VALIDATION PROTOCOL
PROCESS VALIDATION FOR CEFAKID GRANULES
PROTOCOL APPROVAL
Ref. No.: 010012.02/01 Page 1 / 21
Table of Contents
S. No. Content Page No.
1 Objective 3
2 Scope Process Description 3
3 Abbreviations 3
4 Responsibility 4
5 Safety Precautions 5
6 Equipments/ Materials Required for the validation 5
7 Validation Study Plan 7
8 Procedure 10
9 Sampling Plan 16
10 Acceptance Criteria 20
11 Re-Validation 21
12 References 21
1. Objective:
The objective of this proces validation protocol is to establish documented
evidence that the processing for CEFAKID GRANULES will consistency produce
a product, which meets its predetermined specification and quality attributes.
2. Scope Process Description:
The prospective process validation will be performed with qualified equipment in
the Betalactam non-sterile workshop with three consecutive batches of the
product CEFAKID GRANULES.
This process validation (PV) protocol is written in order to document that the
process used in the manufacturing of the product name CEFAKID GRANULES of
batch size: 150.00 kg # 50,000 sachets complies with process parameters
requirement of the Batch Manufacturing Record (BMR) and finished product
specifications.

activities
To coordinate and implement the process validation
activities
Production of BL Solid
Orals
Execution of BMR and protocol
Providing samples wherever necessary as per the protocol
and BMR
Recording of observation, collection of data and filling of
BMR
Engineering &
Maintenance
To ensure that all the required utilities are working as per
the respective SOPs
To ensure that the related instruments and equipments are
in calibrated and validated status
To ensure that the environmental conditions of all the areas
met the requirements
QC
Testing shall be done as per the sampling plan and
respective specifications
QA
Prepare process validation protocol
Sampling as per the sampling plan (IPC)
Preparation and review of the Validation report, documents
and its compliance to meet the acceptance criteria of the
protocol
5. Safety Precautions:
• Ensure that all clean-rooms and equipments are cleaned completely and
sticked appropriate status labels.

Wet granulating machine 22021
IQR-L-XH-1
OQR-L-XH-1
PQR-L-XH-1
Tray dryer 22125 30124
Cubic mixer 1 22017 30104
Metal detecting machine 22027 NA
Vertical sachet packing machine 1 22003 IQR-L-EG-1
OQR-L-EG-1
PQR-L-EG-1
Electronic Balance 22136 30141
Ink-jet printer 22014 IOQ-22014
IPC equipments
Cylinder NA NA
Electronic balance CP224S 22047 IOQ-22047
Leak-test apparatus 22050 IOQ-22050
Digital caliper 22110 NA
QC Laboratory equipments
Analytical Balance
25026 30023
25027 30040
25036 30042
High Performance Liquid Chromatography
25011
IQ.P-K-LC-05
OQ.P-K-LC-05
25012
IQ.P-K-LC-07
OQ.P-K-LC-07
25013

code
Raw material Manufacturer Spec. SPC.No
1 sachet
(mg)
Percent (%)
1 batch (50,000 sachets)
(kg)
TB0C02.DSM
Cephalexin
monohydrate
Spain
In-house
In-house
SPC-RM-046-01
270.00 9.00 13.50 = (2 x 6.75)
Corresp. to Cephalexin
anhydrous)
256.80 8.56 12.84 = (2 x 6.42)
VN4D01.KCP
Sugar milled through
0.8 mm sieve
Vietnam (KCP) EP 6.0 SPC-RM-009-01 1950.00 65.00 97.50 = (2 x 48.75)
NB4A01.AJI Aspartam
Ajinomoto/
Japan
In-house SPC-RM-064-01 40.00 1.33 2.00 = (2 x 1.00)
PH4M01.ROQ Mannitol 60
Roquette/
France
In-house SPC-RM-047-01 700.00 23.33 35.00 = (2 x 17.50)

