In December 2022, the European Medicines Agency (“EMA”) published updated guidance in the form of a Q&A on how clinical trial sponsors can demonstrate oversight of the functions that they delegate to third party service providers through a written agreement.

Article 71 of Regulation (EU) 536/2014 on clinical trials (“CTR”) provides that clinical trial sponsors can authorise third parties to perform clinical trial-related duties on their behalf. The sponsors must ensure that such delegation does not undermine the safety and well-being of clinical trial subjects. Clinical trial data must also remain robust and reliable. This means that, although trial-related tasks can be performed by third parties, clinical trial sponsors remain responsible for compliance of the clinical trials with the applicable regulatory requirements. Therefore, clinical trial sponsors must establish processes and measures to evaluate whether or not:

  1. the third parties to whom clinical trial-related duties are delegated possess the necessary skills, experience and organisational competence to perform these duties;
  2. the delegated activities are appropriately supervised by the clinical trial sponsor; and
  3. the quality of the clinical trial is ensured.

The updated guidance provides a non-exhaustive set of measures for use by sponsors in assessing the suitability of third parties to perform activities on the sponsor’s behalf. These include suitability assessment questionnaires, review of CVs of third-party personnel, and review of approvals or licenses necessary for the third parties to conduct the delegated duties.

Clinical trial sponsors may demonstrate appropriate supervision of the delegated clinical trial activities through documentation. According to the updated guidance, the measures that can be used to demonstrate sponsor oversight of the delegated tasks include those that:

  1. guarantee direct access to essential documents such as SOPs, training documents, etc.;
  2. ensure that significant decisions and actions are recorded, for example in the form of meeting minutes;
  3. archive relevant written and verbal communication;
  4. keep records of access to documentation;
  5. record acknowledgment of quality assurance reports;
  6. document and assess divergence from contractual arrangements, GCPs and regulatory requirements; and
  7. assess and adapt documentation and training requirements as necessary.

Where third parties decide to further sub-contract certain tasks to a different entity, clinical trial sponsors should demonstrate compliance with the oversight requirement on the basis of two additional documents:

  1. a contract that explicitly allows third parties to further delegate tasks to different entities; and
  2. a recorded assessment of the measures used by third parties to evaluate and supervise the subcontracted activities.

It is important if this approach is adopted that the respective liability of the individual parties for any breach of related obligations is clearly documented in a binding manner.

Furthermore, the guidance recommends that clinical trial sponsors establish processes and measures to assess and manage the quality of the clinical trial. The type of quality issues to be taken into account should include incomplete data, high incidences of errors in data entries, defective computerized systems and deceptive practices. If a quality issue results in regulatory non-compliance, the clinical trial sponsor must notify the relevant national competent authorities through the Clinical Trials Information System (“CTIS”) or in accordance with national requirements.

This blog was authored by Elizabeth Anne Wright and Anastasia Vernikou.

Posted by Cooley