Newsletter

The FDA’s Bioresearch Monitoring (BIMO) Program has intensified its focus on Good Clinical Practice (GCP) compliance. In 2024 alone, the agency issued 60 GCP-related Form 483s—a 20% increase over 2023. Warning letters have more than doubled since 2021, signaling a stronger regulatory stance.

These enforcement trends highlight persistent compliance gaps across clinical investigator sites, sponsors, and CROs. Common issues include protocol deviations, inadequate informed consent documentation, and missing case history records. For life sciences companies, the takeaway is clear: FDA scrutiny is rising, and inspection readiness must evolve from reactive to proactive.

This article outlines key inspection findings, regulatory risks, and practical steps companies can take to strengthen GCP compliance.

Key FDA GCP Inspection Trends (2020–Q1 2025) 

• Form 483s have increased from 35 in 2021 to 60 in 2024, marking a five-year high.
• Warning letters rose from 6 in 2021 to 14 in 2024, with 5 already issued in early 2025.
• Findings consistently cite protocol non-compliance, consent process failures, and inadequate safety reporting.

Note: These trends are based on FDA BIMO data for clinical trials (21 CFR Part 312). GLP (21 CFR Part 58) observations are excluded.

Top Clinical Investigator Site Citations (2020–Q1 2025)

More than 80% of clinical investigator site citations are tied to protocol non-compliance (21 CFR 312.60), often due to unreported deviations or insufficient training.

Top Sponsor/CRO Citations (2020–Q1 2025) 

FDA observations for sponsors and CROs reveal consistent documentation gaps, particularly around case histories and investigational product (IP) accountability.

FDA Warning Letter Trends: CAPA Gaps Are a Common Trigger 

Between 2020 and Q1 2025:

• Warning letters more than doubled, driven largely by inadequate responses to Form 483 observations
• Failure to follow the investigational plan (21 CFR 312.60) remains the most cited issue
• Weak Corrective and Preventive Action (CAPA) processes and delayed follow-up are primary contributors to escalation

ICH GCP E6(R3) reinforces the need for proactive, risk-based quality management and active sponsor oversight. Companies that lack these controls face higher escalation risk.

Proactive Compliance Starts Here: How Celito GCP QA Supports Biotech Sponsors

To reduce inspection risk and enhance quality systems, companies should consider the following actions that Celito can help:

• Conduct FDA-style mock inspections to assess readiness
• Implement robust CAPA systems with root cause analysis, timelines, and accountability
• Review protocol compliance metrics across sites, sponsors, and CROs
• Improve documentation governance through SOP alignment and training
• Establish oversight frameworks for CROs, IRBs, and service providers with defined KPIs
• Adopt risk-based QA programs consistent with ICH GCP E6(R3)
• Leverage centralized quality systems (e.g., cloud-based QMS) to ensure consistency and traceability across stakeholders

Conclusion

FDA inspection activity is intensifying—and the data shows a clear trend: recurring issues in protocol compliance, informed consent, and documentation are placing biotech sponsors at increased regulatory risk.

By shifting from reactive corrections to proactive oversight and risk-based QA, sponsors can reduce the likelihood of costly findings and warning letters. Strong inspection readiness, targeted training, and structured CAPA response are now essential components of a resilient GCP compliance program.

References

• ICH GCP E6(R3) 
• FDA BIMO Inspection Metrics: https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/bimo-inspection-metrics 
• FDA Data Dashboard – Clinical Investigator Inspections: https://datadashboard.fda.gov/oii/cd/inspections.htm 
• FDA Inspection Observations: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-observations 
• FDA Warning Letters: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters