Company Name & Address

PROCESS VALIDATION PROTOCOL

(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE

FORMULATION :
PRODUCT NAME :
LINE :
REASON FOR PERFORMING THE VALIDATION STUDY :
Reason ( tick which ever is applicable) Remarks
Department
New product
Modification in the manufacturing process.
Change in Facility and / or location of manufacturing.
Batch fail to meet product & process specifications.

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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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.

 Detailed manufacturing instructions for the production of the validation batches.

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2.0 PERSSONEL RESPONSIBILITIES.

SR ACTIVITY RESPONSIBILITY REMARKS

1 Preparation of validation
protocol
2 Approval of Validation
protocol
3 Production of validation
Batches
4 Testing of validation
samples & Preparation of
validation report
5 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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SR INGREDIENTS/EXCIPIENTS SPECIFICATION MG.CAPS. PER BATCH PER LOT

1
2
3

4
5
6

7
8
9
10

11
12
13

NOTE:

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CAPSULE FLOW CHART

R.M.DISPENSING

SHIFTING

BLENDING 1. MIXING TIME

2. SPEED
GRANULATION
(IF REQUIRED)

DRYING

1. MIXING TIME
COMPECT 2. SPEED
(IF REQUIRED)

MILLING MIXING
(IF REQUIRED) BULK ANALYSIS

FILLING
1.0 WEIGHT VERIATION

QUARANTINE

BLISTER/ STRIP PACKING/

COUNTING

FINAL PACKING

QUARANTINE

F.G.STORE FINISHED PRODUCT ANALYSIS

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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 SOP’S , VALIDATION & QUALIFICATION REPORT USED AS

REFERENCES=
SR ID. NUMBER TITLE VERIFIED DATE
BY
1. Equipment cleaning procedure for Master sifter #20,#40
2. Equipment operating procedure for Master sifter #20,#40
3. Equipment cleaning procedure for Rapid mixer
granulator.
4. Equipment operating procedure for Rapid mixer
granulator.
5. Equipment cleaning procedure for Octagonal Blender.
6. Equipment operating procedure for Octagonal blender.
7. Equipment cleaning procedure for capsule filling
machine.
8. Equipment operating procedure for capsule filling
machine.
9. Equipment cleaning procedure for capsule polishing &
Checking machine.
10. Equipment operating procedure for capsule polishing &
Checking machine.
11. Equipment cleaning procedure for strip packing machine.
12. Equipment operating procedure for strip packing
machine.
13. Equipment cleaning Procedure for Blister Packing
machine.
14. Equipment operating procedure for Blister Packing
machine.
15. Equipment cleaning procedure for Cap counting machine
16. Equipment operating procedure for Cap counting

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machine
17. Equipment cleaning procedure for Fluid Bed Dryer.
18. Equipment operating procedure for Fluid Bed Dryer.
19. Enter any other reference sop.

4.2 DETAILS OF EQUIPMENT TO BE USED.

EQUIPMENT DETAILS
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.:

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M.O.C.
DRYING TYPE :
MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.

CAPSULE FILLING TYPE :

MACHINE: MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
CAPSULE POSISHING & TYPE :
CHECKING MACHINE MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
STRIP PACKING TYPE :
MACHINE: MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:
M.O.C.
BLISTER PACKING TYPE :
MACHINE: MODEL:
CAPACITY:

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MANUACTURER:
TAG.NO.:
M.O.C.
CAPSULE COUNTING TYPE :
MACHINE MODEL:
CAPACITY:
MANUACTURER:
TAG.NO.:

REMARKS:

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4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER.

4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:

MATERIAL MIXING AIR DRYING POLISHING

SIFTING

LOAD SIZE

ACTIVE

SPEED

MIXER
EXCIPIENT

SPEED

MIXER

WEIGHT
LEAK TEST

BLENDING GRANULATION FILLING STRIPING/

( IF REQUIRED) BLISTERING/COUNTING
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CRITICAL PROCESS PARAMETERS (CPP’s) :

SR CRITICAL PROCESS RESPONSE REMARKS
VARIABLE PARAMETER
1. Granulation

2. BLENDING Fixed order of addition

Blend uniformity
Sequence of excipient Fixed batch size

addition

Load blending vessel. Fixed, no variation of

blending speed.
Blending time Variation of blending time

3. FILLING

Weight of capsule Fixed weight as per label

claim
Locking length. Weight uniformity

Capsule filling speed Fixed , no variation of

filling speed.
D.T.

4. STRIPING/BLISTERING/COUNTING

Leak test Leakage No leakage

5. Bottle Sealing

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Critical process variable (CPV):

SR PROCESS / MACHINE SETTING REMARKS
VARIABLE (CONTROL
VARIABLES)
1 Mixing Mixing time
2 Filling Speed, locking Setting and conditions as
3 Stripping/ blistering Leak test, speed. mentioned in the batch
manufacturing record to be
followed.

