02/07/2023

The European Medicines Agency (EMA) Good Clinical Practice Frequently Asked Questions (FAQ) webpage offers guidance on GCP and is updated regularly as additional questions are received. Several of the questions were previously revised in March 2022.

Under section “GCP matters”, questions 16 and 17 were added in late 2022. Question 16 was covered in an earlier blog HERE.

Question 17 (December 2022): “How can sponsors demonstrate oversight for those activities that are delegated by written contract?”

Answer summary: Sponsors are responsible for all trial related activities carried out on their behalf. Under the Clinical Trial Regulation (Regulation EU No 536/2014), a sponsor may choose to delegate any or all of their clinical trial tasks to an appropriately selected CRO. The responsibility for the protection of participants and the quality of the data still lies with the sponsor. The Clinical Trial Directive (Directive 2001/20/EC) is in phase out but has a similar provision. Per the ICH E6(R2) GCP guideline, the sponsor is responsible for oversight of all trial related activities delegated to a CRO. A risk based approach should be used for selection of CROs and oversight of activities.

Some suggestions of ways to ensure oversight per the FAQ are:

“Questionnaires to assess suitability
Curriculum Vitae review
Pre-qualification including review of prior (relevant) experience
Detailed contracts/master-service agreements and work orders
Regular document review, of particular importance is the review of any relevant approvals and licenses required to perform the contracted duties and functions (tasks)
Re-qualification activities (e.g. regular re-assessments of suitability, follow-up audits)
Interoperability of different parts of the TMF, especially if migration steps are planned”

Some suggestions of ways to demonstrate oversight per the FAQ are:

“Ensuring that (direct) access to essential documents that are retained at the contracted service provider can be made available, for example validation/qualification documentation, training documentation, standard operating procedures (SOPs), etc.
Documentation of access (e.g. access log)
Recording of significant decisions and actions (e.g. in meeting minutes)
Archiving of relevant communication (e.g. emails)
Logging of document (and data) review steps (e.g. audit trail);
Logging of relevant phone calls (help desk) (e.g. ticket system, minutes of the call)
Documented acknowledgement of quality assurance reports (e.g. audit report)
A life cycle process (change management / project management) to adapt and re-evaluate documentation and training requirements (e.g. change management SOP) as deemed necessary
Recording and evaluation of deviations from contractual agreements, GCP or regulatory requirements”

Quality management processes should be in place to assure trial quality. Signals for quality deviation or issues should be monitored. Issues should be communicated through appropriate escalation pathways and managed through corrective and preventive measures.

It is permissible for CROs to subcontract tasks, if permitted in the written agreement, as long as:

trial quality is maintained,
the sponsor evaluates the subcontracted provider’s processes for adequacy, and
the sponsor has access to all trial related documentation for adequate oversight.