1st Edition

Cleaning Validation Practical Compliance Approaches for Pharmaceutical Manufacturing

By Destin A. LeBlanc Copyright 2023

    Pharmaceutical manufacturers and upper management are encouraged to meet the

    challenges of the science-based and risk-based approaches to cleaning validation.

    Using some of the principles and practices in this volume will help in designing a

    more effective and efficient cleaning validation program.


    • Timely coverage of cleaning validation for the pharmaceutical industry,

    a dynamic area in terms of health-based limits.

    • The author encourages pharmaceutical manufacturers, and particularly

    upper management, to meet the challenges of the science-based and riskbased

    approaches to cleaning validation.

    • Draws on the author’s vast experience in the field of cleaning validation

    and hazardous materials.

    • Discusses EMA vs. ISPE on Cleaning Limits and revised Risk-MaPP for

    highly hazardous products in shared facilities.

    • A diverse list of topics from protocol limits for yeasts and molds to

    cleaning validation for homeopathic drug products.


    1. Use of the Term "Product"
    2. Use of the Terms Grouping and Matrixing
    3. Deviations and Nonconformances
    4. Clarifying Terms: Blanks vs. Controls
    5. Meaning of "Dedicated"?
    6. Words (Again??)
    7. Health-based Limits

    8. What's at Stake with HBELs
    9. A Look at the Revised Risk-MaPP
    10. EMA's Q&A Clarification: Part 1
    11. EMA's Q&A Clarification: Part 2
    12. The EMA Q&A "Clarification" on Limits
    13. The EMA Q&A on Routine Analytical Testing
    14. Other Issues in EMA's Q&A
    15. Highly Hazardous Products in Shared Facilities
    16.  Limits - General

    17. EMA vs. ISPE on Cleaning Limits?
    18. Does a High "Margin of Safety" Protect Patients?
    19. What If the Next Product is the Same Product?
    20. Limits for "Product A to Product A"
    21. Surfaces Areas in Carryover Calculations
    22. Carryover Calculation Errors to Avoid
    23. Protocol Limits for Yeasts/Molds?
    24. Cleaning Validation for Homeopathic Drug Products
    25. A Possible Approach for Biotech Limits
    26. Establishing Clearance for Degraded Protein Actives
    27.  Visually Clean

    28. Avoiding "Visually Dirty" Observations
    29. What's a Visual Limit?
    30. Visual Residue Limits – Part 1
    31. Visual Residue Limits – Part 2
    32. Analytical and Sampling Methods

    33. Two More Nails in the Coffin?
    34. More Swab Sampling Issues
    35. Timing for Swab Sampling in a Protocol?
    36. Pass/Fail Analytical Test Methods
    37. Product Grouping

    38. Issues in Product Grouping
    39. Toxicity as a Worst-Case Grouping Factor
    40. Another "Worst Case" Product Grouping Idea
    41. Protocols and Procedures

    42. Issues in Rinsing - Part 1
    43. Issues in Rinsing - Part 2
    44. Routine Monitoring for Highly Hazardous Products
    45. "Concurrent Release" for Cleaning Validation
    46. Dirty and Clean Hold Time Protocols
    47. API Manufacture

    48. A Critique of the APIC Guideline
    49. Another Issue for API Synthesis
    50. Contaminants in API Manufacture
    51. Miscellaneous

    52. Significant Figures: Back to Basics
    53. The Value of a Protocol Worksheet for Manual Cleaning
    54. Dealing with Used and New Equipment
    55. Solving Cleaning Validation Problems by Analogy
    56. Causing Cleaning Validation Problems by Analogy


    Appendix A: Acronyms Used in this Volume

    Appendix B: Shorthand Notations for Expressing Limits



    Destin LeBlanc is a consultant at Cleaning Validation Technologies. He has extensive experience in product development and technical services for cleaning and antimicrobial applications. He is an international lecturer on contamination control and has written widely on cleaning validation topics including four volumes in the "Cleaning Validation: Practical Compliance Solutions for Pharmaceutical Manufacturing" series published by PDA and DHI. He is a member of PDA and ISPE and has trained FDA personnel on cleaning validation. He is a graduate of the University of Michigan and the University of Iowa.