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5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA

5.1 Sampling Locations:

Side view: 2

1 3

Top view:

Sampling location in blender

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5.3 SAMPLING

STAGE/ TEST SAMPLING REMARKS

PARAMETER ( SIZE,LOCATION,TIME)
MIXING After 20 min of mixing time
ASSAY  N=3 samples at each
interval
 Sample size: 1.0 – 1.5 g
CAPSULE FILLING Draw the sample at interval of Each sample comprises
Appearance 30 min. during Filling . the amount for the
Weight of 20 caps.  N=____ sample different tests required.
Weight variation  Sampling : at start,
Disintegration time every two hours,
immediately after the
brake time , end of
filling..
 Sample size:_____

STAGE / TEST EQUIPMENT ACCEPTANCE

PARAMETER ( SIZE , LOCATION CRITERIA
TIME)
MIXING Sampling thief:  Assay 95 % to 105
ASSAY %
 Rel. std. : < 3.0 %
CAPSULE FILLING

Appearance Visual inspection, As specified in the BMR.

Weight of 20 caps. Analytical balance

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Weight variation Analytical balance

Disintegration time 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.

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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 :_________________________ Date:___________________
Sieves : _________________________
Integrity of the sieve (before): ___________________ (After)__________________

MIXING :
Equipment name :_______________________
Identification no :_______________________ Date:____________________
Capacity : ______________________lt.

DRYING:
Equipment Name :_______________________ Date:___________________
Identification No :_______________________

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

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POINTS
Method of analysis adopted
Ref No.:
Anlyst:
Date
Meet acceptance criteria. YES ( ) NO ( )
CONCLUSIONS:_______________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
_______________________

CHECKED BY:_________________________ DATE____________________

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DATE RECORDING SHEET #2

BLENDING:

Equipment name: OCTAGONAL BLENDER

Identification no:
_____________________________Date:_________________________
Capacity :______________________lt.
Ingredients & sequence of material addition:__________
Procedure : as outlined in the batch manufacturing record.
Plan : 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 ( )

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CONCLUSIONS:_________________________________________________________
________________________________________________________________________
________________________________________________________________________
__________________________________________

CHECKED BY:_________________________

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DATA RECORDING SHEET# 3

Equipment Name: Capsule filling machine
Identification Name : ___________________________________
Date:____________________
Ejection side: Left /Right
Sample no: B/M/E
BATCH NO:

APPEARANCE Visual inspection

WEIGHT OF 20 capsule Analytical balance
WEIGHT VARIATION Analytical balance As specified in the B.M.R.
DISINTEGRATION TIME DT apparatus with water at
37 + 20 C , with discs.

ASSAY 95 % TO 105 %

TEST APPEARANCE AV.WT. WT. Variation D.T Assay

( MG) ( MG) (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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REMARKS:
________________________________________________________________________
________________________________________________________________________
____________________________

Checked By: _______________________________Date:____________________________

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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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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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DATA RECORDING SHEET # 5

SR NAME OF CRITICAL QUALIFICATION/ DATE OF

EQUIPMENT/UTILITIES VALIDATION FILE QUALIFICATION /
REF.NO. 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

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DATA RECORDING SHEET # 6

NAME OF PRODUCT:

SR Parameters Type of Actual Observed Analysis Analysis Ref.

sample reading reading performed checked Work
by by sheet
1 Accuracy Sample
% Recovery of A(known
known amount. amount
of
analysis.
90 % of
A
110 % of
A
2 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)
3 Reproducibility Sample
under different A1
conditions. On
______

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Test by Sample
different A2
analyst on On
different days. ______

Sample
A3
On
______
4 Linearity and 25 % of
range A
Response 50 % of
concentration A
curve on graph 75 % of
paper. A
100 % of
A
125 % of
A

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SR Parameters Type of Actual Observed Analysis Analysis Ref.

sample reading reading performed checked Work
by by sheet
5 Specificity/ Sample A1
selectivity( by 15 min.
larger degradation
communication
of analytical
method.) for
identification
of impurities Sample A2
assay of active 30 min.
component degradation
etc…Temp &
humidity /
degradation
factored to
main Sample A3
ingredients by 45 min.
15 min, 30 degradation
min,45 min or
known
degraded
products.
6 Limit of 0.1 % of A
detection
( LOD) & limit 1% of A
of quantitative
(LOQ) 5 % of A
Qualitative &
Quantitative 10 % of A
result
20 % of A

7 Analysis Method A
method (for
non Method B
pharmacopoeial

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to be performed Method C
by other public
lab.

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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