Process Validation Protocol For Gliclazide Modified Release Tablets

Label claim :
Each uncoated modified release tablet contains
Gliclazide Ph. Eur 60 mg
Master Formula No. :
Product Code :
Batch Size :
Shelf Life :

Protocol No. :
Effective Date :

PROTOCOL CONTENTS
Sr.No. Section Title Pages No.
NA Protocol Contents
NA Protocol Approval Sheet
1.0 Objective
2.0 Scope
3.0 Responsibility
4.0 Validation Team Members
5.0 Abbreviations
6.0 Pre-requisite for Validation
7.0 Manufacturing Procedure
8.0 Critical Process Steps and Process
Parameters for Validation with Justification
9.0 Process steps Sampling and Analysis
Plan with Acceptance Criteria
10.0 Hold Time study
11.0 Revalidation
12.0 OOSs and Investigations
13.0 Validation Report
14.0 Reference Documents
15.0 List of Annexures / formats Attached

PROTOCOL APPROVAL SHEET

This is a specific protocol for Process Validation of uncoated modified release tablet
of Gliclazide Modified Release 60 Tablets which is manufactured at solid oral manufacturing
facility in Pharmaceutical company
This protocol has been approved by the following:
Prepared by:
Functional Area Name Designation Signature Date

Quality Assurance

Checked by:
Functional Area Name Designation Signature Date

Process
Development
Quality Assurance

Approved by:
Functional Area Name Designation Signature Date

R&D
Production
Quality Control
Regulatory Affairs
Quality Assurance

Objective
To provide documented evidence with high degree of assurance that the manufacturing
process is capable of producing the finished product consistently of required quality, meeting
its predetermined specifications and quality attributes.

Scope
This concurrent process validation protocol is applicable to carry out the process validation
for Gliclazide Modified Release 60 Tablets on three consecutive batches at formulation Plant
of pharmaceutical company.

Responsibility
Quality Assurance : Preparation, review and approval of process validation protocol.
R&D : R&D to approve the process validation protocol
Production : Production to approve the process validation protocol.
Quality Control : QC to approve the process validation protocol.
Process Development : To review the process validation protocol.
IPQA : Sampling of samples as per the sampling plans discussed in
this process validation protocol.
Engineering : To provide support with respect to utilities and equipment
Regulatory Affairs : Regulatory Affairs to approve the process validation protocol

4.0 Validation Team Members

Validation team is comprises of the Trained representatives from following departments:
Production
R&D
Process Development
Quality Control
In-process Quality Assurance
Quality Assurance
Engineering

Abbreviations
R&D : Research and Development
QC : Quality Control
IPQA: In-process Quality Assurance
RSD : Relative Standard Deviation
NMT : Not More Than
NLT : Not Less Than
STP : Standard Test Procedure
LOD : Loss on Drying
GTP : General Test Procedure
ID No.: Identification Number
Spec. No.: Specification No.
RH% : Relative Humidity
SOP : Standard Operating Procedure
IQ : Installation Qualification
OQ : Operational Qualification
PQ : Performance Qualification
IH : In-house
IPCs : In Process Containers

Representative Sample :A sample collection from one location / place; representing

the characteristics of the whole batch / lot.

Composite Sample :A desired amount of sample shall be taken after collection of

samples from different location in one sample bag.

Pre-requisites for Validation

Process Equipments
All equipments to be used for the manufacturing process are qualified as per IQ/OQ/PQ
acceptance criteria. The following equipments are to be used for manufacturing of Gliclazide
Modified Release 60 Tablets
S.No. Equipment Process Make Equipment Capacity Qualification
Name Step& Area ID No. status(report
no.)
1. Vibro Sifter Sifting
2. Conta Blender Mixing
3. Roll Compactor Slugging
4. Comminuting-Mill Milling
5. Compression M/C Tablet
Compression
6. Blister Packing Packing
Machine

Equipments / Instruments used for In-process checks

The following calibrated equipments / Instruments are used for in-process checks.
S. No. Equipment /Instrument Equipment ID. No. Calibration status
Name (kit-used for
calibration)
1. Analytical weighing Balance
2. Friability Test Apparatus
3. Hardness Tester
4. Vernier Caliper

Following specifications and Standard Test Procedures are referred for carrying out testing
of validation samples.
 *SPECIFICATIONS No. *STP No.
In-process:
Finished Product -Release:
*Testing of samples is done as per current version of STPs and GTPs

