Vial Washing Machine: Streamlining Sterile Pharmaceutical Packaging

Vial Washing Machine: Streamlining Sterile Pharmaceutical Packaging

In the pharmaceutical industry, maintaining the integrity and cleanliness of packaging materials is crucial for ensuring the safety and efficacy of drugs. Vial washing machines play a vital role in the production of sterile pharmaceuticals by efficiently cleaning and sanitizing vials before they are filled with medications. These machines employ advanced technology and processes to remove contaminants, such as particles, microorganisms, and residues, ensuring the highest standards of quality and compliance. In this blog post, we will explore the concept of vial washing machines, their importance, key features, validation considerations, and best practices for optimal performance in the pharmaceutical manufacturing process.

I. Understanding Vial Washing Machines

A. Definition and Purpose:

1. Definition: Explain vial washing machines as automated equipment designed to clean and sanitize vials used in pharmaceutical packaging.
2. Purpose of Vial Washing Machines: Discuss how these machines remove contaminants, such as particles, microorganisms, and residues, ensuring vials are clean and ready for sterile drug filling.

B. Types of Vial Washing Machines:

1. Rotary Vial Washing Machines: Discuss the operation and features of rotary vial washing machines, which utilize a rotating motion to clean vials in a continuous manner.
2. Linear Vial Washing Machines: Explain the operation and features of linear vial washing machines, which clean vials in a linear or linear-indexing motion.

C. Key Features and Components:

1. Washing Chambers: Describe the washing chambers in vial washing machines, which are equipped with nozzles or jets that spray cleaning solutions and rinse water onto the vials.
2. Cleaning Mechanisms: Explain the different cleaning mechanisms employed by vial washing machines, such as air jet cleaning, water jet cleaning, or brushing, to remove contaminants from vials.
3. Drying Systems: Discuss the drying systems integrated into vial washing machines, such as hot air or compressed air, to ensure vials are dry before further processing.

II. Importance of Vial Washing Machines in Pharmaceutical Packaging

A. Compliance with Regulatory Standards:

1. Good Manufacturing Practices (GMP): Explain how vial washing machines are crucial for complying with GMP regulations, which require thoroughly cleaning and validating packaging materials in the pharmaceutical industry.
2. Pharmacopoeial Guidelines: Highlight relevant pharmacopoeial guidelines, such as USP <1236>, EP 5.5, or JP 16, that provide specific requirements for vial washing processes.

B. Contamination Control and Product Safety:

1. Particle Removal: Discuss how vial washing machines effectively remove particles, including visible and non-visible contaminants, to ensure product safety and reduce the risk of particulate contamination.
2. Microbial Decontamination: Explain the importance of vial washing machines in eliminating or reducing microbial contamination on vials, preventing microbial growth and product spoilage.

C. Process Efficiency and Cost Savings:

1. Increased Throughput: Discuss how vial washing machines enable high-speed, automated cleaning processes, allowing for increased production throughput and efficiency.
2. Water and Energy Conservation: Highlight the sustainability benefits of vial washing machines, designed to optimize water and energy consumption, leading to cost savings and reduced environmental impact.

III. Validation and Qualification of Vial Washing Machines A. Installation Qualification (IQ) and Operational Qualification (OQ):

1. IQ Activities: Discuss the installation qualification activities, including verification of equipment installation, utilities, and environmental requirements.
2. OQ Activities: Explain the operational qualification activities, such as functional testing, performance verification, and process parameter optimization, to ensure the machine operates within predefined specifications.

B. Performance Qualification (PQ) and Process Validation:

1. PQ Activities: Discuss the performance qualification activities, including testing the vial washing machine with actual vials and evaluating the cleaning effectiveness, cycle times, and process parameters.
2. Process Validation: Explain the importance of process validation for vial washing machines, which involves demonstrating the consistency and repeatability of the cleaning process through statistical analysis and performance monitoring.

C. Cleaning Validation and Analytical Methods:

1. Cleaning Validation Protocols: Discuss the development and execution of cleaning validation protocols to demonstrate that vial washing machines effectively remove residues and contaminants from vials.
2. Analytical Methods: Explain the analytical methods used in cleaning validation, such as visual inspection, particle counting, total organic carbon (TOC) analysis, or microbial testing.

IV. Best Practices and Operational Considerations

A. Cleaning Process Optimization:

1. Cleaning Agents and Parameters: Discuss the selection of appropriate cleaning agents, concentrations, temperatures, and contact times for efficient and effective vial cleaning.
2. Water Quality: Highlight the importance of using high-quality water, such as purified water or water for injection (WFI), in the vial washing process to avoid introducing contaminants.

