Capsule Process Validation

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)

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:

________________________________________________________________________

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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.  Reference to relevant documents.

1.2.2 Batch manufacturing records.  Detailed manufacturing instructions for the production of the validation batches. Prepared by

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2.0 PERSSONEL RESPONSIBILITIES. SR ACTIVITY 1 Preparation of validation

RESPONSIBILITY

REMARKS

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

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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 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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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

1.

Equipment cleaning procedure for Master sifter #20,#40

2.

Equipment operating procedure for Master sifter #20,#40

3.

5.

Equipment cleaning procedure for Rapid mixer granulator. Equipment operating procedure for Rapid mixer granulator. Equipment cleaning procedure for Octagonal Blender.

6.

Equipment operating procedure for Octagonal blender.

7.

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.

4.

8. 9. 10. 11. 12.

15.

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

16.

Equipment operating procedure for Cap counting

13. 14.

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17.

machine 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 SIFTING : TYPE : MODEL: CAPACITY:

DETAILS

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

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

MIXER :

MILLING

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

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M.O.C. DRYING

CAPSULE FILLING MACHINE:



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:

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MANUACTURER:

CAPSULE COUNTING MACHINE

TAG.NO.: M.O.C. 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: MATERIAL SIFTING

MIXING

AIR DRYING

POLISHING

LOAD SIZE

ACTIVE

SPEED

MIXER EXCIPIENT

SPEED

MIXER WEIGHT LEAK TEST

BLENDING Prepared by

GRANULATION ( IF REQUIRED)

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FILLING Approved by

STRIPING/ BLISTERING/COUNTING


DATE OF EFFECTIVE

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

BLENDING

REMARKS

Fixed order of addition Blend uniformity

Sequence of excipient

Fixed batch size

addition Load blending vessel.

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

Blending time 3.

FILLING Weight of capsule Locking length.

Fixed weight as per label claim Weight uniformity

Capsule filling speed

Fixed , no variation of filling speed.

D.T. 4.

STRIPING/BLISTERING/COUNTING Leak test

5.

Leakage

No leakage

Bottle Sealing

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Critical process variable (CPV): SR PROCESS / MACHINE SETTING VARIABLE (CONTROL VARIABLES) 1 Mixing Mixing time

REMARKS

2

Filling

Speed, locking

Setting and conditions as

3

Stripping/ blistering

Leak test, speed.

mentioned in the batch manufacturing record to be followed.

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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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5.3 SAMPLING STAGE/ TEST

SAMPLING

PARAMETER

( SIZE,LOCATION,TIME)

REMARKS

CAPSULE FILLING

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

MIXING 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

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As specified in the BMR.

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Weight variation

Analytical balance

Disintegration time

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.

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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.

BATCH NO:

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

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

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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. BATCH NO: ______________________

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.

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YES (

)

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.

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 ( %)


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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:

Average wt

Polishing

B M E

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

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

QUALIFICATION/ VALIDATION FILE REF.NO.

DATE OF QUALIFICATION / VALIDATION

UTILITIES: 1

AHU SYSTEM

2

WATER SYSTEM

3

COMPRESSED AIR

4

STEAM

5

LIGHTNING

6

DRAIN

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DATA RECORDING SHEET # 6 NAME OF PRODUCT: SR Parameters

1

2

3

Type of sample

Actual reading

Observed reading

Analysis performed by

Analysis checked by

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 ______

Linearity and range Response concentration curve on graph paper.

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

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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 reading

Analysis Analysis performed checked by by



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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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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Capsule Process Validation

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