Solution for Expiry Labels, DtP, and Study Timelines Due to EU 536/2014 Clinical Trials Regulation

The new regulation improves many aspects of clinical preparation and activation but brings certain new challenges for sponsors.


Quick hits:

  • The regulation is switching the emphasis from the first country and site approved to the last country and site ready.
  • The regulation has strict timelines sponsors must adhere to, with the submission process being split into two parts for the reporting country and the member states concerned.
  • Annex VI chapter nine of the regulation stipulates that the expiration date is required to be printed on the label, which leads to challenges with relabeling and more.
  • The industry is proactively searching for and providing guidance on potential solutions to these challenges, though no one solution will be a fix-all and many are not yet approved by the European Commission.

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Hi, I’m Melissa Griffen, Contributing Editor at Healthcare Packaging. Regulation EU No 536/2014 on clinical trials—which is a binding legislative act for each member state, overruling national law—is coming into force on January 31, 2022, to simplify clinical trial preparation and activation. With it will come many changes that will impact the clinical sponsors’ preparation, submission process, and administration methods.

On an XTalks webinar titled “How to Avoid Significant Delays in Multi-Country Studies Due to EU 536/2014 Clinical Trial Regulation,” Elvin Thalund, director of industry strategy at Oracle Health Sciences explained that this regulation is switching the emphasis from the first country and site approved to the last country and site ready. This will be done through submitting one to two submissions through a clinical trials information system to simplify outreach to European regulatory agencies across countries.

The downside of this method, as explained by Thalund, is that it will require more time before clients can begin enrollment by about 2 or 3 months as the new regulation will not allow the selection process and activation process to run in parallel. Instead, the submission process will be split into two parts for the reporting country and the member states concerned. Clinical sponsors must then adapt in order to operate within the framework.

If the timelines are not met by the clinical sponsor, then the submission lapses and delays and can even require a restart. Other important factors that can affect study timeline are the individual member states’ final decisions as each can reject Part 1 and Part 2 decisions, and substantial modifications due to protocols, which must be submitted after the initial Part 1 submission is complete. Though, the webinar experts explain that individual Part 2 applications can be submitted at different times, based on the amount of information available for the desired sites, after the conclusion of the Part 1 acceptance.

Essentra Packaging, a global manufacturer of cartons, leaflets, and labels for the pharmaceutical industry, is running a three-part webinar called “The Evolution of Clinical Trial Packaging,” also meant to help clinical sponsors adapt to the changes coming with the new regulation. The first part of the series discusses changes, issues, and possible solutions for Annex VI expiry labeling.

Annex VI chapter nine of the EU 536/2014 Clinical Trial Regulation stipulates that the expiration date is required to be printed on the label. Joe Monteiro, technical account manager of clinical trials at Essentra Packaging, listed in the webinar a number of challenges that this poses for sponsors, including increased cost of rework—especially around kits, which have multiple primary containers per kit, each required to have an updated expiry label; the purchase of new labels for relabeling, which must be performed in a controlled GMP-compliant environment under quality QP release; the potential of damage to packs as well as to biological drugs which  must be taken out of cold storage for pack labeling; and more.

Monteiro explained that the industry has been proactively searching for and providing guidance on potential solutions to these challenges, though he points out that no one solution will be a fix-all. Oftentimes, sponsors will need to apply multiple solutions to fit their needs. A number of these solutions are also still under consideration and have not yet been accepted by the European Commission.

Potential solutions given in the webinar were to label the primary container with the initial expiry date and include a statement referencing the outer pack for the most current expiry date; the use of an electronic label with a barcode that can be scanned by participants using a smart device to link them to all necessary information regarding the medicine they are taking; operational strategies, such as limiting the batch sizes and the use of just-in-time labeling, which would entail keeping supplies at a central packaging site and printing labels with the latest expiry date just prior to distribution; and having labeling supplies based on countries and regions, meaning alternative packaging arrangements with an EU-only supply of products that are labeled with the expiry date.

For more on direct-to-patient considerations for clinical trials, check out the full story at the URL on screen. Thanks and see you next time on Take Five video with Healthcare Packaging.

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