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
IPC’s : 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 Name | Process Step& Area | Make | Equipment
ID No. |
Capacity
|
Qualification
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 Machine | Packing |
- Equipments / Instruments used for In-process checks
The following calibrated equipments / Instruments are used for in-process checks.
| S. No. | Equipment /Instrument Name | Equipment ID. No. | Calibration status
(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 STP’s and GTP’s
- 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 Status | Item Code | Standard Quantity
Per batch In kg |
Pharmaceutical
role |
| Gliclazide | * | Active | ||
| Calcium Hydrogen Phosphate
Dihydrate |
Filler | |||
| Cellactose 80 | Filler | |||
| Hypromellose | Rate controlling excipients | |||
| Hypromellose | Rate controlling excipients | |||
| Silica, Colloidal Anhydrous | Glidant | |||
| 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 Blender’s 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 :
- Manufacturing procedure in brief comprise of following steps:
- 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 Blender’s bin.
- b) Sift Magnesium Stearate, Talc through Vibro Sifter fitted with sieve of mesh size 60 & transfer to Blender’s 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 aids | Influence the stability and manufacturing of product |
| SIFTING | Sieve size , sifting time and integrity of sieve. | To evaluate the sifting time
during sifting process |
| DRY-MIXING | Dry-mixing time,and Blending RPM | After completion of sifting, the process of 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, Speed of rollers. For detail refer Annexure-01. | To record and evaluate the variability of critical process variables for process step of slugging to achieve granules size of desired properties. |
| DESLUGGING/ MILLING | Feed rate of slugs. Milling speed, Blade orientation and Screen size. For detail refer Annexure-01. | Effective deslugging is achieved by adjusting the feed rate to 10.0 kg/ 40-60 minutes. |
| SIFTING | Sieve size , sifting time and integrity of sieve for detail refer annexure -01 | To record and evaluate the variability of critical process variables during sifting. |
| LUBRICATION/ BLENDING | Blender speed (rpm) and Blending time etc. For detail refer annexure-01 | After addition of sifted Magnesium Stearate,Talc to the granules; blending is done using Conta Blender. This process 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, Description, Average Weight, Uniformity of Weight, Thickness, Length, Width, Hardness, Friability etc. For detail refer Annexure-01. | Tablets are Compressed using 37 Station Double Rotary Compression Machine. This process is evaluated through sampling the compressed tablets from both sides (left & right) produced at different intervals (Start, Middle and towards the end of compression). 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 |
|
BLENDING / LUBRICATION
TABLET COMPRESSION
|
About 300 gms material from blended mass is kept under simulating conditions. The material is subjected to analysis for Assay of 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 25ºC 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% Loss on drying: Between 1.0% to 3.2% w/w, determined at 1050 C 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 25ºC 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
Name |
Process Variables | Observation
|
|||||||
| Sifting ( Gliclazide, Calcium Hydrogen Phosphate Dihydrate, Hypromellose ,Colloidal Anhydrous, Povidone K-30,Magnesium stearate , Talc) | Vibrosifter
|
Sieve size |
