As the implementation of a new Annex VI European labelling regulation approaches, Clinical Trials Insight talks to industry experts to review its impact on supply chain management. Jennifer Worsfold, senior director of supply chain solutions and strategic projects, and Elizabeth Gallagher, director of global logistics at Fisher Clinical Services; and Mike Donahue, senior label programme director of Clintrak Clinical Labeling, share best practices on how to manage these changes.
Clinical trial regulations are becoming increasingly stringent, and failure to plan in advance and ensure compliance can jeopardise the trial. Understanding the new Annex VI regulation and determining how it will impact your organisation's upcoming studies is a crucial first step, followed by fostering open communication and thoughtful planning across functions. Advanced forecasting will enable collaboration and innovation required to address issues earlier in the process.
It is also necessary to manage return logistics of supplies for relabelling, and choose the most appropriate carriers for the required lanes and routes based on parameters for cost and performance. Select best-in-class external shippers that will maintain the proper temperature controls across the supply chain.
Finally, engage experts to help create strategies and/or contingency plans that can be implemented downstream in the supply chain. Clinical Trials Insight finds out more.
Jennifer Worsfold: First published in May 2014 and set to be implemented in October 2018, European Clinical Trial Regulation 536/2014-2, known as Annex VI, requires expiry or retest dates to be printed on primary and secondary packaging. Currently, the period-of-use information is printed on the outer packaging of the medical product, and regulations allow immediate packaging under defined circumstances such as for a small immediate unit, which enables updating to be performed at the clinical research site. Under Annex VI, this will change.
Elizabeth Gallagher: These amendments will increase the handling required to perform the updates, restrict flexibility and compromise the amount of supplies readily available to treat patients. Until now, small supplies such as vials were monitored leniently, but that won't continue for much longer. As we approach the implementation date, clinical teams must determine which items require labels with expiration dates and where labels can be revised without compromising patient safety.
JW: Our teams have been working closely with several customers to develop packaging, labelling and distribution strategies that will meet the new standards. In addition, we recommend that all clinical teams incorporate new labelling options into their current plans for upcoming trials.
Mike Donahue: It's essential to have clear communication channels between packaging and labelling teams to ensure a complete understanding of the overall pack design, how the label will be used on each component and how the final kit will be assembled. Furthermore, it is important for the packaging team to have a clear understanding of label application and placement during initial kit assembly because this will be instrumental in how the container is handled when applying an expiry update label after the pack is reopened. This is especially relevant to vials as there needs to be enough room to accommodate more than one expiry date.
If booklets are being used, an option would be to use one version across all geographic locations. Once it is determined where the packaging will be, the labelling project manager would choose the correct variable fields to be computerised on the booklet in a secondary print operation. Fortunately, labels for bulk supplies will not change.
EG: Since the mandate only applies to clinical trials conducted in Europe, organisations in Asia-Pacific, the US and South America will face critical decisions about how they manage global trials. One option is to divide supplies between those targeted for use in Europe versus the rest of the world. The choice to adopt this as a global standard may be expensive and separate supplies may cause storage concerns. Another choice could be to only source supplies within the local European region, where label requirements are standard. Yet, it might be complicated to manage inventory for a global trial depending on enrolments for each site as well as increased concerns about managing wastage.
JW: Another matter to keep in mind is the historical relationships between regulatory authorities and countries that follow European rules. Some examples include Australia, Canada, Israel and Singapore. We anticipate that these countries will adhere to the new regulations. This is an important nuance for supply chain teams to consider during the planning process.
MD: Traditionally, the label process could take an average of 120 business days, which can delay clinical trials and compromise development schedules. In anticipation of the Clinical Trial Regulation database going live and the new Annex VI regulation being implemented, Clintrak formed a design/engineering team to collaborate with clients on possible solutions for the upcoming change.
Another consideration is the use of an approved phrase library that automatically includes label standards for each organisation and manages language translation seamlessly. This improves the label cycle time, clarity and consistency for clinical teams and their counterparts. We use ATLAS [alternative translation and label approval system], a web-based product management tool, as a reliable way of reducing complications and delays in the label manufacturing process. Other benefits are 24/7 access from any location, specific users selected by administrators and listings of updated, current phrases.
JW: I would counsel clients to prioritise forecasting of inventory. Retrieving stock from sites for additional labelling in a GMP-certified facility has traditionally caused logistical issues, especially for global sites that face lengthy import/export timelines and accompanying paperwork. Additionally, sites with small storage spaces must consider what is required for the run-up phase. They must carefully manage their inventory and order new supplies in time for patient administration.
EG: CROs and inventory management teams need to be deeply aware of the dosing schedule for patients, how much product is available and which supplies need their expiry updated. This will alleviate supply depletion and shipment delays. Since our sole focus is clinical supplies, an innovative approach is taken to design packaging and labelling solutions for our clients based on their individual requirements. Our clinical supply optimisation services team develops plans and forecasts in advance, including inventory and supply management.
JW: Expiry and retest information can only be marked in a GMP-certified facility. Although some vendors will claim certification, it is important for sponsors to conduct frequent audits, ensuring that the provider's capabilities include relabelling in a GMP-certified environment.
EG: For example, there is no risk at Fisher Clinical Services. As we work in GMP-certified facilities, we can open packaging to relabel supplies without compromising product integrity. This is particularly critical for cold-chain and ambient products that need to be handled in specific temperature-controlled environments.