Serious Breaches of the Regulation

Regulation (EU) no. 536/2014 on clinical trials on medicinal products for human use (the “Regulation”) provides a number of obligations to report breaches of clinical trial procedures 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 trial.

Sponsors must notify Member States Concerned (“MSCs”) though the Clinical Trial Information System (“CTIS”) of such serious breaches at the time of the breach, or when the breach is discovered.
If a sponsor has reasonable grounds to believe that a serious breach has occurred, the sponsor must first report the breach within seven calendar days. The Sponsor may investigate and take action during the seven day period or after notification.
Where any potential breaches become evident at a trial site, the principal investigator must have an appropriate contact point at the sponsor for reporting such incidents.
Once reported, the MSC will perform an assessment of the alleged breach, and may seek further information. The MSC may conduct inspections of any premises concerned in its assessment of the breach. Once the MSC has completed its investigation, and assuming it finds no immediate action is required, it may ask the sponsor or investigator (if the role has been delegated) for its opinion within seven days. The MSC may apply corrective measures, including the revocation of authorisation for the clinical trial, suspension of the clinical trial or the modification of any aspect of the clinical trial that the MSC deems necessary for proper compliance.

Good Clinical Practice Inspections

Good Clinical Practice (“GCP”) inspections, as carried out by the Health Products Regulatory Authority (“HPRA”), have also been updated under the Regulation.
Inspection reports will now be publicly available on the CTIS once an inspection has been completed. The HPRA will redact staff names with the exception of the Principal Investigator.
The Regulation intends to adopt a more a proportionate risk based approach in clinical trials. In particular, the new concept of a low interventional clinical trial has been introduced, covering investigational medicinal products which have already been granted a market authorisation.
An application for a low interventional trial may include a simplified Investigational Medicinal Product Dossier (“IMPD”), which will refer to other pre-existing documentation, such as the summary of product characteristics and routinely maintained pharmacy documentation, or other independently submitted documentation.
No additional insurance will be required for low interventional trials if potential injury to the trial subjects is already covered by any pre-existing compensation system.

Investigational and Auxiliary Medicinal Products

The Regulation introduces an exemption from the requirement to hold an authorisation for the manufacture/import of Investigational Medicinal Products (“IMPs”). The Regulations provide that the requirement should not apply to:

  1. re-labelling or re-packaging of the product;
  2. preparation of radiopharmaceuticals used as diagnostic IMPs; or
  3. preparation of IMPs in accordance with a doctor’s prescription or in accordance with a pharmacopoeial monograph,

where those processes are carried out in hospitals, health centres or clinics, by pharmacists or other persons legally authorised in the MSC to carry out such processes, and if the IMPs are intended to be used exclusively in hospitals, health centres or clinics taking part in the same clinical trial in the same Member State.
Member States must make the above processes subject to appropriate and proportionate requirements to ensure subject safety, reliability and the robustness of the data generated
The HPRA will implement a registration process for sites intending to operate under the above exemptions after 31 January 2022. Details of how to register, applications forms and supporting information will be published on the HPRA’s website
The Regulation also introduces the term “Auxiliary Medicinal Products” (“AxMP”), replacing the term “Non-Investigational Medicinal Product” (“NIMP”). AxMPs are medicinal products used for the needs of a clinical trial as described in the protocol, but not as an IMP, for example rescue medication. Only authorised AxMP may be used in clinical trials, unless the use of an unauthorised AxMP is justified and provided that it is manufactured to a GMP or equivalent standard.
If you would like to know more about the legal, regulatory and contractual aspects of clinical trials in Ireland, please contact Colin Kavanagh or Bridget McGrath.