Approved Raw Materials

The raw material used for manufacturing process are from approved vendors and all the
Raw Materials are tested before manufacturing process to ensure that material are of the
acceptable quality prior to their use in the manufacturing .
Approved Raw Materials List
Ingredient Pharmacopoeial Item Standard Pharmaceutical
Status Code Quantity role
Per
batch In kg
Gliclazide * Active
Calcium Hydrogen Filler
Phosphate
Dihydrate
Cellactose 80 Filler
Hypromellose Rate controlling
excipients
Hypromellose Rate controlling
excipients
Silica, Colloidal Glidant
Anhydrous
Povidone (K-30) Binder
Magnesium Stearate Lubricant
Talc Lubricant
Magnesium Stearate Lubricant
Talc Lubricant
*Given quantity of Gliclazide is BASED ON ASSAY (ODB) = 100.00 % W/W
L.O.D = 0.00 % W/W

Manufacturing Procedure :
Manufacturing procedure in brief comprise of following steps:
SIFTING : Sift Gliclazide, Calcium Hydrogen Phosphate Dihydrate, Hypromellose, Silica,
Colloidal Anhydrous, Povidone (K-30) Magnesium Stearate, Talc through Vibro Sifter fitted
with sieve of mesh size 80, and retention through Vibro Sifter fitted with sieve of mesh size
60 collect the sifted material in IPCs.
SIFTING : Sift Cellactose 80 through Vibro Sifter fitted with sieve of mesh size 30 collect the
sifted material in IPCs.
DRY MIXING : Perform dry mixing of materials of Previous step in Blenders bin. ( mix for
20 minutes at 5 rpm)
SLUGGING : Slug the mass of step in Roll-Compactor, adjust and record Feed screw rate
and speed of rollers and weigh the slugs.
DESLUGGING : Mill the Slug mass by comminuting mill fitted with 5.0 mm Screen at knife
forward orientation and at slow speed .
SIFTING :Sift the milled mass through Vibro Sifter fitted with sieve of mesh size 20 and pass
the retention through comminuting mill fitted with 2.0 mm Screen at knife forward orientation
and at slow speed , repeat the above process till all the material passed through sieve of
mesh size 20 .
SIFTING :
a) Sift the material through Vibro Sifter fitted with sieve of mesh size 40,collect and weigh
the retention.
b) If the retention of sifting is less than 45 % then collect & weigh (using calibrated balance
)separately the fines.
If the fines percentage is more than 55 % then repeat process steps slugging,milling and
sifting for fines until fines % is less than 55 % ,if it is less 55 % then directly proceed for
next step
LUBRICATION OF GRANULES : a) Transfer the Milled material to a Blenders bin.
b) Sift Magnesium Stearate, Talc through Vibro Sifter fitted with sieve of mesh size 60 &
transfer to Blenders bin of milled material. Blend for 10 minutes at 5 rpm.
WEIGHING :Weighing of lubricated granules is done by using a calibrated balance and
calculate the actual .
SAMPLING : Inform to IPQA Department through In-process Analytical Request to collect
the sample of blended granules , IPQA personnel send the sample to Quality Control
Department for testing as per In-process Specification.
COMPRESSION : After getting approval from IPQA Department, compress the lubricated
blend , into tablets of required specification using 37 station compression machine fitted with
oval dies and standard concave punches (14.00 0.05 mm x 00 0.05 mm),plain on both
sides.

COMPRESSION PARAMETERS
Description : White to off-white, oval , biconvex uncoated tablets, plain on both sides.
Average Weight: 422.0 to 438.0 mg
Thickness: 5.00 0.20 mm
Length : 14.15 0.05 mm
Width : 7.05 0.05 mm
Hardness : 70 100 N
Friability : NMT 1.0 %w/w
Weight variation : Individual mass of 20 tablets should not deviate by more than 5.0 % of the
average weight.

IPQA CHECKS : Carry out in-process control /check as per SOP.

SAMPLING : Inform to IPQA Department through In-process Analytical Request to collect

