Electronic Trial Master Files (eTMF) is gaining significant focus by regulatory agencies and has already become a central place to validate compliance of the Trial. When it comes to Archival of study, TMF continues to be at central place in driving the compliance. A lot of studies are still managed in Paper TMF format. However, electronic format of TMF has become first choice for most to host their study TMF, due to shear advantages that eTMF applications provide over Paper. However, as with any technological advancement, eTMF comes with its own set of challenges, particularly when it comes to archival practices. Let’s delve into some of these challenges and explore potential solutions.
Regulatory Expectations on TMF Archival:
- US FDA 36905975dftrv1 III.A: Records needed for FDA to reconstruct a clinical investigation that are maintained and archived under predicate rules in electronic format in place of paper format or where the electronic record is relied on to perform regulated activities.
- US FDA 36905975dftrv1 Q6: There are various ways to retain electronic records, including in durable electronic storage devices and using cloud computing services. Sponsors, clinical investigators, and other regulated entities must ensure the authenticity, integrity, and confidentiality of the data from the point of creation and also ensure that the meaning of the record is preserved. The relationship between records, source data, and all associated metadata should be preserved in a secure and traceable manner.
- ICH-GCP E6(R3) C.2.6: The sponsor and investigator/institution should retain the essential records in a way that ensures that they remain complete, readable and readily available and are directly accessible upon request by regulatory authorities. Alteration to the essential records should be traceable.
- EMA EMA/INS/GCP/856758/2018 6.0: Articles 58 and 57 of the Regulation, both state that “the content of the clinical TMF shall be archived in a way that ensures that it is readily available and directly accessible, upon request, to the Member States.” Article 58 of the Regulation and Article 20 of Directive 2005/28/EC, also state that “any alteration to the content of the clinical trial master file shall be traceable”
- EMA EMA/INS/GCP/856758/2018 6.1: The sponsor’s TMF may be transferred to a CRO for archiving (e.g. an external archive), but the ultimate responsibility for the quality, integrity, confidentiality and retrieval of the documents resides with the sponsor.
- EMA EMA/INS/GCP/856758/2018 6.3: As per Article 58 of the Regulation “unless other Union law requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical TMF for at least 25 years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national law.”
Challenges and Solutions in eTMF Archival Process:
Challenge 1: Regulatory Compliance
Stringent guidelines are in place for document retention and archival, being a regulated industry. Ensuring compliance with these regulations while transitioning to electronic systems can be critical. Additionally, regulations may vary across different regions, basis nature of study, indication, application type, etc, adding layers of complexity.
Solution:
- Thorough Documentation: Maintain meticulous records detailing the archival process, including
- Location of archival
- Responsible personal handling archival
- Archival execution workflow
- Risk evaluation and mitigation in archival
- Timestamps of activities
- Review and approval workflows
- Any deviations from standard procedures
- Regular Audits: Conduct regular audits to ensure compliance with regulatory requirements.
- Set-up periodic review plan for archived studies
- Define scope of review to evaluate integrity, accessibility, traceability of data
- Train staff to conduct the periodic compliance reviews
- Document the review outcomes
- Utilize automated tools to streamline audit processes and minimize errors
Challenge 2: Data Integrity and Security
Security and Integrity of sensitive clinical data stored electronically, is critical when archival a TMF. The risk of data breaches, unauthorized access, or loss due to system failures poses significant challenges in the regulated environment.
Solution:
- Encryption: Implement robust encryption protocols to safeguard data both in transit and at rest.
- Establish Security and Data Integrity Plan
- Ensure secured file transfers for Archival
- Validate the source, transit and destination systems for data integrity compliance
- Access Controls: Restrict access to authorized personnel through role-based access controls (RBAC) and multi-factor authentication (MFA).
- Know the various roles that exist for Archived TMF
- Validate the access control features
- Conduct access compliance review periodically
- Regular Backups: Implement automated backup systems to regularly duplicate data and mitigate the risk of data loss.
- Build Data Backup Plan
- Perform Fall Back-Forward Validations with Data back-ups
- Ensure integrity of backed data and access controls
Challenge 3: Scalability
As clinical trials expand in scope and complexity, the volume of documentation generated grows exponentially. Managing and archiving this vast amount of data in a scalable manner presents a significant challenge.
Solution:
- Cloud-Based Solutions: Leverage cloud-based eTMF platforms that offer scalable storage and processing capabilities, eliminating the need for manual infrastructure upgrades.
