Injectable are one of the highly critical products in the pharmaceutical industry and have more impact than non-injectable or liquid products.  They are sterile drug products directly injected into the human body for dosing purposes, and for this purpose. To ensure product safety they are subject to strict sterility and sterilization processes typically more than that of liquid dose. 

Among many, sterilization is a process that is carried out during the manufacturing process of injectable products at various stages; some examples include empty ampoules/vials, terminal sterilization, and the like. The depyrogenation tunnel is slightly older, yet it is an innovative way of sterilizing empty ampoules/vials before the product fills them.

A depyrogenation tunnel is commonly part of a combined washing-sterilization-filling line for producing the filled ampoules or vials of injectable products. A depyrogenation tunnel can be used for both ampoules and vials.

What is a depyrogenation Tunnel?

A depyrogenation tunnel ensures sterilization and depyrogenation of glass containers used in injectable products using high-temperature air at around 300?C. The temperature in the tunnel is controlled at a set point. The glass containers continuously travel on a conveyor belt as they are sterilized and are discharge at clean side at the input fed of filling machine.

The temperature is gradually increased up to the set point, and after sterilization, the temperature is cooled down for easy handling by humans. The different temperatures are generated simultaneously at various tunnel zones, and they perform their function when glass containers pass through these regions. 

The glass containers enter from one side enter, pass through different temperature zones, and are discharged from the machine. The inside of the tunnel is air-tight so that outside air does not penetrate the tunnel and inside air does not leak to the outside environment. 

The depyrogenation tunnel is connected to the washing and filling machine – the washed containers enter the tunnel, while sterilized containers enter the filling machine. 

What is the purpose of a depyrogenation tunnel?

The primary purpose of a depyrogenation or sterilization tunnel is to eliminate all pyrogenic substances involving high temperatures using dry air.

Endotoxins pose a risk to sterile products administered through intravenous or intrathecal, and the sterile manufacturing process includes measures to reduce endotoxins as a part of safety and quality enhancement procedures. Additionally, during the fill/finish process, glass containers (used to fill product in it) must be dehydrogenated using dry heat at high temperatures. The traditional method to perform this purpose is an Oven or Dry Heat Sterilizer – DHS, and the newest method is a depyrogenation tunnel. 

Depyrogenation by tunnel is a quality test to prevent endotoxins from becoming part of medicine. Because it is possible that glass containers could contain these endotoxins that could result in immunological responses from the human body, causing infection. 

Construction of depyrogenation tunnel

Some critical parts of the tunnel include the following

Body

The body of the depyrogenation tunnel is made of stainless steel. The glass containers' contact parts are made up of SS 316L to prevent affecting the physical characteristics of glass containers. Non-contact parts are made of SS304. 

The body encloses all the critical sections, such as electrical and mechanical. All cycles occur in an enclosed body structure.

Belt

A metallic belt is installed inside the tunnel to transfer glass containers from pre-heating to heating to cooling zone. The belt moves at a defined speed. The belt speech d depends on the time required for glass containers to be exposed to temperature values. 

The speed of the belt is adjustable and can be increased/decreased depending on the product requirements. 

Heater

Heaters are responsible for generating the required temperature, and their capacity & quantity depend on the tunnel size, temperature required, and output capacity – a big tunnel will need more heaters, whereas a small tunnel will require a smaller number of heaters. 

They are installed inside the tunnel in such a position that air generated by the blower passes through it to increase the blowing air temperature. Heaters are controlled automatically through the centralized controller that regulates them to maintain the desired temperature. 

A temperature sensor senses temperature; the temperature difference is compensated by generating more heat from heaters. 

Filters

Filters are installed in the tunnel to filter out particles, microorganisms, and foreign particles. The main aim of filters is to protect glass containers because, inside the tunnel, glass containers come in direct contact with the air. If filtration is not provided, the air will contaminate the glass containers. 

The type of filter used in the tunnel is called HEPA filter and is installed directly above the belt on which glass containers move from one zone to another. The efficiency of HEPA filters is around 99.99% for 0.3μm particles. 

