VIAL WASHING MACHINE PQ PROTOCOL

VIAL WASHING MACHINE PQ PROTOCOL

TABLE OF CONTENTS
S. No.	Description
1.0	Protocol approval
2.0	Overview
2.1	Purpose
2.2	Scope
2.3	Responsibilities and identification of execution team
3.0	Pre-Validation requirement
4.0	Equipment description
5.0	Validation procedure
6.0	Sampling plan and Acceptance criteria
7.0	Validation report
8.0	Validation approval
9.0	Observed deviation
10.0	List of attachment
11.0	Re-qualification Criteria
12.0	Reference document

Protocol Approval

The signing of this approval page of protocol indicates agreement with the qualification approach described in this document. If any modification in the equipment qualification approach becomes necessary, a revision through change control shall be prepared, checked, and approved. This protocol cannot be executed unless approved by the following personnel.

Overview

To establish the methodology for the validation of vial washing machine, which is used for washing of different size glass vials of size 10 ml, 15 ml, 20 ml, 50 ml and 100 ml having eight Different washing stages includes treatment of Recirculating Purified water, Purified water, Water for injection and Compressed air.

Purpose

The purpose of this Protocol is to carry out validation of vial washing machine to:

• Demonstrate that Vial Washing Machine shall perform washing of different sizes of vials which meets the desired acceptance criteria in a consistent manner when operated as per the standard operating procedure.
• The validation shall be tested at extreme and optimum operation condition

Scope

The scope of this validation exercise is limited to the validation of vial washing machine located in production injection area.

RESPONSIBILITIES AND IDENTIFICATION OF EXECUTION TEAM 

Responsibilities: The group comprising of representatives from each of the following departments and they shall be responsible for the overall compliance with this protocol. 

Department	Responsibility
Engineering & Utility	Arranging for execution of the document and providing facilities
Production	Participate and provide necessary support for the qualification.
Quality Control	For testing of the sample involved
Quality Assurance	Monitoring the qualification activities. Data compilation and review of the generated data. Preparation of the Qualification report in consultation with the qualification team. Authorization of the qualification report.

 Identification of Executors: The personnel involved in the execution of this protocol shall be recorded Name, Designation, Signature, and Date.

Training:

Training Date :                                                                                                                                                                             Subject:

Name of the Trainer(s):

Designation:

Duration:                      

S. No.	Name of the Trainee	Designation	Sign / Date

Pre – Validation Requirements

Following chemical/equipment shall be required for the validation of Vial Washing Machine.

• Sodium Chloride.
• Activated Charcoal Powder
• Bacterial endotoxin
• Liquid Particle Counter
• Weighing balance
• 10 ml moulded glass vials USP type –I
• 15 ml moulded glass vials USP type –I
• 20 ml moulded glass vials USP type-1
• 50 ml moulded glass vials USP type –I
• 100 ml moulded glass vials USP type –1
• System / Equipment Description
• System/Equipment Details

The vial washing machine shall be used for washing of different sizes of glass vials from 10 to 100 ml in eight different washing stages which include treatment of Recirculating water purified water, purified water, water for injection, and compressed air.

Description:

Equipment Tag Number                                                                                                                                                                        Location : Washing And Sterilization Room – 1

Name of the system/Equipment: Vial washing Machine

Manufacturer’s Name / Address :

Model

Dimensions

Width : 2220 mm

Height:1675 mm

Length:3840 mm

Design

Working Principle:

The Vial Washing Machine  is designed to wash vials of different sizes. Complete washing of vials will occur in eight different washing stages comprising of Re-circulated purified water, Purified Water, Water for Injection and Compressed Air.

