Cleaning Validation Protocol Powder Manufacturing Line-1

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CLEANING VALIDATION PROTOCOL FOR POWDER MANUFACTURING LINE MACHINES

(Doc # PR01001)
Product Name: Machine #: Room #:

Issue: 001 Production approval QC approval QA approval
Issue date: Sign. Date / / Sign. Date / / Sign. Date / /
CHANGE CONTROL
ISSUE # ISSUE DATE PAGE # SUMMARY OF CHANGE

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Content Page
1. Background
2. Objective
3. Scope
4. Responsibility
5. System function and description
6. Documentation required
7. Sampling Procedure
8. Testing Procedure
9. Acceptance criteria
10. Revalidation
11. Procedure
12. Results
12.1 Validation report
12.2 Final cleaning validation report
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1. OBJECTIVE:
1.1. Generate documented evidence providing reasonable assurance that the cleaning procedure of the powder manufacturing Line machines
system effectively removes remaining product residues and / or detergent residues.
1.2. Show that the specific cleaning method performs as expected and produces results that consistently meet predetermined specifications.
2. SCOPE:
2.1
S.N Machine Name Manufacturer Model S.No. Code No
1. Weighting Scoops
2. Sieving Machine
3. V.Shape mixer
4. Filling machine
3. RESPONSIBILITY:
3.1. Engineering: equipment structure and equipment surface area determination.
3.2. Production department: cleaning process and procedure.
3.3. QC: sampling, testing, reviewing the results and acceptance criteria determination.
3.4. Production, QC and QA managers: reviewing and final approval of the qualification package.
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4. SYSTEM FUNCTION AND DESCRIPTION:

4.1. Description of the equipment to be cleaned: Machine:
S.N Machine Name Manufacturer Model S.No. Code No
1. Weighting Scoops
2. Sieving Machine
3. V.Shape mixer
4. Filling machine
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4.2. List of parts to be cleaned and their surface area

Machine Name Machine parts to be cleaned Surface area in cmᶟ
Weighting Scoops St.St. surface
Mesh
Outlet
Sieving
Chopper
Sieve
Inlet
V-Shape Mixer
Outlet
Powder Hooper Tank
Transferring tube from hopper tank to
Auger
Filling machine
Auger
Sieve
Rubber fan
Brush
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4.3. Cleaning agents:

4.3.1. For fixed parts, detergent Ultra Clean at a concentration 20-50ml/1Liter (2 %-5 %).
4.4. Choice of product:
4.4.1. Product Max Muscle Creatine represents the worst case among NUTRITION products according to worst case selection sop #
S01015
5. DOCUMENTATION REQUIRED:
5.1. Machines Cleaning SOPs:
5.1.1. Sieving Machine (SOP#).
5.1.2. L-V-Shape Machine (SOP#).
5.1.3. Filling Machine (SOP#).
6.2 Cleaning validation (SOP# S01014).
6.3 Analytical Method Validation: (SOP#).
6.4 Swabs in cleaning validation: (SOP#).
6.5 Analytical monograph of product A(SOP#).
6. Sampling Procedure:
. Remove swab and rinse samples from the equipment
6.1. Swab Samples:
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6.1.1. Weighting Scoops:

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6.1.2. Sieving Machine:

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6.1.3. L-V Shape Mixer:

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6.1.4. Filling machine:

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. All sampling details (swab, rinse and microbiological) should be referenced in the following table :
Sampling
Sampling
Technique
Technique for No.Of
Material to Area Surface Sample for Signature
Equipment Sample sites microbiologic samples
be tested swabbed Area Ref.No chemical /date
al
analysis
analysis
Weighting Scoop St.St. Swabbing Swabbing 2

100 cm² 1125 cm²
Surface
Sieving Mesh 100 cm² 5476.16 Swabbing Swabbing 2
Creatine Outlet 100 cm² cm² Swabbing Swabbing 2
Mohohydrate
Caffeine Inlet 100 cm² 47885 cm² Swabbing Swabbing 2
V Shape Mixer
anhydrous Outlet 100 cm² Swabbing Swabbing 2
Hopper tank 100 cm² 23800 cm² Swabbing Swabbing 2
Creatine Transferring 100 cm² Rinse Rinse 2

