Without careful management, labeling can quickly become a significant bottleneck in the clinical trial supply chain, with any delays potentially derailing the progress of a study. One of the most complex and lengthiest aspects of clinical trial labeling is efficiently managing the wide array of country-specific labels that are required for a multi-national trial, ensuring that all the label information is correctly translated and that the design and other label elements comply with the relevant local regulations. Without the use of integrated systems, this activity is incredibly labor-intensive, and as trials get more complex and geographically diverse, it gets exponentially harder.
This challenge is compounded whenever a clinical trial opts to use multi-page booklets; a common practice when IMPs (Investigational Medicinal Products) are destined for multiple countries as a single panel label typically only has sufficient space for a couple of languages. Each booklet is effectively a collection of single-panel labels, each of which can cause delays to booklet creation while its content is being approved, if for instance, countries are added at a late stage to address issues with patient recruitment. Consequently, it is not uncommon for booklet label creation, approval, and printing to take over 16 weeks.
The shift to agile trial protocols has also complicated matters, with some materials now needing to be produced on-demand to incorporate the latest changes to patient information.
Events of the past few years have led to a reset of sponsor expectations thanks to conclusive proof that trials can be conducted at speed without excessive cost or risk to patient safety. This has resulted in demand for all therapies in development to benefit from an accelerated clinical trial process, allowing them to reach patients faster and offering an improved experience. This supports pledges to deliver more patient centric care, while also fast-tracking the route to market and maximizing the return on investment before patent expiration.
As sponsors and their partners in the outsourcing community seek to identify how they can find efficiencies in the clinical trial process, the clinical supply chain is in the spotlight with organizations recognizing that automation and the creation of streamlined workflows can deliver results.
A clinical trial label or booklet contains many different elements that need to be managed for country specific labels, with a combination of text, phrases, variables, barcodes, and graphics. All content, whether it is text or image based, must go through an approval process before it is added to a label.
Some of the regulatory requirements that need to be printed include:
When creating labels for a clinical trial, it is normal practice to create a ‘master label’ in English from which country-specific labels are derived; translations of the master-level phrases need to be sourced before the localized labels can be created and sent for approval.
There are occasions where a booklet is likely to be required even if the trial is being conducted within a single country. For example, some countries have multiple official languages and numerous regional dialects, such as India which is playing an ever-greater role in clinical research. Each of these languages and dialects need to be accounted for in labeling to ensure patient adherence and safety throughout each study.
In addition to ensuring that label content is correctly translated, organizations need to maintain compliance with other local and regional regulations, which could dictate the use of specific fonts or symbols. Despite most national regulators opting to set regulations based on US or EU standards, there are still numerous country-specific requirements, even for EU member states; it is a challenge to ensure that label designs comply with all regulations for many different territories covered by a multinational trial.
With a general industry emphasis on speed of delivery, there is now an increased likelihood that target countries taking part in the trial will change at short notice due to the availability of eligible subjects. Organizations need to be able to quickly source translations for label content and ensure that their label template design adheres to local regulations.
Phrase libraries allow organizations to safely recycle content, providing a repository of approved translated master-level phrases that can be used without reference to an external translation house and repeating lengthy internal approval processes every time a phrase is used. This method can effectively save time and reduce costs without having an impact on safety.
All the ’approved phrases’ and ’sets of phrases’ should be managed and stored independently of specific trial information and the platform should offer tools to help language experts monitor the impact of proposed and actioned changes to phrases.
The library allows for more effective standardization of phrases across different studies. Most phrases can be correctly expressed in a variety of ways and while technically correct, inconsistent phrasing is frowned upon by regulators due to the potential for patient confusion and health risk.
Phrases should be stored as Unicode with a specification for the approved font, point size, spacing, kerning etc. This ensures that phrases are used in the format that they were originally approved, ensuring legibility.
For efficient GxP compliant translation management, any software-based system must involve:
It has been argued that the industry could compile a common phrase pack containing translations of master-level phrases common to all companies and trials e.g., “Keep out of reach of children” to provide consistency across studies (regardless of the sponsor and trial delivery partners). This pack could be used as the foundation of an organization’s wider phrase library and could potentially also include images and iconography.
This would emulate practices used in other industries, for example:
In addition, there are several quality-of-life features that are highly desirable. These account for the various approaches to managing language data, offering flexibility to the user. For example, it is helpful if a solution provides support for:
There are considerable risks when using a manual system or a phrase library solution that is not tightly integrated into the labeling workflow. Many organizations are currently reliant on Word or Excel documents, or archaic custom software solutions that operate independently of the labeling solution. Organizations that use translation management systems independent of their labeling workflow will often encounter the following issues:
Some of the regulatory requirements that need to be printed include:
Designed specifically for clinical trials, Loftware Prisym 360 is an end-to-end labeling solution. The software has unique features and capabilities to build and maintain an integrated phrase library which allows an organization to significantly reduce the amount of time it takes to create, approve and print labels. The platform can also easily collate multiple labels to generate artwork PDFs of single -panel and multi-page label booklets ready for printing.
The whole labeling process can be achieved in days rather than months, with the generation of country-specific labels based on a master-level template, complete with translations, at the push of a button. This allows for quick and accurate updates in response to changes in the trial protocol or alterations to the study locations with little notice.
Alongside a model GxP-compliant phrase library, the platform supports the creation of translated country-specific labels through:
Clinical trial supplies specialist RxSource needed to find a labeling solution that would allow them to meet increasingly short deadlines for packaging jobs. By implementing Prisym 360 they were able to produce labels for clinical trial products in hours rather than weeks, allowing them to offer a 48-hour express service while reducing their traditional packaging timeline from up to six weeks to only two weeks.
The translation management functionality integrated into Prisym 360 was one of the key reasons that RxSource selected the platform after their team identified that the phrase library could increase the speed of creating country-specific labels while also reducing their reliance on expensive external translation houses.
As we moved to offer the demand-led approach requested by sponsors we recognized that translation of label content was a consistent roadblock to getting trial packs out of the door at pace. The Prisym 360 phrase library has been transformative, allowing us to create country specific labels at the push of a button. Since moving to Prisym 360 we have streamlined many aspects of our operations, allowing us to significantly reduce lead times to the point where we can now package and supply a trial pack in less than 48 hours.
Rhys Evans
Senior Director, CTS and Global Supply