The Vial Washing Machine  works on the principle of jet  washing of the individual vials in inverted position by a series of jets, 25 pockets are used for washing of 10, 15 and 20 ml vials. 12 Pockets are used for washing of 50 and 100 ml Vials.  The maximum rated capacity of the machine is 18000 vials per hour incase of 25 pockets, and 6000 vials per hour in case of 12 pockets. In feed lifter carries the vials in to the pockets & moving on a chain horizontal conveyor with vertical up spray nozzles, entering the vials co-axially and injected re circulated purified water, purified water, water for injection & compressed air at specified station

Brief Instrument Description

The Vial washing Machine comprises of following parts:

• Vial Infeed zone
• Vial washing zone
• Outfeed zone
• Outfeed conveyor
• Pump,Tanks,Pipe fittings & Pressure gauges
• Filter housing & Filter housing

Vial In feed Zone:-.

The process of washing begins with loading of vials on infeed platform and pushing manually to the conveyor. The conveyor carries the vials on the infeed lifter by the help of loosening device. The infeed lifter carries the vials into the pockets.

Vial Washing Zone:

The vials set up in to the pockets after feeding. The index channel of vials carries forward at a time. During each stoppage of this movement, nozzles manifold raises up and nozzles enters the mouth of each individual vials. A solenoid valve in the water and air lines is activated and a jet of air/water hits the inside of the vials to clean it. .An external cleaning station cycle is also provided. Standard washing cycle occurs as per following sequence:-

Washing Cycle

1st wash: Compressed Air  (Internal wash)

2nd wash: Recirculated purified water (External wash)

3rd wash: Recirculated purified water (Internal wash)

4th wash: Purified water (External wash)

5th wash: Purified water (Internal wash)

6th wash: WFI water (External wash)

7th wash: WFI water  (Internal wash)

8th wash: Compressed Air  (Internal wash)

Outfeed Zone:

After washing these washed vials are taken away from the pockets with support of vials guide plate and come out of the outfeed lifter. Outfeed lifter come down and the pusher pushes the vials on the outfeed platform and conveyor

Outfeed Conveyor:

The outfeed conveyor is chain linked with mesh conveyor made up of stainless steel 316 which conveys the washed vials from the unloading unit to the infeed of sterilizing tunnel. The speed of conveyor is controlled from the control panel of the machine

Validation Procedure:    

The following tests shall be carried out to establish the validation of Vial Washing Machine:

• Chemical decontamination study (By spiking with Sodium chloride)
• Particulate decontamination study (by spiking with Charcoal powder).
• Endotoxin decontamination study (By spiking with Endotoxin).

Test Matrix

The following matrix shall be followed for the validation of vials washing machine:

Table-1

S. No.	Vial Size		No. of Trails	Tests
	Size (ml)	Tubular / Moulded		Sodium Chloride	Charcoal Powder	Endotoxin
	10	Moulded	3	√	√	√
	15	Moulded	1	√	√	√
	20	Moulded	1	√	√	√
	50	Moulded	1	√	√	√
	100	Moulded	3	√	√	√

 Table-2

S. No.	Vial Size (ml)	Volume of rinse fluid (WFI)
1.	10 ml	7 ml
2.	15 ml	10 ml
3.	20 ml	15 ml
4.	50 ml	30 ml
5.	100 ml	50 ml

Table-3

Vial spiked for each test

S. No.	Vial Size		No. of Trails	No. of Vials spiked for test*
	Size (ml)	Tubular / Moulded		Sodium Chloride	Charcoal Powder	Endotoxin
1.	10	Moulded	3	3 x 25	3 x 25	3 x 25
2.	15	Moulded	1	25	25	10
3.	20	Moulded	1	25	25	10
4.	50	Moulded	1	12	12	10
5.	100	Moulded	3	3 x 12	3  x 12	3 x 10

* 2 vials as positive control for each test shall be spiked and preserved separate.

Chemical Decontamination Study

The following tests shall be carried out to establish the efficiency of vial washing machine to removed chemical matter.

Spiking of vials with Chemical (Sodium chloride)

Preparation of sodium chloride solution

Weigh 40 gm of sodium chloride & dissolve in purified water to make up the volume 200 ml.

Spiking of vials with chemical

Spiked the no. of vials as per the table 3 for test.