Filling machine
Mohohydrate tube
Auger 100 cm² Swabbing Swabbing 2
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 Testing Procedure :
Rinse samples should be tested for:
-Product residues in accordance with analytical protocol
-Cleaning agent residues in accordance with analytical protocol
Swab samples should be tested for:
-Product residues in accordance with analytical protocol
-Cleaning agent residues in accordance with analytical protocol
Microbiological test samples should be tested for:

Total germ number
● Dirty Hold Times and Clean Hold Times :
The period and when appropriate, conditions of storage of equipment before cleaning, commonly referred to as The Dirty Hold Time (DHT)
and the time between cleaning and equipment reuse, prior to additional cleaning, commonly referred to as The Clean Hold Time (CHT), should
from part of the validation of cleaning procedures. This is to provide confidence that routine cleaning procedure and does not allow potential for
build up of degradation products that may not be removed by the standard cleaning procedure and does not allow potential for microbial
contamination of equipment and to ensure that these potential risks are properly assessed and controlled.
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7. ACCEPTANCE CRITERIA
7.1. Visual inspection of container after cleaning to ensure the absence of physically apparent residues.
7.2 Ensure that not more than 1/1000 of the smallest dose manufactured / administered appears in the normal maximum daily therapeutic
dose of the next product.
7.3 Validation experiments should demonstrate consistency of cleaning effectiveness by repeating evaluation after 3 consecutive batches.
8. REVALIDATION:
8.1. The validation study is to be repeated in case of :
8.1.1. Change in Analytical Method Validation (mainly items of LOD & LOQ)
8.1.2. Change in product formula.
8.1.3. Change in cleaning procedures.
8.1.4. Change in equipment configuration.
8.1.5. Change in detergent or solvents used.
9. PROCEDUER:
9.1. Cleaning procedure For the (Fixed parts)
Cleaning step Critical parameters Influence on cleaning efficiency Testing points
Gross cleaning by mopping -None -Removal of powder Visual inspection
-Appearance of parts
Manual cleaning for all external -Exposure Time -Cleaning of system parts Visual checking
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surface fixed machine parts using -Amount of water -Removal of sticky powders and
Ultraclean( ), rinse with -Concentration of detergent granules
potable water ( ) by hose
C.I.P cycle ( )( ) -Temperature -Cleaning of system parts Visual inspection
Removal of sticky powders and
granules
Manual cleaning for all internal -None -Cleaning of system parts Visual checking
surfaces of fixed machine parts -Removal of sticky powders and
using Ultra clean (2%-5%) and granules
rinse with potable water ( )
by hose .*
1 CIP cycle (water) ( ) -Temperature -Cleaning of system parts from Swab or rinse from testing
both product and detergent points.
Drying using clean dry wiper or -None -Drying of cleaned parts. -Visual inspection.
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compressed air
Cleaning procedure For the (Movable parts)
Cleaning steps Critical parameters Influence on cleaning efficiency Testing points
-Rinse by hot city -Temperature of water -Removal of sticky Visual checking
Water with detergent -Detergent concentration powders and granules
Ultraclean -Time of exposure from the these parts
-Time :10-15 min
1 Rinse with water ( ) -Temperature Cleaning of system parts from -Rinse and swab from the
-Time :10-15 min -Time of exposure both product and detergent movable parts
residuals
residuals
residuals
-Drying using clean dry wiper or -None -Drying of cleaned parts. -Visual inspection.
compressed air.
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Cleaning procedure flow chart:

. Clean the machine according to the following flow chart for cleaning process (fixed parts):
Gross cleaning
Mopping
Manual cleaning Ultra clean

