Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by FORMULATION :
PRODUCT NAME : LINE :
REASON FOR PERFORMING THE VALIDATION STUDY :
Reason ( tick which ever is applicable) Remarks Department
New product
Modification 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:
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by APPROVALS:
DEPARTMENT SIGN & DATE PRODUCTION QUALITY ASSUARANCE QUALITY CONTROL PRODUCT DEVLOPMENT ENGINEERING 1.0 GENERAL: 1.1 INTRODUCTION:
The process validation will be performed as prospective validation. The complete documentation for the validation comprises several independent documents, references to relevant documents will be given as part of this protocol, (see below). The results of the validation activities will be summarized in the validation report.
1.2 List of Documents for Validation:
Validation protocol,
Details of sampling for the validation batches, test parameters ( Product
performance characteristics) with reference to test methods & Acceptance criteria. (acceptable Limit)
Methods for recording / evaluating results including statistical analysis. Reference to relevant documents.
1.2.2 Batch manufacturing records.
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 2.0 PERSSONEL RESPONSIBILITIES.
SR ACTIVITY RESPONSIBILITY REMARKS 1 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 MATERIAL 2.0 SHIFTING
3.0 GRANULATION (if required). 4.0 BLENDING 5.0 MIXING 6.0 FILLING 7.0 BLISTERING/ STRIPPING/COUNTING. 3.1 FORMULATION: BATCH SIZE:
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by
SR INGREDIENTS/EXCIPIENTS SPECIFICATION MG.CAPS. PER BATCH PER LOT
1 2 3 4 5 6 7 8 9 10 11 12 13 NOTE:
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by
CAPSULE FLOW CHART
R.M.DISPENSING SHIFTING GRANULATION (IF REQUIRED) COMPECT (IF REQUIRED) MILLING (IF REQUIRED) FILLING
BLISTER/ STRIP PACKING/ COUNTING MIXING FINAL PACKING QUARANTINE F.G.STORE BULK ANALYSIS QUARANTINE
FINISHED PRODUCT ANALYSIS 1. MIXING TIME 2. SPEED
BLENDING 1. MIXING TIME
2. SPEED
1.0 WEIGHT VERIATION
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 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.
15. Equipment cleaning procedure for Cap counting machine 16. Equipment operating procedure for Cap counting
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 4.2 DETAILS OF EQUIPMENT TO BE USED.
EQUIPMENT DETAILS SIFTING : TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. BLENDER: TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. MIXER : TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. MILLING TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: machine
17. Equipment cleaning procedure for Fluid Bed Dryer. 18. Equipment operating procedure for Fluid Bed Dryer. 19. Enter any other reference sop.
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 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: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. BLISTER PACKING MACHINE: TYPE : MODEL: CAPACITY:
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by MANUACTURER: TAG.NO.: M.O.C. CAPSULE COUNTING MACHINE TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: REMARKS:
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by
4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER.
4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:
MATERIAL SIFTING
MIXING AIR DRYING
BLENDING GRANULATION ( IF REQUIRED) FILLING EXCIPIENT ACTIVE LOAD SIZE MIXER SPEED MIXER SPEED WEIGHT LEAK TEST POLISHING STRIPING/ BLISTERING/COUNTING
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by CRITICAL PROCESS PARAMETERS (CPP’s) :
SR CRITICAL PROCESS VARIABLE RESPONSE PARAMETER REMARKS 1. Granulation 2. BLENDING Blend 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
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by Critical process variable (CPV):
SR PROCESS / VARIABLE MACHINE 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.
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA
5.1 Sampling Locations:
Side view:
Top view:
Sampling location in blender 1 2 3 1 2 3
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 5.3 SAMPLING STAGE/ TEST PARAMETER SAMPLING ( SIZE,LOCATION,TIME) REMARKS MIXING ASSAY
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 MIXING ASSAY
Sampling thief: Assay 95 % to 105 % Rel. std. : < 3.0 % CAPSULE FILLING Appearance Weight of 20 caps. Visual inspection, Analytical balance As specified in the BMR.