the sample of tablets for analysis as per approved in process specification No.
WEIGHING : Collect the Compressed tablets in HDPE containers lined with double poly
ethylene bags & weigh and calculate the final yield of Compressed Tablet.
PACKAGING : After getting approval from IPQA Department, pack the approved tablets as
per approved BPR.
Critical Process Steps and Process Parameters for Validation with Justification :
Process Step Process Parameters Justification
DISPENSING % RH & Dispensing Influence the stability and manufacturing
aids of product
SIFTING Sieve size , sifting To evaluate the sifting time
time and integrity of during sifting process
sieve.
DRY-MIXING Dry-mixing time,and After completion of sifting, the process of
Blending RPM dry mixing is evaluated for Homogeneity
of drugs through sampling of the mixed
blend after 20 minutes at 5 rpm. Blending
is done using Conta Blender. This
process step is evaluated for adequate
blending time assessment through the
determination of blend uniformity
analysis of samples collected from
different locations. .Refer Annexure-02
for sampling plan and analytical data
compilation and acceptance criteria.It
can influence both the content uniformity
& assay of product.
SLUGGING Feed screw rate, To record and evaluate the variability of
Speed of rollers. For critical process variables for process step
detail refer Annexure- of slugging to achieve granules size of
01. desired properties.
DESLUGGING/ Feed rate of slugs. Effective deslugging is achieved by
MILLING Milling speed, Blade adjusting the feed rate to 10.0 kg/ 40-60
orientation and minutes.
Screen size. For
detail refer Annexure-
01.
SIFTING Sieve size , sifting To record and evaluate the variability of
time and integrity of critical process variables during sifting.
sieve for detail refer
annexure -01
LUBRICATION/ Blender speed (rpm) After addition of sifted Magnesium
BLENDING and Blending time Stearate,Talc to the granules; blending is
etc. For detail refer done using Conta Blender. This process
annexure-01 step is evaluated for adequate blending
of the lubricant by sampling of the
blended granules from different locations
from the blender bin after 10 minutes of
blending. The assessment is taken
through the determination of blend
uniformity analysis in samples collected
from different locations. The blend to be
monitored for Bulk Density & Tapped
Density on the composite sample
collected after 5 minutes to determine
the flow properties of the blended
granules. Sampling is done by using
suitable sampling thief. Refer Annexure-
03 for sampling plan and analytical data
compilation and acceptance criteria.
COMPRESSION Machine Speed, Tablets are Compressed using 37
Description, Average Station Double Rotary Compression
Weight, Uniformity of Machine. This process is evaluated
Weight, Thickness, through sampling the compressed tablets
Length, Width, from both sides (left & right) produced at
Hardness, Friability different intervals (Start, Middle and
etc. For detail refer towards the end of compression).
Annexure-01. Samples are checked for the
determination of Description, Average
Weight, Uniformity of Weight, Thickness,
Length, Width, Hardness & Friability
against the established specifications at
IPQA Laboratory
Compressed tablets are subjected for the
determination of Uniformity of dosage
units (by content uniformity for total
Gliclazide Ph.Eur & Drug release .
One composite sample is subjected for
complete analysis as per the established
specifications. Refer Annexure-04 for
sampling and analysis plan compilation
with acceptance criteria
Process Steps Sampling and Analysis Plan with Acceptance Criteria

Sampling is done as per mentioned in Sampling plan. The process parameters are
challenged in the three validation batches.

Process Step Sampling and Analysis Plan with Acceptance Criteria

Dry Mixing Refer Annexure-02
Lubrication Refer Annexure-03
Compression Refer annexure-04
Hold time Studies

Process Step Hold Time Studies Sampling and Analysis Plan with
Justification

About 300 gms material from blended mass is kept under simulating
BLENDING / conditions. The material is subjected to analysis for Assay of
LUBRICATION Gliclazide Ph.Eur. Related substances and LOD at 0 day, after 7th
day & after 15th day. These samples are tested for Bulk Density,
Tapped Density, Compressibility Index and Hausner Ratio to rule out
the de-blending of the materials. Hold time Study shall be carried out
in one batch only.

Samples are also subjected separately for microbiological testing at

0 day, 7th day and 15th day.

Storage Environment (Bulk Storage Area)

Temperature : NMT 25C
Relative Humidity: NMT 45%
Closed S.S. Container / IPC lined with double polyethylene bags of
appropriate size.

Test Method
Description, Assay of Gliclazide, LOD: Refer STP.
Related substances: Refer STP.
Microbial Limit Test :

Refer GTP for microbiological testing as per Ph.Eur.

