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Company Name & Address
PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
FORMULATION :
PRODUCT NAME :
LINE :
REASON FOR PERFORMING THE VALIDATION STUDY :
Reason ( tick which ever is applicable) RemarksDepartmentNew productModification in the manufacturing process.Change in Facility and / or location of manufacturing.Batch fail to meet product & process specifications.
Number of batches studied: ________________ Batch numbers: 1. _______________
2.. _______________3. _______________
Validation activity authorized By: _____________________________Date:_______________________
Validation Team:DEPARTMENT VALIDATION TEAM
PRODUCTION
QUALITY ASSURANCE
QUALITY CONTROL
REMARKS:
________________________________________________________________________
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Company Name & Address
PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
APPROVALS:DEPARTMENT SIGN & DATE
PRODUCTION
QUALITY ASSUARANCE
QUALITY CONTROL
PRODUCT DEVLOPMENT
ENGINEERING
1.0 GENERAL:
1.1 INTRODUCTION:
The process validation will be performed as prospective validation. The complete
documentation for the validation comprises several independent documents,
references to relevant documents will be given as part of this protocol, (see below).
The results of the validation activities will be summarized in the validation report.
1.2 List of Documents for Validation:
Validation protocol,
Details of sampling for the validation batches, test parameters ( Product
performance characteristics) with reference to test methods & Acceptance criteria.
(acceptable Limit)
Methods for recording / evaluating results including statistical analysis.
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Reference to relevant documents.
1.2.2 Batch manufacturing records.
Detailed manufacturing instructions for the production of the validation batches.
2.0 PERSSONEL RESPONSIBILITIES.
SR ACTIVITY RESPONSIBILITY REMARKS1 Preparation of validation
protocol
2 Approval of Validation
protocol
3 Production of validation
Batches
4 Testing of validation
samples & Preparation of
validation report
5 Approval of validation
report.
3.0 PROCESS DESCIRPTION / FLOW SHEET The information given below provides a general description of the process. Detailed information for the manufacturing will be supplied separately in the batch manufacturing record.
1.0 DISPENSING OF MATERIAL2.0 SHIFTING
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3.0 GRANULATION (if required).4.0 BLENDING5.0 MIXING6.0 FILLING 7.0 BLISTERING/ STRIPPING/COUNTING.
3.1 FORMULATION:
BATCH SIZE:
SR INGREDIENTS/EXCIPIENTS SPECIFICATION MG.CAPS. PER BATCH PER LOT
1
2
3
4
5
6
7
8
9
10
11
12
13
NOTE:
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
CAPSULE FLOW CHART
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R.M.DISPENSING
SHIFTING
GRANULATION(IF REQUIRED)
COMPECT (IF REQUIRED)
MILLING(IF REQUIRED)
FILLING
BLISTER/ STRIP PACKING/ COUNTING
MIXING
FINAL PACKINGQUARANTINEF.G.STORE
BULK ANALYSIS
QUARANTINE
FINISHED PRODUCT ANALYSIS
1. MIXING TIME2. SPEED
BLENDING 1. MIXING TIME2. SPEED
1.0 WEIGHT VERIATION
DRYING
Company Name & Address
PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: 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 SOP’S , VALIDATION & QUALIFICATION REPORT USED AS REFERENCES=
SR ID. NUMBER TITLE VERIFIED BY
DATE
1. Equipment cleaning procedure for Master sifter #20,#40
2. Equipment operating procedure for Master sifter #20,#40
3. Equipment cleaning procedure for Rapid mixer granulator.
4. Equipment operating procedure for Rapid mixer granulator.
5. Equipment cleaning procedure for Octagonal Blender.
6. Equipment operating procedure for Octagonal blender.
7. Equipment cleaning procedure for capsule filling machine.
8. Equipment operating procedure for capsule filling machine.
9. Equipment cleaning procedure for capsule polishing & Checking machine.
10. Equipment operating procedure for capsule polishing & Checking machine.
11. Equipment cleaning procedure for strip packing machine.
12. Equipment operating procedure for strip packing machine.
13. Equipment cleaning Procedure for Blister Packing machine.
14. Equipment operating procedure for Blister Packing machine.
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
15. Equipment cleaning procedure for Cap counting machine
16. Equipment operating procedure for Cap counting machine
17. Equipment cleaning procedure for Fluid Bed Dryer.
18. Equipment operating procedure for Fluid Bed Dryer.
19. Enter any other reference sop.
4.2 DETAILS OF EQUIPMENT TO BE USED.EQUIPMENT DETAILSSIFTING : 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.
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
MILLING TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
DRYING TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
CAPSULE FILLING MACHINE:
TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
CAPSULE POSISHING & CHECKING MACHINE
TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
STRIP PACKING MACHINE:
TYPE :MODEL:
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
BLISTER PACKING MACHINE:
TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:M.O.C.