20-50 ml/ 1 L at 60 ºC
At
C.I.P cycle Ultra clean

20-50 ml/ 1 L at 60 ºC
Manual cleaning Ultra clean

20-50 ml/ 1 L at 60 ºC
1st CIP cycle

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QC
Take swab and rinse
from different places No residual detected
for detection of
residuals of
detergent and
product
End of cleaning process
Detection of detergent or product residuals
2nd C.I.P cycle

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QC
Take swab and rinse
from different places No residual detected
for detection of
residuals of
detergent and
product
Detection of detergent or product residuals
3rd C.I.P cycle

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QC
Take swab and rinse
from different places
for detection of
residuals of
detergent and
product
Detection of detergent or product residuals No residual detected
Repeat cycle using different detergent and conditions. End of cleaning process
&
Drying using non lint wiper or
compressed air.
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Flow chart for cleaning process (movable parts)
Rinse with hot tap

water and
detergent
Ultraclean) in the
washing bay
Ultra clean
20-50 ml/ 1 L at 60 ºC
QC
Takes swab and
rinse for detection of No residual detected
residual of product
or detergent
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2nd rinse with water
QC
Take swab and rinse
for detection of No residual detected
residual product or
detergent
Presence of residual product or detergent

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3rd rinse with water
QC
Take swab and rinse
for detection of No residual detected
residual product or
detergent

&
Drying using non lint wiper or
Presence of residual product or detergent compressed air.
Repeat cycle using different detergent and conditions.

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9.2. Samples are taken by swabbing techniques according to SOP (Doc #).
9.3. Analysis of the swabs takes place according to (SOP # SP).
9.4. Cleaning procedure, sampling and analysis must be repeated for 3 consecutive runs.
9.5. The validated analytical method of product A shows limit of detection ( ) mg/swab and limit of quantitation ( ) mg/swab
appears that the method is sufficiently sensitive to detect the established acceptable level of product A residue.
9.6. Calculation:
9.6.1. Recovery calculation:
9.6.1.1. Recovery calculation should be carried out by spiking a known quantity of the active material (Product A) on 100 cm2
area of the machine, swabbing this area and analysis of the product according to (SOP # SPC) and calculating the peak area
for the standard and test material using the following equation.
Peak area test
%Recovery = X P X 100
Peak area STD
Where: P: Potency of the standard

9.6.2. Swab limit calculation:
I K
mg of ingredient (A) / swab = X X M X % Recovery
J L
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Where
I : maximum acceptable level of contaminant = 1/1000 of normal daily therapeutic dose of contaminant product.
 If the contaminant is a detergent the LD50 shall substitute the normal daily therapeutic dose.
J : maximum dosage units of product B taken per day.
K : number of dosage units per batch of final mixture of product B.
L : equipment surface area common between the two products expressed in cm2 .
M : 100 cm2 .
9.6.3. Swab calculation:

Peak area test Conc. of STD
Conc. / swab (mg / swab) = XPX XZ
Peak area STD 100
Where: P: Potency of the standard. Z: Dilution factor
9.6.4. Rinse calculation
Peak area test Conc. of STD
Conc. / rinse (mg / rinse) = XPX XZXV
Peak area STD 100
Where
P: Potency of the standard.
Z: dilution factor.
V: volume of rinse equivalent to 100 cm2 of the surface area
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9.7. RESULTS:
Results are documented in the cleaning validation format report A, B (attachments 12.1. – 12.2.) For the 3 runs, any deviation or out of
specification results must be reported and fully investigated.
10.VALIDATION REPORT
11.FINAL CONCLUSION AND APPROVAL FORM:
11.1. Includes the summary of the validation package and the approval of Production, QC and QA managers.
12.ATTACHMENT:
12.1. Cleaning validation report (A)
12.2. Cleaning validation report (B)
12.3. Cleaning validation report (C)
12.4. Validation report
12.5. Final cleaning validation report
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12.1. Cleaning Validation Report (A)

