Hidden TMF Clinical Compliance Risks

Inspectable Content Housed OUTSIDE the TMF

In the fast-paced world of clinical trials, maintaining a robust and compliant Trial Master File (TMF) is essential for inspection readiness.  Yet, many sponsors inadvertently overlook critical TMF content that they generate during the trial, only to scramble for it during preparation for regulatory inspections or asset transfers. This oversight can create unnecessary stress and risk for organizations.  

The TMF is defined as the collection of records that show that the trial is being conducted to regulatory requirements.  This is often a compilation of systems where content is maintained.  The electronic TMF (eTMF) is a content management system specifically configured and validated to support the organization and retrieval of these records.  Here, we explore the challenges sponsors face with TMF content management and provide insights into effective solutions. 

The Overlooked TMF Content Problem 

Sponsors often outsource TMF management responsibilities to their Clinical Research Organizations (CROs). While CROs are tasked with maintaining much of the TMF, sponsors retain responsibilities for generating significant content related to their oversight of vendors, including the CRO. This includes documentation of decisions, communications, and activities demonstrating oversight and compliance. 

Unfortunately, a large portion of this sponsor-generated content often resides outside the TMF. Emails, shared drives, or unvalidated SharePoint sites become default repositories, leading to disorganization and accessibility challenges. Sponsors may not realize the importance of this content until they are preparing for a regulatory inspection or planning to transfer an asset. At this point, retrieving and organizing this content becomes a time-intensive endeavor. 

Why Does it Matter Where TMF-Related Content is Stored?

Regulatory authorities, such as the FDA, MHRA, and EMA, consider all TMF content inspectable. This includes not only the records in the official eTMF system but also any records that support the sponsor’s oversight activities that may be held in other systems. Failure to appropriately manage and maintain these records in a validated system can lead to inspection findings, delayed approvals, or reputational damage. 

What’s the Worst that Could Happen? 

• Non-compliance with regulatory requirements:  Shared drives and unvalidated systems like SharePoint often lack the necessary controls for electronic record management, such as audit trails and access restrictions. 
• Disorganization during inspections: Critical content scattered across multiple systems creates delays and inconsistencies when trying to respond to inspector requests. 
• Compromised data integrity: Without proper metadata assignment or validation, records can lose their context and traceability. 

Are You Sharing Content on a Validated Clinical System? 

One prevalent misconception is that storing content in SharePoint or similar tools is sufficient. While these platforms may offer convenience, they typically do not meet regulatory requirements for maintaining electronic records. For example, they often lack: 

• Validation to ensure the system operates as intended. 

• Audit trails to track who accessed or modified a document. 

• Secure access controls to protect sensitive information. 

• The ability to easily retrieve a record during the inspection 

• The ability to give the inspector direct access to the record 

Regulators expect sponsors to use validated systems for managing trial records. Content stored in non-compliant systems must be transferred to the eTMF with appropriate oversight. 

The Value of TMF Remediation 

For companies preparing for regulatory inspections or asset transfers, remediation becomes an essential step. This involves reviewing shared drives and other repositories, identifying inspectable content, and ensuring it is appropriately filed in the eTMF. 

Remediation activities may include: 

• Reviewing: Reviewing and filing sponsor-generated content from emails and shared drives into the eTMF. 

• Content Uploading: Ensuring records are moved into validated eTMF systems. 

• Metadata Assignment: Properly tagging content for easy retrieval and traceability. 

• Post-Migration Quality Checks: Verifying the accuracy and completeness of migrated content. 

By addressing these gaps proactively, sponsors can avoid last-minute chaos and ensure that their TMF aligns with regulatory expectations. 

The Solution

At Just in Time GCP, we specialize in records management services tailored to the needs of pharmaceutical and biotech companies. Whether you are preparing for an inspection, transferring an asset, or simply seeking to improve your TMF processes, our team can: 

• Conduct comprehensive reviews of shared drives and other repositories to identify potential TMF content. 

• Identify and organize inspectable content. 

• QC and upload the content into your eTMF 

• Ensure your TMF is inspection-ready and compliant with regulatory standards. 

Proactive management of TMF content not only supports regulatory readiness but also enhances clinical operational efficiency and reduces risks. 

Conclusion

Overlooking sponsor-generated TMF content can lead to significant challenges during regulatory inspections or asset transfers. By addressing this gap now, you can ensure compliance, maintain data integrity, and demonstrate robust oversight. Don’t let disorganized records jeopardize your success—partner with us to streamline your TMF management and achieve peace of mind. 

If your organization is facing these challenges, contact us to learn more about how our records management services can help.