Cleaning Validation: Practical Compliance Approaches for Pharmaceutical Manufacturing

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.

Features

• 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.

Terminology

2. Use of the Term "Product"
4. Use of the Terms Grouping and Matrixing
6. Deviations and Nonconformances
8. Clarifying Terms: Blanks vs. Controls
10. Meaning of "Dedicated"?
12. Words (Again??)
    

13. Health-based Limits

14. What's at Stake with HBELs
16. A Look at the Revised Risk-MaPP
18. EMA's Q&A Clarification: Part 1
20. EMA's Q&A Clarification: Part 2
22. The EMA Q&A "Clarification" on Limits
24. The EMA Q&A on Routine Analytical Testing
26. Other Issues in EMA's Q&A
28. Highly Hazardous Products in Shared Facilities
    

29. Limits - General

30. EMA vs. ISPE on Cleaning Limits?
32. Does a High "Margin of Safety" Protect Patients?
34. What If the Next Product is the Same Product?
36. Limits for "Product A to Product A"
38. Surfaces Areas in Carryover Calculations
40. Carryover Calculation Errors to Avoid
42. Protocol Limits for Yeasts/Molds?
44. Cleaning Validation for Homeopathic Drug Products
46. A Possible Approach for Biotech Limits
48. Establishing Clearance for Degraded Protein Actives
    

49. Visually Clean

50. Avoiding "Visually Dirty" Observations
52. What's a Visual Limit?
54. Visual Residue Limits – Part 1
56. Visual Residue Limits – Part 2

57. Analytical and Sampling Methods

58. Two More Nails in the Coffin?
60. More Swab Sampling Issues
62. Timing for Swab Sampling in a Protocol?
64. Pass/Fail Analytical Test Methods
    

65. Product Grouping

66. Issues in Product Grouping
68. Toxicity as a Worst-Case Grouping Factor
70. Another "Worst Case" Product Grouping Idea
    

71. Protocols and Procedures

72. Issues in Rinsing - Part 1
74. Issues in Rinsing - Part 2
76. Routine Monitoring for Highly Hazardous Products
78. "Concurrent Release" for Cleaning Validation
80. Dirty and Clean Hold Time Protocols
    

81. API Manufacture

82. A Critique of the APIC Guideline
84. Another Issue for API Synthesis
86. Contaminants in API Manufacture
    

87. Miscellaneous

88. Significant Figures: Back to Basics
90. The Value of a Protocol Worksheet for Manual Cleaning
92. Dealing with Used and New Equipment
94. Solving Cleaning Validation Problems by Analogy
96. Causing Cleaning Validation Problems by Analogy

Appendix A: Acronyms Used in this Volume

Appendix B: Shorthand Notations for Expressing Limits

Index

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.