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Clean Val Protocol 1
Clean Val Protocol 1
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001
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WRITTEN:
REVIEWED:
Signature:
Position:
Validation Manager
Laboratory Manager
Microbiology Manager
Date:
APPROVED
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Position:
Date:
QA Manager
Engineering Manager
Production Manager
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001
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Table of Contents
1.
OBJECTIVE
2.
SCOPE
3.
4.
REFERENCED DOCUMENTS
5.
6.
Equipment to be Cleaned
Common vs Dedicated Equipment .
Cleaning Procedure(s) and Cleaning Equipment
Holding Times
7.
VALIDATION PLAN
7.1 Worst Case Conditions
7.2 Chemical and Microbiological Analytical Method
7.3 Acceptance Criteria:
8.
SAMPLING LOCATIONS
8.1
13.
REQUIRED DOCUMENTS
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1.
OBJECTIVE
The objective of this protocol is to define the cleaning validation studies and acceptance
criteria for the cleaning (manual and automated ) procedures used to clean the Liquid Filling
line process equipment located in the Liquids Manufacturing Facility Line #4
To demonstrate the effectiveness of cleaning procedures on the direct product contact
surfaces, a worst case challenge is applied that will evaluate the most difficult to remove
residuals from the most difficult to clean areas of the equipment surfaces.
This protocol will also aim to establish appropriate maximum holding times for dirty equipment
prior to cleaning.
2.
SCOPE
The scope of the cleaning validation covers all aspects of the manual and automated cleaning
procedures stated in this protocol and will include both products that are processed in this
equipment:
Products:
The cleaning covers the following product range:
FCP 50mg, 75mg, 100mg,and 250mg C&C range
FCP X Strength Elixer
FCP 100mg C &C (oily excipient)
Equipment:
The product contact surface common equipment is:
Bulk Manufacturing Tank # xxx
Transfer piping from the tank to the filling line. Refer P&ID diagram # yyy
Filling Machine # zzz
The dispensary is also to be validated for cleaning however this is handled via a separate
protocol.
Cleaning Procedures:
Cleaning of the liquid fill process equipment is achieved by common cleaning technologies,
which include an automated CIP system and manual cleaning procedures, as described in
Section 5 of this protocol.
The cleaning procedures to be validated are:
SOP #145 CIP Cleaning of the Bulk Tank and the Filling Line Version # 02
SOP #004 COP (Manual) Cleaning of the Filling Line Components Version # 07
Note: SOPs # 1 and SOP#2 relate to the Dispensary and will be validated on other protocols
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3.
Activity
Responsibility
Protocol preparation
Protocol approval for execution
Protocol execution:
4.
Validation Manager
Validation Manager
Production Manager
Quality Assurance Manager
Production Operator
Validation Supervisor
Microbiologist
Laboratory Manager
Laboratory Manager
Microbiology Manager
Validation Manager
Validation Manager
Production Manager
Quality Assurance Manager
REFERENCED DOCUMENTS
CV VMP 001
SOP #145
SOP #003
QP002
TM 002
5.
Position
Equipment to be Cleaned
This protocol will address the cleaning of the following product contact equipment used to
manufacture liquid products.
Bulk Tank # 4
Liquid Filling Line
Transfer Piping
Dedicated Flexible hoses to connect the bulk tank to the fill line
5.2
The products chosen for cleaning validation are different strengths of the same actives and
different composition types and cannot be campaigned during manufacture therefore the
equipment is classified as common however the flexible Silastic tubing is dedicated to each
product.
Minor cleaning is required between batches of the same product and major cleaning is
required between product changeover.
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5.3
The Cleaning Procedure SOP 003 Ver # 05 provides details of the procedure, equipment and
materials required in order to conduct automated (CIP) cleaning of the liquids manufacture
process equipment.
5.4
Holding Times
6.
The worst case product range has been determined by several factors including strength, toxicity,
excipients and solubility.
6.1 Evaluation of the Product Mix to select the worst case product or marker product
Doses and Batch Size Information
Product
FCP 50mg C&C Liquid
FCP 75mg C&C Liquid
FCP 100mg C&C Liquid
FCP 250mg C&C Liquid
FCP X Strength C&C Elixer
FCP 100mg C&C Oily Liquid
Strength
50mg
75 mg
100 mg
250 mg
1000 mg
100mg
Solubility
High
High
High
High
Medium
Low
Batch Size
50 kg
100 kg
100 kg
25 kg
150 kg
100 kg
Decision
Bracket
Bracket
Marker
Bracket
Marker
Marker
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VALIDATION PLAN
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(d) flush the detergent residue to drain with100 litres of purified water
(e) Apply a final 100 litre flush
Ensure these conditions are met and recorded in the cleaning record for each cleaning validation run.
7.2 Chemical and Microbiological Analytical Method
Quality Control Laboratory will analyse all swab samples for product as per the validated method TM
123: Validation of the Analytical Methodology for the Determination of Residual Levels of FPC active in
swab and flush samples.
Quality Control Microbiology Laboratory will analyse all swab samples for microbial bioburden as
per the validated method TMM 124: Validation of the Microbiology Recovery Method for the
Determination of microbial bioburden Levels of FPC active in swab and flush samples.
7.3 Acceptance Criteria:
(a) Three successful chemical residue (swabbing and flushing) evaluations of the equipment after
cleaning of the worst case products.
(b) Three successful visual inspections of the equipment after cleaning of the worst case product, both
initially and after the relevant holding time.
(c) Three successful microbiological evaluations of the equipment after cleaning of the worst case
product, both initially and after the relevant holding time.
TPC
(cfu/100cm2)
SALMONELLA
sp/100cm2 or
swab
PSEUDOMONAS
spp/100cm2
COLIFORMS/
100cm2
Target
NMT 1
Not detected
Not detected
Not detected
Limit
NMT 5
Not detected
Not detected
Not detected
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9.
SAMPLING LOCATIONS
8.1 Swab and Flush sampling locations
Sample locations are identified on the schematic diagram included in Appendix 1 and are as
described below:
Swab Number
S2
S3
S4
Drain valve
S5
Transfer pipe
S6
Filling head
Flush Number
9.
S1
F1
F2
REQUIRED DOCUMENTS
The following documents are required to be appended to this protocol in order to complete the
validation report.
Number
Description
No. of
Sheets