Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
FORMULATION
DATE OF EFFECTIVE
PRODUCT NAME :
LINE
REASON FOR PERFORMING THE VALIDATION STUDY :
Reason ( tick which ever is applicable)
Department
New product
Modification in the manufacturing process.
Change in Facility and / or location of manufacturing.
Batch fail to meet product & process specifications.
Remarks
Number of batches studied: ________________
Batch numbers:
1. _______________
2.. _______________
3. _______________
Validation activity authorized By:
_____________________________Date:_______________________
Validation Team:
DEPARTMENT
VALIDATION TEAM
PRODUCTION
QUALITY ASSURANCE
QUALITY CONTROL
REMARKS:
________________________________________________________________________
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Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
APPROVALS:
DEPARTMENT
SIGN & DATE
PRODUCTION
QUALITY ASSUARANCE
QUALITY CONTROL
PRODUCT DEVLOPMENT
ENGINEERING
1.0 GENERAL:
1.1 INTRODUCTION:
The process validation will be performed as prospective validation. The complete
documentation for the validation comprises several independent documents,
references to relevant documents will be given as part of this protocol, (see below).
The results of the validation activities will be summarized in the validation report.
1.2 List of Documents for Validation:
Validation protocol,
Details of sampling for the validation batches, test parameters ( Product
performance characteristics) with reference to test methods & Acceptance criteria.
(acceptable Limit)
Methods for recording / evaluating results including statistical analysis.
Reference to relevant documents.
1.2.2 Batch manufacturing records.
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
Detailed manufacturing instructions for the production of the validation batches.
2.0 PERSSONEL RESPONSIBILITIES.
SR
ACTIVITY
1 Preparation of validation
2
protocol
Approval of Validation
protocol
Production of validation
Batches
Testing of validation
RESPONSIBILITY
REMARKS
samples & Preparation of
5
validation report
Approval of validation
report.
3.0 PROCESS DESCIRPTION / FLOW SHEET
The information given below provides a general description of the process. Detailed
information for the manufacturing will be supplied separately in the batch manufacturing
record.
1.0 DISPENSING OF MATERIAL
2.0 SHIFTING
3.0 GRANULATION (if required).
4.0 BLENDING
5.0 MIXING
6.0 FILLING
7.0 BLISTERING/ STRIPPING/COUNTING.
3.1 FORMULATION:
BATCH SIZE:
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
SR
DATE OF EFFECTIVE
INGREDIENTS/EXCIPIENTS
SPECIFICATION
MG.CAPS.
PER BATCH
1
2
3
4
5
6
7
8
9
10
11
12
13
NOTE:
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PER LOT
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
CAPSULE FLOW CHART
R.M.DISPENSING
SHIFTING
1. MIXING TIME
2. SPEED
BLENDING
GRANULATION
(IF REQUIRED)
DRYING
1. MIXING TIME
2. SPEED
COMPECT
(IF REQUIRED)
MILLING
(IF REQUIRED)
MIXING
FILLING
BULK ANALYSIS
1.0 WEIGHT VERIATION
QUARANTINE
BLISTER/ STRIP PACKING/
COUNTING
FINAL PACKING
QUARANTINE
F.G.STORE
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FINISHED PRODUCT ANALYSIS
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
4.0 EQUIPMENT / FACTORY.
A detailed list of equipment used for validation together with the cleaning status
will be provided in the manufacturing documents.
4.1 LIST OF SOPS , VALIDATION & QUALIFICATION REPORT USED AS
REFERENCES=
SR
ID. NUMBER
1.
2.
3.
TITLE
VERIFIED
BY
Equipment cleaning procedure for Master sifter #20,#40
Equipment operating procedure for Master sifter #20,#40
Equipment cleaning procedure for Rapid mixer
granulator.
Equipment operating procedure for Rapid mixer
granulator.
Equipment cleaning procedure for Octagonal Blender.
Equipment operating procedure for Octagonal blender.
Equipment cleaning procedure for capsule filling
machine.
Equipment operating procedure for capsule filling
machine.
Equipment cleaning procedure for capsule polishing &
Checking machine.
Equipment operating procedure for capsule polishing &
Checking machine.
Equipment cleaning procedure for strip packing machine.
Equipment operating procedure for strip packing
machine.
Equipment cleaning Procedure for Blister Packing
machine.
Equipment operating procedure for Blister Packing
machine.
Equipment cleaning procedure for Cap counting machine
Equipment operating procedure for Cap counting
machine
Equipment cleaning procedure for Fluid Bed Dryer.
Equipment operating procedure for Fluid Bed Dryer.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
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DATE
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
19.
DATE OF EFFECTIVE
Enter any other reference sop.
4.2 DETAILS OF EQUIPMENT TO BE USED.
EQUIPMENT
SIFTING :
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
BLENDER:
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
MIXER :
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
MILLING
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
DRYING
TYPE :
MODEL:
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DETAILS
Approved by
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
CAPSULE FILLING
MACHINE:
CAPSULE POSISHING &
CHECKING MACHINE
STRIP PACKING
MACHINE:
BLISTER PACKING
MACHINE:
Prepared by
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
Checked by
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Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
CAPSULE COUNTING
MACHINE
DATE OF EFFECTIVE
M.O.C.
TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
REMARKS:
4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER.
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:
MATERIAL
SIFTING
MIXING
AIR DRYING
POLISHING
LOAD SIZE
ACTIVE
SPEED
MIXER
EXCIPIENT
SPEED
MIXER
WEIGHT
LEAK TEST
BLENDING
Prepared by
GRANULATION
( IF REQUIRED)
Checked by
FILLING
Approved by
STRIPING/
BLISTERING/COUNTING
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
CRITICAL PROCESS PARAMETERS (CPPs) :
SR CRITICAL PROCESS
RESPONSE
VARIABLE
PARAMETER
1.
Granulation
2.
BLENDING
Sequence of excipient
Blend uniformity
addition
Load blending vessel.
3.
4.
5.
Fixed weight as per label
claim
Weight uniformity
Fixed , no variation of
filling speed.
D.T.
STRIPING/BLISTERING/COUNTING
Leak test
Leakage
Bottle Sealing
Critical process variable (CPV):
SR
PROCESS /
MACHINE SETTING
VARIABLE
(CONTROL
VARIABLES)
1
Mixing
Mixing time
2
Filling
Speed, locking
Prepared by
Fixed order of addition
Fixed batch size
Fixed, no variation of
blending speed.
Variation of blending time
Blending time
FILLING
Weight of capsule
Locking length.
Capsule filling speed
REMARKS
Checked by
No leakage
REMARKS
Approved by
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
Stripping/ blistering
DATE OF EFFECTIVE
Leak test, speed.
Setting and conditions as
mentioned in the batch
manufacturing record to be
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Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA
5.1 Sampling Locations:
Side view:
Top view:
3
Sampling location in blender
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
5.3 SAMPLING
STAGE/ TEST
PARAMETER
MIXING
SAMPLING
REMARKS
CAPSULE FILLING
( SIZE,LOCATION,TIME)
After 20 min of mixing time
N=3 samples at each
interval
Sample size: 1.0 1.5 g
Draw the sample at interval of
Each sample comprises
Appearance
30 min. during Filling .
the amount for the
ASSAY
Weight of 20 caps.
N=____ sample
Weight variation
Sampling : at start,
Disintegration time
different tests required.
every two hours,
immediately after the
brake time , end of
filling..
Sample size:_____
STAGE / TEST
PARAMETER
MIXING
EQUIPMENT
( SIZE , LOCATION
TIME)
Sampling thief:
ASSAY
ACCEPTANCE
CRITERIA
Assay 95 % to 105
%
Rel. std. : < 3.0 %
CAPSULE FILLING
Appearance
Visual inspection,
Weight of 20 caps.
Analytical balance
Weight variation
Analytical balance
Prepared by
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As specified in the BMR.
Approved by
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
Disintegration time
DATE OF EFFECTIVE
DT apparatus with water at
NMT ____minutes.
37 + 10C, with discs.
Assay:
___________
6.0 RECORDING OF DATA & DATA TREATMENT
DATA RECORDING SHEET NO.
1.
For recording mixing assay observation & results
2.
For recording blending observations & results.
3.
For recording Drying observation & results.
4.
For recording filling observations and results
5.
For recording polishing observation and results
6.
For recording blister / stripping/ counting observation and record.
7.
For recording general utilities /equipment / method Analytical /results.
8.
For recording analytical method validation.
9.
For recording blister / stripping/counting observation and record.
10.
For recording general utilities /equipment / method Analytical /results.
11.
For recording analytical method validation.
6.1DATA RECORDING
The data obtained from the various analysis & observations shall be recorded in
the DATA RECORDING SHEET for first three commercial batches.
DATA RECORDING SHEET #1
SIFTING:
Equipment Name
Identification no
Sieves
Integrity of the sieve
MIXING :
Equipment name
Prepared by
:_________________________
:_________________________
Date:___________________
: _________________________
(before): ___________________ (After)__________________
:_______________________
Checked by
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Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
Identification no
Capacity
DRYING:
Equipment Name
Identification No
:_______________________
Date:____________________
: ______________________lt.
:_______________________
:_______________________
Date:___________________
Ingredients and sequence of material addition: ____________________
Total weight of ingredients
: _______________kg/lot.
Mixing time: 20 minutes
Setting Mixer: slow
Granulator : OFF
Procedure : As outlined in the batch manufacturing record.
Plan
: Samples to be drawn at of 20 minutes of mixing from 3 different locations
FOR DRY MIXING RESULTS.
BATCH NO:
Sample no:
1
2
3
Average std.Dev.
Range
RSD
LCL
UCL
POINTS
Method of analysis adopted
Ref No.:
Anlyst:
Date
Meet acceptance criteria.
YES (
)
NO (
)
CONCLUSIONS:_______________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
_______________________
CHECKED BY:_________________________
Prepared by
Checked by
DATE____________________
Approved by
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
DATE RECORDING SHEET #2
BLENDING:
Equipment name: OCTAGONAL BLENDER
Identification no:
_____________________________Date:_________________________
Capacity
:______________________lt.
