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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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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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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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

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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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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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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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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:

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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.:
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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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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

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GRANULATION
( IF REQUIRED)

Checked by

FILLING

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STRIPING/
BLISTERING/COUNTING

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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
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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

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No leakage

REMARKS

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Stripping/ blistering

DATE OF EFFECTIVE

Leak test, speed.

Setting and conditions as

mentioned in the batch
manufacturing record to be

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5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA

5.1 Sampling Locations:

Side view:

Top view:

3
Sampling location in blender

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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

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As specified in the BMR.

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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

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:_________________________
:_________________________

Date:___________________
: _________________________
(before): ___________________ (After)__________________
:_______________________

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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:_________________________

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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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DATE OF EFFECTIVE

________________________________________________________________________
__________________________________________
CHECKED BY:_________________________
DATE____________________

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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
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
( %)

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DATE OF EFFECTIVE

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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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

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Ref.
Work
sheet

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(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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Response
concentration
curve on graph
paper.

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50 % of
A
75 % of
A
100 % of
A
125 % of
A

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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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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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