Bulk Density, Tapped Density, Compressibility Index and

Hausner Ratio

Acceptance Criteria
Description: White to off white, flowing granules. sampled after 7th
day and 15th day are comparable with that of 0 hr (initial).
Assay: Each 430 mg of granules contain not less than 97.5% and
not more than 102.5% (58.5 mg to 61.5 mg) of the label claim of
Gliclazide Ph.Eur., C15H21N3O3S (60 mg).
Related substances:
Single highest impurity : Not more than 0.75%
(specified RRT about 0.30)
Single highest unknown impurity : Not more than 0.3%
Total impurities : Not more than 1.0%
TABLET Loss on drying: Between 1.0% to 3.2% w/w, determined at 1050 C
COMPRESSION for 7 minutes.
Bulk Density, Tapped Density, Compressibility Index and
Hausner Ratio: Results of the samples sampled after 7th day & 15th
day should be comparable with that of 0 day (initial)

Microbial Limits:
Total aerobic microbial count: NMT 500 cfu/g.
Total combined molds and yeasts count: NMT 50 cfu/g.
Escherichia coli: should be absent
Salmonella species: should be absent
Pseudomonas aeruginosa: should be absent
Staphylococcus aureus: should be absent

After completion of compression about 200.0 gms of compressed

tablets are kept under simulating conditions for carrying hold Time
studies. The sampling is done at 0 day, after 7th day & after 15th
day. The sample is evaluated for the tests like Description, Assay
and Related substances. Hold Time studies shall be carried out in
one batch only.

Samples shall be subjected separately for microbiological testing at 0

day, after 7th day & after 15th day.

Storage Environment(Bulk storage Area)

Temperature : NMT 25C
Relative Humidity: NMT 45%
Closed HDPE lined with double polyethylene bags container of
appropriate size.

Description, Assay: Refer STP.

Related substances: Refer STP.
Drug Release: Refer STP..
Microbial Limits:
Refer GTP for microbiological testing as per Ph.Eur.

Acceptance Criteria (0 day, 7th day and 15th day)

Description: White to off white oval, biconvex uncoated tablets, plain
on both sides.
Assay: Each uncoated tablet contains not less than 95.0% and not
more than 105.0% (57.0 mg to 63.0 mg) of the label claim of
Gliclazide Ph.Eur., C15H21N3O3S (60 mg)
Drug Release :
Complies with the test .Percentage of the labeled amount of
Gliclazide is dissolved with in the range stated at each of following
points.
2 Hrs. : NLT 14% and NMT 32 % of the label claim.
4 Hrs. : NLT 32% and NMT 55 % of the label claim.
12Hrs. : NLT 85% of the label claim.

Related substances:
Single highest impurity : Not more than 0.75%
(specified RRT about 0.30)
Single highest unknown impurity : Not more than 0.3%
Total impurities : Not more than 1.0%

Microbial Limits:
Total aerobic microbial count: NMT 500 cfu/g.
Total combined molds and yeasts count: NMT 50 cfu/g.
Escherichia coli: should be absent
Salmonella Species: should be absent
Pseudomonas aeruginosa: should be absent
Staphylococcus aureus: should be absent
Revalidation
If required, revalidation is considered and carried out when any of the following conditions
occur or prevail:
Change in critical formulation component i.e. raw material
Change in manufacturer or vendor of Active Pharmaceutical Ingredient
Change in critical specifications of the product
Change in manufacturing process which may affect the quality of the products.
Change in the facility and /or plant (location or site)
Change in batch size, if more than ten times of the present batch size

Note: In case of the requirements for revalidation, because of above mentioned reasons,
the validation of the critical steps shall be undertaken through addendum attached to this
protocol .
 Annexure -I
Critical Process Variables
Batch Number :__________
Stage Equipment Process Variables Observation
Name
Sifting ( Gliclazide, Vibrosifter Sieve size
Calcium Hydrogen Integrity of sieves Before
Phosphate After
Dihydrate, Sifting time
Hypromellose
,Colloidal
Anhydrous,
Povidone K-
30,Magnesium
stearate , Talc)
Sifting ) Cellactose Vibrosifter Sieve size
80 Integrity of sieves Before
After
Sifting time
Dry mixing Conta blender Blender rpm
Mixing time
Capacity of Blender
Bin
Slugging Roll- compactor Feed screw rate.
Speed of rollers
Deslugging Comminuting Feed rate of slugs
mill Screen size
Screen integrity Before
After
Milling speed
Sifting of Post Vibro sifter Sieve Size
Granulation Integrity of Sieve Before
Ingredients After
Sifting time
Stage Equipment Process Variables Observation
Name
Lubrication Conta Blender Blender rpm
Blending time
Capacity of Blender
Bin
Compression 37 station Machine Speed
Double rotary Feed frame (open/
compression forced)
machine Compression force
Packaging Blister Sealing plate Intial
(Blistering) Packing temperature End
Machine Strip size
CH 240 Leak test Intial
Middle
End

Prepared by____________ Authorized By ____________

(Sign & Date) (Sign & Date)
 Annexure -II
SAMPLING PLAN, ANALYTICAL DATA COMPILATION & ACCEPTANCE CRITERIA

STAGE: DRY MIXING

(Sampling Plan)

Batch Number : Equipment Name: Conta Blender

Sampling Time & speed = after 14,15 & 16 minutes mixing at 6 rpm.