• Dispense 1.0 ml of the sodium chloride solution to vial to be spiked.
• Swirl the vial so that the solution is distributed throughout the vial.
• Mark the vials with a permanent marker resistant to washing.
• Dry the vials at 60°C till no water traces are observed in the vial.

Initial chemical concentration determination (Positive control)

Determine the initial chemical concentration in the vial as per the following procedure the initial concentration of NaCl solution shall be determined by quality control.

Chemical Matter decontamination study

Objective

The objective of this test is to determine that the vial washing machine is capable of removing chemicals matter, if present in the vials.

Test Requirements

• Sodium chloride spiked vials

Test Procedure

The procedure for the chemical decontamination study is defined below

• Load the In-feed belt to the Vial Washing machine with vials of one of the selected pack size.
• Set up a vial washing machine as per procedure. Fix the Water Jet Heights, Machine Speed and Water Tanks Refill Time properly.
• Switch “ON” The Vial Washing Machine and operate as per SOP No. PI-SP-006.
• Allow the machine to run & place 25 vials of spiked & marked vials in between the other vials while machine is running as per conditions as defined.
• Allow the spiked / challenge vials to go through washing cycle.
• Collect the washed (spiked) vials after completion of washing cycle. Separate the marked vials
• Transfer the collected vial to Q.C. laboratory for testing.
• Fill the vials with filtered water as per the quantity defined in Table-2 and vortex the vials for 2-3 minutes.
• Pool the sample and Perform the analysis for a spiked vial as defined in previous section.

Acceptance Criteria

Sodium chloride content in spiked and washed vial should not be more than 2 ppm.

Results

The result shall be recorded in Text Datasheet.

Particulate Matter decontamination study

Objective

The objective of this test is to determine that the machine is suitable to remove particulate matter from the spiked vials.

Test Requirements

• Liquid Particle counter
• Charcoal powder

Spiking of vials with charcoal

Preparation of charcoal solution (0.6 %)

Weigh 20 gm of charcoal & dissolve in purified water to make up the volume of 300 ml.

Spiking of vials with chemical

Spiked the no. of vials as per the table 3 for test.

• Dispense 1.0 ml of the charcoal solution to vial to be spiked.
• Swirl the vial so that the solution is distributed throughout the vial.
• Mark the vials with permanent marker resistant to washing.
• Dry the vials at 60°C till no water traces are observed in the vial.

Test Procedure

Following the procedure defined below for the particulate decontamination study

• Load the In-feed belt to the Vial Washing machine with vials of one of the selected pack size.
• Set up a vial washing machine as per procedure. Fix the Water Jet Heights, Machine Speed and Water Tanks Refill Time properly.
• Switch “ON” The Vial Washing Machine and operate as per SOP No. PI-SP-006.
• Allow the machine to run & place 25 vials of spiked & marked vials in between the other vials while machine is running.
• Allow the spiked / challenge vials to go through washing cycle.
• Collect the washed (spiked) vials after completion of washing cycle. Separate the marked vials & store them under LAF so as to avoid any contamination from environment.
• Transfer the collected vial to IPQA area.
• Fill the vials with filtered water (WFI) as per the quantity defined in Table-2 and vortex the vials for 2-3 minutes.
• Pool the water sample and perform the analysis for a spiked vial also and use the same as positive control and filter water (WFI) as blank.
• Calculate the particles count in the spiked washed vials be subtracting the particles of the water blank

Acceptance Criteria

LBPC: for ≥ 10µ: 6000/100 ml

for ≥ 25µ: 600/100 ml

Result: 

The result shall be recorded in text Data Sheet.

Endotoxin decontamination study

Spiking of vials with endotoxin

• Spiked the no. of vials as per the table 3 for test.
• Reconstitute Endotoxin Indicators vial containing 100,000 Endotoxin units with 10 ml Lal Reagent Water [LRW] to give the concentration of 10,000 EU/ml.
• Vortex it for 20 to 25 minutes.
• Transfer 0.1 ml of the content (1000 EU) in each vial to be spiked.
• Swirl the vial gently so that solution is wets the entire inner surface area of the vial to be spiked.
• Air dry the spiked vial at room temperature under LAF.