CAPSULE COUNTING MACHINE
TYPE :MODEL:CAPACITY:MANUACTURER:TAG.NO.:
REMARKS:
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER.
4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:
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MATERIALSIFTING
MIXING AIR DRYING
BLENDING GRANULATION ( IF REQUIRED)
FILLING
EXCIPIENT
ACTIVE
LOAD SIZE
MIXER
SPEED
MIXER
SPEED
WEIGHTLEAK TEST
POLISHING
STRIPING/ BLISTERING/COUNTING
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CRITICAL PROCESS PARAMETERS (CPP’s) :SR CRITICAL PROCESS
VARIABLERESPONSE
PARAMETERREMARKS
1. Granulation
2. BLENDINGBlend uniformity
Fixed order of addition
Sequence of excipient
addition
Fixed batch size
Load blending vessel. Fixed, no variation of blending speed.
Blending time Variation of blending time
3. FILLING
Weight of capsule
Weight uniformity
Fixed weight as per label claim
Locking length.
Capsule filling speed Fixed , no variation of filling speed.
D.T.
4. STRIPING/BLISTERING/COUNTING
Leak test Leakage No leakage
5. Bottle Sealing
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Critical process variable (CPV):SR PROCESS /
VARIABLEMACHINE SETTING
(CONTROL VARIABLES)
REMARKS
1 Mixing Mixing time
Setting and conditions as
mentioned in the batch
manufacturing record to be
followed.
2 Filling Speed, locking
3 Stripping/ blistering Leak test, speed.
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA
5.1 Sampling Locations:
Side view:
Top view:
Sampling location in blender
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1
2
3
1
2
3
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5.3 SAMPLING
STAGE/ TEST
PARAMETER
SAMPLING
( SIZE,LOCATION,TIME)
REMARKS
MIXINGASSAY
After 20 min of mixing time N=3 samples at each
interval Sample size: 1.0 – 1.5 g
CAPSULE FILLING
Appearance
Weight of 20 caps.
Weight variation
Disintegration time
Draw the sample at interval of
30 min. during Filling .
N=____ sample
Sampling : at start,
every two hours,
immediately after the
brake time , end of
filling..
Sample size:_____
Each sample comprises
the amount for the
different tests required.
STAGE / TEST PARAMETER
EQUIPMENT( SIZE , LOCATION
TIME)
ACCEPTANCE CRITERIA
MIXINGASSAY
Sampling thief: Assay 95 % to 105
%
Rel. std. : < 3.0 %
CAPSULE FILLING
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PROTOCOL NO: DATE OF EFFECTIVE
Appearance
Weight of 20 caps.
Weight variation
Disintegration time
Assay:
Visual inspection,
Analytical balance
Analytical balance
DT apparatus with water at
37 + 10C, with discs.
As specified in the BMR.
NMT ____minutes.
___________
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.
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PROTOCOL NO: DATE OF EFFECTIVE
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 #1SIFTING:Equipment Name :_________________________Identification no :_________________________ Date:___________________Sieves : _________________________Integrity of the sieve (before): ___________________ (After)__________________
MIXING : Equipment name :_______________________Identification no :_______________________ Date:____________________Capacity : ______________________lt.
DRYING:Equipment Name :_______________________ Date:___________________Identification No :_______________________
Ingredients and sequence of material addition: ____________________Total weight of ingredients : _______________kg/lot.Mixing time: 20 minutesSetting – Mixer: slowGranulator : OFFProcedure : 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
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23Average std.Dev.RangeRSDLCLUCL
POINTSMethod of analysis adoptedRef No.:Anlyst:Date
Meet acceptance criteria. YES ( ) NO ( )CONCLUSIONS:__________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
CHECKED BY:_________________________ DATE____________________
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PROCESS VALIDATION PROTOCOL(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
DATE RECORDING SHEET #2
BLENDING:
Equipment name: OCTAGONAL BLENDER
Identification no:
_____________________________Date:_________________________
Capacity :______________________lt.
