The Foundation of Regulatory Trust

Data integrity is not merely a regulatory checkbox. It is the foundation upon which regulatory trust is built. When you submit non-clinical safety data to the FDA, EMA, or other regulatory authorities, you are making a promise that the data is accurate, complete, and reliable. GLP audits are designed to verify that promise.

In recent years, data integrity has become a major focus of regulatory inspections worldwide. The FDA has issued numerous Warning Letters citing data integrity violations, and the EMA has published guidance emphasizing the importance of data integrity in GLP studies. Organizations that fail to maintain data integrity face serious consequences, including study rejection, regulatory delays, and potential legal action.

This article explores why data integrity plays a major role in GLP audits and provides practical guidance for ensuring your data meets regulatory expectations.

What Is Data Integrity in the GLP Context?

Data integrity refers to the accuracy, completeness, consistency, and reliability of data throughout its lifecycle. In the GLP context, data integrity encompasses all data generated during a non-clinical study, from raw observations to final reports.

Regulatory agencies expect that data will be:

• Accurate: Free from errors and reflecting true observations

• Complete: Including all data generated during the study, with no omissions

• Consistent: Free from contradictions and logical inconsistencies

• Reliable: Trustworthy and verifiable through audit trails

• Traceable: Allowing reconstruction of the study from raw data to final report

Data integrity is not just about preventing fraud. It is about ensuring that decisions made based on your data are sound and that regulators can have confidence in your submissions.

The ALCOA+ Framework Explained

Regulatory agencies worldwide use the ALCOA+ framework to assess data integrity. ALCOA+ was originally developed by the FDA and has been adopted by the EMA, WHO, and other regulatory bodies as the standard for data integrity assessment.

The ALCOA+ principles are:

• Attributable
  Every data point must identify who generated it, when it was generated, and on what system. This requires user identification and authentication for electronic systems and signatures for paper records.
• Legible
  Data must be readable throughout its retention period. This means using permanent ink for paper records and ensuring electronic records remain accessible as technology evolves.
• Contemporaneous
  Data must be recorded at the time of the activity, not hours or days later. Contemporaneous recording reduces the risk of errors and omissions and provides a more accurate picture of study conduct.
• Original
  Data must be the first recording or a certified true copy. Original recordings provide the most reliable evidence of study conduct.
• Accurate
  Data must be accurate, with verified calculations and consistent units. Inaccurate data, even if unintentional, can compromise study validity.
• Plus Principles
  The ALCOA+ framework adds five additional principles:
• Complete: All data must be included, with no omissions.
• Consistent: Data must be logically consistent, with no contradictions.
• Enduring: Data must be stored in durable media that will survive throughout the retention period.
• Available: Data must be accessible for regulatory inspection throughout the retention period.
• Traceable: Data must be traceable through all transformations and manipulations.

Common Data Integrity Violations in GLP Audits

Data integrity violations are among the most common findings in GLP audits. Some of the most frequently cited violations include:

Corrections That Obscure Original Entries
Using correction fluid, overwriting, or obscuring original entries is a serious violation. Correct procedures require striking through the error, entering the correction, and dating and initialing the change.

Missing Signatures and Dates
Auditors frequently find records that are not signed or dated. This makes it impossible to determine who generated the data and when, violating the attributability and contemporaneity principles.

Data Recorded on Loose Notes
Data should be recorded directly into official study records. Recording data on loose notes that are later transcribed increases the risk of errors and omissions.

Undocumented Deviations
Deviations from the approved study plan must be documented and justified. Undocumented deviations suggest that the study may not have been conducted as planned.

Inadequate Audit Trails
Electronic systems must maintain audit trails showing who accessed, modified, or deleted data. Inadequate audit trails make it impossible to verify data integrity.

Data Manipulation
The most serious data integrity violation is deliberate data manipulation. This can include altering data to achieve desired results, deleting data that does not support conclusions, or fabricating data entirely.

Electronic Records and Audit Trails

As laboratories increasingly adopt electronic systems, maintaining data integrity for electronic records has become a major focus of GLP audits. The FDA’s 21 CFR Part 11 establishes requirements for electronic records and electronic signatures, and OECD GLP guidance also addresses computerized systems.

Key requirements for electronic records include:

Validation
Computerized systems must be validated to ensure they perform as intended. Validation documentation must demonstrate that the system meets its specified requirements.

Audit Trails
Electronic systems must maintain audit trails showing who accessed the system, what actions were performed, and when those actions occurred. Audit trails must be enabled and cannot be disabled.

Access Controls
Access to electronic systems must be controlled through user identification and authentication. Users must have appropriate privileges based on their roles.

Backup and Recovery
Electronic records must be backed up regularly to prevent data loss. Disaster recovery procedures must be in place and tested.

Archiving
Electronic records must be archived in a format that remains readable throughout the retention period. As technology evolves, data must be migrated to new formats as needed.

How GxP Cellators Ensures Data Integrity in GLP Audits

At GxP Cellators, we understand that data integrity is the cornerstone of GLP compliance. Our auditors are trained to scrutinize data integrity at every level, from raw data generation to final report preparation.

With over 500 GLP audits successfully completed, our certified GLP and IRCA auditors bring extensive experience in identifying data integrity issues. Our team includes professionals with RQAP-GLP and IRCA Auditor certifications, ensuring that our auditing methodologies comply with international standards.

Our data integrity audit approach includes:

• Raw data scrutiny: We check for the golden rules of direct, prompt, legible, dated, signed data with changes documented and no obscuring of original entries

• Audit trail review: We verify that electronic systems maintain complete audit trails that cannot be disabled

• Deviation analysis: We examine deviation logs to ensure all deviations are documented and justified

• Data reconciliation: We trace data from raw observations through intermediate calculations to final reports, verifying accuracy and completeness

• System validation review: We examine validation documentation for computerized systems

• Backup and archive verification: We confirm that backup and archival procedures are in place and functioning

Our services include:

• Internal gap assessments covering data integrity across all ten OECD GLP sections and corresponding subparts of 21 CFR Part 58

• Sponsor-side audits of CROs with a focus on data integrity

• Full-spectrum GLP study audits including toxicology, pharmacokinetics, bioanalytical method validation, genotoxicity, reproductive toxicology, carcinogenicity, dermal and ocular toxicology, and ecotoxicology

• Detailed audit reports with findings linked to specific regulations and actionable recommendations

• CAPA support and verification to ensure data integrity issues are effectively addressed

Why sponsors choose us: We speak both the regulatory language and the scientific language. Our findings are factual, evidenced, and actionable. As an independent third-party audit firm, we have no organizational biases or conflicts of interest. Our audit reports carry greater credibility with regulatory authorities, clients, and business partners.

Our global presence spans Saskatchewan, Calgary, Toronto, North Carolina, Indiana, and Frankfurt, enabling us to deploy auditors worldwide and understand local regulatory nuances while upholding the OECD framework.

Ready to ensure your data integrity meets GLP standards? Let GxP Cellators help you achieve compliance with confidence.

Reach out to us today to schedule your GLP audit.

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Phone: +1 (306) 715-9460

Website: /gxp-auditing/

GxP Cellators – Your Certified GLP Audit Partners