Sampling Quantity = About 425.2 mg to 1275.6 mg for each location sample and about 5
gm for composite sample

Shape of the blender bin with sampling location from 01 to 11

Sampling is done in triplicate from each sampling location using suitable sampling Device

Shape of the blender bin with sampling location from 01 to 11

Sampling is done in triplicate from each sampling location using suitable sampling Device

Record the following:

Sampling Sampled by Sampling Date & Time
Location (Sign & Date)
14 min 15 min 16 min
1
2
3
4
5
6
7
8
9
10
11
Composite
sample

STAGE: BLENDING
Analysis Plan & Analytical Data Compilation:
Determination of Blend uniformity analysis of samples as per STP for location samples and
determination of assay, L.O.D on the composite sample.

Batch Number: _________________

Claim per unit Mass:

Each 425.2 mg of blended mass contains:
Gliclazide 60 mg Ph. Eur.
Record the analytical findings in following manner:

Sampling Results % variation () from A.R. Number

Location mean value
1
2
3
4
5
6
7
8
9
10
11
Mean Value Acceptance Criteria
All individual values should be within 10% of
the mean value.
% RSD
% RSD for all individual results should be
NMT 5.0

Analysis Plan for composite sample: Determination of assay

Test Results A.R.No.

L.O.D

Assay
Acceptance Criteria
L.O.D.: Between 1.0 % w/w and 3.2 % w/w, Determined at 105 C for 7 minutes.
Assay:
Each 425.2 mg of blend contains
NLT 97.5% and
NMT 102.5 % (58.5 mg to 61.5 mg) of the label claim of Gliclazide Ph. Eur., C15H21N3O3S
(60 mg)
 Annexure -III
SAMPLING PLAN AND ANALYTICAL DATA COMPILATION WITH ACCEPTANCE
CRITERIA
STAGE: LUBRICATION

Sampling Plan:
Batch Number:_______________ Equipment Name: Conta Blender

Equipment ID No.: _________________

Sampling Quantity = 430 mg to 1290 mg from each location in triplicate and about 10 gm
for composite sample.
Shape of the blender bin with sampling location from 01 to 11
Sampling shall be done in triplicate from each sampling location using suitable sampling thief

Sampling Time = after 8 mins. of blending with Magnesium stearate ,Talc.

Blending Time and Speed specified: 10 mins at 5 rpm

Blending Time actual: __________ Minutes Speed Actual: _________RPM

Record the following:

Sampling Location Sampled by
(Sign and Date)
1
2
3
4
5
6
7
8
9
9
10
11
Composite sample

Note: Samples shall be sent to QC through the Analytical Request/ Report as per SOP

STAGE: LUBRICATION
Analysis Plan:
Determination of blend uniformity analysis for Gliclazide Ph.Eur

Batch Number:________________

Claim per unit : Each 430 mg of granules contain not less than 97.5% and not more than
102.5% (58.5 mg to 61.5 mg) of the label claim of Gliclazide Ph.Eur C15H21N3O3S (60
mg)
Record the analytical findings in following manner:
Sampling Results % variation () A.R. Number
Location from mean value
1
2
3
4
5
6
7
8
9
10
11
Mean value Acceptance Criteria
All individual values should be within
% RSD 10% of the mean value.
% RSD should be NMT 5.0%.

Analysis Plan for composite sample:

Determination of assay, bulk density, tapped density, angle of repose, Compressibility Index
and Hausner Ratio.
TESTS Results A.R.No.

Assay

Bulk Density

Tapped Density

Angle of Repose

Compressibility Index
Hausner Ratio

Comments on the Process:

 Annexure-IV
SAMPLING PLAN AND ANALYTICAL DATA COMPILATION WITH ACCEPTANCE
CRITERIA

SAMPLING PLAN

STAGE: COMPRESSION

Batch Number: _______________

Equipment Name: 37 Station Double Rotary Compression Machine
Equipment ID No.:.
60 tablets are collected from machine at START, MID and towards the END of the
compression and given to QC for determination of Uniformity of dosage units (by content
uniformity), Drug release as per STP No. Also the 100 tablets as COMPOSITE SAMPLE
(collected at start, mid and end & then pooled) is subjected to analysis as per STP at QC.

