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CTIS Part II: Document Management Best Practices for CTR Compliance

Written by Toban Zolman | Feb 7, 2023 9:31:00 PM

As highlighted in our previous blog, sponsors submitting trials in the EU will have to adopt a more integrated and collaborative workflow to meet the new submission requirements of EU CTR/CTIS. That in turn, impacts how data and documents are maintained and shared between the different individuals or teams working on a clinical trial submission. The focus of this blog is specifically on the impact of CTIS on document management for sponsors and we will offer recommendations for best practices to maintain compliance with the new regulation.  

1. THE FUTURE IS DIGITAL

With the mandatory implementation of CTIS, paper submissions are now a thing of the past.  

Going forward, the clinical trial application process and the exchange of information between sponsors and regulatory agencies throughout the lifecycle of the clinical trial will be fully electronic. What that means for sponsors is that, now is the time to upgrade from a paper-based system to an electronic document management system.

Documents can be uploaded but not created in CTIS. Currently, the system does not have an API (application programming interface) or allow for structured data uploads (i.e., XML files). As such, to prepare for a submission, sponsors will have to create and assemble all the necessary documents outside of CTIS in their own digital environment and manually upload them to the CTIS portal. The preparation and assembly of submission documents often involves cross-departmental collaboration; therefore, sponsors should consider establishing a document workflow that maximizes efficiency and maintains regulatory compliance.

2. TIME TO UPGRADE YOUR SYSTEMS

Although CTIS is a secure archive of documents and data, the CTIS is not a replacement for a clinical trial management system. Just as documents cannot be created in CTIS, sponsors cannot rely on CTIS to store clinical trial-related information needed for internal compliance. Sponsors are still required to have their own information management system to store and track documentation, and most will have to upgrade their electronic trial master file (eTMF), regulatory information management (RIM) and clinical trial management systems (CTMS) to meet the new demands of CTR.

Throughout a clinical trial, documents and data are shared with regulatory bodies. This information is constantly changing as the trial moves through its lifecycle. As much of the documentation is authored and edited by multiple team members, which may not be co-located, sponsors could run the risk of incomplete or inaccurate information shared with regulatory bodies. Having a system that supports the way we work today, ensuring data integrity, version control, appropriate user access and audit trails is key to ensuring compliance with regulatory requirements.

To maintain EU CTR and GCP compliance, sponsors are required to keep all records in their own eTMF. The eTMF must be up-to-date and contain all the essential documents that enable monitors and inspectors to evaluate compliance. For example, the protocol, the trial’s safe conduct process and the quality of the data, all fall under the critical information monitors and inspectors should review. A challenge with CTIS is that it does not support ‘document like’ exports of certain fields in the system (i.e., approval letters, RFIs, etc.) and, at the moment, sponsors may need to resort to filing screenshots to maintain those records in their eTMF. Sponsors will benefit from an eTMF solution equipped with dashboards that allow for easy assessment of completeness, timeliness and quality of their eTMF.  

Another benefit of upgrading from paper to an eTMF is the complete document management capability from document creation to the eventual submission and archival. With the right eTMF system sponsors can create a document, distribute it for review and approval, and be able fully track it with version control and maintain audit trails for compliance. To maximize efficiency, an eTMF system should also support 21 CFR Part 11 compliant electronic signature capabilities.  

The CTR also mandates that all trial related documents and data must be archived for at least 25 years after the end of the clinical trial, in a way that is secure and readily available to regulatory inspectors upon request.  Therefore, sponsors will need an eTMF solution that allows for archiving completed studies with easy, read-only access that is also secure and reliable.  

3. DEFINE YOUR DEFERRAL & DOCUMENT REDACTION STRATEGY

One of the main goals of CTIS is to increase transparency of information on clinical trials to all stakeholders involved, including the general public. With a few exceptions, data and documents uploaded to CTIS will be made public by default unless the sponsor has been granted a deferral. This poses a challenge to sponsors who are required to conceal personal data of trial subjects (for CTR and GDPR compliance) as well as any relevant information that is considered proprietary and commercially confidential. CTIS allows sponsors to submit a ‘for publication’ and a ‘not for publication’ version of a document, where personal and commercially confidential information is redacted from the ‘for publication’ version. Sponsors are advised to develop and define a redaction and deferral strategy to ensure compliance and avoid massive financial and reputational consequences that come with failure to comply with the transparency requirements of CTR. Sponsors should consider adoption of an eTMF that can effectively manage both redacted and unredacted document copies and recognize the link between them.  

Now is the time to address the impact of CTR/CTIS on your organization. Sponsors will need to adopt technology that can help streamline workflow around clinical trial document management while maintaining regulatory compliance. Kivo with its fully integrated RIM and eTMF solutions, functions as a central platform where clinical and regulatory teams (and in some cases external parties, like CROs) can share data and documents seamlessly. For sponsors feeling overwhelmed with the thought of implementing a new system, Kivo makes it effortless and takes the stress out of deploying a system that is ready for users to use in two weeks' time.

To see how Kivo can help you achieve CTIS readiness, visit our website to view our demo.

For additional information on CTIS requirements and its impact on clinical trial submission please refer to our recent white paper and webinar.

Note: Since our webinar, the maximum document file size uploaded to CTIS has been updated from 10 MB to 50 MB.