Design of Rapid Transfer Ports in Aseptic Isolators

The transfer of materials into confined manufacturing spaces is a very critical operation, especially in the case of an aseptic environment. Depending on the manufacturing step, the failure of containment might have detrimental consequences, from the disruption of the working schedule (repeat preparation activities) to the rejection of the ongoing batch and impact to the sterility assurance of the previous manufacture. This article will provide an overview of the technology systems that allow passage of materials through the sterile barrier without breaking it and some useful tips to design the rapid transfer port.

What is a rapid transfer port?

The rapid transfer port (RTP) is a 2-component system that allows transferring materials between two separated contained areas, in a sterile way without incurring in contamination from the surrounding environment.


The rapid transfer ports are composed of two main parts:

  • Alpha part: this part is anchored on the wall of the fixed contained area (for example the isolator wall). The Alpha part is equipped with a door that communicates both with the contained area (internal, sterile side) and with the surrounding environment (external, non-sterile side).

  • Beta part: this part is embedded in a mobile container. The Beta part is equipped with a door that communicates both with the container area (internal, sterile side) and with the surrounding environment (external, non-sterile side).

Before the transfer of material, the Beta part is docked into the Alpha part. The rotation of the Beta part allows the two doors to connect into a single mobile (Alpha/Beta) port. The ‘non-sterile’ side of the doors is therefore masked to protect the sterility of the transfer. Once the port is opened, the two sterile chambers communicate with each other and the transfer can take place.



Interlock features of the rapid transfer port

Due to the criticality of the operation and the detrimental consequences of sterile barrier failure, the rapid transfer port is endowed with an interlock system that prevents errors. The interlock system works in the following way:

  • The Alpha door cannot be opened if a Beta system is not present or is not perfectly connected. This ensures that the sterile environment of the isolator is protected.

  • Vice versa, the Beta door cannot be opened if the Alpha system is not present or is not perfectly connected. This ensures that the sterile environment of the container is protected.

  • The Beta container cannot be disconnected from the Alpha part unless the alpha/beta port is closed so that the two environments are isolated from the surrounding environment.

What is it used for?

In general, rapid transfer ports can be used for two main purposes:


1. Bring materials inside the confined space. These materials are transferred to support the process, for example:

  • Replenishment of components to sustain the process

  • Supply of spare sterilized mechanical parts to solve an issue with the processing equipment

2. Bring materials outside the confined space, for example:

  • Removal of waste materials from the process.

  • Remove items that are not anymore needed for the process.

Types of rapid transfer ports

While the Alpha part is anchored on a fixed surface (isolator wall), the Beta part can be embedded into different systems according to the nature of the transfer to be performed:


Bags

They are sterilized via gamma irradiation and are used to transfer small quantities of components into the isolator (e.g. stoppers, caps). They can also be used to remove small quantities of waste materials from the isolator (e.g. wraps, rejected glassware, etc…).

Process vessels

Thermally sterilized stainless steel vessels that are used to transfer larger quantities of components into the isolator (e.g. stoppers, caps).

Canisters:

Thermally sterilized stainless steel containers that are used to transfer smaller components, spare parts, and tools into the isolator.

Mobile isolators

Flexible wall isolators that are sanitized via VHP (Vapor Hydrogen Peroxide) and are used to transfer larger quantities of components and spare parts to the processing isolator. They can also be used to remove larger quantities of materials (e.g. waste, finished product, mobile equipment, etc…).


Design of a Rapid transfer port

When a rapid transfer port is designed, several aspects need to be considered to meet the user’s needs and achieve good accessibility and ergonomics.


Size of the Rapid transfer port

The size of the RTP will depend on the nature of the material to be transferred and the kind of systems that need to be docked to the alpha door. Most common RTPs have a diameter of 190 or 270 millimeters. Smaller and larger sizes of RTPs can also be found on the market (110 and 360 millimeters of diameter), but they are less common.


Type of opening

The rapid transfer port can be opened in two ways:

  1. From the inside: Once the alpha and beta parts are connected, the port is opened from the inside of the isolator by one operator using the isolator glove. This is the easiest design to implement, but the opening of such systems might carry some sterility risk because of the manual intervention inside the isolator.

  2. From the outside: Once the alpha and beta parts are connected, the port is opened by operating a level located on the external side of the isolator wall. This design is more complex, but it is safer for the sterility assurance of the isolator barrier as no internal manipulation is required.

Positioning of the alpha part

The RTP needs to be reachable safely and ergonomically, per the nature of the transfer. If the rapid transfer is opened from the inside, the operator should not reach over processing components to operate the port (risk of particle contamination). A mock-up exercise is highly recommended to avoid design errors.


Height of the alpha part on the isolator wall

The RTP needs to be reachable by the system that performs the docking of the beta container. In case the docking of beta containers is performed manually by an operator, careful consideration needs to be made also on the weight of the beta container and its content. In case the docking of beta containers (large stainless steel vessels) is performed by a robotic arm, it is important to consider the space available to avoid clashes with the isolator and the ceiling.


Inclination of the alpha part on the isolator wall

If the rapid transfer port is used to transfer components inside the isolator relying on gravity (even if partially), the alpha part needs to be installed on an inclined wall. The inclination of the isolator wall where the alpha part is installed will depend on the capacity of the components to flow during the transfer.


Compatibility of other beta systems used in the plant

If the alpha part installed in the isolator needs to interact with beta systems that are already in use within the plant, it is important to choose an alpha part that is compatible with them (brand, model). Harmonization of the RTP systems can provide very good flexibility inside the production area.


Choice of right features.

  1. Interlock systems: They provide robustness of the transfer process.

  2. Protection of the “Ring Of Concern” (ROC). The ROC is a very thin line located on the internal side of the RTP for which a small possibility of contamination exchange remains. This is due to engineering tolerances, non-ideal nature of the seals, and potential micro-wear of usage. The ROC can be ‘’bridged’’ with pre-sterilized systems of different design (e.g. slide, funnel, tube) to avoid those items which are transferred into the isolator to get in contact with this line.

  3. Support to sustain beta systems. If the beta system is not rigid (like a metal container or a vessel), but it is a bag or a flexible tunnel leading to a transfer isolator, a supporting structure needs to be designed to sustain it so that damage and containment breakage can be avoided.

Conclusion

Rapid transfer ports are flexible and powerful tools that can sustain and protect the process inside an aseptic isolator. Due to the criticality of such systems, design errors can be very expensive. The ‘first-time-right’ approach to design a rapid transfer port includes a deep knowledge of the systems available on the market, a careful assessment of the user’s needs, and an adequate mock-up exercise challenging the ergonomics of the system.


Blog by Daniele Vellei

References

  • 1. Mounier, C. and Guilmet, C., Rapid transfer port systems – a comparative study, Clean Air and Containment Review

  • 2. Dufour, C. and Guilmet, C., “Ensuring Ergonomic Design in Sterile Transfer Ports”. Pharmaceutical Technology e-Newsletter


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