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by Weight variation
Disintegration time
Assay:
Analytical balance
DT apparatus with water at
37 + 10C, with discs.
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.
10. For recording general utilities /equipment / method Analytical /results.
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 6.1DATA RECORDING
The data obtained from the various analysis & observations shall be recorded in
the DATA RECORDING SHEET for first three commercial batches.
DATA RECORDING SHEET #1 SIFTING:
Equipment Name :_________________________
Identification no :_________________________ 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 minutes Setting – Mixer: slow Granulator : OFF
Procedure : As outlined in the batch manufacturing record.
Plan : Samples to be drawn at of 20 minutes of mixing from 3 different locations FOR DRY MIXING RESULTS. BATCH NO:
Sample no: 1 2 3 Average std.Dev. Range RSD LCL UCL
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by
POINTS
Method of analysis adopted Ref No.:
Anlyst: Date
Meet acceptance criteria. YES ( ) NO ( )
CONCLUSIONS:_______________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ _______________________
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 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: 1 2 3 4( POOL) Average std.Dev. Range RSD LCL UCL
Method of analysis adopted Ref No.:
Anlyst: Date
Acceptance criteria 95 % TO 105 %
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by
CONCLUSIONS:_________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by DATA RECORDING SHEET# 3
Equipment Name: Capsule filling machine
Identification Name : ___________________________________ Date:____________________
Ejection side: Left /Right Sample no: B/M/E BATCH NO:
APPEARANCE Visual inspection
As specified in the B.M.R. WEIGHT OF 20 capsule Analytical balance
WEIGHT VARIATION Analytical balance
DISINTEGRATION 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 sample End sample Avg. X X X S.D. X X X R.S.D. complies X X X
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by REMARKS:
________________________________________________________________________ ________________________________________________________________________ ____________________________
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by DATA RECORDING SHEET # 4
Equipment Name : POLISHING & CHECKING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no: Average wt Polishing B
M E
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria : yes/ no
Conclusion: ________________________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________ Checked by ;___________________________Date_________________________
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by DATA RECORDING SHEET # 5
Equipment Name : BLISTER/STRIP/SCORPIO COUNTING MACHINE
Identification no: ________________________________
Date:______________________
Speed:____________________
Sample no: Leak test Coding
Acceptance criteria : _________________to____________________mg.
Meets Acceptance criteria : yes/ no
Conclusion: ________________________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________ Checked by ;___________________________Date_________________________
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by DATA RECORDING SHEET # 5
SR NAME OF CRITICAL EQUIPMENT/UTILITIES QUALIFICATION/ VALIDATION FILE REF.NO. DATE OF QUALIFICATION / VALIDATION 1 Master sifter
2 Rapid mixer granulator
3 Double cone blender
4 Empty gelatin capsule feeder
5 Capsule filling machine
6 Empty capsule shorting machine
7 Empty capsule shorting machine
8 Strip packing machine
UTILITIES: 1 AHU SYSTEM 2 WATER SYSTEM 3 COMPRESSED AIR 4 STEAM 5 LIGHTNING 6 DRAIN
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by DATA RECORDING SHEET # 6
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 A 110 % 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 ( by taking sample of different quantity) Sample A1 ( from one sample point) Sample A2 ( from second sample point) Sample A3 ( from third sample point) 3 Reproducibility under different conditions. Sample A1 On ______
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by Test by different analyst on different days. Sample A2 On ______ Sample A3 On ______ 4 Linearity and range Response concentration curve on graph paper. 25 % of A 50 % of A 75 % of A 100 % of A 125 % of A
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by 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 A1 15 min. degradation Sample A2 30 min. degradation Sample A3 45 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 7 Analysis method (for non pharmacopoeial Method A Method B
Company Name & Address
PROCESS VALIDATION PROTOCOL
(CAPSULE)
PROTOCOL NO: DATE OF EFFECTIVE
Prepared by Checked by Approved by to be performed
by other public lab.
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.
