Ointment Process Validation

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PROCESS VALIDATION PROTOCOL

(OINTMENT)

PROTOCOL NO: QUALITY ASSURANCE DEPTT BATCH NO. PAGE NO:- 1 0F 25

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: APPROVALS:

DEPARTMENT SIGN & DATE

PRODUCTION QUALITY ASSUARANCE QUALITY CONTROL PRODUCT DEVLOPMENT ENGINEERING Prepared by Checked by Approved by

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PROCESS VALIDATION PROTOCOL

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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.

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.

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PROCESS VALIDATION PROTOCOL

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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 WATER PHASE PREPARATION 3.0 OIL PHASE PREPARATION 4.0 MIXING

5.0 Q.C APPROVAL

6.0 FILLING , CRIMPING & CODING. 7.0 PACKING

3.1 FORMULATION:

BATCH SIZE:

SR Ingredients/excipients Specification Label claim Per batch Qnty of overages Total 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 NOTE: Prepared by Checked by Approved by

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PROCESS VALIDATION PROTOCOL

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PROTOCOL NO: QUALITY ASSURANCE DEPTT BATCH NO. PAGE NO:- 4 0F 25 3.2 FLOW SHEET: 4.0 EQUIPMENT / FACTORY. DISPENSING OF MATERIAL WATER PHASE PURIFIED WATER HEAT ____ MINS./ SLOW OIL PHASE ____ MINS./ SLOW Mixing

With Addition Of Active Ingredient ____ Mins./ Slow

FILLING , CRIPING & CODING FINAL PACKING ADDITIONAL QUALITY OF WATER ADDED. TEMP. SPEED( RPM) MIXING TIME WEIGHT / TUBE CRIPING CODING 1. MIXING TIME 2. SPEED( RPM) 3. TEMP. 1. MIXING TIME 2. SPEED( RPM) 3. TEMP. Addition Of Active Ingredient Addition Of Excipient Q.C APPROVAL

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PROCESS VALIDATION PROTOCOL

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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 Octagonal Steam Jacketed Tank 350 ltr with stirrer ( for Oily Phase) 2. Equipment Operating procedure for Octagonal Steam

Jacketed Tank 350 ltr with stirrer ( for Oily Phase) 3. Equipment operating procedure for 500 ltr.

manufacturing tank with Homonizer and anchor stirrer. 4. Equipment cleaning procedure for 500 ltr manufacturing

tank with Homonizer and anchor stirrer.

5. Equipment cleaning procedure for storage tank. 6. Equipment operating procedure for storage tank

7. Equipment cleaning procedure for Tube filling machine 8. Equipment operating procedure for Tube filling machine 9. Enter any other reference sop.

10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

4.2 DETAILS OF EQUIPMENT TO BE USED.

EQUIPMENT DETAILS BALANCE TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. TYPE : Prepared by Checked by Approved by

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PROCESS VALIDATION PROTOCOL

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WATER PHASE S.S.TANK MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. OIL PHASE TANK : TYPE :

MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. MFG. TANK : TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. EQUIPMENT DETAILS

STORAGE TANK: TYPE : MODEL: CAPACITY: MANUACTURER: TAG.NO.: M.O.C. TUBE FILLING

MACHINE: TYPE :MODEL: CAPACITY: MANUACTURER: TAG.NO.:

M.O.C. TRANSFER PUMP: TYPE :

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

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PROCESS VALIDATION PROTOCOL

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4.3 IDENTIFICATION OF CRITICAL PROCESS VARIABLES/ PARAMETER.

4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:

Prepared by Checked by

Approved by

DISPENSING OF

MATERIAL OIL PHASE SOLUTION PREPARATION TUBE FILLING

WATER PHASE SOLUTION PREPARATION MANUFACTURING EXCIPIENT ACTIVE LOAD SIZE SPEED TEMPERATURE LOAD SIZE SPEED COOLING TEMPERATURE SPEED LOAD SIZE TEMPERATURE PH BOILING TEMPERATURE SPEED WEIGHT/TUBE

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PROCESS VALIDATION PROTOCOL

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PROTOCOL NO: QUALITY ASSURANCE DEPTT BATCH NO. PAGE NO:- 8 0F 25 CRITICAL PROCESS PARAMETERS:

SR CRITICAL PRECESS

VERIABLE RESPONSE PARAMETER REMARKS

1 WATER PHASE SOLUTION PREPARATION

Water phase uniformity

Sequence of excipient addition Fixed order of addition

Water Boiling Temperature Fixed Boiling temperature range

Time Variation of time for boiling

Heating Temperature Fixed Heating temperature range

Time Variation of time for heating

Cooling Temperature Fixed cooling temperature range

Time Variation of time for cooling

PH Fixed limit of Ph

Mixing time Variation of mixing time (RPM)