Ingredients & sequence of material addition:__________
Procedure
Plan
: as outlined in the batch manufacturing record.
: Samples to be drawn at intervals of 20 minutes of mixing from top , middle,
bottom and pool sample.
Lubrication results
BATCH NO: ______________________
Sample no:
1
2
3
4( POOL)
Average std.Dev.
Range
RSD
LCL
UCL
Method of analysis adopted
Ref No.:
Anlyst:
Date
Acceptance criteria 95 % TO 105 %
Meet acceptance criteria.
YES (
NO (
CONCLUSIONS:_________________________________________________________
________________________________________________________________________
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
________________________________________________________________________
__________________________________________
CHECKED BY:_________________________
DATE____________________
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Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
DATA RECORDING SHEET# 3
Equipment Name: Capsule filling machine
Identification Name : ___________________________________
Date:____________________
Ejection side: Left /Right
Sample no: B/M/E
BATCH NO:
APPEARANCE
WEIGHT OF 20 capsule
WEIGHT VARIATION
DISINTEGRATION TIME
Visual inspection
Analytical balance
Analytical balance
DT apparatus with water at
37 + 20 C , with discs.
ASSAY
TEST
As specified in the B.M.R.
95 % TO 105 %
APPEARANCE
AV.WT.
( MG)
WT. Variation
( MG)
D.T
(sec)
Sample qty.
(Beginning
sample)
Middle sample
End sample
Avg.
X
X
X
S.D.
X
X
X
R.S.D.
X
X
X
complies
*All the values are averages of he number of samples mentioned in the table
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Assay
( %)
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
REMARKS:
________________________________________________________________________
________________________________________________________________________
____________________________
Checked By: _______________________________
Date:____________________________
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
DATA RECORDING SHEET # 4
Equipment Name : POLISHING & CHECKING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no:
Average wt
Polishing
B
M
E
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria :
yes/ no
Conclusion:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
__________________________________________
Checked by ;___________________________Date_________________________
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
DATA RECORDING SHEET # 5
Equipment Name : BLISTER/STRIP/SCORPIO COUNTING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no:
Leak test
Coding
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria :
yes/ no
Conclusion:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
__________________________________________
Checked by ;___________________________Date_________________________
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
DATA RECORDING SHEET # 5
DATE:____________________
SR
NAME OF CRITICAL
EQUIPMENT/UTILITIES
QUALIFICATION/
VALIDATION FILE
REF.NO.
DATE OF
QUALIFICATION /
VALIDATION
1
Master sifter
2
Rapid mixer granulator
3
Double cone blender
4
Empty gelatin capsule feeder
5
Capsule filling machine
6
Empty capsule shorting machine
7
Empty capsule shorting machine
8
Strip packing machine
UTILITIES:
1
AHU SYSTEM
2
WATER SYSTEM
3
COMPRESSED AIR
4
STEAM
5
LIGHTNING
6
DRAIN
DATA RECORDING SHEET # 6
DATE:____________________
NAME OF PRODUCT:
SR Parameters
Type of
sample
Sample
A(known
amount
of
analysis.
Accuracy
% Recovery of
known amount.
Prepared by
Actual
reading
Checked by
Observed
reading
Analysis
performed
by
Analysis
checked
by
Approved by
Ref.
Work
sheet
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
90 % of
A
110 % of
A
Precision
Sample
Repeatability
A1
( under same
( from
condition ) Test one
by same
sample
analyst at same point)
time from same Sample
homogenous
A2
validated mass ( from
but from
second
different
sample
sample plan
point)
( by taking
Sample
sample of
A3
different
( from
quantity)
third
sample
point)
Reproducibility Sample
under different A1
conditions.
On
______
Test by
different
analyst on
different days.
Sample
A2
On
______
Linearity and
range
Sample
A3
On
______
25 % of
A
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PROCESS VALIDATION PROTOCOL
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Response
concentration
curve on graph
paper.
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DATE OF EFFECTIVE
50 % of
A
75 % of
A
100 % of
A
125 % of
A
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PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
SR Parameters
Type of
sample
Sample A1
15 min.
degradation
Specificity/
selectivity( by
larger
communication
of analytical
method.) for
identification
of impurities
assay of active
component
etcTemp &
humidity /
degradation
factored to
main
ingredients by
15 min, 30
min,45 min or
known
degraded
products.
Limit of
detection
( LOD) & limit
of quantitative
(LOQ)
Qualitative &
Quantitative
result
Actual
reading
Observed Analysis
Analysis
reading
performed checked
by
by
Sample A2
30 min.
degradation
Sample A3
45 min.
degradation
0.1 % of A
1% of A
5 % of A
10 % of A
20 % of A
Analysis
Method A
method (for
non
Method B
pharmacopoeial
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Ref.
Work
sheet
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO:
DATE OF EFFECTIVE
Method C
to be performed
by other public
REMARKS:
1. Specifically / selectivity analysis(4) and Reproducibility (2B) also given raggedness
and robustness.
2. Limit of Quantitative (5) also gives sensitivity of test procedure.
Above procedure to be repeated over three batches to get minimum nine variables for
each parameter.
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