Excipient Auditing

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  • 1. Implementing GMP Auditing Practices for Excipient Suppliers July 30, 2001
  • 2. Qualifying an Excipient Supplier
    • Confirm adherence to cGMP's
      • Include subcontractors, repackagers, and distributors
    • Periodically reconfirm adherence to cGMP
    • All material traceable during lifecycle
    • Acceptance testing or COA
    • Notification of significant changes
  • 3. Uniqueness of Excipients
    • Manufacturers
    • Manufacturing Process
    • Chemistry
    • Scale of Manufacture
    • Characterization
    • Applications
  • 4. Where does GMP start? Review the scenarios and identify the processing point at which GMP principles should be applied. State your reasons as to why you feel this is the appropriate point to apply GMP.
  • 5. Where does GMP start? NaOH
  • 6. Plant Site Chemistry Higher Vinylethers Methyl Vinylether GAFGARD 233 Maleic Anhydride GANTREZ AN Formaldehyde Methanol NEP Ethyl HEP Hydroxyethyl LP100 Octyl LP300 Dodecyl CHP Cyclohexyl Caprolactam
    • Poly(vinylpyrrolidone )
    • PVP/PLASDONES
    • PVP-I (Iodine)
    • POLYCLAR
    • Copolymers
    • PVP/VA (vinyl acetate)
    • GAFQUAT (DMEAMA)
    • POLECTRON (Styrene)
    • ACRYLIDONE
    • GANEX (Olefins)
    • GAFFIX
    EVE n-BVE HBVE DVE-3 CHVE CVE PEPC DDVE EHVE GANTREZ S water ES 3351 IPA ES 225 ethanol ES 425/ES 435 butanol GANTREZ MS carbonates
  • 7. Povidone Chemistry Formaldehyde Methanol
    • Polyvinylpyrrolidone
    • Povidone
    • Povidone Iodine
    • Crospovidone
  • 8. Assessing Excipient Supplier GMP Conformance
    • First party questionnaire
    • Second party audit
    • Third party audit
      • Regulatory audit
      • ISO Audit
      • IPEA Audit
  • 9. Reference Materials
    • GMP Guide for Bulk Pharmaceutical Excipients
    • GMP Audit Guideline for Bulk Pharmaceutical Excipients
    • GMP Audit Guideline for Distributors of Bulk Pharmaceutical Excipients
    • Significant Change Guide for Bulk Pharmaceutical Excipients
    • COA Guide for Bulk Pharmaceutical Excipients
  • 10. IPEC GMP Guide
    • Introduction
    • Definitions
    • General Guidance
    • Excipient Quality Systems
    • General Auditing Considerations
    • Appendix
  • 11. IPEC Audit Guides
    • Manufacturer-1998
      • Detailed questions-GMP Guide
      • Reminder phrases-GMP Guide
      • Detailed questions-Audit Flow
    • Distributor-2000
      • Includes additional guidance
  • 12. IPEC Audit Guide Manufacturer
    • GMP Audit Flow
      • General information
      • Materials flow from component to excipient
      • Documentation
  • 13. Reconfirm Adherence to cGMP
    • Periodic re-audit
    • Purchase IPEA Audit Report
      • Valid for 2 years
  • 14. IPEC Audit Guide Distributor
    • GMP Audit Flow
      • General information
      • Facilities, warehousing, computers repack/relabel
      • Documentation
    • Additional Guidance
  • 15. Traceable During Lifecycle Manufacture Distribution Pharm User Consumer
  • 16. COA Issues
    • Continuous processing
      • Reduced lot sampling (What is a lot?)