Ingredients & sequence of material addition:__________
Procedure : as outlined in the batch manufacturing record.
Plan : Samples to be drawn at intervals of 20 minutes of mixing from top , middle,
bottom and pool sample.
Lubrication results BATCH NO: ______________________
Sample no:1234( POOL)Average std.Dev.RangeRSDLCLUCL
Method of analysis adopted
Ref No.:
Anlyst:
Date
Acceptance criteria 95 % TO 105 %
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Meet acceptance criteria. YES ( ) NO ( )
CONCLUSIONS:___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
CHECKED BY:_________________________DATE____________________
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PROCESS VALIDATION PROTOCOL(CAPSULE)
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DATA RECORDING SHEET# 3Equipment Name: Capsule filling machineIdentification Name : ___________________________________ Date:____________________Ejection side: Left /RightSample no: B/M/EBATCH NO:
APPEARANCE Visual inspection
As specified in the B.M.R.WEIGHT OF 20 capsule Analytical balanceWEIGHT VARIATION Analytical balanceDISINTEGRATION TIME DT apparatus with water at
37 + 20 C , with discs.
ASSAY 95 % TO 105 %
TEST APPEARANCE AV.WT.( MG)
WT. Variation( MG)
D.T(sec)
Assay( %)
Sample qty.(Beginning sample)Middle sampleEnd sampleAvg. X X XS.D. X X XR.S.D.complies
X X X
*All the values are averages of he number of samples mentioned in the table
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REMARKS: ____________________________________________________________________________________________________________________________________________________________________________
Checked By: _______________________________Date:____________________________
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DATA RECORDING SHEET # 4Equipment Name : POLISHING & CHECKING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no: Average wt Polishing
BME
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria : yes/ no
Conclusion: __________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
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Checked by ;___________________________Date_________________________
DATA RECORDING SHEET # 5Equipment Name : BLISTER/STRIP/SCORPIO COUNTING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no: Leak test Coding
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria : yes/ no
Conclusion: __________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Checked by ;___________________________Date_________________________
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DATA RECORDING SHEET # 5
DATE:____________________
SR NAME OF CRITICAL EQUIPMENT/UTILITIES
QUALIFICATION/ VALIDATION FILE
REF.NO.
DATE OF QUALIFICATION /
VALIDATION1 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
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6 DRAIN
DATA RECORDING SHEET # 6
DATE:____________________NAME OF PRODUCT:
SR Parameters Type of sample
Actual reading
Observed reading
Analysis performed by
Analysis checked by
Ref. Work sheet
1 Accuracy% Recovery of known amount.
Sample A(known amount of analysis.90 % of A110 % of A
2 Precision Repeatability ( under same condition ) Test by same analyst at same time from same homogenous validated mass but from different sample plan
Sample A1( from one sample point)Sample A2( from second sample point)
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( by taking sample of different quantity)
Sample A3( from third sample point)
3 Reproducibility under different conditions.
Test by different analyst on different days.
Sample A1On ______
Sample A2On ______
Sample A3On ______
4 Linearity and range Response concentration curve on graph paper.
25 % of A50 % of A75 % of A100 % of A125 % of A
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SR Parameters Type of sample
Actual reading
Observed reading
Analysis performed by
Analysis checked by
Ref. Work sheet
5 Specificity/ selectivity( by larger communication of analytical method.) for identification of impurities assay of active component etc…Temp & humidity / degradation factored to main ingredients by 15 min, 30 min,45 min or known degraded products.
Sample A115 min. degradation
Sample A230 min. degradation
Sample A345 min. degradation
6 Limit of detection ( LOD) & limit of quantitative (LOQ) Qualitative & Quantitative result
0.1 % of A
1% of A
5 % of A
10 % of A
20 % of A
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7 Analysis method (for non pharmacopoeial to be performed by other public lab.
Method A
Method B
Method C
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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