Note: Samples to be collected for determination of In-process at IPQA laboratory as per

SOP and recording shall be done accordingly.

Date/Time (Hrs) of start of Compression after Machine setting :_______________

Date/Time (Hrs) of completion of Compression : __________________

Sampling Interval No. of tablets sampled for Sampled by Sampling Date

QC Testing(Intial , Middle (Name and
End & Composite Sample Sign/Initials)
R.H.S L.H.S

START (Time :______)

MID (Time :________)

END(Time :________)
Batch Number:___________

ANALYSIS PLAN:

In-Process Controls: Description, Average weight, Uniformity of Weight, Friability, Length,

Width Thickness & Hardness.

Testing at QC: As per STP on the samples of Start, mid and towards the end of
compression and also on composite sample collected after completion of compression.

DESCRIPTION:
Sampling Description Checked By Acceptance
Intervals (Sign and Date) Criteria

START White to off white

(Time:_______) oval, biconvex
MID uncoated
(Time:_______) tablets, plain on
END both sides .
(Time:_______)

THICKNESS, LENGTH & WIDTH:

Sample size=10 tablets

Vernier Caliper ID No.:____________

Equipment calibration date:__________ Equipment calibration due date:__________

Sampling Interval Thickness Length (mm) Width (mm) Checked by

(mm) (Sign and Date)

START
(Time:_________)

Average Acceptance Criteria:

Minimum Thickness = 5.00 0.2 mm
Length = 14.15 0.05 mm
Maximum
Width = 7.05 0.05 mm

THICKNESS, LENGTH & WIDTH :

Sampling Thickness Length (mm) Width (mm) Checked by
Interval (mm) (Sign and Date)
MID
(Time:_______)
Average Acceptance Criteria:
Minimum Thickness = 5.00 0.2 mm
Maximum Length = 14.15 0.05 mm
Width = 7.05 0.05 mm

THICKNESS, LENGTH & WIDTH :

Sampling Thickness Length (mm) Width (mm) Checked by
Interval (mm) (Sign and Date)

END
(Time:________)

Average Acceptance Criteria:

Minimum Thickness = 5.00 0.2 mm
Maximum Length = 14.15 0.05 mm
Width = 7.05 0.05 mm

AVERAGE WEIGHT AND WEIGHT VARIATION:

Sample size=20 tablets

Analytical Weighing Balance ID No.:

Equipment calibration date: Equipment calibration due date:

Sampling Average Weight Checked by

Interval (Sign and Date)
1. 2.

3. 4.

START 5. 6.
(Time :.)
7. 8.

9. 10.
 11. 12.

13. 14.

15. 16.

17. 18.

19. 20.

Average Weight Acceptance Criteria

(mg) Average Weight :
Maximum weight 422.0 mg to 438.0 mg
(mg) Weight Variation :
Minimum weight ndividual weight of
(mg) 20Tablets should not
Variation + % deviate more than 5 %
Variation % of the average weight

AVERAGE WEIGHT AND WEIGHT VARIATION:

Sample size=20 tablets

Analytical Weighing Balance ID No.:

Equipment calibration date: Equipment calibration due date:

Sampling Average Weight Checked by

Interval (Sign and Date)
1. 2.

3. 4.

5. 6.

7. 8.

9. 10.
MID
(Time :.) 11. 12.

13. 14.

15. 16.

17. 18.

19. 20.

Average Weight Acceptance Criteria

(mg) Average Weight :
Maximum weight 422.0 mg to 438.0 mg
 (mg) Weight Variation :
Minimum weight ndividual weight of
(mg) 20Tablets should not
Variation + % deviate more than 5 %
Variation % of the average weight

AVERAGE WEIGHT AND WEIGHT VARIATION:

Sample size=20 tablets

Analytical Weighing Balance ID No.

Equipment calibration date: Equipment calibration due date:

Sampling Average Weight Checked by
Interval (Sign and Date)
1. 2.

3. 4.

5. 6.

7. 8.

9. 10.
END
(Time :.) 11. 12.

13. 14.

15. 16.

17. 18.

19. 20.

Average Weight Acceptance Criteria

(mg) Average Weight :
Maximum weight 422.0 mg to 438.0 mg
(mg) Weight Variation :
Minimum weight ndividual weight of
(mg) 20Tablets should not
Variation + % deviate more than 5 %
Variation % of the average weight

FRIABILITY
Sample size= 10 tablets

Friability Test Apparatus ID. No.:

Equipment calibration date: Equipment calibration due date:

Sampling Interval Friability Obtained Checked by
(Sign and Date)

START (Time:.)

