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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) 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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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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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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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

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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 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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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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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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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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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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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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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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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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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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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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