ointment process validation

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PROCESS VALIDATION PROTOCOL(OINTMENT)

PROTOCOL NO: QUALITY ASSURANCE DEPTTBATCH NO. PAGE NO:- 1 0F 26

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:

APPROVALS:

DEPARTMENT SIGN & DATE

PRODUCTION

QUALITY ASSUARANCE

QUALITY CONTROL

PRODUCT DEVLOPMENT

ENGINEERING

Prepared by Checked by Approved by




1.0 GENERAL:

1.1INTRODUCTION:

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.

1.2LIST 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.

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 WATER PHASE PREPARATION3.0 OIL PHASE PREPARATION4.0 MIXING 5.0 Q.C APPROVAL6.0 FILLING , CRIMPING & CODING.7.0 PACKING

3.1 FORMULATION:

BATCH SIZE:

SR Ingredients/excipients Specification Label claim

Per batch

Qnty of overages

Total

1234567891011121314151617181920

NOTE:





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 / TUBECRIPINGCODING

1. MIXING TIME2. SPEED( RPM)3. TEMP.

1. MIXING TIME2. SPEED( RPM)3. TEMP.

Addition Of Active

Ingredient

Addition Of Excipient

Q.C APPROVAL




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 DETAILSBALANCE TYPE :

MODEL:

CAPACITY:

MANUACTURER:

TAG.NO.:

M.O.C.

WATER PHASE S.S.TANK

TYPE :

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 DETAILSSTORAGE 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:

4.3 IDENTIFICATION OF CRITICAL PROCESS VARIABLES/ PARAMETER.





4.3.1 PROBABLE CAUSES THAT MAY EFFECT FINAL PRODUCT:


DISPENSING OF MATERIAL

OIL PHASE SOLUTION PREPARATION

TUBE FILLING

WATER PHASE SOLUTION PREPARATION

MANUFACTURING

EXCIPIENT

ACTIVE

LOAD SIZE

SPEED

TEMPERATURE

LOAD SIZESPEED

COOLING TEMPERATURE

SPEED

LOAD SIZE

TEMPERATURE

PH

BOILING TEMPERATURE

SPEED

WEIGHT/TUBE




CRITICAL PROCESS PARAMETERS:

SR CRITICAL PRECESS VERIABLE

RESPONSE PARAMETER REMARKS

1 WATER PHASE SOLUTION PREPARATION

Water phase uniformitySequence of excipient addition Fixed order of additionWater Boiling Temperature Fixed Boiling temperature rangeTime Variation of time for boilingHeating Temperature Fixed Heating temperature rangeTime Variation of time for heatingCooling Temperature Fixed cooling temperature rangeTime Variation of time for coolingPH Fixed limit of PhMixing time Variation of mixing time (RPM)

2 OIL PHASE SOLUTION PREPARATION Oil phase uniformity

Sequence of excipient addition Fixed order of additionHeating Temperature Fixed Heating temperature rangeTime Variation of time for heatingCooling Temperature Fixed cooling temperature rangeTime Variation of time for coolingMixing time Variation of mixing time (RPM)

3 MANUFACTURING

Active ingredient uniformitySequence of Active addition Fixed order of additionMixing time Variation of mixing timeCooling Temperature Fixed temperature range

4 Filling, Crimping & Coding1. Weight of tube 2. Crimping

Filling speed Fixed machine speed, no variation.





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.





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




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

Water phase solution preparation Determination on each sample, for 80 + 50C





temperature, sample weight 10 g.

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

80 + 50C

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 %

6.0 RECORDING OF DATA & DATA TREATMENT





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





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..

RESULTESSample no: Temperature Uniformity

123

Average std. Dev.RangeRSDLCLUCL





Assay of after mixing AT 30 MIN..RESULTES

Sample no: Temperature Uniformity123




Average std. Dev.RangeRSDLCLUCLActual Temperature of the water/binder : ___________0C Temperature of the water after heating : ___________0C Temperature of the water after cooling : ___________0C Additional quantity of water added (ltr.):____________

Total time taken : ___________

POINTSMethod of analysis adoptedRef No.:Analyst:DateMeet acceptance criteria. YES ( ) NO ( )CONCLUSIONS:______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

CHECKED BY:_________________________ DATE____________________





DATA RECORDING SHEET # 2OIL PHASE SOLUTION PREPARATION

Equipment Name :_________________________


Capacity : ______________________lt.






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

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


123











123


Actual Temperature of the water/binder : ___________0C

Temperature of the water after heating : ___________0C

Temperature of the water after cooling : ___________0C

Additional quantity of water added (ltr.):____________

Total time taken : ___________

POINTSMethod of analysis adoptedRef No.:Analyst:Date

Meet acceptance criteria. YES ( ) NO ( )CONCLUSIONS:______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

CHECKED BY:_________________________ DATE____________________





DATA RECORDING SHEET # 3

MANUFACTURING :

Equipment Name :_________________________


Capacity : ______________________lt.






Plan : Samples to be drawn at of 20 minutes, 30 minutes, & 40 minutes of mixing


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

Sample no: PH ASSAY REMARK123


Assay of after mixing AT 30 MIN..Sample no: PH ASSAY REMARK

123







Sample no: PH ASSAY REMARK123



Meet acceptance criteria. YES ( ) NO ( )

CONCLUSIONS:______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

CHECKED BY:_________________________ DATE____________________





DATA RECORDING SHEET # 4

FILLING & CRIMPING :

Equipment Name :_________________________


Capacity : ______________________lt.

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


FOR FILLING MACHINE -RESULTS. BATCH NO:

SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION TEST

ASSAY

Initional ( 0 time)Every 2 hoursImmediately after the break timeAt the end of filling







SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION TEST ASSAYInitional ( 0 time)Every 2 hoursImmediately after the break timeAt the end of filling

Average std. Dev.RangeRSDLCLUCLAssay of after mixing AT 40 MIN..

SAMPLE NO: APPEARANCE WEIGHT IDENTIFICATION TEST ASSAYInitional ( 0 time)Every 2 hoursImmediately after the break timeAt the end of filling



Meet acceptance criteria. YES ( ) NO ( )

CONCLUSIONS:______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

CHECKED BY:_________________________ DATE____________________





DATA RECORDING SHEET # 5DATE:____________________

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





DATA RECORDING SHEET # 6DATE:____________________

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 ( 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 A1On ______

Sample A2On ______

Sample A3On ______





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 A50 % of A75 % of A100 % of A125 % of A

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 A115 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 A7 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.


ointment process validation

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