In May 2014, the European Union Clinical Trial Regulation (EU CTR) No. 536/2014 was passed, replacing the EU directive No. 2001/20/EC, to enhance clinical trial safety, efficiency, transparency, and collaboration. At the end of January 2022, the regulation finally went into effect, leaving life sciences companies three years to transition and meet the new requirements.

One of the most significant changes in the new regulation is Annex VI, which covers changes in the labelling requirements for investigational medical products (IMPs). The regulation also places increased emphasis on the main contact of the trial, if there’s an implementation grace period and what will/can be the role of Interactive Voice/Web Response Systems (IxRS). So, what are the implications of these changes and how will they affect outer immediate packaging? 

1.    Expiry date on inner packaging: Previously, the expiry or retesting date for medicinal products was only required on the outer packaging. Annex VI outlines that the date must now be found on the inner packaging as well.

2.    Auxiliary medical product (AMP) updated definition: AMPs, which were not defined previously, are now outlined as medicinal products that are not IMPs, but are still used and part of the study. The updated definition also includes the requirement of labelling non-authorised AMPs to increase patient safety and traceability in case of adverse events.

3.    Streamlined submission process: The EU CTR will introduce a new portal to accept single application dossiers for clinical trials conducted within any country in the EU, intended to streamline the submission process.

4.    Plain language requirements: In efforts to increase transparency and access, the EU CTR requires that the results of clinical trials be translated into the 24 official languages of the EU and that the language itself must be easily understood.

The Implications of Annex VI for Pharma Companies

While all of the changes listed above impact the clinical trial, one of the most notable changes Annex VI brings is requiring an expiry date on immediate packaging. For pharma companies with ongoing clinical trials, particularly blinded ones, this can be a challenge for several reasons:

1.    Space: Often, immediate or inner packaging already has limited space. Adding more information into an already tightly packed area can decrease readability.

2.    Tampering: Having to include the expiry date on the inner packaging means tamper seals may need to be broken and completely replaced.

3.    Delayed Timelines: Without proper preparation and planning, including the expiry date on the immediate packaging also means accounting for additional time in the supply chain. Previously, if re-labelling was necessary, it could be done on site. With the new requirement, the product must be shipped back to an authorised manufacturing site.

4.    Quality: For IMPs that require special storage conditions, such as being stored below a certain temperature, this amendment could also be a challenge. Opening the outer packaging to add or update the expiry date on the immediate packaging can compromise the IMP’s function or quality. For blinded clinical trials, there is an even greater risk for clinical trial quality.

Are you prepared for the implementation of the EU CTR? If not, don’t stress! We’re here for you if you want to chat more about the new regulations and the implications for your medicinal product development, and how our services can help with the transition process.