B. Preventive Maintenance and Calibration:

1. Maintenance Schedule: Discuss the significance of implementing a preventive maintenance schedule to ensure the proper functioning of vial washing machines and minimize downtime.
2. Calibration and Performance Checks: Explain the importance of regular calibration and performance checks of critical parameters, such as water pressure, temperature, and drying air flow, to maintain consistent cleaning performance.

C. Personnel Training and Good Documentation Practices:

1. Training Programs: Highlight the importance of comprehensive training programs for operators and maintenance personnel to ensure proper operation, maintenance, and troubleshooting of vial washing machines.
2. Documentation Practices: Discuss the importance of maintaining accurate and up-to-date documentation, including standard operating procedures (SOPs), equipment logs, and cleaning validation records.

V. Conclusion

Vial washing machines are vital equipment in the pharmaceutical industry, ensuring the cleanliness and integrity of vials used in sterile drug packaging. These machines remove contaminants and residues, complying with regulatory standards, and contributing to product safety and quality. By understanding the importance of vial washing machines, their key features, validation considerations, and best practices for optimal performance, pharmaceutical manufacturers can streamline their packaging processes, enhance efficiency, and uphold the highest standards of cleanliness and compliance. Vial washing machines play a critical role in maintaining the integrity of pharmaceutical products, safeguarding patient health, and ensuring the success of the pharmaceutical industry as a whole.

VIAL WASHING MACHINE PQ PROTOCOL

TABLE OF CONTENTS

• Description
• Protocol approval
• Overview
• Purpose
• Scope
• Responsibilities and identification of the execution team
• Pre-Validation requirement
• Equipment description
• Validation procedure
• Sampling plan and Acceptance criteria
• Validation report
• Validation approval
• Observed deviation
• List of attachment
• Re-qualification Criteria

Protocol Approval: The signing of this approval page of the 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 a vial washing machine, which is used for washing different size glass vials of size 10 ml, 15 ml, 20 ml, 50 ml, and 100 ml having eight Different washing stages including 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 the vial washing machine to:

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

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

RESPONSIBILITIES AND IDENTIFICATION OF EXECUTION TEAM 

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

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.

Pre – Validation Requirements

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

• Sodium Chloride.
• Activated Charcoal Powder
• Bacterial endotoxin
• Liquid Particle Counter
• Weighing balance
• 10 ml molded 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 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
• 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 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 an inverted position by a series of jets, 25 pockets are used for washing 10, 15, and 20 ml vials. 12 Pockets are used for washing 50 and 100-ml Vials.  The maximum rated capacity of the machine is 18000 vials per hour in case of 25 pockets, and 6000 vials per hour in case of 12 pockets. In feed lifter carries the vials into the pockets & moves on a chain horizontal conveyor with vertical up spray nozzles, entering the vials co-axially and injecting circulated purified water, purified water, water for injection & compressed air at a 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 the loading of vials on an infeed platform and pushing them manually to the conveyor. The conveyor carries the vials on the infeed lifter with the help of a loosening device. The infeed lifter carries the vials into the pockets.

Vial Washing Zone: The vials are set up in the pockets after feeding. The index channel of vials carries forward at a time. During each stoppage of this movement, the nozzle manifold raises up and nozzles enter the mouth of each vial. 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. The standard washing cycle occurs as per the 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 the support of the vials guide plate and come out of the outfeed lifter. The outfeed lifter comes down and the pusher pushes the vials on the outfeed platform and conveyor

Outfeed Conveyor: The outfeed conveyor is chain linked with a mesh conveyor made up of stainless steel 316 which conveys the washed vials from the unloading unit to the infeed of the sterilizing tunnel. The speed of the 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 the vials washing machine:

Table-1

 Table-2

Table 3:A vial spiked for each test

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

Chemical Decontamination Study: The following tests shall be carried out to establish the efficiency of the vial washing machine to remove 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 of 200 ml.

Spiking of vials with chemical: Spiked the no. of vials as per Table 3 for the test.

• Dispense 1.0 ml of the sodium chloride solution to the 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 chemical 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 sizes.
• Set up a vial washing machine as per procedure. Fix the Water Jet height, Machine Speed, and Water tank refill time properly.
• Switch “ON” The Vial Washing Machine and operate it as per SOP.
• Allow the machine to run & place 25 vials of spiked & marked vials in between the other vials while the machine is running as per the conditions as defined.
• Allow the spiked / challenge vials to go through the washing cycle.
• Collect the washed (spiked) vials after completion of the washing cycle. Separate the marked vials
• Transfer the collected vial to the 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 the previous section.