8.3These trials may include worst case conditions but not necessarily simulate the
failure range of the product processing conditions.
8.4A summary report will be prepared on the effect of different variables and final
conclusion will be drawn on the effect of different variables on the processing of
the product.
8.5Manufacturing process and sampling for validation is performed as per the follow
chart
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8.6Manufacturing process description
Flow of manufacturing process
• Dispensing
In this stage, dispensing will be carried out as per the BMR and SOP 120003
after line-clearance given by IPC person. Before dispensing, all the
requirement materials with approved status will be verified by IPC, production,
warehouse person.
Dispensed raw materials and intermediate product are transferred to
respective process areas as per material movement plan as per SOP 120003.
• Weighing and Checking
The weight of the materials received from dispensing area will be checked by
IPC, production person against the dispensing labels as per SOP 120003.
• Sifting (all dispensed materials)
Sift Aspartam and sugar, manitol 60 through 24 mesh sieve and contain it in
PE bags
Sift Cephalexin monohydrate through 14 mesh sieve and contain it in PE bags
Check the integrity of sieve before and after use: clean and integrity
• Formulation of paste solution
Pour 10.20 kg 96% ethanol into tank of the stirring mixer. Add PVP K29-32
slowly when stirring.
Stir until the viscous solution become transparent. Stir and put slowly
Quinoline yellow lake mixture, stir until the viscous mixture become yellow.

Before start up of the sachet packing operation, verify and record the
temperature (18 – 25
o
C) and relative humidity (NMT 55%).
8.7Critical process step
• Critical process control variables at each critical manufacturing step and
measured parameters are as follows:
S.
No.
Process
steps
Process
parameter
setting
Rationale Testing
1
Raw material
and packaging
material
NA
Raw material and
packaging material
used are supplied by
approved vendors and
released by QC
NA
2
Dispensing of
raw material
Weighing

Sieve integrity
before and after
sifting
4
High speed
mixing
Time and RPM
To demonstrate the
blend uniformity with
binder solusion
Appearance
5 Final mixing
Mixing time and
mixing speed
To demonstrate the
blend uniformity on
completion of
lubrication
Mixing time
Mixing speed
Appearance
Moisture/ Water
content
Distribution
granule size
Bulk/ Tape density
Blend uniformity
S.
No.
Process

1 filled sachet
Average mass
Length
Leak test
Identification
Uniformity of
mass
Uniformity of
content
Water content
Dissolution
Assay
9. Sampling Plan:
The sampling plan is defined for a batch as per table below:
9.1 Stage of Final mixing (Granules)
• In-process control:
S. No. Test Item Time Q’ty / sample
Number of
samples
Sampling points
Testing
procedure
1.
Appearance
After completion of
final mixing
60 gram for
each sample
05 As per the figure 1 SOP 020018
2.

• Done by IPC:
S. No. Test Item Time/ Frequency Sample Q’ty Testing procedure Remarks
1. Appearance During sachet filling stage NA SOP 020018 NA
Granules level
1
2
3
8
9
10
4
5
6
7
BMR No.: 50.C45/P01/03
2.
Uniformity of mass Once 2 hours, start of working day
10 filled
sachets
3.
Sachet length
Starting, middle, end of batch
process stage, start of working
day, or unschedule (if any)
10 filled
sachets
4.
Leak test
Once two hours, start of working
day, whenever change new alu roll

2. Identification
3.
Uniformity of mass
4.
Water
5.
Dissolution
6.
Uniformity of content
7.
Assay
10. Acceptance Criteria:
Each validation batch must meet the specifications of CEFAKID GRANULES.
S.
No.
Mfg. Process
Steps
Test Item Acceptance Criteria
1
Final mixing
(Granules)
Appearance
Identical light – yellow granules, no dark spots
and strange coloured trace
Moisture content (LOD) 0.7% - 1.4%
Bulk/ Tape density For information testing
Distribution granule size For information testing
Water content 0.7% - 1.4%
Identification
In the assay, the chromatogram obtained with

Water Not more than 5.0%
Dissolution Meet the requirement.
Uniformity of content
• 85 percent to 115 percent of the
average content
• RSD ≤ 5.0%
Assay
Content of Cephalexin (C
16
H
17
N
3
O
4
S) is not
less than 90.0% and not more than 110.0% of
the labelled amount, calculated on average
mass of granules.
• Expanded testing on three batches of CEFAKID GRANULES should
demonstrate reproducible results for the process to be considered
validated.
• Acceptable results on each of the three consecutive batches are needed to
satisfy the validation requirements.
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• If possible, control charts for quantitative validation tests will be analysed for
trends and to show satisfactory process control.
• Batches may be dropped from the validation study only if events not related to
the process (e.g. mechanical failure) cause a change in the process. Such
occurrences must be fully documented.

• STP-01019 – Thin – layer chromatography.
• STP-01001 – Test for uniformity of mass of single-dose preparations
• Validation Master Plan
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