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61
Julie A. Thomas
Introduction
Responsibilities
There are many departments and disciplines
involved in planning for and executing a cleaning
validation. It is necessary to list each contributing
area and the associated tasks for which it is respon
sible. This serves to clarify roles and to ensure that
tasks are not overlooked. Typically, representatives
from Validation, Manufacturing, Quality Control,
Engineering, and Research and Development (R&D)
will be needed. The following are some examples of
departmental responsibilities:
Validation Specialist
Review cleaning procedures
Assist the cleaning validation team in iden
tifying equipment test sites for swab or
rinse samples
Write cleaning validation protocols
Coordinate execution of the cleaning pro
cess with the appropriate departments and
laboratories
Prepare the sampling schedule
Assemble the test data into final report
form for approval
Manufacturing
Provide technical information for the devel
opment of protocols and reports
Review and approve protocols and reports
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Julie A. Thomas
Development Phase
The initial phase of the cleaning validation plan is
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Julie A. Thomas
Figure 1
Development Phase
Analytical Method
Validation
Analytical Method
Development
D
egradant
identification
Transfer
Recovery
Surface types
Planning Phase
Equipment
S
ample site
selection
Surface area
calculation
Schematic
Analyte Selection
and Acceptance
Criteria
Protocol
Development
rite
W
Approve
Train
ctive ingredient
A
Cleaning agent
Cleaning
SOP
rite
W
Approve
Train
Execution Phase
Protocol Execution
C
lean
Sample
Test
Pass?
No
Incident
Investigation
Yes
Validation Report
W
rite
Approve
Maintenance Phase
Monitoring
Change Control
Revalidation
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Julie A. Thomas
Figure 2
Planning Phase
The next phase of preparation is the planning phase.
This is a broad category that focuses on equipment
information, analyte selection, acceptance criteria,
cleaning procedures, and protocol development. At this
point, you are starting to think about what equipment
will be included in the validation, which analytes will
be chosen, and how you will determine acceptance cri
teria. This leads to an in-depth review of the procedures
and, finally, to protocol development.
Figure 3
Recovery Surface:
1. Equipment Information
This section should detail the methodology for
providing specific equipment information. One
option is to prepare a binder containing detailed
surface area calculations, swab sampling sites (with
justification), photos, and schematic diagrams for
each piece of equipment. This binder can be main
tained separately and used as an attachment to the
cleaning validation protocol as needed.
a) Sample Site Selection
Explain how you will select sampling sites to rep
resent the product contact surface area of the equip
ment. One of the best sources of information is the
operator who routinely cleans the equipment. He or
she can certainly point out the areas they find most
difficult to clean. Make the operator part of a larger
team of experts to include representatives from
Validation, QA, and Operations, and let the team
determine the product contact surface areas that are
most difficult to clean and those that are most repre
sentative of the equipment. Sampling these sites will
represent the entire equipment surface area using
the assumption that residue will be evenly distrib
uted over the equipment and that the most difficult
to clean locations will represent the worst case for
residue removal. Include the basis for selecting each
Polyethylene Silicone
Material Used:
316L Coupon
Hose
To Represent:
304 Stainless
Aluminum
Brass
Teflon
Lexan
HDPE
Rubber
EPDM
Neoprene
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Julie A. Thomas
Kason Separator
Swab Site
Surface Area
Screen/ring interface
gasket
3,171.2
15.6
Figure 6
Julie A. Thomas
Execution Phase
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Julie A. Thomas
Maintenance Phase
The final phase of the Plan should specify how
you will maintain the conditions you have just
validated. This includes periodic monitoring, using
a control of change process, and potentially, revali
dating.
1. Monitoring
This section details how you will ensure that the
conditions used during validation remain in con
trol during routine production. This is especially
important for manual cleaning procedures, where
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Julie A. Thomas
Summary
There are many aspects of cleaning validation
that must be carefully planned to guarantee a suc
cessful validation program. If you begin with a phi
losophy, this will set the stage for you to develop a
structured approach. By dividing the approach into
sections, such as development, planning, execu
tion, and maintenance, it breaks down the project
into manageable segments. To complete the Plan,
generate a tactical schedule and begin monitoring
progress towards your new and improved cleaning
validation status. o
References
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