MID (Time:...)

END (Time:.....)
Acceptance Criteria
Not more than 1%w/w

HARDNESS:
Sample size=10 tablets
Tablet Hardness Test Apparatus ID No.:
Equipment calibration date: Equipment calibration due date:

Sampling Interval Hardness Obtained Checked by

(N) (Sign and Date)

START
(Time:.)

Average hardness Acceptance Criteria:

60-100 N
Minimum hardness
Maximum hardness

HARDNESS:
Sampling Interval Hardness Obtained Checked by
(N) (Sign and Date)

MID
(Time:.)
Average hardness Acceptance Criteria:
60-100 N
Minimum hardness
Maximum hardness

HARDNESS

Sampling Interval Hardness Obtained Checked by

(N) (Sign and Date)

END
(Time:.)

Average hardness Acceptance Criteria :

70-100 N
Minimum hardness
Maximum hardness
Analysis Plan for uniformity of dosage units by content uniformity: (Tested as per
STP)

Results from QC at START of compression

S. No. LEFT HAND SIDE RIGHT HAND SIDE
Assay (%) Assay (%)
1
2
3
4
5
6
7
8
9
10
Mean Value
% RSD
L1 Value
Acceptance Criteria
Mean value shall be 95 105% of the target potency value.
None of the individual assay value shall deviate by 10 % of average assay value.
% RSD should be NMT 5.0%.
The acceptance value of the 10 dosage units is less than or equal to L1 (L1=15)

DRUG RELEASE :
Sample Tablet- Tablet- Tablet-3 Tablet-4 Tablet- Tablet-6 A.
1 2 5 R.
No.
% DISSOLUTION IN 2 % DISSOLUTION IN % DISSOLUTION IN 12
Hrs 4 Hrs. Hrs
LHS

RHS

Acceptance Criteria:
2 Hrs. : NLT 14% and NMT 32 % of the label claim.
4 Hrs. : NLT 32 % and NMT 55 % of the label claim
12 Hrs. : NLT 85 % of the label claim.

Results from QC at MID of compression

S. No. LEFT HAND SIDE RIGHT HAND SIDE
Assay (%) Assay (%)
1
2
 3
4
5
6
7
8
9
10
Mean Value
% RSD
L1 Value
Acceptance Criteria
Mean value shall be 95 105% of the target potency value.
None of the individual assay value shall deviate by 10 % of average assay value.
% RSD should be NMT 5.0%.
The acceptance value of the 10 dosage units is less than or equal to L1 (L1=15)

DRUG RELEASE :
Sample Tablet- Tablet- Tablet-3 Tablet-4 Tablet- Tablet-6 A.
1 2 5 R.
No.
% DISSOLUTION IN 2 % DISSOLUTION IN % DISSOLUTION IN 12
Hrs 4 Hrs. Hrs
LHS

RHS

Acceptance Criteria:
2 Hrs. : NLT 14% and NMT 32 % of the label claim.
4 Hrs. : NLT 32 % and NMT 55 % of the label claim
12 Hrs. : NLT 85 % of the label claim.

Results from QC at END of compression

S. No. LEFT HAND SIDE RIGHT HAND SIDE
Assay (%) Assay (%)
1
2
3
4
5
6
7
8
9
 10
Mean Value
%RSD
L1 Value
Acceptance Criteria
Mean value shall be 95 105% of the target potency value.
None of the individual assay value shall deviate by 10 % of average assay value.
% RSD should be NMT 5.0%.
The acceptance value of the 10 dosage units is less than or equal to L1 (L1=15)

DRUG RELEASE :
Sample Tablet- Tablet- Tablet-3 Tablet-4 Tablet- Tablet-6 A.
1 2 5 R.
No.
% DISSOLUTION IN 2 % DISSOLUTION IN % DISSOLUTION IN 12
Hrs 4 Hrs. Hrs
LHS