Recovery of Endotoxin from spiked vials (Positive control):

• Add 4.0 ml LRW into the into the spiked containers (Assumed potency on the basis of 100% recovery = 1000 EU/ml.
• Sonicate the container for 10-15 minutes
• Dilute the reconstituted container as follows :

Dil. No.	Dilution step	Concentration	Total dilution
1	0.1 mL of 1000 EU/mL + 3.9 mL of LRW	25 EU/mL	1 :40
2	0.1 mL of 25 EU/mL + 0.9 mL of LRW	2.5 EU/mL	1 :400
3	0.1 mL of 2.5 EU/mL + 0.9 mL of LRW	0.25 EU/mL	1 :4000
4	0.5 mL of 0.25 EU/mL + 0.5 mL of LRW	0.125 EU/mL	1 :8000
5	0.5 mL of 0.125 EU/mL + 0.5 mL of LRW	0.06 EU/mL	1 :16000

• Perform the LAL Gel Clot test from dilution no. (3), (4) and (5).
• Record the results.
• Calculation

Calculate by following formula:

Recovery = Reciprocal of last dilution which was positive x lambda [l].

Endotoxin decontamination study

Objective

The objective of this test is to determine that the vial washing machine is capable of removing endotoxin load, if present in the vials.

Test Requirements

• Endotoxin Kit
• Endotoxin spiked vials

Test Procedure

Following the procedure defined below for the endotoxin decontamination study

• Load the In-feed belt to the Vial Washing machine with vials of one of the selected pack size.
• Set up a vial washing machine as per procedure. Fix the Water Jet Heights, Machine Speed and Water Tanks Refill Time properly.
• Switch “ON” The Vial Washing Machine and operate as per SOP No. PI-SP-006.
• Allow the machine to run & place 10 vials of spiked & marked vials in between the other vials while machine is running.
• Allow the spiked / challenge vials to go through washing cycle.
• Collect the washed (spiked) vials after completion of washing cycle. Separate the marked vials
• Transfer the collected vial to laboratory for testing.
• Determine the endotoxin content in the washed spiked containers.
• Put 1 ml of LRW in washed vial to obtain 10 EU/ml and perform the test as per dilution given below:

Dil. No.	Dilution step	Conc	Dilution
1	0.1 ml of 10 EU/mL + 3.9 mL of LRW	0.25 EU/mL	1 :40
2	0.5 mL of 0.25 EU/mL + 0.5 mL of LRW	0.125 EU/mL	1 :80
3	0.5 mL of 0.125 EU/mL + 0.5 mL of LRW	0.06 EU/mL	1 :160

• Perform the LAL Gel Clot test from dilution no. (1), (2) and (3).
• Calculation: Calculate the log reduction by following formula:
• Log reduction in endotoxin = log of recovered endotoxin from spiked container
• Log of recovered endotoxin from exposed containers.

Acceptance Criteria

A minimum log reduction of 2 log should be achieved.

Results

Results shall be recorded Test Datasheet.

Critical processing variable

Process variables: The validation shall be tested at extreme and optimum operation conditions as described below

S. No.	Speed of machine (10-20 ml vials)	Parameters	Values set
01	250 Vials/min	compressed air blowing time	2.0 sec
		Recirculating purified water wash time	2.0 sec
		Purified water wash time	2.0 sec
		Water for injection	2.0 sec
02	275Vials/min	Compressed air blowing time	2.5 sec
		Recirculating purified water wash time	2.5 sec
		Purified water wash time	2.5 sec
		Water for injection	2.5 sec
03	300Vials/min	Compressed air blowing time	2.5 sec
		Recirculating purified water wash time	2.5 sec
		Purified water wash time	2.5 sec
		Water for injection	2.5 sec

