On 23 May 2017, the European Medicines Agency (the “EMA”) launched a public consultation regarding its draft guideline for the notification of serious breaches of Regulation (EU) No 536/2014 (the “Regulation”) of the clinical trial protocol.
The guideline is intended to set out the practical arrangements for the notification of serious breaches, provide advice on what should be classified as a serious breach and to outline possible actions that may be taken by the relevant Member State(s) in response to such a notification. The scope of the guideline excludes urgent safety measures or other reporting obligations related to public safety.
Article 52 of the Regulation provides that a sponsor must notify a serious breach of the Regulation or the relevant clinical trial protocol to the Member States concerned no later than seven days of becoming aware of that breach and defines a ‘serious breach’ as “a breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial.”
The draft guideline sets out detailed guidance as to what may amount to a serious breach, including a non-exhaustive list in Appendix I of scenarios that may be considered to amount to serious breaches depending on the context. By way of example:
- Regarding an investigational medicinal product (“IMP”), Appendix I sets out an example where temperature excursions were reported in the IMP. It is stated that this would amount to a serious breach if the situation was not managed and subjects were dosed with IMP assessed as unstable, which resulted in actual or potential harm to subjects. However, this would not amount to a serious breach if the exclusions had been managed appropriately, for example if the IMP was moved to an alternative location or quarantined as necessary and an assessment by qualified personnel illustrated that there was no impact on subject safety and data integrity, and stability data showed it was stable.
- In relation to consent, Appendix I refers to a scenario where a patient information leaflet and informed consent were updated but not relayed to patients at one trial site until approximately 2-3 months after approval. Appendix I states that more information on the potential consequences of the delay should have been provided. This breach is stated not to amount to a serious breach if it was not a systematic or persistent problem and if no harm to trial subjects resulted from the delay. On the other hand, this would amount to a serious breach if there was a significant impact on the integrity of trial subjects, for example if key safety information was not relayed to subjects in a timely manner.
- Regarding randomisation/stratification errors, Appendix I sets out an example of a breach where patients were incorrectly randomised/stratified according to the protocol. This is stated to amount to a serious breach as it is likely to have a significant impact on the data.
The draft guideline also sets out the responsibilities of the parties involved in the notification of a serious breach, namely the responsibilities of the sponsor and the responsibilities of the investigator and any third party involved, as well as, at Appendix II, certain points to consider in assessing a breach.
The consultation will close on 22 August 2017.