1. Clinical QA Data Audits A GCP Point of View Linda Del Paggio GCP Compliance BioBridges, LLC

2. Agenda Introduction ICH and GCP GCP and Data Integrity Investigator Site Audits Data Vendor Audits

3. The ICH E6 Good Clinical Practice Consolidate Guideline: Good Clinical Practice is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.

4. The ICH E6 Good Clinical Practice Consolidate Guideline: Compliance with the standard provides public assurance that the rights, safety and well-being of subjects are protected, consistent with principles that have their origin in the Declaration of Helsinki and that the clinical trial data are credible.

5. GCP & Data Integrity What is GCP? A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provide assurance that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are protected.

6. GCP & Data Integrity Selected Principles of the ICH GCP All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation, and verification. Systems with procedures that assure the quality of every aspect of the trial should be implemented.

7. GCP & Data Integrity Specific ICH Regulations ICH 5.1.1 – the sponsor is responsible for maintaining quality assurance and quality control systems with written SOPs to ensure trials are conducted and data are generated, recorded, and reported in compliance with the protocol, GCP, and applicable regulatory requirements.

8. GCP & Data Integrity Specific ICH Regulations ICH 5.1.3 – Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly.

9. Investigator Site Audits First line of data retrieval ALCOA Attributable Legible Contemporaneous Original Accurate

10. Investigator Site Audits Processes Protocol Adherence Investigator supervision Protocol Deviations/waivers Monitoring Safety Monitoring

11. Data Vendor Audits Types Of Vendors Standard Data Management Data Vendors Clinical Laboratories ECG Vendors PK Analysis Vendor Phase I Facility

12. Data Vendor Audits Types Of Audits Qualification Audits Ongoing Study Audits Data Audits

13. Data Vendor Audits Qualification/Ongoing Audits Evaluation of: Organization Facilities Systems Processes

14. Data Vendor Audits Organization Organizational Chart Number of facilities Who, What,Where Number of employees, FTE Departmental Structures Turn over rates Average length of employment

15. Data Vendor Audits Facilities Adequate to support functions Work Flow Adequate security Adequately protected Adequate back-up of data

16. Data Vendor Audits Systems Quality Function Standard Operating Procedures Work Instructions Employees Job Descriptions CVs Training

17. Data Vendor Audits Processes How is the data received How is the data verified How is the data transferred How is the data stored How is the data secured How is the data saved

18. Data Vendor Audits Ongoing Study Audits Systems Processes Data Audits

19. Data Vendor Audits Ongoing Study Audits Systems Standard Operating Procedures Work Instructions Employees Job Descriptions CVs Training

20. Data Vendor Audits Ongoing Study Audits Processes Study Set Up Data Flow Data Analysis

21. Data Vendor Audits Study Set Up Contracted Functions Transfer of Obligations Personnel Training Project Management Project Oversight

22. Data Vendor Audits Data Flow Documentation of Data/Samples: Receipt &Condition Verification & Problem Resolution System Entry/Tracking Transfer Storage Analysis

23. Data Vendor Audits Data Verification Was the data generated per protocol and internal procedures? Does the raw data generated match the final data set?

24. Data Vendor Audits Data Verification Vendor Types Data Management Vendor Clinical Laboratory ECG Vendor

25. Data Vendor Audits Data Verification Methods Data Management Database Audit CRF Data to Database Audit Trails Data Management Plan

26. Data Vendor Audits Clinical Laboratory Raw data to CRF, eCRF or database Audit Trails Comparison with normal ranges Turn around time to site

27. Data Vendor Audits ECG Vendor Transfer of Data Reading of Data Reporting of Data Over read of Data Data matches CRF/Database Audit Trails

28. Data Vendor Audits Conclusion