2 OIL PHASE SOLUTION

PREPARATION Oil phase uniformity

Sequence of excipient addition Fixed order of addition

Heating Temperature Fixed Heating temperature range

Time Variation of time for heating

Cooling Temperature Fixed cooling temperature range

Time Variation of time for cooling

Mixing time Variation of mixing time (RPM)

3 MANUFACTURING

Active ingredient uniformity

Sequence of Active addition Fixed order of addition

Mixing time Variation of mixing time

Cooling Temperature Fixed temperature range

4 Filling, Crimping & Coding

1. Weight of tube 2. Crimping

Filling speed Fixed machine speed, no

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PROCESS VALIDATION PROTOCOL

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CRITICAL PROCESS VARIABLE:

SR PROCESS / VARIABLE MACHINE SETTING (CONTROL VARIABLES)

REMARKS

1 Water Phase Solution Preparation

Quantity of water

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

2 Oil Phase Solution Preparation

Quantity of paraffin & wax & other oil.

3 Manufacturing Mixing time Cooling Time

4 Filling Speed, weight / tube.

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PROCESS VALIDATION PROTOCOL

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5.0 SAMPLING , TEST PARAMETERS, ACCEPTANCE CIRTERIA

5.1 Sampling Locations: Mfg. Tank. 5.3 SAMPLING 1. TOP –SAMPLE A1 2. MIDDLE –SAMPLE A2 3. BOTTAM –SAMPLE A3 BOTTOM VALVE

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PROCESS VALIDATION PROTOCOL

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STAGE/ TEST PARAMETER SAMPLING

( SIZE,LOCATION,TIME)

REMARKS

Water phase solution preparation After the completion of water phase solution ,

 N=1 sample ( pooled from different locations)

 Sample size =20 gm

Record amount of water , Temperature & time required to achieve desired end point/ ampere reading.

Oil phase solution preparation After the completion of Oil phase solution ,

 N=1 sample ( pooled from different locations)

Sample size =20 gm

Record amount of oil,

Temperature & time required to achieve desired end point/ ampere reading.

MANUFACTURING PH,

ASSAY

After 20 min of mixing time, After 30 minutes & after 40 minutes.

 N=3 samples at each interval  Sample size: 20 gm

Record the pH and assay of active content .

Filling

Identification test Appearance

Uniformity of Weight Assay of active content.

Draw the sample entire filling assembly, consisting of transfer pump & holding tank and filling machine.

 Sample draw from each syringes as a set weight at different time interval.

 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

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PROCESS VALIDATION PROTOCOL

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Water phase solution preparation Determination on each sample, for temperature, sample weight 10 g.

 80 + 50_C

Oil phase solution preparation Determination on each sample, for

temperature, sample weight 10 g.  80 + 5

0_C

Manufacturing

ASSAY PH

Sampling thief:  Assay 90 % to 110 %  Rel. std. : FILLING Appearance Weight of Tubes. Weight variation Identification test Assay: Visual inspection, Analytical balance Analytical balance H.P.L.C. As specified in the BMR. _____ gm (_____gm - _____ gm) _______ % of average weight. Test should complies to its specifications.

90 % to 110 %

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PROCESS VALIDATION PROTOCOL

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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 NO.

SHEET NO 1 For recording water phase mixing observation & results SHEET NO 2 For recording oil phase mixing observations & results. SHEET NO 3 For recording Bulk manufacturing observations & results. SHEET NO 4 For recording assay results after filling and crimping operation.

SHEET NO 5 For recording general utilities /equipment / method Analytical /results. SHEET NO 6 For recording analytical method validation.

SHEET NO 7 SHEET NO 8 SHEET NO 9 SHEET NO 10 Prepared by Checked by Approved by

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PROCESS VALIDATION PROTOCOL

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DATA RECORDING SHEET #1

WATER PHASE SOLUTION PREPARATION

Equipment Name :_________________________

Identification no :_________________________ Date:___________________ Capacity : ______________________lt.

Ingredients and sequence of material addition: ____________________

Total weight of ingredients : _______________kg/lot. Mixing time : 20 minutes

Setting – stirrer : slow

Procedure : As outlined in the batch manufacturing record.

Plan : Samples to be drawn at of 20 minutes, 30 minutes, & 40 minutes of mixing from 3 different locations

FOR WATER PHASE SOLUTION TANK-RESULTS. BATCH NO:

Assay of after mixing AT 20 MIN..

