Capsule Process Validation [PDF]

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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



FORMULATION



DATE OF EFFECTIVE



:



PRODUCT NAME : LINE



:



REASON FOR PERFORMING THE VALIDATION STUDY : Reason ( tick which ever is applicable) Department New product Modification in the manufacturing process. Change in Facility and / or location of manufacturing. Batch fail to meet product & process specifications.



Remarks



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.  Reference to relevant documents. 1.2.2 Batch manufacturing records. Prepared by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



 Detailed manufacturing instructions for the production of the validation batches. 2.0 PERSSONEL RESPONSIBILITIES. SR ACTIVITY 1 Preparation of validation 2



protocol Approval of Validation



3



protocol Production of validation



4



Batches Testing of validation



RESPONSIBILITY



REMARKS



samples & Preparation of 5



validation report 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: Prepared by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



SR



DATE OF EFFECTIVE



INGREDIENTS/EXCIPIENTS



SPECIFICATION



MG.CAPS.



PER BATCH



1 2 3 4 5 6 7 8 9 10 11 12 13 NOTE:



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PER LOT



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



CAPSULE FLOW CHART R.M.DISPENSING



SHIFTING 1. MIXING TIME 2. SPEED



BLENDING



GRANULATION (IF REQUIRED) DRYING



1. MIXING TIME 2. SPEED



COMPECT (IF REQUIRED) MILLING (IF REQUIRED)



MIXING



FILLING



BULK ANALYSIS



1.0 WEIGHT VERIATION



QUARANTINE BLISTER/ STRIP PACKING/ COUNTING FINAL PACKING QUARANTINE



F.G.STORE Prepared by



FINISHED PRODUCT ANALYSIS



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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



1. 2. 3.



TITLE



VERIFIED BY



Equipment cleaning procedure for Master sifter #20,#40 Equipment operating procedure for Master sifter #20,#40 Equipment cleaning procedure for Rapid mixer granulator. Equipment operating procedure for Rapid mixer granulator. Equipment cleaning procedure for Octagonal Blender. Equipment operating procedure for Octagonal blender. Equipment cleaning procedure for capsule filling machine. Equipment operating procedure for capsule filling machine. Equipment cleaning procedure for capsule polishing & Checking machine. Equipment operating procedure for capsule polishing & Checking machine. Equipment cleaning procedure for strip packing machine. Equipment operating procedure for strip packing machine. Equipment cleaning Procedure for Blister Packing machine. Equipment operating procedure for Blister Packing machine. Equipment cleaning procedure for Cap counting machine Equipment operating procedure for Cap counting machine Equipment cleaning procedure for Fluid Bed Dryer. Equipment operating procedure for Fluid Bed Dryer.



4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.



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DATE



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



19.



DATE OF EFFECTIVE



Enter any other reference sop. 4.2 DETAILS OF EQUIPMENT TO BE USED. EQUIPMENT 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.: M.O.C. DRYING TYPE : MODEL: Prepared by



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DETAILS



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



CAPACITY: MANUACTURER: TAG.NO.: M.O.C.



CAPSULE FILLING MACHINE:



CAPSULE POSISHING & CHECKING MACHINE



STRIP PACKING MACHINE:



BLISTER PACKING MACHINE:



Prepared by



TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: Checked by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



CAPSULE COUNTING MACHINE



DATE OF EFFECTIVE



M.O.C. TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.:



REMARKS:



4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER. Prepared by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT: MATERIAL SIFTING



MIXING



AIR DRYING



POLISHING



LOAD SIZE ACTIVE



SPEED



MIXER EXCIPIENT



SPEED MIXER WEIGHT LEAK TEST



BLENDING



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GRANULATION ( IF REQUIRED)



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FILLING



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STRIPING/ BLISTERING/COUNTING



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



CRITICAL PROCESS PARAMETERS (CPP’s) : SR CRITICAL PROCESS RESPONSE VARIABLE PARAMETER 1. Granulation 2.



BLENDING Sequence of excipient



Blend uniformity



addition Load blending vessel. 3.



4. 5.



Fixed weight as per label claim Weight uniformity Fixed , no variation of filling speed.



D.T. STRIPING/BLISTERING/COUNTING Leak test Leakage Bottle Sealing



Critical process variable (CPV): SR PROCESS / MACHINE SETTING VARIABLE (CONTROL VARIABLES) 1 Mixing Mixing time 2 Filling Speed, locking Prepared by



Fixed order of addition Fixed batch size Fixed, no variation of blending speed. Variation of blending time



Blending time FILLING Weight of capsule Locking length. Capsule filling speed



REMARKS



Checked by



No leakage



REMARKS



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



3



Stripping/ blistering



DATE OF EFFECTIVE



Leak test, speed.