High-temperature HEPA filters are used in depyrogenation tunnels to prevent damage to HEPA filters due to high temperatures. 

Blower

The blower is a component that generates a high volume of air, which then blows in the entire tunnel and provides the required heating requirements. The air passes through the air to increase its temperature, and after it is blown to relevant zones or areas. 

The blower is driven by a motor, which in turn is operated through a Variable Frequency Drive – VFD. It takes input from the central controller to start/stop and increase/decrease the blower speed.

The blower(motor) is operated automatically through a central controller. The volume of air generated through the blower depends on the system requirements. An airflow sensor continuously senses the airflow and compensates for the required error. 

Zones of depyrogenation tunnel

The depyrogenation tunnel is technically divided into three zones designed to perform specific functions, and this is also the entire working of the tunnel. Let's elaborate on the three zones of the depyrogenation tunnel. 

The three zones of the depyrogenation tunnel are 

? Pre-Heating zone

? Sterilization zone

? Cooling Zone

Pre-Heating Zone

Also called the Infeed Zone, it is the first section of the tunnel when glass containers enter the tunnel.  It contains a laminar airflow that prevents foreign particles or objects from entering the tunnel. 

This zone pre-heats glass containers at a temperature lower than the temperature of the heating zone to prepare glass containers for high temperatures. The containers remain in this zone for a specified time defined by the speed of the belt, which is pre-calculated to match the exact time required for glass containers to stay in the pre-heating zone.

Heating Zone

The sterilization or heating zone is the section where the primary purpose of the tunnel is carried out. The temperature of the heating zone is the same as that the container requires to become dehydrogenated. 

The belt speed in the heating zone matches the time required for the glass containers to get exposed to temperatures. As with other zones, a laminar hot air passes through this zone to increase temperatures. 

Cooling Zone

The cooling zone is the last stage of the depyrogenation tunnel, and glass containers exit the tunnel. In this zone, low temperature air is blown to reduce the temperature at the inis section. Its purpose is to lower the glass container temperature, making it easy for humans to handle. 

After the cooling zone, glass containers are sent to the outfeed section for further processing. 

What sis the Temperature and time of depyrogenation tunnel

Temperature and time of heat in the depyrogenation tunnel are critical values selected according to the set standards. Otherwise, it will fail to serve the purpose of the tunnel. Additionally, tunnel temperature and time relationships are different from traditional DHS or ovens due to the difference in designs and operations of both types of equipment.

For a depyrogenation tunnel, the temperature is higher than that of a standard DHS or oven because in the tunnel, the dwell time is shorter, (items are exposed to heat for a shorter period) and temperature should be increased to kill all endotoxins

For a depyrogenation tunnel, an endotoxin reduction of 3 logs or 6 logs is acceptable, which would lead to the required sterility condition for the items. 

Based on the studies showing endotoxin reduction, the expected temperature in a depyrogenation tunnel is around 250^oC for about 30 minutes. It means that a tunnel's temperature in the heating zone must be 250^oC, and the conveyor bet's speed must be such that glass containers should remain in the heating zone for about 30 minutes. 

Some common concepts related to depyrogenation tunnel

There are some common concepts related to depyrogenation tunnel that affects their overall performance and include the following

Differential Pressure

Differential pressure is the difference in pressure between two different areas. A depyrogenation tunnel measures the pressure difference between the pre-heating & heating zone and the heating zone & cooling zone. Some tunnels include pressure differential between washing, sterilization, and filling areas. 

The differential pressure must be adjusted and set according to the manufacturer's specifications and should prevent air from entering from dirty areas and clean areas. 

Air Velocity

Air velocity is the amount of air flowing across different areas of the depyrogenation tunnel.  It must have a laminar airflow of 90 fpm or 28 m/min for efficient performance.

Particulate count

The particulate count is the number of particulates in a given enclosed area and is used to indicate the effectiveness of installed filters. It must be under range. Otherwise, the system should be improved before production starts.

The tunnel value of the depyrogenation tunnel must be 0.5 microns per cubic foot for the class 100 area and 0.5 microns per cubic foot.

About the Author:

Muhammad Asim Niazi

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.