RESULTES Sample no: Temperature Uniformity

1 2 3 Average std. Dev. Range RSD LCL UCL

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PROCESS VALIDATION PROTOCOL

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Actual Temperature of the water/binder : ___________0_C

Temperature of the water after heating : ___________0_C

Temperature of the water after cooling : ___________0_C

Additional quantity of water added (ltr.):____________ Total time taken : ___________

POINTS

Method of analysis adopted Ref No.:

Analyst: Date

Meet acceptance criteria. YES ( ) NO ( )

CONCLUSIONS:________________________________________________________________________ ______________________________________________________________________________________ ______________________________________________________________________________________ __

CHECKED BY:_________________________ DATE____________________

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PROCESS VALIDATION PROTOCOL

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DATA RECORDING SHEET # 2

OIL PHASE SOLUTION PREPARATION

Equipment Name :_________________________

Total weight of ingredients : _______________kg/lot.

Mixing time : 20 minutes

FOR OIL PHASE SOLUTION TANK-RESULTS. BATCH NO: Assay of after mixing AT 20 MIN..

RESULTES

Sample no: Temperature Uniformity 1 2 3 Average std. Dev. Range RSD LCL UCL

RESULTES

Sample no: Temperature Uniformity 1 2 3 Average std. Dev. Range RSD LCL UCL

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PROCESS VALIDATION PROTOCOL

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Actual Temperature of the water/binder : ___________0_C

Temperature of the water after heating : ___________0_C

Temperature of the water after cooling : ___________0_C

Additional quantity of water added (ltr.):____________ Total time taken : ___________

POINTS

Analyst: Date

CONCLUSIONS:________________________________________________________________________ ______________________________________________________________________________________ ______________________________________________________________________________________ __

CHECKED BY:_________________________ DATE____________________

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PROCESS VALIDATION PROTOCOL

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MANUFACTURING :

Equipment Name :_________________________

Total weight of ingredients : _______________kg/lot. Mixing time : 20 minutes

FOR MANUFCTURING TANK-RESULTS. BATCH NO: Assay of after mixing AT 20 MIN..

Sample no: PH ASSAY REMARK 1 2 3 Average std. Dev. Range RSD LCL UCL

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PROCESS VALIDATION PROTOCOL

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Sample no: PH ASSAY REMARK 1 2 3 Average std. Dev. Range RSD LCL UCL POINTS

Analyst: Date

CONCLUSIONS:________________________________________________________________________ ______________________________________________________________________________________ ______________________________________________________________________________________ __

CHECKED BY:_________________________ DATE____________________

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PROCESS VALIDATION PROTOCOL

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FILLING & CRIMPING :

Equipment Name :_________________________

Mixing time( filling hopper) : Continues stirring during filling Setting – stirrer : slow ( R.P.M._________)

Plan : Samples to be drawn from each syringes as set weight at different time interval as mention below:

1. Initional ( 0 time) 2. Every 2 hours

3. Immediately after the break time 4. At the end of filling

from 3 different locations

FOR FILLING MACHINE -RESULTS. BATCH NO:

SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION

TEST ASSAY

Initional ( 0 time) Every 2 hours

Immediately after the break time

At the end of filling

Average std. Dev. Range

RSD LCL UCL

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PROCESS VALIDATION PROTOCOL

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SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION TEST ASSAY

Average std. Dev. Range

RSD LCL UCL

SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION TEST ASSAY

Average std. Dev. Range RSD LCL UCL POINTS

Analyst: Date

CONCLUSIONS:________________________________________________________________________ ______________________________________________________________________________________ ______________________________________________________________________________________ __

CHECKED BY:_________________________ DATE____________________

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PROCESS VALIDATION PROTOCOL

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DATE:____________________

SR NAME OF CRITICAL EQUIPMENT/UTILITIES QUALIFICATION/

VALIDATION FILE REF.NO.

DATE OF QUALIFICATION /

VALIDATION

1 S.S 350 Octagonal Steam Jacketed Tank. 2 S.S 350 Octagonal Steam Jacketed Tank.

( OIL PHASE)

3 500 Octagonal Steam Jacketed Tank 4 Storage Vessel

6 Filling ,crimping & Coding machine

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

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.

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PROCESS VALIDATION PROTOCOL

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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. Test by different analyst on different days. Sample A1 On ______ Sample A2 On ______ Sample A3 On ______ SR Parameters Type of sample Actual reading Observed reading Analysis performed by Analysis checked by Ref. Work sheet 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 Prepared by Checked by Approved by

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PROCESS VALIDATION PROTOCOL

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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 of heating 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 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.

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