1. INTERNAL AUDITS OF LABORATORIES Sanjay S Shetgar 1

2. Quality Systems Guidance

3. Quality System The requirements of a good Quality System are no more than common sense and good business practice A comprehensive pharmaceutical quality system – Management Involvement for resource and review – Promotes a lifecycle approach to product quality. – Promotes innovation and continual improvement. – Provides opportunity to optimize regulatory processes.

4. Typical Quality Management Review Critical / Major audit findings and status of closure ( Regulatory / Internal ) Trends and Status of Quality Indicators like Deviations, Non-conformances, OOS, Complaints, Environment, Rejections Product / facility / personnel issues if any CAPA status Major change controls

5. Audits It is a systematic and independent examination to determine whether or not the quality activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve the objective. These can be formal or informal, random and unannounced.

6. Why Audits Why is there a need to audit ? Health of Quality System Identify gaps and avoid potential big problems Mitigate risk Simplification and better allocation of resources Continuous improvement Assurance to management Audit ready at all times

7. Requirements Carried out by trained and qualified personnel Personal preferably independent of activity being audited Set the scope for the audit Divide laboratory based on risk and audit one by one each of the identified area Use of checklist Documentation Develop Corrective and Preventive actions Escalation and review by Management Follow up for effectiveness check Periodic Audit

8. Auditing What a auditor should know -Finding will not be in a open platter to pick up -You have to search for it ( or else auditee would have anyway identified ) Look at type of findings from previous audits. Evaluate and check where the maximum number of observations are seen however small Concentrate on this area during the audit

9. Example of Plan ( Cont.) Category of observationObservations Personal related5 % Standard Maintenance8 % Specification and test methods 5 % Calibration and Preventive maintenance 20 % Method validation5 % Out-of-specifications and investigations 22% Chromatographic data20 % Management Reviews15 % Calibration, OOS, and Chromatographic Data areas would require priority reviews

10. Methods Develop a plan for the audit right from start to end ( including a start up meeting and close up meeting ) Draw up a checklist Typical Checklist for EquipmentTypical Checklist for Equipment Questions should be – open ended as far as possible Observe behavior and body language and tone of speech Make the auditee feel at home Listen Collect facts and relate it to the committed practice Make a audit report that is Clear, Concise, Complete, Concrete and Courteous. Classify the observations into categories of non- conformances based on findings Communicate the findings to management. Template Audit ReportTemplate Audit Report

11. Expectations on Good Laboratory Practices as part of Schedule L-I Effective 1 st November 2010 This rule makes specific mention and controls in following areas -General Requirements -Premises -Personnel -Equipment -Chemical & Reagents -Good House keeping and Safety -Maintenance, calibration and validation of equipment -Reference materials -Microbiological cultures -Quality Systems -Internal Quality System Audits -Management Reviews -SOPs -Protocols and Specification Archive -Raw Data -Storage and Archival

12. Frequent Warning Letter Citations Laboratory Testing and Controls – 40 % Validation and Qualification – 20 % Inadequate Investigations – 20 % Quality Unit Approval and Oversight - 10% Documentation and Recordkeeping - 10 %

13. Typical Observations Laboratory Testing and Controls General Laboratory Controls Failure to perform system suitability testing Failure to re qualify reference standards Failure to follow USP test methods Laboratory computer system security Use of common passwords Reassignment of administrator privileges (to modify and delete data) to other laboratory personnel

14. Typical Observations Stability Testing Failure to establish a stability indicating test method Failure to have an approved stability protocol Failure to follow protocol requirements Failure to perform stability testing

15. Typical Observations Validation and Qualification Failure to validate and/or qualify - Analytical test methods - Laboratory computer systems - Manufacturing equipment and laboratory instruments

16. Typical Observations Validation and Qualification Failure to maintain specifications for equipment qualification Drawings Purchase orders Failure to re qualify equipment after modification

17. Typical Observations Quality Control Unit (QCU) No SOP defining the responsibilities of the QCU QCU not fulfilling responsibility to ensure product quality and GMP compliance

18. Typical Observations Quality Control Unit (QCU) Inappropriate QCU release Releasing products with failing results Releasing products based on satisfactory retest results without an investigation Releasing products made with microbiologically contaminated raw and in- process materials, based on satisfactory final product testing results

19. Typical Observations Quality Control Unit (QCU) Failure to detect errors in batch records Approval of batches with inaccurate and incomplete test results Allowing failing products to remain in distribution Failure to investigate deviations and test failures

20. Typical Observations Recordkeeping and Documentation Failure to document at the time of performance Inadequate master and batch record instructions and documentation No documentation for component weighing No time limits for aseptic processing

21. Typical Observations Recordkeeping and Documentation No documentation for: In-process test results Quality control unit release Investigations Calibration Microbiological media preparation and growth promotion

22. Typical Checklist for Equipment S.NoChecksObservations Y / N / NA Comments 1Is there a system to have a unique code for each piece of equipment 2Are the equipment placed in a environment as per its need and is there a status log available ? 3Are there SOPs which define the calibration and maintenance of the equipment ? 4Are calibration and maintenance schedules adhered to ? 5Is there are a check on equipment suitability after a modification? -Do such modifications go through a change control process - Is there a mechanism to capture history of the equipment 6Is there a system to indicate defective equipment ? - Are they calibrated prior to next use ?

23. Template Audit Report Audit Number : Department : Date(s) of audit : Auditors : Scope of Audit : Type of Audit : ----------------------------------------------------------------------------------------------------------------------------------------------------- Executive Summary : Lead Auditor : ( Sign / Date ) ________________________________________________________________________________________________ __________________________________________________________________________________________ Audit Closure Statement : Head Quality ( Sign/Date) : ________________________________________________________________________________________________ Sl.noNon- conformanceClassificationAgreed Corrective and Preventive Action Responsibilit y / Date Status Open / Closed

24. QUESTIONS