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Pharma IT Solutions
Quality & Compliance
Safety & Vigilance
13 october 2021
Efforts to harmonize the assessment and supervision of clinical trials have moved a step closer with the announcement that the EU clinical trials portal and database is now fully functional. This portal, the EU Clinical Trial Information System (CTIS), is integral to the Clinical Trials Regulation (CTR) since it provides collaboration tools, workflow, and reporting and document management capabilities for both sponsors and authorities across the life cycle of a clinical trial.
The CTIS, which was originally expected to be launched in September 2018, has been going through an audit by the European Medicines Agency (EMA) and the European Commission. While the authorities are continuing to audit the portal, they have noted that it is now fully functional. Once the European Commission is confident that all conditions for the regulation have been met, a notice will be published in the official journal of the European Union, and six months later the CTIS will go live and the CTR will apply. It is expected that this will happen by 31 January 2022.
Once the CTR is applicable, sponsors will have meet specific timelines. For all new clinical trial application, the initial submission must be conducted using the CTIS at latest at the beginning of the second year of the transition phase. After three years all clinical trial applications will be required to switch to the new regulation.
Using the CTIS
The CTIS comprises two restricted and structured workplaces, one for the sponsor and one for the authorities (EMA, the European Commission, national competent authorities, and ethics committees). In addition, a public website is accessible to patients, healthcare professionals, scientists, clinical research associations, media, and members of the public. This is integral to the overall goal of the European Commission, which is to ensure greater transparency of clinical data.
To start with, sponsors must create a user account to connect to the portal, after which they can begin to use the tools to submit information regarding a new clinical trial and continue to update with modifications to the trial.
When using the CTIS, the sponsor submits an initial clinical trial application using clearly defined forms that enable the sponsor to set the trial category and define the timelines for the publication of data/documents. Companies can select the member state concerned (MSC) where the trial will be conducted. The first phase is validation of the documentation, which takes 10 days, followed by a two-part evaluation.
Part 1 of the dossier contains the information that is assessed by the competent authorities, led by the reporting member state (RMS) and in collaboration with the MSC. This part of the review concerns the drug in question, including the investigational brochure, laboratory data, agreements, manufacturing information, importation documentation, and benefit-risk for the patient.
Part 2 of the dossier is the national evaluation and contains information relevant for the MSC. The review is carried out first by the ethics committee and then the national authority. It contains information about the trial and site, including the informed consent for the patient, the number of patients, inclusion/exclusion criteria, data protection, the capacity of the site and investigator, compensation to trial members and the investigator, as well as data regarding the biologic samples for testing.
The evaluation period allowed for these two parts is 45 days, plus a 31-day extension for any specific questions that arise. Sponsors should inform the MSC of any critical moments during the conduct of a clinical trial within 15 days of the start of the event. These include the start of the trial, the start of recruitment, end of recruitment, and end of trial. The trial can also be interrupted on specific grounds, including a temporary halt, which may be related to subject safety or benefit-risk balance.
For part 1, the authority of the selected RMS has 26 days to review documentation with a further 12 days for documentation to be reviewed by the MSCs, then the RMS has 7 days to finalize these conclusions.
An evaluation section in the portal allows sponsor users to access any requests for information and conclusions from the assessments carried out by the RMS and MSC.
After the initial application has been authorized, the sponsor can submit a modification to the dossier which is likely to substantially affect the safety or rights of the subjects or the reliability and robustness of the data from the trial. Furthermore, the sponsor can also apply to add a new MSC after the initial authorization.
The benefits and challenges of the CTIS
Under the previous directive, the approval process was handled country-by-country by the local competent authorities, which could often lead to a delay of a year or more between the first and last country to initiate clinical trials. The new process involves just one submission for all EU countries with all information centralized, and just a single RMS or state member coordinator which acts as the key contact with all member states.
The process is therefore much quicker and more streamlined, and, in addition, the documentation in the portal can be used for several clinical trials, rather than sponsors having to keep uploading the same documentation for different projects.
Nevertheless, this is a new system and it will take time for all users to become accustomed to using it. The EMA is offering training to clinical trial sponsors and staff of the EU Member States, European Commission, and other organisations who will use the system. However, not everyone will be able to make use of the training and it will take time for some users to work through the information on the EMA website and become comfortable with using the tools.
Our recommendation at ProductLife Group is that companies adopt a stepwise approach, perhaps piloting one clinical trial before switching all projects to the CTIS. This gives the company an opportunity to handle all aspects of the trial in the new system, including data submission, data updates, safety management, SUSAR (suspected unexpected serious adverse reaction) reporting, and so on.
Ideally, companies should also have a strategy in place for transitioning to the CTIS. ProductLife Group has a team of experts who can offer guidance on strategy and transitioning to the new portal based on regulatory intelligence. We can also assist clients with protocol writing for the clinical trial and provide full support with all clinical trial safety requirements, including individual case safety reports, SUSAR reporting, annual safety reporting, and so on.
The CTIS will likely become mandatory by the end of January 2025. The sooner companies become comfortable with using the new system, the better – for the regulatory authorities, for the sponsor and for patients and healthcare providers.
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