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PROTOCOL NO: DATE OF EFFECTIVE

FORMULATION

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. Number of batches studied: ________________ Batch numbers: 1. _______________ 2.. _______________ 3. _______________ Validation activity authorized By: _____________________________Date:_______________________ Validation Team: DEPARTMENT PRODUCTION QUALITY ASSURANCE QUALITY CONTROL REMARKS: Remarks

VALIDATION TEAM

________________________________________________________________________

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APPROVALS: DEPARTMENT PRODUCTION QUALITY ASSUARANCE QUALITY CONTROL PRODUCT DEVLOPMENT ENGINEERING

SIGN & DATE

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. Detailed manufacturing instructions for the production of the validation batches. Prepared by Checked by Approved by

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2.0 PERSSONEL RESPONSIBILITIES. SR ACTIVITY 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: Prepared by Checked by Approved by RESPONSIBILITY REMARKS

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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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CAPSULE FLOW CHART

R.M.DISPENSING

SHIFTING BLENDING GRANULATION (IF REQUIRED) DRYING

1. MIXING TIME 2. SPEED 1. MIXING TIME 2. SPEED

COMPECT (IF REQUIRED)

MILLING (IF REQUIRED) FILLING

MIXING

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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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 SOPS , VALIDATION & QUALIFICATION REPORT USED AS REFERENCES= SR 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Prepared by ID. NUMBER TITLE 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 Checked by Approved by VERIFIED BY DATE

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17. 18. 19.

machine Equipment cleaning procedure for Fluid Bed Dryer. Equipment operating procedure for Fluid Bed Dryer. 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. TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: Prepared by Checked by

DETAILS

MILLING

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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 & TYPE : CHECKING MACHINE MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. STRIP PACKING TYPE : MACHINE: MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. BLISTER PACKING MACHINE: TYPE : MODEL: CAPACITY: Checked by Approved by

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

CAPSULE COUNTING MACHINE

REMARKS:

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4.3 IDENTIFICATION OF CRITICAL PROCESS VARIBLES/ PARAMETER. 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 Prepared by

GRANULATION ( IF REQUIRED)

FILLING Approved by

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STRIPING/ BLISTERING/COUNTING

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CRITICAL PROCESS PARAMETERS (CPPs) : SR CRITICAL PROCESS RESPONSE VARIABLE PARAMETER Granulation 1. 2. BLENDING Blend uniformity Sequence of excipient addition Load blending vessel. Blending time 3. FILLING Weight of capsule Locking length. Capsule filling speed D.T. 4. STRIPING/BLISTERING/COUNTING Leak test 5. Bottle Sealing Leakage Weight uniformity

REMARKS

Fixed order of addition Fixed batch size

Fixed, no variation of blending speed. Variation of blending time

Fixed weight as per label claim

Fixed , no variation of filling speed.

No leakage

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Critical process variable (CPV): SR PROCESS / MACHINE SETTING VARIABLE (CONTROL VARIABLES) 1 Mixing Mixing time 2 3 Filling Stripping/ blistering Speed, locking Leak test, speed.

REMARKS

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

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

Side view:

Top view:

3 Sampling location in blender

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5.3 SAMPLING STAGE/ TEST PARAMETER MIXING

ASSAY

SAMPLING ( 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 30 min. during Filling . N=____ sample Sampling : at start, every two hours, immediately after the brake time , end of filling.. Sample size:_____

REMARKS

CAPSULE FILLING Appearance Weight of 20 caps. Weight variation Disintegration time

Each sample comprises the amount for the different tests required.

STAGE / TEST PARAMETER MIXING

ASSAY

EQUIPMENT ( SIZE , LOCATION TIME) Sampling thief:

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

CAPSULE FILLING Appearance Weight of 20 caps. Visual inspection, Analytical balance As specified in the BMR.

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Weight variation

Analytical balance

Disintegration time

DT apparatus with water at 37 + 10C, with discs.

NMT ____minutes.

Assay:

___________

6.0 RECORDING OF DATA & DATA TREATMENT

DATA RECORDING SHEET NO. 1. For recording mixing assay observation & results 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. For recording blending observations & results. For recording Drying observation & results. For recording filling observations and results For recording polishing observation and results For recording blister / stripping/ counting observation and record. For recording general utilities /equipment / method Analytical /results. For recording analytical method validation. For recording blister / stripping/counting observation and record. For recording general utilities /equipment / method Analytical /results. For recording analytical method validation.

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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 Identification no Capacity DRYING: Equipment Name Identification No :_________________________ :_________________________

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

:_______________________ :_______________________

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. Sample no: 1 2 3 Average std.Dev. Range RSD LCL UCL BATCH NO:

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

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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 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 ( ) BATCH NO: ______________________

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CONCLUSIONS:_________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________ CHECKED BY:_________________________

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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.

As specified in the B.M.R.

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. X X X complies *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 # 4 Equipment Name : POLISHING & CHECKING MACHINE Identification no: ________________________________ Date:______________________ Speed:____________________

Sample no: B M E

Average wt

Polishing

Acceptance criteria : _________________to____________________mg. Meets Acceptance criteria : yes/ no

Conclusion: ________________________________________________________________________ ________________________________________________________________________ ________________________________________________________________________ __________________________________________

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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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DATA RECORDING SHEET # 5

SR

NAME OF CRITICAL EQUIPMENT/UTILITIES

QUALIFICATION/ VALIDATION FILE REF.NO.

DATE OF QUALIFICATION / VALIDATION

1 2 3 4 5 6 7 8

Master sifter Rapid mixer granulator Double cone blender Empty gelatin capsule feeder Capsule filling machine Empty capsule shorting machine Empty capsule shorting machine Strip packing machine

UTILITIES: 1 2 3 4 5 6 AHU SYSTEM WATER SYSTEM COMPRESSED AIR STEAM LIGHTNING DRAIN

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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

Accuracy % Recovery of known amount.

Sample A(known amount of analysis. 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 ______

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Test by different analyst on different days.

Sample A2 On ______ Sample A3 On ______ 25 % of A 50 % of A 75 % of A 100 % of A 125 % of A

Linearity and range Response concentration curve on graph paper.

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SR Parameters

Type of sample Sample A1 15 min. degradation

Actual reading

Observed reading

Analysis Analysis performed checked by by

Ref. Work sheet

Specificity/ selectivity( by larger communication of analytical method.) for identification of impurities assay of active component etcTemp & 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

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

Analysis Method A method (for non Method B pharmacopoeial Checked by Approved by

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to be performed Method C by other public lab. 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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