D. Arrangements For Notification, Guidance for the Notification of Serious Breaches of GCP or the Trial Protocol Version 6, 08 Jul 2020, MHRA

Who should notify?

The Sponsor or a person legally authorised by the Sponsor to perform this function (for example, a legal representative or contract research organisation (CRO)), if this function has been delegated by the Sponsor to another party. In accordance with Statutory Instrument 2004/1031 as amended by Statutory Instrument 2006/1928, the Sponsor retains legal responsibility even if the function is delegated (Regulation 3.12). The CRO is also legally responsible for compliance with the legislation in relation to functions delegated by the Sponsor to the CRO (Regulation 3.8). However, in the interests of subject safety, reporting should not be delayed by discussion over reporting responsibility.

When should the notification be made?

• Within 7 days of the Sponsor becoming aware of the breach. If the notification function has been delegated by the Sponsor to another party e.g. a CRO, the 7-day timeline applies to the other party.

• If the Sponsor retains the notification function, then it is recommended that agreements between the Sponsor and other parties involved in the trial e.g. CROs, contractors, co-development partners, investigators, should state that the other party will promptly notify the Sponsor of a serious breach (as defined in Regulation 29A) that they become aware of, in order for the Sponsor to meet their legal obligation. In this case, the clock starts when the Sponsor becomes aware of the serious breach.

• If the Sponsor obtains clear and unequivocal evidence that a serious breach has occurred (as defined in Regulations 29A), the default position should be for the Sponsor to notify the MHRA first, within 7 days, and investigate and take action simultaneously or after notification. In this case, the Sponsor should not wait to obtain all of the details of the breach prior to notification. In other cases, some degree of investigation and assessment may be required by the Sponsor prior to notification, in order to confirm that a serious breach has actually occurred.

• A pragmatic approach to clock start should be employed. Inspectors will review the process for notification during MHRA GCP inspections and delays in notification may be classified as a non-compliance. If in doubt about whether and when to notify, contact the MHRA GCP Inspectorate.

Who should be notified?

• Notify serious breaches to the MHRA GCP Inspectorate. Notifications should primarily be made using the following email address:

E-mail to: GCP.SeriousBreaches@mhra.gov.uk

Organisations should also consider if there are any other relevant MHRA units that should be notified to comply with other legislation (for example, notification to the Clinical Trials Unit (CTU) if the breach constitutes an urgent safety measure or if a substantial amendment is required due to a temporary halt in the study or to the Defective Medicines Report Centre if the breach involves defective medicines or IMP recall etc.) NRES SOPs also require that the research ethics committee is notified.

• A template form for notifications of serious breaches to the MHRA is available on the MHRA GCP webpage (https://www.gov.uk/guidance/good-clinicalpractice-for-clinical-trials). It is strongly recommended that organisations use this form to ensure all required information is submitted to the GCP Inspectorate. If the MHRA template form is not used, the written report should clearly state that it relates to the notification of a serious breach.
   
• The Sponsor may initially contact the MHRA Inspectorate by telephone to discuss the breach and follow up with a written notification within 7 days of the Sponsor becoming aware of the breach. For current contact details for the Inspectorate, please refer to the MHRA web site.
  
   
•  Wherever possible, the MHRA will provide an acknowledgement of receipt for notifications. 
   
• It is recommended that the sponsor also informs the relevant Chief Investigator and/or Principal Investigators (as applicable) of the breach notification. Communication in this regard facilitates the implementation of corrective and preventative actions.

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