Auditing Chromatographic Electronic Data. Jennifer Bravo, M.S. QA Manager Agilux Laboratories

Transcription

1 Auditing Chromatographic Electronic Data Jennifer Bravo, M.S. QA Manager Agilux Laboratories

2 Outline Raw data paper or electronic record? Controls for electronic data Auditing electronic records Warning letters and 483s Slide 2

3 The Big Question When does the electronic record = raw data? Slide 3

4 Raw Data 21 CFR 58.3 (k): Raw data means any laboratory worksheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities of a nonclinical laboratory study and are necessary for the reconstruction and evaluation of the report of that study Raw data may include photographs, microfilm or microfiche copies, computer printouts, magnetic media, including dictated observations, and recorded data from automated instruments. Slide 4

5 Electronic Record 21 CFR 11.3 (b)(6): Electronic record means any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system. 21 CFR (c): Protection of records to enable their accurate and ready retrieval throughout the records retention period. Slide 5

6 What does it mean? Evaluate the nature of the system and the electronic record If electronic format is used in lieu of paper printouts = part 11 applies If paper printouts are used, then those printouts must meet predicate rule requirements and maintain the meaning and content of the source electronic record. If the printouts do not meet these requirements, then the source electronic record = raw data Predicate Rule Requirement Preserves Content Preserves Meaning Raw Data i.e. Underlying requirements set forth in the Federal Food, Drug, and Cosmetic Act, Public Health Service Act and FDA regulations. Ability to expand baselines Ability to check audit trails Ability to query / sort Slide 6

7 Comparison Printouts = raw data Electronic record = raw data X Scientist decides what to print Supervisory personnel review the printouts QA audits the printouts Not accurate and complete! Scientist cannot pick and choose what supervisory personnel or QA can view Review and audit performed on electronic record Accurate and complete Slide 7

8 Electronic Record Controls Must meet Part 11 requirements Checks Document Controls Audit Trails CDS must be validated Accuracy Reliability Consistent intended performance Ability to discern invalid or altered records Training VALIDATION Security Archival [21 CFR (a)] Slide 8

9 Audit Considerations Slide 9

10 Workflow Mobile Phases Needle Rinses Guard Column HPLC Column Sequence LC method MS method Quantitation Method Instrument Setup Acquisition Processing Results Electronic Audit Trail Slide 10

11 Paper vs. Electronic Record Paper Injection sequence LC method MS method Result table Chromatograms Electronic Record Same information as paper Must be reviewed by PI or supervisory personnel Must be audited by QA Plus metadata (i.e. data about data), such as audit trails Must be audited by QA Slide 11

12 Where to Start? Audit Trails Chronological record of system actions that is sufficient to reconstruct, review and examine an operation. Creation Modification Deletion Secure Independent of Operation Audit Trail Computer Generated Time / Date Stamped Slide 12

13 Caveat Deletion events not captured in audit trail Work around Define in SOP Slide 13

14 Audit Trails Are They Useful? Audit trails available in Analyst Software Instrument Records events at the instrument level (e.g. login/logout events) Project Records events at the project level, including opening, closing and printing events Quantitation Records events for the result table, such as sample and peak information Slide 14

15 Instrument Audit Trail Login / logout events Batch submissions Slide 15

16 Project Audit Trail Close / access modules Open / close files Printing events Slide 16

17 Quantitation Audit Trail Review Creation Saving Modification Slide 17

18 Modified Records Slide 18

19 Potential Issues? Acceptance criteria for LLOQ accuracy ± 20% 2/3 of QCs must meet acceptance criteria Slide 19

20 Look at the Audit Trail Slide 20

21 Finishing the Audit Slide 21

22 FDA s Message WARNING LETTERS AND 483s Slide 22

23 Failure to Validate There was a failure to validate the [redacted] software to assure that all data generated by the system was secure. This software runs the laboratory HPLC equipment, generates and stores data, and performs calculations during testing of raw materials, in-process materials, finished products, and stability samples. [File No: 07-NWJ-10] Slide 23

24 Failure to Exercise Appropriate Controls All laboratory personnel were given roles as [redacted] Managers, which allowed them to modify, delete, and overwrite results files Your laboratory computer system lacks necessary controls to ensure that data is protected from tampering, and it also lacks audit trail capabilities to detect data that could be potentially compromised. [File No: 08-ATL-13] Slide 24

25 Failure to Maintain Electronic Records Laboratory records do not include a complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation prior to November 2004, your firm did not maintain documentation of [redacted] operating conditions and settings used for [redacted] analysis nor the complete raw data. After November 2004, the operating parameters were maintained with the relevant [redacted]. However, the [redacted] electronic raw data was not saved [WL: ] Slide 25

26 Failure to Review Electronic Records The Quality Unit failed to: review electronic data as part of batch release, review computer audit trails in the Waters Empower Data Acquisition System... These practices led to the Quality Unit releasing batches of drug products which failed to meet specifications These practices lead to the submission of erroneous data The lack of Quality oversight resulted in: the ceasing of manufacturing on 5/19/05, the ceasing of distribution of all drug products on 5/26/05 5/13/05, the recall of all batches of drug products and the withdrawal of at least five Abbreviated New Drug Applications. [FEI# ] Slide 26

27 Discrepancy Between Paper and Electronic Records There was a failure to check for accuracy the inputs to and outputs from the "Total Chrom Data Acquisition System," which is used to run your firm s HPLC instruments during analysis of drug products. For example, electronic data files were not routinely checked for accuracy and, as mentioned in the above observations, our investigators found numerous discrepancies between the electronic data files and documentation in laboratory notebooks. [File No: 07-NWJ-06] Slide 27

28 Failure to Review Audit Trail Due to the common password and lack of varying security levels, any analyst or manager has access to, and can modify any HPLC analytical method or record. Furthermore, review of audit trails is not required. [File No: 06-NWJ-14] Slide 28

29 Conclusions Slide 29

30 Transition Challenges Cultural shift for QA Learn how to navigate through the chromatography software Learn how to audit electronic records For hybrid systems ensure electronic record is consistent with paper record Preservation of electronic records Slide 30

31 Opportunities Benefits of auditing the electronic record Ability to perform queries Focus on high risk items Re-integrations Manual integrations Improve auditor-to-auditor consistency Increased efficiency Speak the same language as scientist Better communication Collaborative interaction Slide 31

32 Acknowledgements Jim Jersey, Brian Lilley and Chris Fuller from Agilux Labs. Monica Cahilly from Green Mountain Quality Assurance, LLC Chris Tudan from BioAccurate Enterprises, Inc. Slide 32

33 Questions? Slide 33