Before making a submission to the CTIS, sponsors transitioning clinical trials previously approved under the EU Clinical Trials Directive must take several preparatory steps. These can be time consuming and are not always well-understood so it’s important that you take time to prepare yourself before making the transition.
To get started, you will need to have a statement to say all documents being submitted have been approved by an ethics committee and the competent authorities before they have been transitioned into CTIS. You will also require a General Data Protection Regulation (GDPR) statement to declare all data has been collected and processed in accordance with the privacy law.
There is now also an obligation for the legal representative to ensure the sponsor is compliant with the regulation, which means the legal rep needs to see evidence in the sponsor’s quality management system that they do have the resources and processes in place to comply with the regulation. That takes time and must be done before the sponsor registers in CTIS.
Then there’s the systems training that you, or your administrator, must undergo. The EMA has various online training modules for CTIS users that you should review. You will also need to fill out a Transitional Trials application form and include a cover letter, which requires specific details.
What’s required after transitioning?
After the transition, there are also a number of key differences that sponsors need to be aware of. First, all notifications will go through CTIS, rather than by letter or email as was the case with the Clinical Trial Directive. It’s therefore important that you are familiar with CTIS or have a very good relationship with your CRO so the communication is promptly sent to all parties.
There are also specific requirements around safety reporting and archiving. An annual safety report (ASR) must be submitted to a specific part of CTIS. This report concerns the monitoring and evaluation of the ongoing safety profile of the Investigational Medicinal Product and steps to mitigate any potential risks.
There are also stricter timelines for responding to requests for information (RFIs) with regards to ASRs. While this is set at 14 days, the safety assessing Member State can modify this before issuing the RFI.
Preparing before submission
The processes involved with the CTIS do require careful planning and resource allocation in terms of your submission strategy. With parallel submissions not possible, it’s incumbent on you to coordinate your data and document submission.
Consider the resources you will need to maintain and complete registrations and systems, the time it might take to renew or amend contracts with CROs and, where relevant, understand the responsibilities that may be delegated to the CRO to transition to and maintain CTIS.
Importantly, even if you have delegated the responsibilities to your CRO, as the sponsor you are still responsible for the clinical study. We had one sponsor say they planned to outsource everything and asked if they could use this to get around the fact that they didn’t have an adequate quality management system (QMS). Unfortunately, that won’t fly with the regulators. You, as the sponsor, are responsible and as such you must have a QMS that is compliant with the regulation.
The benefits of CTR
While moving to CTR and CTIS does require an investment of time and resources, there are many positives to consider. In future, you will be able to do just one submission for all countries in the EU and EEA, which will save time. It’s noteworthy that, despite differences, the 30 countries across Europe agreed to pull together for the CTR.
“Consider the resources you will need to maintain and complete registrations and systems, the time it might take to renew or amend contracts with CROs and, where relevant, understand the responsibilities that may be delegated to the CRO to transition to and maintain CTIS.”