Professional Documents
Culture Documents
Definitions PAT Overview CIP Overview Design Requirements Process Flow Diagrams Controls Cycle Development Commissioning Validation Questions What Will Be Covered?
CIP = Clean In Place PAT = Process Analytical Technology RODI = Reverse Osmosis Deionized WFI = Water-For-Injection USP = United States Pharmacopoeia ROI = Return On Investment OIT = Operator Interface Terminal
Abbreviations
A process which allows the repeatable cleaning of a manufacturing system Process Tanks Reactors Piping System Portable Tanks
This discussion will concentrate on a two tank CIP system. What is Clean In Place?
A scientific risk based approach using scientific principles and tools to assist manufacturing in producing a quality product and comply with regulatory requirements.
Basis of Design
Points of Use
Process Flow Diagram (PFD) General Arrangement Drawing (GA) Piping and Instrumentation Diagram (P&ID)
Layout
PFD
PFD
PID
PID
PID
PID
Cleaning Parameter Chemicals Time Temperature Different For Each Equipment on System Recipes in memory
Sequence of Operations
Sequence of Operations
Pre-Rinse Cycle Typical Sequence of Operation 1. Fill CIP holding tank with 70 gallons of RODI water 2. Pump RODI water through system, one time 3. Send RODI Rinse to drain 4. Open drain valves in system and drain lines 5. Air Blow at 20 psi for 3 minutes 6. Fill tank with 70 gallons RODI water 7. Pump RODI water through system 8. Return to CIP tank and re-circulate for 2 minutes 9. Open drain valves in system and drain lines 10. Air Blow at 20 psi for 3 minutes 11. Drain CIP holding tank 12. Fill tank with 70 gallons RODI water 13. Pump RODI water once through system 14. Return to CIP skid and divert to drain 15. Open drain valves in system and drain lines 16. Air Blow at 20 psi for 3 minutes 17. Drain CIP holding tank 18. End of cycle
Sequence of Operation
Caustic Wash Cycle Typical Sequence of Operation 1. Fill CIP holding tank with 50 gallons of RODI water 2. Add 1.2 gallons of caustic solution, CIP 100, to tank 3. Check conductivity at skid and adjust as required 4. Circulate and heat to temperature of 70 C at skid 5. Blend mixture at skid for 1 minute prior to pumping to plant system 6. Pump caustic mix to plant system 7. Return to CIP tank and re-circulate trough plant loop 8. Re-circulate through system for 6 minutes 9. Open drain valves in system and drain lines 10. Air Blow at 20 psi for 3 minutes 11. Drain CIP holding tank to process waste system 12. End of cycle
Sequence of Operation
Acid Wash Cycle Typical Sequence of Operation 1. Fill CIP holding tank with 50 gallons of RODI water 2. Add 1.4 gallons of acid solution, CIP 200, to tank 3. Check conductivity at skid and adjust as required 4. Circulate and heat to temperature of 70 C at skid 5. Blend mixture at skid for 1 minute prior to pumping to plant system 6. Pump acid mix to plant system 7. Return to CIP tank and re-circulate trough plant loop 8. Re-circulate through system for 5 minutes 9. Open drain valves in system and drain lines 10. Air Blow at 20 psi for 3 minutes 11. Drain CIP holding tank to process waste system 12. End of cycle
Sequence of Operation
Final Rinse Cycle Typical Sequence of Operation 1. Fill tank with 70 gallons hot WFI from plant loop 2. Pump HWFI water through system 3. Return to CIP tank and re-circulate for 5 minutes 4. Open drain valves in system and drain lines 5. Air Blow at 20 psi for 3 minutes 6. Drain CIP holding tank to process waste system 7. Fill tank with 70 gallons hot WFI from plant loop 8. Pump HWFI water through system 9. Return to CIP tank and re-circulate for 5 minutes 10. Open drain valves in system and drain lines 11. Air Blow at 20 psi for 3 minutes 12. Drain CIP holding tank to process waste system
Sequence of Operation
Final Rinse Cycle Typical Sequence of Operation (continued) 13. Fill tank with 70 gallons hot WFI from plant loop 14. Pump HWFI water through system 15. Return to CIP tank and re-circulate for 3 minutes 16. Open drain valves in system and drain lines 17. Air Blow at 20 psi for 3 minutes 18. Drain CIP holding tank to process waste system 19. Fill tank with 70 gallons of hot WFI from plant loop 20. Pump HWFI water through system 21. Return water to CIP skid and directly to process drain 22. Continue to circulate HWFI until resistivity meter reads predetermined setting 23. Pump any residual HWFI to drain after resistivity is obtained 24. Repeat if steps 19 to 23 if resistivity is not obtained
Sequence of Operation
Layouts Equipment Set-up Skid Equipment Pumps Heat Exchanger Tanks Instrumentation
Controls
Components
CIP Instrumentation
CIP PLC
Time Tank Level Pressure Flow Temperature Conductivity of acid wash Conductivity of caustic wash Conductivity of final rinse Valve position Variables to Define
Time Tank Level Pressure Flow Temperature Conductivity of acid wash Conductivity of caustic wash Conductivity of final rinse Valve position Variables to Control
Framework using scientific principals and tools Understanding of process and sequence of operation Define process variables with limits Understanding of product quality Define product quality with limits Define where controls (alarms) should be inserted PAT Factors
When Process Variability is defined, managed and controlled; Quality can be predicted.
PAT Factors
Commissioning
Commissioning
Commissioning
Reduces the Chance of System Failure How Compares to Design Reduces Field Rework to Correct Reduces Schedule Impact Minimizes Modification Cost
Expedites Validation How Eliminates Missing Documentation Minimizes Request for Corrections Facilitates Protocol Completion
Review System Specification Collect Manufacturers Documentation & Drawings Perform Field Inspection Complete Commissioning Protocol
Validation
Validation
Installation Qualification
Pre-Approval Purpose Scope Introduction Responsibility Exceptional Conditions Procedure Final Approval
IQ Table Of Contents
Operational Qualification
Pre-Approval Purpose Scope Introduction Responsibility Exceptional Conditions Procedure Final Approval
Table of Contents
Performance Qualification
1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0
Pre-Approval Purpose Scope Responsibility Description PQ Procedure Parameters Procedure Acceptance Criteria References General Form
PQ Table of Contents
?? QUESTIONS ??
John E. Dusky, PE (864-949-9960) Janit Buccella (973-579-7890)