Medicinal Products

The ICH GCP R3 guideline is now published and will be effective from 23 July 2025. Until then, there is a transition period during which clinical trial sponsors and other participants in clinical trials need to prepare themselves as best they can. Appropriate and adequate training for ICH GCP R3 is essential as it helps maintain compliance with:

• regulatory requirements,
• improving the quality and reliability of clinical trial data and ensuring the protection of trial participants

This text refers to the two main pillars on which a clinical trial relies and for both sides one of the basic premises on which the new guideline is based is “fit for purpose” – that everything is in accordance with its purpose, the guideline accustoms us to think in exactly that way.

Principal Investigator and Study Team or Parties to whom the Investigator has delegated activities related to the clinical trial

According to ICH GCP R3:

The investigator should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial (2.1.1) and should provide evidence of such qualifications and should be familiar with the appropriate use of the investigational product as described in the protocol, in the applicable Investigator’s Brochure, in other product information and/or in other sources of information provided by the sponsor.

The investigator should also have sufficient time, an adequate number of available and qualified personnel and adequate conditions for the intended duration of the clinical trial to conduct the same properly and safely (2.2.2).

With respect to study personnel or parties to whom the investigator has delegated trial-related activities, the investigator should ensure that they are appropriately qualified and adequately informed about the relevant aspects of the protocol, the investigational product, and the assigned study procedures (including activities performed by personnel provided by other parties in accordance with local regulatory requirements). The training of personnel assisting in the clinical trial should correspond to that necessary to enable them to fulfill delegated responsibilities that go beyond their usual training and experience (2.3.2).

It is important to note the last sentence in the paragraph above. ICH GCP R3 focuses on study activities that go beyond their usual training and experience. Training (or retraining) is not required for every member of the study team regarding ICH GCP R3, it depends on their role in the clinical trial. For example, a study nurse (lab technician) who takes blood samples as they do routinely (in standard practice) do not need any training for what they are supposed to do in the study, while e.g. the principal investigator will need to be fully familiar with the guideline, and sub-investigators will need to be trained for the study activities they perform e.g. obtaining informed consent, registering and reporting adverse events, etc. When including an individual or other party in a clinical trial, consideration should be given to the tasks that the individual or party will be performing and their current level of experience in relation to the trial in which they will be included.

The same applies to retraining. When determining the need for retraining, it should be consider whether clinical trial performance is standard practice for the individual or party or whether the individual or party is only occasionally involved in clinical trials, in which case individual training is more appropriate. Retraining should be particularly considered whenever there are significant updates to the guidelines, such as the publication of a new revision of ICH GCP R3.

In particular, for ICH GCP R3, the Agency expects principal investigators to be familiar with and trained in ICH GCP R3 as they are one of the two legally responsible parties to the trial (along with the sponsor). For individuals or parties to whom the investigator has delegated clinical trial activities, the need for retraining will depend on their tasks. The fit for purpose principle outlined above should be considered here. If the individual is performing tasks in areas where the guideline has not changed, retraining is not necessary; however, it is likely that some degree of new training will be required for most clinical trial personnel due to significant changes in the guideline. It should be noted that some protocols and manuals (instructions) already describe the tasks of delegated individuals and/or parties to such an extent that training and retraining may be reduced, depending on their tasks. There is no expected standard for the number, frequency and type of training/training. The responsible parties (principal investigator and sponsor) should ensure that the training and qualifications are adequate for the delegated tasks. Since trials vary, this is not a one-size-fits-all approach.

Since the sponsor is responsible for selecting the investigator(s)/institution(s) (3.7.1), the sponsor has a shared responsibility to ensure that each investigator is qualified by education, training, and experience.

Sponsor

According to ICH GCP R3:

The sponsor should use appropriately qualified individuals (and service providers) for the activities assigned to them (broadly – biostatisticians, physicians, data managers, auditors and monitors) during the specified processes of the clinical trial (3.4, 3.11.2.1.(b.), 3.11.4.2 (a), 3.16.1. (x), 4.3.2 and C.3.1.(l, m)).

When using service providers, the sponsor is responsible for assessing the suitability and selecting the service providers to ensure that they can appropriately undertake the activities delegated to them (3.6.7). This includes assessing the suitability of the training of the service provider’s personnel.

The same reasoning applies here as described above, in the section for investigators.

Gap analysis and pre-implementation supervision/inspection

ICH GCP R3 enters into force 6 months after its publication on the European Medicines Agency website (i.e. effective from 23.07.2025). In the meantime, responsible parties (sponsors and investigators) should prepare for future implementation by conducting gap analyses or otherwise identifying new or revised training requirements for new or ongoing clinical trials.

The Agency may assess the gap analysis during GCP supervision and assess whether the training requirements set out in ICH GCP R3 are adequately implemented and documented.