Transfer between two containers usually is achieved with a valve-to-valve connection, followed by steam sterilization of the space between the two valves. This procedure is well established, mostly in the context of large stainless steel equipment, and takes at least two hours, including a cooling down period. In addition, it requires clean steam, the evacuation of condensates, and a system of recording the sensed parameters.

This technique is not especially attractive for applications that involve disposable equipment or more-frequent connections of multiple, smaller containers. Blood banks typically perform these types of transfers. In the early 1980s, the technique of flame-sterilizing the tubing ends under laminar flow was replaced by hot-plate welding (also called "tube fusion"). This technique is suitable for small-diameter thermoplastic tubing made of polyvinyl chloride, thermoplastic elastomer, or other materials.

The addition of barriers and isolators around critical aseptic processes created a new environment for aseptic transfer. In such systems, it clearly is preferable to leave containers such as bulk containers outside the protected environment. Sterile liquid must then cross the wall through a connection mechanism. It is quite difficult to introduce the container in the protected environment because the container's exterior cannot be thoroughly sterilized.

The first transfer system also originated in the context of large, infrequent transfers involving the well known rapid-transfer port (RTP) transfer container from La Calhène (Vendôme, France). It consists of steam-sterilizing tubing in a stainless steel transfer container docked to the barrier wall, unfolding the tubing, and introducing it into the barrier or isolator. In some cases, it is possible to sterilize the preassembled system (e.g., the RTP container and the empty tank), but in many cases, the classic valve-to-valve steam sterilization is still necessary.

Because of the increased use of flexible pouches, Stedim (Aubagne, France) introduced its rapid aseptic fluid transfer (RAFT) system, which connects to pouches using a Biosafe port. The stainless steel container described previously is replaced by a plastic bag equipped with a disposable flange that is docked to an RTP port. The disposable part is attached beforehand to the flexible pouch and gamma sterilized with it as a closed system. Unfortunately, the docking system does not allow multiple uses because reclosing and reopening is not feasible unless multiple flanges are attached to the bag.

This article describes a new approach for aseptic fluid transfer: the Sartorius Aseptic Rapid Transfer (SART) connection technology. The system incorporates a SART port and a disposable Gammasart aseptic transfer device (ATD) connector and was developed to provide a high-quality aseptic connection and simplify passage through a wall. The authors will discuss SART's product-qualification results to show that this technology and its various components meet the stringent pharmacopeial product-qualification requirements.

Principle of the technology

The SART technology was developed for the aseptic transfer of liquid through a barrier or any separating wall. The system has the following features:

• a port of minimal size that is fixed on the separation (in many isolators, wall space is restricted);
• an RTP system comprising four matching "V-shaped profiles," two of which have seals at the tip. The four components' small size enables accurate matching of the shaped profiles.
• an incoming-liquid tube that does not rotate or twist during docking in the port;
• a mechanical-interlock system that prevents accidental opening of the port when the connector is absent;
• a disposable connector to be attached to the external container's tubing. The connector should be small to accommodate small containers.
• rigid plastic not subject to pinholes that provides sterility protection for the connecting inner tubing;
• a leak-test limit that meets standards comparable with those in place for the closure integrity of the attached container. All connectors are tested individually during the manufacturing process.
• a maximum of five reclosing and reopening cycles to withstand the partial emptying of a container and to provide flexibility if operation is interrupted;
• compatibility with rigid liquid containers (e.g., stainless steel, glass, plastic) and flexible container (e.g., pouches);
• simplicity and low cost that enable multiple volumes or a small volume of liquid to be transferred.

• The Gammasart ATD disposable connector is introduced into the port and secured with two clamping devices on the external port (see Figure 3a).
• The internal port's clamping system firmly holds the connector cover inside. The objective is to contain all the connector cover's exposed outer parts inside the port (see Figure 3b). The internal port is sanitized in a clean environment in parallel with the rest of the main equipment (e.g., with a vaporized hydrogen peroxide cycle).
• The port is opened by rotating the internal port (see Figure 3c).
• The tubing (e.g., silicone) is placed in the contained area on the connector's sterile tubing (see Figure 3d).