In May 2014, European Union Clinical Trial Regulation (EU CTR) No. 536/2014 was passed, replacing EU Directive No. 2001/20/EC to enhance clinical trial safety, efficiency, transparency, and collaboration. At the end of January 2022, the regulation 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 labeling requirements for investigational medicinal products (IMPs) and harmonizes them throughout EU countries (no further local specificities other than translations). So, what are the implications of these changes, and how will they affect outer immediate packaging? 

Implications of Annex VI

Expiry Dates Must Be on Inner Packaging

Previously, the expiry or retesting date for medicinal products was only required on the outer packaging. Annex VI initially outlined that the date must be found on the inner packaging as well. Due to the significant operational impacts highlighted by the industry, this was finally alleviated via a delegated regulation published on November 15, 2022 (effective December 5, 2022).

Updated Definition for Auxiliary Medicinal Products (AMPs)

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 labeling non-authorized AMPs to increase patient safety and traceability in case of adverse events.

A Streamlined Submission Process

The EU CTR will introduce a new portal to provide a single entry point for application dossiers for clinical trials conducted within any country in the EU, which is intended to streamline the submission process. The dossier includes a core scientific part (Part I) and country-specific information pertaining to informed consent, site and principal investigator suitability, financial arrangements with the sites, and other local information as applicable (Part II). 

Increased Transparency and Plain Language Requirements

In an effort to increase transparency and access, the EU CTR via the EU Portal and database requires greater transparency on clinical trial proceedings and documentation. In addition, summary results of clinical trials must be published after the trial ends in a language easily understood by the public and translated into the languages of the countries that participated in that trial.

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 brought was requiring an expiry date on immediate packaging for pharma companies with ongoing clinical trials, particularly blinded ones. With this update to the regulation, expiry date requirements are now less of a concern. Transition considerations now become a critical area of focus for several reasons.

Ongoing Clinical Trials

Ongoing trials may continue to be conducted under the EU Clinical Trial Directive (EU CTD) until January 31, 2025 (no change to labeling required under EU CTD). By that date, trials falling under the scope of the regulation will either need to be transitioned under EU CTR or ended in Europe. Adding a new country to an ongoing trial after January 31, 2022, will only be possible if that trial is transitioned (and no initial application under EU CTD is possible after January 31, 2022).

New Clinical Trials

Rules detailed in Annex VI apply to the start of those trials submitted directly under EU CTR. As Annex VI is part of EU CTR, this takes precedence over any local legislation, meaning that no further national specificities apply other than translations. For trials transitioned from EU CTD, relabeling may not be required for already released IMPs.

Supply Chain Impacts

Careful assessment of the IMP labeling strategy will be required in order to define the impact of EU CTR on ongoing and new trials and their supply chains. Of particular importance is that ongoing trials will need to be carefully assessed to determine whether they need to be transitioned and for the impact on labeling for IMPs based on release status and eventual new manufacturing runs after the transition date. 

Conclusion

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