RHS

Acceptance Criteria:
2 Hrs. : NLT 14% and NMT 32 % of the label claim.
4 Hrs. : NLT 32 % and NMT 55 % of the label claim
12 Hrs. : NLT 85 % of the label claim.
QC ON COMPOSITE SAMPLE
Analysis Plan on Composite Sample (Sample to be tested as per STP):
Tests Acceptance Criteria Results A.R.
Number
Description White to off white oval, biconvex
uncoated tablets, plain on both sides .
Identification The retention time of Gliclazide peak in
By HPLC the chromatogram of the test solution
corresponds to that standard solution, as
obtained in the assay
Drug Release Complies with the test .Percentage of the
labeled amount of Gliclazide is dissolved
with in the range stated at each of
following points.
2 Hrs. : NLT 14% and NMT 32 % of the
label claim.
4 Hrs. : NLT 32% and NMT 55 % of the
label claim.
12Hrs. : NLT 85% of the label claim.
Average mass Between 422.0 and 438.0 mg
Uniformity Of The acceptance value of the 10 dosage
Dosage Units units is less than or equal to L1 (L1=15)
(By content
uniformity
Related Single highest impurity
substances: (Specified RRT about 0.30):
Not more than 0.75%
Single highest unknown impurity :
Not more than 0.3%
Total impurities :
Not more than 1.0%
Assay Each uncoated tablet contains not less
than 95.0% and not more than 105.0%
(57.0 mg to 63.0 mg) of the label claim of
Gliclazide Ph.Eur., C15H21N3O3S (60
mg)

Comments on the Process:

 Annexure -VI
SAMPLING PLAN AND ANALYTICAL DATA COMPILATION WITH ACCEPTANCE
CRITERIA

HOLD TIME STUDIES FOR BLENDED MASS AFTER BLENDING/LUBRICATION

Batch Number :
Material Storage Area : Bulk Storage Area
Sampling Plan
Sample Quantity: 300.0 gms
Sampling Environmental Conditions at the Sampled by Sampling Date
Intervals time of sampling (Name and & Time
(days) (Temp.: NMT 25C Sign)
RH: NMT 45%)
0
7th
15th

ANALYSIS PLAN :
SAMPLING INTERVAL (days)
TESTS 0 7th 15th
Description
( White to off white, flowing
granules )
Assay
Each 430 mg of granules
contain not less than 97.5%
and not more than 102.5%
(58.5 mg to 61.5 mg) of the
label claim of Gliclazide
Ph.Eur., C15H21N3O3S (60
mg).
LOD
Between 1.0% to 3.2% w/w,
determined at 1050C for 7
minutes
Related substances:
Single highest impurity
(specified RRT about 0.30) :
Not more than 0.75%
Single highest unknown
impurity :
Not more than 0.3%
Total impurities :
Not more than 1.0%
Bulk Density
Tapped Density
Compressibility Index
Hausner Ratio
Microbiological Evaluation*
A.R. Number
*Acceptance limits :
Total aerobic microbial count: NMT 500 cfu/ g
Total combined molds and yeasts count: NMT50 cfu / g.
Escherichia coli: should be absent
Salmonella Species: should be absent
Pseudomonas aeruginosa: should be absent
Staphylococcus aureus: should be absent
HOLD TIME STUDIES AFTER COMPRESSION

Batch Number :
Material Storage Area : Bulk Storage Area
Sampling Plan: 200 gms
Sampling Environmental Sampled by Sampling Date &
Intervals Conditions at the (Name and Sign) Time
(days) time of sampling
(Temp.: NMT 25C
RH: NMT 45%)
0
7th
15th

Analysis Plan
SAMPLING INTERVAL (days)
TESTS 0 7th 15th
Description
White to off white oval,
biconvex uncoated tablets
plain on both sides .
Assay
Each uncoated tablet contains
not less than 95.0% and not
more than 105.0% (57.0 mg to
63.0 mg) of the label claim of
Gliclazide Ph.Eur.,
C15H21N3O3S (60 mg)
Uniformity of dosage units :
( By Content Uniformity )
The acceptance value of the
10 dosage units is less than or
equal to L1 (L1=15)
Drug Release :
Complies with the test
.Percentage of the labeled
amount of Gliclazide is
dissolved with in the range
stated at each of following
points.
2 Hrs. : NLT 14% and NMT
32 % of the label claim.
4 Hrs. : NLT 32% and NMT
55 % of the label claim.
12Hrs. : NLT 85% of the
label claim.
Related substances:
Single highest impurity
(specified RRT about 0.30) :
Not more than 0.75%
Single highest unknown
impurity :
Not more than 0.3%
Total impurities :
Not more than 1.0%
Microbiological Evaluation*
A.R. Number
*Acceptance limits :
Total aerobic microbial count: NMT 500 cfu/ g
Total combined molds and yeasts count: NMT50 cfu / g.
Escherichia coli: should be absent
Salmonella Species: should be absent
Pseudomonas aeruginosa: should be absent
Staphylococcus aureus: should be absent