Regulation Surrounding ISF Retention
Retention Timelines
Retention of the Investigator Site File (ISF) is a critical aspect of clinical trial management. Regulatory authorities around the world require that all essential documents be retained for a specified period after the completion or termination of a study. The purpose of this retention is to ensure that study data can be verified, audits can be conducted, and patient safety can be assessed if questions arise in the future.
It is essential that the retention period is clearly defined in the study protocol, ISF SOPs, and sponsor agreements. Investigators are responsible for ensuring that the ISF remains accessible, complete, and secure throughout the retention period.
What does ICH E6 (R3) Say About Retention?
In addition to country-specific requirements, the ICH E6(R3) guideline provides a harmonised framework for the retention of essential clinical trial records, including the Investigator Site File (ISF). According to Section 2.12.12 (“Essential Documents”), essential records should be retained for a period consistent with applicable regulatory requirements or until the sponsor confirms they are no longer needed, whichever is longer.
The guideline emphasises that records must be maintained to ensure availability, accessibility, readability, and protection from unauthorised access or accidental loss. Furthermore, it stresses the importance of version control, traceability, and secure storage, enabling efficient retrieval for monitoring, auditing, and regulatory inspections. By aligning local regulations with these principles, ICH E6(R3) supports a consistent, risk-based approach to document retention in global clinical trials.
Inspections and ISF Review
During regulatory inspections, audits, or sponsor monitoring visits, the ISF is a primary focus. Inspectors will review the ISF to:
- Verify that the study was conducted according to the protocol and Good Clinical Practice (GCP).
- Ensure that informed consent was properly obtained and documented.
- Confirm that adverse events and other safety reports were accurately recorded.
- Evaluate staff qualifications, delegation logs, and training records.
A well-maintained ISF that is complete, organised, and easily accessible can greatly facilitate inspections, reduce findings, and demonstrate compliance with regulatory requirements. Conversely, a poorly managed ISF can lead to negative inspection outcomes and long-term consequences for both investigators and sponsors.
Consequences of Failing to Retain the ISF
Failure to retain the ISF for the required period can have serious consequences:
- Regulatory Action: Inspectors from regulatory authorities can issue findings, observations, or formal warnings. In severe cases, it may result in fines or suspension of the investigator’s ability to conduct clinical trials.
2. Study Data Integrity Risk: Missing or incomplete ISFs can undermine the credibility of study data and may lead to rejection of study results by regulators.
3. Legal Liability: Investigators may face legal consequences if documentation supporting patient safety, consent, or adverse events is unavailable.
4. Sponsor Repercussions: Sponsors may terminate contracts, prevent future study participation, or require costly reconstruction of missing documentation.