 

S. No	Speed of machine (50 & 100 ml vials)	Parameters	Values set
01	80 vials/min	compressed air blowing time	4.5 sec
		Recirculating purified water wash time	4.5 sec
		Purified water wash time	4.5 sec
		Water for injection	4.5 sec
02	120 vials /min	compressed air blowing time	4.5 sec
		Recirculating purified water wash time	4.5 sec
		Purified water wash time	4.5 sec
		Water for injection	4.5 sec
03	150 vials/min	compressed air blowing time	4.5 sec
		Recirculating purified water wash time	4.5 sec
		Purified water wash time	4.5 sec
		Water for injection	4.5 sec

Sampling Plan and Acceptance Criteria:

Stage	Sampling Criteria		Test to be performed	Sample quantity		Acceptance Criteria
Before vial washing	Recirculated Water	Visual Check and LBPC			Around 100 ml	1. Shall be free of visible particles 2. ≥10 µ =NMT 60/ml ≥25 µ NMT 6/ml
	WFI quality		Visual Check and LBPC	Around 100 ml
	Compressed air quality (Bubbling of compressed air in 100 ml water)		Visual Check and LBPC	Around 100 ml
After Vial washing	Sodium chloride spiked vials		Removal of chemical matter	25 spiked vials  for 10, 15 & 20 ml vials		Less than 2 ppm
				12 spiked vials  for 50 & 100 ml vials
After Vial washing	Charcoal spiked vials		Removal of particulate matter	25 spiked vials  for 10, 15 & 20 ml vials		1. Shall be free of visible particles 2. ≥10 µ =NMT 60/ml ≥25 µ NMT 6/ml
				12 spiked vials  for 50 & 100 ml vials
After Vial washing	Bacterial Endotoxin spiked vials		Endotoxin decontamination study	As per point 5.4.1		Should show more than 2 log reduction

Validation Report

The validation report shall consist of a summary document, in narrative form, which shall briefly describe the activity performed along with the observations recorded in relevant exhibits.

This report shall also include the related documents and attachments/exhibit which were completed at the time of Validation activity.

Approval of Validation Report

The report shall be evaluated and proper references/conclusions/recommendations shall be recorded by quality assurance.

The validation report shall be evaluated and finally approved by quality assurance.

Test Data Sheet # 1

Chemical decontamination study

Date of trial
Trial No,
Test Parameter
Solenoid valve timer
Vial Type
The conductivity of Blank ions:

Vial type	10 ml moulded glass vials USP type –III
	15 ml moulded glass vials USP type –I
	100 ml moulded glass vials USP type –I
Phase I	At low speed with 10 ml, 15 ml & 100 ml glass vials
Phase II	At medium speed with 10 ml, 15 ml & 100 ml glass vials
Phase III	At high speed with 10 ml, 15 ml & 100 ml glass vials

Chemical/Reagent Used	Sodium Chloride
Acceptance criteria	The conductivity of washed vials should not be more than 1. 3µs/cm of WFI

S. No.		Parameters		Values Set
01	Machine Speed (Vials/mins.)
02	Compressed Air Blowing Time (Seconds)
03	Re-circulating purified water wash time (Seconds)
04	Purified water wash time (Seconds)
05	Water For Injection Wash Time (Seconds)

Sr. No.	Conductivity (µs/cm)	Acceptance (Yes/No)	Sr. No.	Conductivity (µs/cm)	Acceptance (Yes/No)
1			2

Results

Qualified

Not qualified

 

Test Data Sheet # 2

Removal of Insoluble Matter

Date of trial
Trial No,
Test Parameter
Solenoid valve timer
Vial Type

Vial type	10 ml moulded glass vials USP type –III
	15 ml moulded glass vials USP type –I
	100 ml moulded glass vials USP type –I
Phase I	At low speed with 10 ml, 15 ml & 100 ml glass vials
Phase II	At medium speed with 10 ml, 15 ml & 100 ml glass vials
Phase III	At high speed with 10 ml, 15 ml & 100 ml glass vials