Acceptance Criteria: Sodium chloride content in spiked and washed vials should not be more than 2 ppm.

Results: The result shall be recorded in the Text Datasheet.

Particulate Matter decontamination study

Objective: The objective of this test is to determine whether 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 Table 3 for the test.

• Dispense 1.0 ml of the charcoal solution to the 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.

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 sizes.
• 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 it as per SOP.
• Allow the machine to run & place 25 vials of spiked & marked vials in between the other vials while the machine is running.
• Allow the spiked / challenge vials to go through the washing cycle.
• Collect the washed (spiked) vials after the completion of the washing cycle. Separate the marked vials & store them under LAF to avoid any contamination from the environment.
• Transfer the collected vial to the 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 particle count in the spiked washed vials by 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 the text Data Sheet.

Endotoxin decontamination study

Spiking of vials with endotoxin

• Spiked the no. of vials as per table 3 for the 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 the solution 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 spiked containers (Assumed potency based on 100% recovery = 1000 EU/ml.
• Sonicate the container for 10-15 minutes

Dilute the reconstituted container as follows :

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

Calculate by the following formula:

Recovery = Reciprocal of the 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 sizes.
• Set up a vial washing machine as per procedure. Fix the Water Jet height, Machine Speed, and Water tank refill time properly.
• Switch “ON” The Vial Washing Machine and operate it as per SOP.
• Allow the machine to run & place 10 vials of spiked & marked vials in between the other vials while the machine is running.
• Allow the spiked / challenge vials to go through the washing cycle.
• Collect the washed (spiked) vials after completion of the washing cycle. Separate the marked vials
• Transfer the collected vial to the laboratory for testing.
• Determine the endotoxin content in the washed spiked containers.
• Put 1 ml of LRW in the washed vial to obtain 10 EU/ml and perform the test as per the dilution given below:

• Perform the LAL Gel Clot test from dilution no. (1), (2) and (3).
• Calculation: Calculate the log reduction by the 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

Sampling Plan and Acceptance Criteria:

Stage 1: WFI quality

Sampling Criteria: Visual Check and LBPC

Sample quantity: Around 100 ml

Stage 2: Compressed air quality (Bubbling of compressed air in 100 ml water)

Sampling Criteria: Visual Check and LBPC

Sample quantity: Around 100 ml

Acceptance Criteria

1. Shall be free of visible particles
2. ≥10 µ =NMT 60/ml & ≥25 µ NMT 6/ml

Stage 3:  After Vial washing

Sample quantity: Sodium chloride spiked vials

Acceptance Criteria : Removal of chemical matter

• 25 spiked vials for 10, 15 & 20 ml vials
• 12 spiked vials for 50 & 100 ml vials

Acceptance Criteria: Less than 2 ppm

Stage 4:  After Vial washing

Sample quantity: Charcoal spiked vials

Acceptance Criteria

1. Shall be free of visible particles
2. ≥10 µ =NMT 60/ml & ≥25 µ NMT 6/ml

Stage: After Vial washing

Sample quantity: Bacterial Endotoxin spiked vials

Acceptance Criteria: Endotoxin decontamination study – 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/exhibits that were completed at the time of the 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

Machine Speed (Vials/mins.)
Compressed Air Blowing Time (Seconds)
Re-circulating purified water wash time (Seconds)
Purified water wash time (Seconds)
Water For Injection Wash Time (Seconds)

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.

Subvisible particles :
>10 µ: Not more than 60 / ml
> 25 µ: Not more than 6 / ml

Parameters
Machine Speed (Vials/mins.)
Compressed Air Blowing Time (Seconds)
Re-circulating purified water wash time (Seconds)
Purified water wash time (Seconds)
Water For Injection Wash Time (Seconds)

Test Data Sheet # 3 : Removal of Glass Fragments

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

Parameters
Machine Speed (Vials/mins.)
Compressed Air Blowing Time (Seconds)
Re-circulating purified water wash time (Seconds)
Purified water wash time (Seconds)
Water For Injection Wash Time (Seconds)

Test Data Sheet # 4: Residual Water Determination in Washed Vials

Parameters
Machine Speed (Vials/mins.)
Compressed Air Blowing Time (Seconds)
Re-circulating purified water wash time (Seconds)
Purified water wash time (Seconds)
Water For Injection Wash Time (Seconds)

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

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