Why Missing Continuing Review Approvals Are Recurring IRB Audit Findings

Introduction: The Importance of Continuing Review

Continuing review approvals are a cornerstone of Institutional Review Board (IRB) or Ethics Committee (EC) oversight. They ensure that ongoing clinical trials remain ethically justified, scientifically valid, and safe for participants. Regulatory agencies such as the FDA, EMA, and MHRA require IRBs to conduct and document continuing reviews at least annually, or more frequently if necessary. Missing continuing review approvals are a recurring audit finding that undermines both participant protection and regulatory compliance.

Failure to obtain timely continuing review approvals can result in trial suspension, data invalidation, or enforcement actions. This finding often signals systemic weaknesses in IRB processes, site compliance, or sponsor oversight.

Regulatory Expectations for Continuing Review Approvals

Authorities require that IRBs conduct continuing reviews according to strict standards:

• Ongoing trials must undergo continuing review at intervals appropriate to the level of risk, but no less than annually.
• Review must include evaluation of cumulative safety data, protocol deviations, and informed consent processes.
• Approval documentation must be issued before expiration of the previous approval period.
• All continuing review approvals must be archived in the Trial Master File (TMF).
• Sponsors must verify that sites maintain valid IRB approvals throughout the study.

The ClinicalTrials.gov registry emphasizes transparency in trial oversight, underscoring the need for timely and documented continuing reviews.

Common Audit Findings on Missing Continuing Reviews

1. Expired Approvals

Auditors frequently cite trials continuing without valid IRB approval beyond the expiration date.

2. Missing Documentation

Inspection reports often highlight absent or incomplete approval letters in the TMF.

3. Delayed Reviews

Auditors note lapses where IRBs conducted reviews months after approvals had expired.

4. Sponsor Oversight Failures

Sponsors are cited for failing to verify that all sites had current continuing review approvals.

Case Study: FDA Audit on Continuing Review Gaps

In a Phase II neurology trial, FDA inspectors found that several sites had allowed IRB approvals to expire for over three months. Enrollment continued during this period without valid approvals, leading to a major audit finding. The sponsor was required to suspend enrollment and implement immediate CAPA to restore compliance.

Root Causes of Missing Continuing Review Approvals

Root cause investigations often reveal:

• Absence of tracking systems for IRB approval expiration dates.
• Administrative bottlenecks within IRBs causing delays in reviews.
• Poor coordination between investigators, sites, and IRBs.
• Inadequate sponsor oversight of multi-site IRB approvals.
• Lack of SOPs specifying responsibilities for continuing review compliance.