      • Process control through SPC
    • Batch processing
      • Periodic (skip lot testing)
    • Compendia requirements versus commitments in NDA filing
      • additional testing
    • Inventory shelf life
  • 17. COA Content
    • Manufacturers name and facility address
    • Expiration or Re-evaluation date
    • Reference to test result if not on finished lot sample
    • Date retested (if appropriate)
    • Identify results not from QC approval sample
  • 18. COA and Distributors
    • Manufacturer name and site
    • Identify source of test data
    • Retest if repackaged
  • 19. Significant Change Definition
    • A change that alters an excipient physical or chemical property from the norm
    • A change that may alter the excipient performance in the dosage form
  • 20. Significant Change Considerations
        • Site
        • Scale
        • Equipment
        • Process
        • Packaging
        • Specification
  • 21. Significant Change Evaluation Criteria
    • Chemical Properties
    • Physical Properties
    • Impurity Profile
    • Moisture
    • Functionality
    • Bioburden
  • 22. Significant Change Risk Levels
    • Level 1-Minor Change
    • Level 2-Might be Significant
    • Level 3-Always Significant
  • 23. Excipient GMP Audit
    • Audit Scope
    • Audit Purpose
    • Safety Considerations
      • Attire
      • Facial hair
    • Audit Plan
  • 24. Auditing Techniques
    • Stop talking
    • Calm the auditee
    • Focus on listening
    • Remove distractions
    • Empathize
    • Patience
    • Hold your temper
    • Question
    • Be humble
    • LISTEN
    • Judge
    • Embellish
    • Inattentive
    • Speak unclearly
    • Talk excessively
    • Phrase yes/no questions
    • Display an attitude
    • Argue
    • Criticize
    • Answer your question
    Do Don’t
  • 25. Audit Documentation
    • SOP Index and SOPs
    • Quality Manual
    • FDA Inspection & Response
    • Records
      • Training
      • Pest Control
      • Inventory
      • Calibration
      • Batch
      • Laboratory
    • Reports
      • Laboratory Investigations
      • Complaint
      • Annual Product Quality Review
    • Validation
      • Equipment Qualification
      • Process
      • Analytical
      • Cleaning
  • 26. Audit Findings
    • State observations
      • Include supporting documentation
    • Note omissions or concerns
      • Use examples of corrective measures for illustration
  • 27. Audit Report
    • Format
      • Preferably use format of audit flow
      • Complete facility overview
      • Note observations in body of the report
      • List attendees
    • Note corrective actions taken during audit
  • 28. Auditor Etiquette
    • Safety rules
    • Attire
    • Don’t touch
    • Stay clear
    • Stay with escort
    • Don’t question in noisy areas
  • 29. A. Company Overview
    • Quality Policy
      • Management commitment
      • Annually reviewed
    • Organization Charts
    • Customer Requirements
      • Documented
      • Process
      • Written
  • 30. B. Personnel
    • Staffing
    • Hygiene and Attire
    • Training
    • Consultants
  • 31. C. Quality Systems
    • Quality Manual
    • Quality Unit
      • Independence
      • Approval activities
      • Second check of data
    • Audit
  • 32. D. Management of Components
    • Purchasing
    • Traceability
    • Incoming Inspection and Test
    • Water System
  • 33. E. Facilities
    • Adequate Space
    • Maintenance
      • Housekeeping
    • Environment
    • Pest Control
  • 34. F. Warehousing
    • Receiving & Shipping
      • Packaged
      • Bulk
    • Records
      • Shipping
      • Recall
  • 35. G. Equipment (1)
    • Identification
    • Qualification
    • Closed System
    • Dedicated
    • Cleaning
      • Procedures
      • Validation
      • Log
  • 36. G. Equipment (2)
    • Post Maintenance
    • Utensils
    • Contamination
      • From operations
        • worker
      • From equipment
        • environment
    • Construction
    • Product Exposure
  • 37. G. Equipment (3)
    • Maintenance
      • Production equipment
      • Lab equipment
    • Calibration
      • Production equipment
      • Lab equipment
    • Computer Systems
  • 38. H. Production (1)
    • Materials ID
      • Status
      • Traceability
    • Processing
      • Lot definition
      • Uniformity
      • Batch records
      • Process change
      • In-process testing
      • Rework, recycle, recovery
  • 39. H. Production (2)
    • Packaging & Labeling
      • Label approval
      • Label reconciliation
      • Label content
      • Package approval
      • Package storage
      • Container/closure
      • Bulk shipments
    • Computerized System
    Sugar Salt
  • 40. I. Finished Product Management (1)
    • Testing and Release
      • Sampling plan
      • Methods
      • OOS
    • Non-conforming Product
      • Disposition
      • Investigation
    • Corrective and Preventive Actions
      • Investigation
      • Efficacy
  • 41. I. Finished Product Management (2)
    • Stability
      • Market container
      • SOP
    • Retained Samples
      • Storage
    • Returned Products
      • Disposition
  • 42. J. Documentation
    • Standard Operating Procedures
      • Document control
      • Availability
    • Production Records
      • Second check
      • Retention