 

Chemical/regent Used	Activated charcoal powder
Acceptance criteria	Visible particles
	The vials should be free from visible particles.
Sub visible particles	>10 µ: Not more than 60 / ml
	> 25 µ: Not more than 6 / ml

S. No.	Parameters	Values Set
01	Machine Speed (Vials / mins.)
02	Compressed Air Blowing Time (Seconds)
03	Re-circulating purified water wash time (Seconds)
04	Purified water wash time (Seconds)
05	Water For Injection Wash Time (Seconds)

Vial Number	Visible Particulate Matter				Visible Particulate Matter
	Black	White	Fibers		Black	White	Fibers
1				2

Results

Qualified

Not qualified

 

Container no.	Sub Visible Particulate Matter		Acceptance (Yes /No)	Container no.	Sub Visible Particulate Matter		Acceptance (Yes /No)
	³10 micron	³25 micron			³10 micron	³25 micron
1				2

Results

Qualified

Not qualified

Test Data Sheet # 3

Removal of Glass Fragments

Date of trial
Trial No,
Test Parameter
Solenoid valve timer
Vial Type

Vial type	10 ml moulded glass vials USP type –III
	15 ml moulded glass vials USP type –I
	100 ml moulded glass vials USP type –I
Phase I	At low speed with 10 ml, 15 ml & 100 ml glass vials
Phase II	At medium speed with 10 ml, 15 ml & 100 ml glass vials
Phase III	At high speed with 10 ml, 15 ml & 100 ml glass vials

Chemical/regent Used	Fine glass fragments
Acceptance criteria	The vials should be free from the glass particles when observed visually

 

S. No.	Parameters	Values Set
01	Machine Speed (Vials / mins.)
02	Compressed Air Blowing Time (Seconds)
03	Re-circulating purified water wash time (Seconds)
04	Purified water wash time (Seconds)
05	Water For Injection Wash Time (Seconds)

Vials Number	Glass fragments (Yes / No)	Vials Number	Glass fragments (Yes / No)
1		2

Results

Qualified

Not qualified

Test Data Sheet # 4

Residual Water Determination in Washed Vials

Date of trial
Trial No,
Test Parameter
Solenoid valve timer
Vial Type

Vial type	10 ml moulded glass vials USP type –III
	15 ml moulded glass vials USP type –I
	100 ml moulded glass vials USP type –I
Phase I	At low speed with 10 ml, 15 ml & 100 ml glass vials
Phase II	At medium speed with 10 ml, 15 ml & 100 ml glass vials
Phase III	At high speed with 10 ml, 15 ml & 100 ml glass vials

Chemical/regent Used	Activated charcoal powder
Acceptance criteria	The weight of residual water should not be more than
	A. 0.4 g – For 10ml & 15ml Vials
	B. 1.0g – For 100 ml vials.

 

S. No.	Parameters	Values Set
01	Machine Speed (Vials / mins.)
02	Compressed Air Blowing Time (Seconds)
03	Re-circulating purified water wash time (Seconds)
04	Purified water wash time (Seconds)
05	Water For Injection Wash Time (Seconds)

 

Vials Number	Initial Weight in grams(A)	Final Weight in grams(B)	Weight of Residual Water in grams(B-A)	Acceptance (Yes / No)
1

Result : Pass /Fail

Test Data Sheet # 5

Insoluble Particulate Matter in WFI after filtration, before washing

 Acceptance criteria                     :

Visible particles                       : The vials should be free from visible particles

Sub visible particles                :   >10 µ: Not more than 60 / ml

> 25µ: Not more than 6 / ml

Container  identification	Visible Particulate Matter
	Black	White	Fibers
WFI

Results

Qualified

Not qualified

 

Container  identification	Sub Visible Particulate Matter		Acceptance (Yes /No)
	³10 micron	³25 micron
WFI

Results

Qualified

Not qualified

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