How to handle Expiry Dates under the CTR

Recommendation

4-6 June 2024
Munich, Germany

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Sponsors have previously contacted the regulatory agencies with requests to omit the expiry date on investigational medicinal products (IMPs) in the case of interactive response technologies (IRT) use. The claimed advantage of this approach included avoiding issues related to relabelling of the expiry date on site, which can often cause issues in themselves with poor control of the expiry update labels. However, based on experience from recent GCP inspection findings around IRT validation and the dispensing of expired study medication to patients, the request of sponsors raises concerns. Therefore an updated Reflection paper on the use of IRT has been published by the GCP IWG.

Revised Annex 13 of the EU GMP Guide

The revised Annex 13 changes the approach to the management of issues at the interface between GMP and GCP. These include the two-step release procedure, handling and shipping of IMPs and contractual arrangements between the sponsor and the IMP manufacturer. There are also changes to the labelling of IMPs (e.g., changing the approach to providing expiry information, moving labelling requirements from GMP guidance into the text of the CTR). 

Updated Reflection paper on the use of IRT

The reflection paper on the use of IRT was initially published in December 2013. It has been updated in view of the entry into application of the EU Clinical Trials Regulation (CTR) No. 536/2014 on 31 January 2022, to "clarify that the removal of expiry dates from the labels is not allowed for clinical trials conducted under the CTR". The rest of the reflection paper was not amended and reflects the state of thinking at the time of initial publication. Additional information on the expected requirements for IRT (e.g. regarding validation) may be found in the GCP IWG Draft Guideline on electronic systems and electronic data in clinical trials. In addition, the GCP IWG published a notice for clinical trial sponsors to highlight the requirements for qualification and validation of computerized systems.

Removal of expiry dates

Section 2.3 "Circumstances where the removal of expiry dates could be justified" of the Reflection paper only applies to clinical trials conducted under the Clinical Trial Directive (2001/20/EC). The removal of expiry dates from any label is not allowed for clinical trials conducted under the CTR. The responsibility for the expiry date remains with the sponsor regardless of whether or not the expiry date appears on the labels.  

More information can be found in the Reflection paper on the use of interactive response technologies (interactive voice/web response systems) in clinical trials, with particular emphasis on the handling of expiry dates published on EMA´s GCP Inspectors Working Group website.