|
|||||||
| Integrity of sieves | Before | |||||||||
| After | ||||||||||
| Sifting time | ||||||||||
| Sifting ) Cellactose 80 | Vibrosifter
|
Sieve size | ||||||||
| 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 –
mill |
Feed rate of slugs | ||||||||
| Screen size | ||||||||||
| Screen integrity | Before | |||||||||
| After | ||||||||||
| Milling speed | ||||||||||
| Sifting of Post Granulation Ingredients | Vibro sifter | Sieve Size | ||||||||
| Integrity of Sieve | Before | |||||||||
| After | ||||||||||
| Sifting time | ||||||||||
| Stage | Equipment
Name |
Process Variables | Observation
|
|||||||
| Lubrication
|
Conta Blender | Blender rpm | ||||||||
| Blending time | ||||||||||
| Capacity of Blender Bin | ||||||||||
| Compression | 37 station Double rotary compression machine | Machine Speed | ||||||||
| Feed frame (open/ forced) | ||||||||||
| Compression force | ||||||||||
| Packaging (Blistering) | Blister Packing Machine
CH 240 |
Sealing plate temperature
|
Intial | |||||||
| End | ||||||||||
| Strip size | ||||||||||
| 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 Location | Sampled by
(Sign & Date) |
Sampling Date & Time
|
||
| 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 the following manner:
| Sampling Location | Results | % variation (±) from mean value | A.R. Number
|
| 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 for all individual results should be NMT 5.0 |
||
| % RSD | |||
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 ºC 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 |
| 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 Location | Results | % variation (±) from mean value | A.R. Number
|
|
| 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 should be NMT 5.0%. |
||
| % RSD | ||||
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 QC Testing(Intial , Middle End & Composite Sample | Sampled by
(Name and Sign/Initials) |
Sampling Date | |
| 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 Intervals | Description | Checked By
(Sign and Date) |
Acceptance
Criteria |
|
START (Time:… |
|
White to off white oval, biconvex uncoated tablets, plain on both sides . | |
| MID
(Time:… |
|||
| END
(Time:……….) |
THICKNESS, LENGTH & WIDTH:
Sample size=10 tablets
Vernier Caliper ID No.:……………………
Equipment calibration date:………………. Equipment calibration due date:………………….
| Sampling Interval | Thickness (mm) | Length (mm) | Width (mm) | Checked by
(Sign and Date) |
| START
(Time:……….) |
||||
| Average | Acceptance Criteria:
Thickness = 5.00 ± 0.2 mm Length = 14.15 ± 0.05 mm Width = 7.05 ± 0.05 mm |
|||
| Minimum | ||||
| Maximum |
THICKNESS, LENGTH & WIDTH :
| Sampling Interval | Thickness (mm) | Length (mm) | Width (mm) | Checked by
(Sign and Date) |
| MID
(Time:……….) |
||||
| Average |
Acceptance Criteria:
Thickness = 5.00 ± 0.2 mm Length = 14.15 ± 0.05 mm Width = 7.05 ± 0.05 mm |
|||
| Minimum | ||||
| Maximum |
THICKNESS, LENGTH & WIDTH :
| Sampling Interval | Thickness (mm) | Length (mm) | Width (mm) | Checked by
(Sign and Date) |
| END
(Time:……….) |
||||
| Average | Acceptance Criteria:
Thickness = 5.00 ± 0.2 mm Length = 14.15 ± 0.05 mm Width = 7.05 ± 0.05 mm |
|||
| Minimum | ||||
| Maximum |
AVERAGE WEIGHT AND WEIGHT VARIATION:
Sample size=20 tablets
Analytical Weighing Balance ID No.:………………
Equipment calibration date:………….. Equipment calibration due date:………………
| Sampling Interval | Average Weight | Checked by
(Sign and Date) |
|||
| START
(Time :……….) |
1. | 2. | |||
| 3. | 4. | ||||
| 5. | 6. | ||||
| 7. | 8. | ||||
| 9. | 10. | ||||
| 11. | 12. | ||||
| 13. | 14. | ||||
| 15. | 16. | ||||
| 17. | 18. | ||||
| 19. | 20. | ||||
| Average Weight (mg) | Acceptance Criteria
