Laboratory Data Integrity Issues Found in Audits and Inspections

Transcription

1 Laboratory Data Integrity Issues Found in Audits and Inspections Presented by: Chris Wubbolt, BS, MS IVT Laboratory Data Integrity December 12 14,

2 Objectives Brief Overview of Data Integrity Related Guidance and Regulations pertaining to Laboratory Data Integrity Review and discuss data integrity issues identified during audits and regulatory inspections 2

3 Current Regulatory Requirements and Guidance March 2015 MHRA - GMP Data Integrity Definitions and Guidance for Industry September 2015 WHO - Guidance on Good Data and Record Management Practices April 2016 FDA Data Integrity Guidance and Compliance with CGMP 3

4 Current Regulatory Requirements and Guidance July 2016 MHRA - GxP Data Integrity Definitions and Guidance for Industry August 2016 PIC/S - Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments August 2016 EMA Data Integrity Guidance Q&A 4

5 Data Integrity Completeness, consistency, and accuracy of data. Attributable Legible Contemporaneous Original (or true copy) Accurate Enduring Complete Consistent Retrievable 5

6 FDA Guidance Key Terms Can CGMP data be excluded from decision making? Should access to systems be restricted? Use of Shared Logins Are electronic copies accurate reproductions? Can static records be retained instead of electronic? 12/13/

7 FDA Guidance When does electronic data becomes a GMP record? Can electronic signatures be used instead of handwritten? Is it Acceptable to only save final results from chromatographs? Handle internal tips of data integrity issues informally? Training on detecting data integrity issues? How should data integrity issues be addressed? 7

8 Data Lifecycle Specify Design Configure Generate Modify Review / Approve Use Retain / Retrieve Destroy Verify Validation

9 Data Lifecycle Non-Standard Build Standard Build X Date/time stamp controls Network backup Access controls Audit logs not backed up User access not controlled 9

10 Static FDA Guidance Static & Dynamic Records Fixed-data document such as a paper record or an electronic image. Dynamic Format that allows interaction between the user and the record content. Chromatographic Record Allows user to change the baseline. Reprocess chromatographic data. Resulting peaks may appear smaller or larger. Spreadsheet User modification of formulas or entries used to compute test results. 10

11 Static / Dynamic Data

12 Static / Dynamic Data System Suitability: %RSD < 2.0% %RSD 3.9% X 12

13 Data Integrity throughout the Lifecycle Generate Modify Review / Approve Use Retain / Retrieve Destroy 13

14 Backup and Restore Backup and Restore Bioanalytical Laboratory Backup and Restore SOP Failed backup required a help desk ticket 3 failed backups require notification to Director of Infrastructure Technology 5 failed backups require notification to CTO Requested backup logs for three months No successful backups for June or first two weeks of July No help desk tickets generated for month of June Director and CTO were not notified Director and CTO were not aware of failures Potential Data Integrity Issue 14

15 Data Integrity Good Documentation Practices Use indelible (permanent blue or black ink). Do not use pencil, correction fluid or tape. Do not obliterate original entry. Use single line cross-out, initial, date, reason for change. Record data only on GMP documents. Do not record data on unofficial documents (paper towels, note pads, etc.). Record data when activities are completed. 15

16 Data Integrity Good Documentation Practices - Error Codes Codes: TE Transcription Error CE Calculation Error WD Wrong Date WT Wrong Time WO Write Over EE Entry Error Use of foot notes is acceptable 16

17 Documentation Practices Single Line Reason Initial and Date 17

18 Certificate of Analysis Laboratory Record Review ph Result was originally recorded as 5.4; the spec is 5.8 to 6.5. A reason for this change was recorded as entry error. Polysorbate 80 Gross weight changed from to , but change was only made after net weight was calculated. 12/13/

19 FD-483 July

20 Warning Letter Cadila Healthcare (Dec 2015) Your firm failed to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data. Our inspection team found that the laboratory manager had the ability to delete data from the Karl Fischer Tiamo software. We found that one file had been deleted. However, because the audit trail function for the Karl Fischer Tiamo software was not activated, and because eight different analysts share a single username and password, you were unable to demonstrate who performed each operation on this instrument system. The inspection also found that a file containing the moisture content results for (b) (4) API batch (b)(4) had been deleted. This deletion was not identified and reviewed as part of your batch release decision. 20

21 Sekisui Warning Letter November 8,

22 Sekisui Warning Letter November 8,

23 Sekisui Warning Letter November 8, 2016

24 Sekisui Warning Letter November 8, 2016

25 Summary Provided a brief Overview of Data Integrity Related Guidance and Regulations pertaining to Laboratory Data Integrity Reviewed data integrity issues identified during audits and regulatory inspections 25

26 Questions Chris Wubbolt QACV Consulting, LLC Telephone: