Cleaning In Place
IN
PHARMACEUTICAL STERILE APPLICATIONS
CIP System Consideration:
Applications of CIP Systems
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Solution Preparation vessels in sterile injectable in built CIP System
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CIP skid mounted System
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BFS and FFS machine in line CIP function (Filling Machines)
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Pharmaceuticals water systems (CIP systems)
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Storage tanks in water systems
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CIP System in Oral Formulations
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Autocoater
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FBD & FBP
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Liquid syrup System (Tanks)
CIP System Consideration:
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What is Clean-In-Place System?
Clean-In-Place ( CIP ) System is an automated method of cleaning the interior
surfaces of pipes, tanks, lines, process equipment, and associated fittings without
requiring the operator to disassemble the equipment. ”
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Advantage of Automated CIP System
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Less Time consuming
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Operator involvement is very less and Safety concern is very high
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More focus on monitoring of process parameter instead of other manual
attachment concern.
Important Factors influencing CIP
process
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Considerable points while going to validate CIP Process
Spray Ball Qualification
 Cleaning Agent or Hot WFI
 Riboflavin Challenge
 No Dead leg Formation
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The basic components of a Clean-In-Place system include:
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Tank Dome and Dome Nozzles including filters and housings
Spray ball and inner (Shell) surface and magnetic mixer
Bottom Outlet valve, Sampling valve
Piping and transfer lines
Centrifugal supply pump
Suction, return valves
Instrumentation and automated controls
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CIP System Consideration: CIP VALIDATION
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CIP VALIDATION
To evaluate that the system is efficient to clean the tank, through automated CIP
(Clean-In-Place) using hot WFI.
Study with Riboflavin Challenges

To evaluate that performance of the spray ball for coverage and uniform
cleaning throughout the manufacturing tank.

To evaluate that system cleaning procedure is efficient to clean in worst case
scenario as using Riboflavin material as contaminating agent.
CIP System Consideration: CIP VALIDATION
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Selection Criteria for Riboflavin:
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Food Grade Material
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Showing Fluorescence
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Vitamin B 12 Properties
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Requirements In CIP Validation
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Hot WFI as cleaning agent
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Riboflavin solution
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UV light lamp for detection Fluorescence
CIP System Consideration: CIP VALIDATION
 Under
Standing The CIP Validation:
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Simulate the tank inner surface or product contact parts especially which is
difficult to clean i.e.
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Dome part above the spray ball, steam in valve pipe, WFI in valve pipe, Air
Valve, vent valve pipe and pressure sensor pipe – Difficult to clean.
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Sampling valve - Difficult to clean.
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Near magnetic mixer and high shear mixer - Difficult to clean.
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Near temperature sensor - Difficult to clean.
CIP System Consideration: CIP VALIDATION
CIP System Consideration: CIP VALIDATION
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Observe the all contaminated location or parts under UV light for presence of
fluorescence.
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Perform the CIP of the tank as per respective SOP (ensure that the WFI supply
valve is 100 % open).
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During CIP observe the spray ball performance visually through view glass of the
tank.
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Post completion of the CIP, open the tank dome and observe visually for
presence of any visible particle.
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Observe the tank under UV light for the presence of the fluorescence.
CIP System Consideration: CIP VALIDATION
CIP System Consideration
How to design a CIP Recipe or Cycle
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Consider for 100 Liter vessel for example:
(I) Mixing Cycle – Mixing with cleaning agent
(II) Recirculation Cycle – Rinsing solution is recirculated in vessel by recirculated
line.
(III) Drain Cycle – Solution is drained after completion of CIP cycle
(IV) Purging Cycle – To remove stagnant water and water droplets from difficult to
access parts and pipeline.
CIP System Consideration
How to design a CIP Recipe or Cycle

Consider for 100 Liter vessel for example:
(I) Mixing Cycle – Take 1/3 rd quantity of water and add required
quantity of cleaning agent and mix for 10 to 15 minutes.
(II) Recirculation Cycle – Then this solution is recirculated by recirculated
line to cover pipeline and transfer line for at least 2-3 times.
(III) Drain Cycle – Solution is drained after completion of CIP cycle
(IV) Purging Cycle – Compressed air is purged to remove stagnant water
and droplets.
Thank You