Average Weight : 422.0 mg to 438.0 mg Weight Variation : |
||||
| Maximum weight (mg) | |||||
| Minimum weight (mg) | |||||
| Variation + % | |||||
| Variation–– % | |||||
AVERAGE WEIGHT AND WEIGHT VARIATION:
Sample size=20 tablets
Analytical Weighing Balance ID No.:………………
Equipment calibration date:………….. Equipment calibration due date:………………
| Sampling Interval | Average Weight | Checked by
(Sign and Date) |
|||
| MID
(Time :……….) |
1. | 2. | |||
| 3. | 4. | ||||
| 5. | 6. | ||||
| 7. | 8. | ||||
| 9. | 10. | ||||
| 11. | 12. | ||||
| 13. | 14. | ||||
| 15. | 16. | ||||
| 17. | 18. | ||||
| 19. | 20. | ||||
| Average Weight (mg) | Acceptance Criteria
Average Weight : 422.0 mg to 438.0 mg
Weight Variation : |
||||
| Maximum weight (mg) | |||||
| Minimum weight (mg) | |||||
| Variation + % | |||||
| Variation–– % | |||||
AVERAGE WEIGHT AND WEIGHT VARIATION:
Sample size=20 tablets
Analytical Weighing Balance ID No.:………………
Equipment calibration date:………….. Equipment calibration due date:………………
| Sampling Interval | Average Weight | Checked by
(Sign and Date) |
|||
| END
(Time :……….) |
1. | 2. | |||
| 3. | 4. | ||||
| 5. | 6. | ||||
| 7. | 8. | ||||
| 9. | 10. | ||||
| 11. | 12. | ||||
| 13. | 14. | ||||
| 15. | 16. | ||||
| 17. | 18. | ||||
| 19. | 20. | ||||
| Average Weight (mg) | Acceptance Criteria
Average Weight : 422.0 mg to 438.0 mg
Weight Variation : |
||||
| Maximum weight (mg) | |||||
| Minimum weight (mg) | |||||
| Variation + % | |||||
| Variation–– % | |||||
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 (N) | Checked by
(Sign and Date) |
| START
(Time:……….) |
||
| Average hardness | Acceptance Criteria:
60-100 N
|
|
| Minimum hardness | ||
| Maximum hardness |
HARDNESS:
| Sampling Interval | Hardness Obtained (N) | Checked by
(Sign and Date) |
| MID
(Time:……….) |
||
| Average hardness | Acceptance Criteria:
60-100 N
|
|
| Minimum hardness | ||
| Maximum hardness |
HARDNESS
| Sampling Interval | Hardness Obtained (N) | Checked by
(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
|
||
DRUG RELEASE :
| Sample | Tablet-1 | Tablet-2 | Tablet-3 | Tablet-4 | Tablet-5 | Tablet-6 | A. R. No. | ||
| % DISSOLUTION IN 2 Hrs | % DISSOLUTION IN 4 Hrs. | % DISSOLUTION IN 12 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
|
||
DRUG RELEASE :
| Sample | Tablet-1 | Tablet-2 | Tablet-3 | Tablet-4 | Tablet-5 | Tablet-6 | A. R. No. | ||
| % DISSOLUTION IN 2 Hrs | % DISSOLUTION IN 4 Hrs. | % DISSOLUTION IN 12 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
|
||
DRUG RELEASE :
| Sample | Tablet-1 | Tablet-2 | Tablet-3 | Tablet-4 | Tablet-5 | Tablet-6 | A. R. No. | ||
| % DISSOLUTION IN 2 Hrs | % DISSOLUTION IN 4 Hrs. | % DISSOLUTION IN 12 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
By HPLC
|
The retention time of Gliclazide peak in 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 Dosage Units (By content uniformity | The acceptance value of the 10 dosage units is less than or equal to L1 (L1=15) |
|
|
| 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% |
||
| 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 Intervals
(days) |
Environmental Conditions at the time of sampling
(Temp.: NMT 25ºC RH: NMT 45%) |
Sampled by
(Name and Sign) |
Sampling Date & Time |
| 0 | |||
| 7th | |||
| 15th |
ANALYSIS PLAN :
|
TESTS |
SAMPLING INTERVAL (days) | ||
| 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 Intervals
(days) |
Environmental Conditions at the time of sampling
(Temp.: NMT 25ºC RH: NMT 45%) |
Sampled by
(Name and Sign) |
Sampling Date & Time |
| 0 | |||
| 7th | |||
| 15th |
Analysis Plan
|
TESTS |
SAMPLING INTERVAL (days) | ||
| 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