Setting and conditions as mentioned in the batch manufacturing record to be



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA 5.1 Sampling Locations:



2



Side view:



1



3



Top view:



2



1



3 Sampling location in blender



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



5.3 SAMPLING STAGE/ TEST PARAMETER MIXING



SAMPLING



REMARKS



CAPSULE FILLING



( SIZE,LOCATION,TIME) After 20 min of mixing time  N=3 samples at each interval  Sample size: 1.0 – 1.5 g Draw the sample at interval of



Each sample comprises



Appearance



30 min. during Filling .



the amount for the



ASSAY



Weight of 20 caps.



 N=____ sample



Weight variation



 Sampling : at start,



Disintegration time



different tests required.



every two hours, immediately after the brake time , end of filling..  Sample size:_____



STAGE / TEST PARAMETER MIXING



EQUIPMENT ( SIZE , LOCATION TIME) Sampling thief:



ASSAY



ACCEPTANCE CRITERIA  Assay 95 % to 105 %  Rel. std. : < 3.0 %



CAPSULE FILLING Appearance



Visual inspection,



Weight of 20 caps.



Analytical balance



Weight variation



Analytical balance



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Checked by



As specified in the BMR.



Approved by



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



Disintegration time



DATE OF EFFECTIVE



DT apparatus with water at



NMT ____minutes.



37 + 10C, with discs. Assay:



___________



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. 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 #1 SIFTING: Equipment Name Identification no Sieves Integrity of the sieve MIXING : Equipment name



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:_________________________ :_________________________



Date:___________________ : _________________________ (before): ___________________ (After)__________________ :_______________________



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



Identification no Capacity DRYING: Equipment Name Identification No



:_______________________



Date:____________________ : ______________________lt.



:_______________________ :_______________________



Date:___________________



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 POINTS Method of analysis adopted Ref No.: Anlyst: Date Meet acceptance criteria. YES ( ) NO ( ) CONCLUSIONS:_______________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ _______________________ CHECKED BY:_________________________



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DATE____________________



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Company Name & Address 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 Plan



: as outlined in the batch manufacturing record.



: 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 % Meet acceptance criteria.



YES (



)



NO (



)



CONCLUSIONS:_________________________________________________________ ________________________________________________________________________ Prepared by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



________________________________________________________________________ __________________________________________ CHECKED BY:_________________________ DATE____________________



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



DATA RECORDING SHEET# 3 Equipment Name: Capsule filling machine Identification Name : ___________________________________ Date:____________________ Ejection side: Left /Right Sample no: B/M/E BATCH NO:



APPEARANCE WEIGHT OF 20 capsule WEIGHT VARIATION DISINTEGRATION TIME



Visual inspection Analytical balance Analytical balance DT apparatus with water at 37 + 20 C , with discs.



ASSAY



TEST



As specified in the B.M.R.



95 % TO 105 %



APPEARANCE



AV.WT. ( MG)



WT. Variation ( MG)



D.T (sec)



Sample qty. (Beginning sample) Middle sample End sample Avg. X X X S.D. X X X R.S.D. X X X complies *All the values are averages of he number of samples mentioned in the table



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Assay ( %)



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



REMARKS: ________________________________________________________________________ ________________________________________________________________________ ____________________________



Checked By: _______________________________ Date:____________________________



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



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_________________________ Prepared by



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



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: ________________________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



DATA RECORDING SHEET # 5 DATE:____________________ 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 DATA RECORDING SHEET # 6 DATE:____________________ NAME OF PRODUCT: SR Parameters



Type of sample



1



Sample A(known amount of analysis.



Accuracy % Recovery of known amount.



Prepared by



Actual reading



Checked by



Observed reading



Analysis performed by



Analysis checked by



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Ref. Work sheet



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



2



3



4



DATE OF EFFECTIVE



90 % of A 110 % of A Precision Sample Repeatability A1 ( under same ( from condition ) Test one by same sample analyst at same point) time from same Sample homogenous A2 validated mass ( from but from second different sample sample plan point) ( by taking Sample sample of A3 different ( from quantity) third sample point) Reproducibility Sample under different A1 conditions. On ______ Test by different analyst on different days.



Sample A2 On ______



Linearity and range



Sample A3 On ______ 25 % of A



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



Response concentration curve on graph paper.



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DATE OF EFFECTIVE



50 % of A 75 % of A 100 % of A 125 % of A



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Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



SR Parameters



Type of sample



5



Sample A1 15 min. degradation



6



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. Limit of detection ( LOD) & limit of quantitative (LOQ) Qualitative & Quantitative result



Actual reading



Observed Analysis Analysis reading performed checked by by



Sample A2 30 min. degradation



Sample A3 45 min. degradation



0.1 % of A 1% of A 5 % of A 10 % of A 20 % of A



7



Analysis Method A method (for non Method B pharmacopoeial



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Ref. Work sheet



Company Name & Address PROCESS VALIDATION PROTOCOL (CAPSULE) PROTOCOL NO:



DATE OF EFFECTIVE



Method C to be performed by other public 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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