- Validate security of cloud storage
- Ensure Data retention protocol for cloud storage
- Automated Archival Workflows: Implement automated archival workflows to streamline the process and ensure consistency across different trials.
- Optimize processes to reduce risks significantly
- Chose vendor that has simple, straightforward processes
- Evaluate Time in archival of TMF
Challenge 4: Legacy Data Migration
Archiving legacy paper-based or electronic TMFs to modern eTMF systems poses logistical and technical challenges. Ensuring the accuracy and completeness of migrated data is crucial.
Solution:
- Data Validation and Cleansing: Prioritize data validation and cleansing processes to identify and rectify any discrepancies or inconsistencies before migration.
- Evaluate TMF application that aligns with needs
- Build Migration and Data Validation Plan
- Document the outcomes
- Keep room for exception handling
- Phased Approach: Adopt a phased approach to data migration, starting with critical documents and gradually expanding to encompass the entire TMF.
- Perform migration in phases
- Evaluate associated risks
- Tackle with one risk at a time
- Define scope for migration by considering possible technological advantages
Challenge 5: Long-Term Preservation
Ensuring the long-term preservation and accessibility of eTMF data is essential for post-trial analysis, regulatory inspections, and future research endeavors. However, maintaining data integrity and accessibility over extended periods presents unique challenges.
Solution:
- Data Standardization: Standardize data formats and metadata to facilitate interoperability and long-term accessibility.
- Define the metadata expectations for archived studies
- Validate the performance of metadata fields
- Standardize the data that needs to be migrated
- Ensure handling of exceptions
- Regular Maintenance: Implement regular maintenance and data validation procedures to detect and address any issues that may compromise data integrity over time.
- Build Data Integrity evaluation plan
- Perform periodic compliance reviews
- Document the outcomes of the review
- Future-Proofing Strategies: Stay abreast of emerging technologies and industry standards to future-proof archival practices and adapt to evolving regulatory requirements.
- Keep looking for evolution of Archival practices
- Evaluate applicability of technology for future archivals
While eTMF offers numerous benefits over traditional paper-based systems, effective archival practices are essential to realize its full potential. By addressing challenges such as regulatory compliance, data integrity, scalability, legacy data migration, and long-term preservation through proactive measures and strategic solutions, organizations can navigate the eTMF archival maze with confidence and ensure the integrity, accessibility, and longevity of clinical trial documentation.
CLIN STREET’s eTMF platform offers a comprehensive suite of features designed to ensure best in class eTMF Archival and streamline management, all from a single location. Key features include:
- Comprehensive Document Tracking : Compliance driving feature of creating list of documents based on source TMF and tracking further progress per document till archival.
- Archival Stage Confirmations : Dedicated view for Archival managers to review progress of Archival per archival stage, allowing quality driven decision making.
- Audit Trail : Track of every activity right from Study creation till Archival confirmation in the audit trail ensuring compliance, integrity and quality of system.
- Instant Access : Ability to provide access to users instantaneously for archived TMF documents.
- Reconstruct of Trial : First class solution offering ability to review quality of archived documents using audit trails that are generated outside of CLIN STREET eTMF prior to archival.
- Metadata Mapping : Automated mapping of metadata with archived documents that are generated outside of CLIN STREET eTMF prior to archival, ensuring integrity.
- Archival Compliance Verification : System driven alerts driving compliance for open tasks associated with TMF, driving overall quality compliance of the TMF.
- Preserving Structure : Preservation of TMF Structure that was in effect during course of the trial, ensuring compliance.
- Source TMF Audit Trail : Tailored feature supporting migration of audit trail per document and system, keeping entire lifecycle of document accessible.
- Transparency : Visibility of archival process from star-to-end, coupled with decision making capability to determine further progress of archival.
- Archival Manager Role : Dedicated role to manage TMF Archival process.
- Cloud infrastructure : Cloud based application, ensuring all time accessibility to archived TMF.
We understand that overcoming challenges in the TMF Archival can be tricky and your needs are unique. That’s why we’re here to offer a tailor-made walkthrough of our CLIN STREET eTMF platform, designed to simplify and enhance your clinical trial management process. Let’s explore together how our solutions can be precisely aligned with your project’s requirements by scheduling a personalized demonstration here. Alternatively, you can also contact us at hello@clinstreet.com. Our team is available around the clock to accommodate your schedule and provide the support you need.
About the Author: Shounak Damle is a seasoned clinical trial professional with extensive experience in TMF management and other eClinical technologies. With a passion for quality assurance and compliance.
