Roles & Responsibilities

Sponsor Responsibilities in ISF Retention

The sponsor has significant responsibilities in defining and supporting ISF retention practices according to ICH GCP, regional regulations, and the evolving guidance under ICH E6(R3).

Under ICH E6(R3), there is a greater emphasis on sponsor accountability in the following areas:

  • Ensuring that trial documentation (including the ISF) is retained, protected, and accessible for the required duration
  • Establishing clear procedures and agreements for document retention, transfer, and destruction
  • Demonstrating effective oversight of delegated tasks, such as when retention responsibilities are handed over to a CRO, investigator, or archive vendor
  • Using risk-based approaches to ensure essential documents remain complete, accurate, and available for inspection

Job Functions & When They’re Needed

Function
Key Role in ISF Retention
When They're Involved
Principal Investigator (PI)
Ultimately responsible for the ISF’s accuracy, completeness, and accessibility; ensures delegation of maintenance tasks is documented and supervised.
Throughout the trial: from site initiation, through conduct, to closure and archiving.
Archivists
Manage physical/digital long-term storage
End of trial or after site closure
Records Managers
Establish retention schedules, classification systems, and retrieval processes for ISFs; ensure compliant disposition at end of retention period
Primarily post-study through retention period; consulted at trial start for retention requirements
QA/Auditors
Review ISF integrity & compliance
During audits, inspections, or QA checks
Regulatory Affairs
Align ISF documents with regulatory submissions
Post-study; before filing
Legal & Compliance
Define roles in contracts & CTAs
Startup and negotiation phase
IT/Data Managers
Ensure secure digital archiving systems
If eISF or centralised storage is used
Monitors (CRA)
Confirm ISF completeness & compliance
Throughout trial; during close-out

The Importance of the Principle Investigator

Both the EMA (Europe) and U.S. FDA regulations emphasise that the Investigator Site File (ISF) is a record of accountability. The Principal Investigator is ultimately responsible for ensuring that the ISF is accurate, complete, and readily available for inspection, with any delegated maintenance tasks clearly documented and supervised. Under EU CTR, this responsibility extends across the entire trial lifecycle, requiring the site team to demonstrate compliance with Good Clinical Practice at all times.

Similarly, FDA requirements under 21 CFR 312.62 for drug trials and 21 CFR 812.140 for device trials make clear that investigators must maintain and retain case histories, informed consent forms, investigational product accountability, and correspondence, with these records available for inspection.

Around the PI, roles such as study coordinators, archivists, records managers, and QA personnel contribute to daily upkeep, quality checks, and long-term retention, but regulations underline that accountability for the ISF cannot be transferred away from the investigator.

Regulations

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Good Practice

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