinical trial labelling.