Product A : ---------------------------------- ID No.: ---------------------------------- Batch No. : ------------------------------- Batch size: -------------------
Product B : ---------------------------------- ID No.: ---------------------------------- Batch No. : ------------------------------- Batch size: -------------------
‫ تعااهتت‬Run No. : -----------------------
CHT Results
Amount of
A.1day from A.3day from A.5day from
product
Machine Machine Surface Limit Pass / cleaning cleaning cleaning
residue
Name Part Name area Cm2 Mg/swab Failed
/100 cm²
TAMC TYMC TAMC TYMC TAMC TYMC
(swab)
Weighting St.St.
scoops surface
Sieving Mesh
Outlet
Ultra clean
(C.A)
L-V-Shape Inlet
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Outlet
CA
Hopper tank
Transferring
Filling
tube
machine
Auger
CA
Comment:
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12.2. Cleaning Validation Report (B)

‫ تعااهتت‬Run No. : -----------------------
CHT Results
Amount of
product
residue
/100 cm²
(swab)
Weighting St.St.
scoops surface
Sieving Mesh
Outlet
Ultra clean
(C.A)
L-V-Shape Inlet
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Outlet
CA
Hopper tank
Transferring
Filling
tube
machine
Auger
CA
Comment:
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12.3. Cleaning Validation Report (C)

‫ تعااهتت‬Run No. : -----------------------
CHT Results
Amount of
product
residue
/100 cm²
(swab)
Weighting St.St.
scoops surface
Sieving Mesh
Outlet
Ultra clean
(C.A)
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L-V-Shape Inlet
Outlet
CA
Hopper tank
Transferring
Filling
tube
machine
Auger
CA
Comment:
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12.4. Validation report

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Production manager QC Manager QA Manager
Sign.: Sign.: Sign.:
Date: Date: Date:
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12.5. Final cleaning validation report

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Production manager QC Manager QA Manager

Sign.: Sign.: Sign.:
Date: Date: Date:

Cleaning Validation Protocol Powder Manufacturing Line-1

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Page 1 of 35

CLEANING VALIDATION PROTOCOL FOR POWDER MANUFACTURING LINE MACHINES

Product Name: Machine #: Room #:

ISSUE # ISSUE DATE PAGE # SUMMARY OF CHANGE

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

4. SYSTEM FUNCTION AND DESCRIPTION:

Product Name: Machine #: Room #:

4.2. List of parts to be cleaned and their surface area

Product Name: Machine #: Room #:

4.3. Cleaning agents:

Product Name: Machine #: Room #:

6.1.1. Weighting Scoops:

Product Name: Machine #: Room #:

6.1.2. Sieving Machine:

Product Name: Machine #: Room #:

6.1.3. L-V Shape Mixer:

Product Name: Machine #: Room #:

6.1.4. Filling machine:

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

Weighting Scoop St.St. Swabbing Swabbing 2

Hopper tank 100 cm² 23800 cm² Swabbing Swabbing 2

Creatine Transferring 100 cm² Rinse Rinse 2

Product Name: Machine #: Room #:

Microbiological test samples should be tested for:

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

Cleaning procedure flow chart:

Manual cleaning Ultra clean

C.I.P cycle Ultra clean

Manual cleaning Ultra clean

1st CIP cycle

Product Name: Machine #: Room #:

End of cleaning process

Detection of detergent or product residuals

2nd C.I.P cycle

Product Name: Machine #: Room #:

Product Name: Machine #: Room #:

End of cleaning process

Detection of detergent or product residuals

3rd C.I.P cycle

Product Name: Machine #: Room #:

Detection of detergent or product residuals No residual detected

Product Name: Machine #: Room #:

Flow chart for cleaning process (movable parts)

Rinse with hot tap

Product Name: Machine #: Room #:

End of cleaning process

2nd rinse with water

End of cleaning process

Presence of residual product or detergent

Product Name: Machine #: Room #:

3rd rinse with water

End of cleaning process

Repeat cycle using different detergent and conditions.

Product Name: Machine #: Room #:

Where: P: Potency of the standard

Product Name: Machine #: Room #: