Reason for Performing the Validity Study

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Protocol No.: / Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department / Page 24 of 25
Title : Validation Protocol for / B. No. :

Formulation: Oral Liquid

Product’s Name:

Reason for Performing the Validity 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 fails to meet product & process specifications.

Number of batches studied: First Three Batches

Batch numbers: 1. 2. 3.

Validation activity Approved by: ______Date:______

Validation Team:

Department / Validation Team
Production
Quality Control
Quality Assurance

Approvals:

Department / Sign & Date
Production
Engineering
Quality Control
Quality Assurance

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:

v  Validation protocol,

v  Details of sampling for the validation batches, test parameters (Product performance characteristics) with reference to test methods & Acceptance criteria. (acceptable Limit)

v  Methods for recording / evaluating results including statistical analysis.

v  Reference to relevant documents.

1.2.2 Batch manufacturing records.

v  Detailed manufacturing instructions for the production of the validation batches.

2.0 Personnel Responsibilities:

Sr No / Activity / Responsibility / Remarks
1 / Preparation of validation protocol / QA Department
2 / Review of validation report. / Q.A In charge
3 / Production of validation Batches / Production In charge
4 / Testing of validation samples & Preparation of validation report / Q.C In charge
5 / Approval of Validation protocol / Manager (Q.A)

3.0 Process Description / 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  / DISPENSING OF MATERIAL
2  / SUGAR SYRUP PREPARATION
3  / BULK MANUFACTURING
4  / PH ADJUSTMENT
5  / VOLUME MAKE UP
6  / FILTRATION
7  / WASHING, FILLING AND SEALING

3.1 Formulation:

Batch Size:

Sr No / Ingredients/Excipients / Unit per ml / Quantity in Kgs / Overages / Quantity with Overages / Dispensed
Quantity / Function
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22

Note:

3.2 FLOW SHEET:

MANUFACTURING PROCESS DIAGRAM:- ______syrup

4.0 Equipments/ 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

SrNo / Equipment / Equipment No. / SOP No
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 

4.2 Details of equipment to be used.

Equipment / Details
S.S. Manufacturing Tank / Type :
Model:
Capacity:
Manufacturer:
Tag No.
RPM
M.O.C.
S.S. Storage Tank / Type :
Model:
Capacity:
Manufacturer:
Tag No.
RPM
M.O.C.
Filter Press / Type :
Model:
Capacity:
Manufacturer:
Tag No.
Type of filter
M.O.C.
Transfer Pump / Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.
Washing Machine / Type :
Model:
Capacity:
Manufacturer:
Tag No.
Speed
M.O.C.
Filling Machine / Type :
Model:
Capacity:
Manufacturer:
Tag No.
Speed
M.O.C.
Sealing Machine / Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.
Labeling Machine / Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.

Remarks:

4.3 Identification of Critical process variables parameter.

4.3.1 Probable causes that may effect final product:

Critical Process PARAMETERS:

Sr No / Critical process variable / Response parameter / Remarks
1 / Sugar Syrup Preparation
Mixing time
Load charge in to a Blender / Uniformity of sugar / Fixed speed.
Fixed batch size
2 / Final mixing and volume make up
Mixing time
Load charge in to a Blender / Uniformity of Active Drugs / Fixed speed.
Fixed batch size
3 / Washing
D.M. Water pressure
D.M. Water temperature
Compressed air pressure
Washing cycle
Alignment & blockage of needles / Cleaning Of Bottle
Washing efficiency / Fixed pressure for washing.
Fixed temperature for washing
Fixed pressure of air
Fixed cycle
Fixed direction
4 / Filling & Sealing
Speed of filling machine
Leak test / Volume Uniformity / Fixed speed
Volume variation
Leakage
5 / Labeling & Packing / Clean, Position & Proper Sealing / Clean Label
Position
Sealing
Sr No / Process / Variable / Machine setting
( Control Variables) / Remarks
1 / Sugar syrup preparation / Mixing Time
Temperature
2 / Manufacturing
Load time
Mixing time / Mixing Time
3 / Bottle washing / Washing Pressure
4 / Bottle filling & Sealing / Adjustment Of Volume

5.0 Sampling, Test Parameters, Acceptance criteria

5.1 Sampling locations:

Sampling site: - Top (A), Middle (B), Bottom(C) position; use the sample tube for A&B and bottom valve for Position C

Sampling Qty.: -About 100 ml from each sample site

Sampling Time: - While mixing is on: - After ____ minutes, after ____ minutes, After _____ minutes

______minutes A,B & C / ______minutes A,B & C / ______minutes A,B & C
Total samples:______

5.2 Sampling:

Stage / Test Parameter / Equipment
(Size, Location & Time) / Acceptance Criteria
Sugar syrup Preparation / Determination on each sample, for temperature, & Clarity / Not more than ______minutes
Manufacturing
Appearance
pH
weight per ml
Identification
Assay / Sampling thief / Ø  As specified in the BMR
Ø  Ref. std. :
Ø  As specified in the BMR
Ø  As per standard testing procedure
Ø  Assay 90 % to 110 %
Bottle washing / Visual inspection / inspected for particulate matter
Filling & sealing
Volume
Appearance
Odour
Colour / Measuring cylinder
Visual inspection,
Visual inspection
Visual inspection / Not less than label claim.
As specified in the BMR.
As specified in the BMR
As specified in the BMR
Capping / Leak test
Cap breaking and recapping / Complies leak test
Labeling & Packing / Clean, Position & Proper Sealing / Clean label and proper sealing

6.0 Recording of data & Data treatment:

6.1 Data 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 sugar syrup preparation & results
Sheet No 2 / For recording of bulk manufacturing and results
Sheet No 3 / For recording of bottle washing and results
Sheet No 4 / For recording of bottle filling and sealing
Sheet No 5 / For recording of capping
Sheet No 6 / For recording of labeling and packing
Sheet No 7 / For recording of analysis report
Sheet No 8 / For recording general utilities /equipment / method qualitical /results.
Sheet No 9 / For recording analytical method validation.

Data recording sheet no I

Sugar syrup preparation:

Equipment name :______

Identification no :______Date:______

Capacity : ______lt.

Ingredients and sequence of material addition: ______

Total Volume of ingredients : ______ltr.

Mixing time : ______minutes

Setting – stirrer : slow

Procedure : As outlined in the batch manufacturing record.

Plan : Samples to be drawn at of ___ minutes of mixing from 3 x 100 ml different locations

For Sugar syrup preparation:

Result after mixing ______minutes

Points / Temperature / Clarity / Weight per ml
Sample A
Sample B
Sample C
Analyst: / Date

Conclusions:

Checked By: ______Date: ______

Data recording sheet no II

Manufacturing (Manufacturing Tank):

Equipment Name :______

Identification no :______Date:______

Capacity : ______lt.

Ingredients and sequence of material addition: ______

Total weight of ingredients : ______ltr.

Mixing time : ______minutes

Setting – stirrer : slow

Procedure : As outlined in the batch manufacturing record.

Plan : Samples to be drawn at of ______minutes, ______minutes, & ______minutes of mixing from 3 different locations

For manufacturing tank result:

Assay of after mixing ______minutes

Location / Appearance / pH / Weight per ml / Identification / Assay
Between to / Between to / 90 to 110%
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

N.B. Calculation sheet attached

Assay of after mixing ______minutes

Location / Appearance / pH / Weight per ml / Identification / Assay
Between to / Between to / 90 to 110%
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

N.B. Calculation sheet attached

Assay of after mixing ______minutes

Location / Appearance / pH / Weight per ml / Identification / Assay
Between to / Between to / 90 to 110%
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

N.B. Calculation sheet attached

Conclusion:

Data recording sheet III

Equipment Name: Bottle washing Machine

Identification no :______Date:______

Capacity : ______(Bottle per minutes)

Method reference: Visual inspection.

Observation : Washed bottle shall be inspected for particulate matter.

Stage / Inspected
by / 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8 / 9 / 10
After machine setting
Beginning of washing
Middle of washing
End of washing

Conclusion:

Data recording sheet IV

Equipment Name: Monoblock filling & sealing machine

Identification no: ______

Machine Speed:______

Standard volume: ______ml

Procedure: As per In-process check procedure for volume check.

Observation: Volume shall be more than label claimed.

Plan: Samples to be drawn from each roller as set for sealing at after machine setting , Beginning of filling, Middle of filling and end of filling.

Stage / Volume measured in measuring Cylinder / Appearance / Inspected by
1 / 2 / 3 / 4 / 5 / 6 / 7 / 8
After machine setting
Beginning of filling
Middle of filling
End of filling

Conclusion:

Checked by: ______Date______

Data recording sheet V

Equipment Name: Monoblock filling & sealing machine

Identification no: ______

Machine Speed:______

Procedure: Capped bottles to be checked for seal breaking and recapping.

Method reference: Leak test procedure for Capped bottles.

stage / No of bottle tested / Recapping / Seal breaking / No of Leakers
After machine Setting
Beginning of Capping
Middle of Capping
At the end of Capping

Data recording sheet VI

Equipment Name: Bottle labeling machine / Domino printing machine

Identification no: ______

Machine Speed: ______

Procedure: Labeled bottles to be checked for clean, position of label and crossed label.

Method reference: Leak test procedure for Capped bottles.

stage / No of bottle tested / Clean / Position of label / Crossed label
After machine Setting
Beginning of Capping
Middle of Capping
At the end of Capping

Data recording sheet VII

Analysis Report

Product Name:

Batch No.: Batch size:

Mfg. Date: Exp. Date:

Composition:

Test method reference: In house

Sr. No. / Test /

Specification

/

Results

/

Remark

01 / Description
02 / pH
03 / Specific Gravity
04 / Uniformity Of volume
05 / Assay
5.1 / % Labeled amount: 90 % - 110 %
Quantity Found:
5.2 / % Labeled amount: 90 % - 110 %
Quantity Found:
5.3 / % Labeled amount: 90 % - 110 %
Quantity Found:
5.4 / % Labeled amount: 90 % - 110 %
Quantity Found:

Remark:

Result: The sample referred above complies / does not comply with the standard prescribed as per In house Specification.

N.B. Calculation sheet attached

Data recording sheet VIII

Sr No / Name of critical equipment / Utilities / Qualification / Validation file reference No / Date of Qualification / Validation
1 / S.S. Manufacturing tank
2 / S.S. Storage vessel
3 / Filter press
4 / Transfer Pump
5 / Washing Machine
6 / Filling Machine
7 / Sealing Machine
8 / Labeling Machine
Utilities:
1 / AHU System
2 / Water System
3 / Compressed Air
4 / Steam
5 / Lightning
6 / Drain

Data recording sheet IX

Remark:

Analytical Method Validation protocol attached

Conclusion

Sr. No. / Stage / Acceptance criteria / Observation
1.  / Sugar Syrup Preparation / Uniformity of sugar
2.  / Manufacturing / Complies as per BMR
3.  / Bottle Washing / No particulate matter observed
4.  / Filling and Sealing / Volume shall be more than labeled claim
5.  / Capping / Leak test
6.  / Labelling and packing / Crossed label shall not be more than 2 mm at the edge, label shall not be peeled off after drying

Conclusion:

Product ______manufactured as per B.M.R. No ______meets predefined acceptance criteria.

Analysis By / Approved By
Date / Date
Prepared By / Checked By / Approved By