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.Disposable connection devices have been introduced for applications requiring connections between two tubes. Kleenpak from Pall (East Hills, NY), DAC from BioQuate (Clearwater, FL), and Lynx S2S from Millipore (Billerica, MA) are presterilized disposable systems that reportedly are safe for low-classification or unclassified environments.
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:
Both the connector body and the connector cover are made of polybutylene terephthalate and molded in a classified environment. A seal made of Santoprene (Advanced Elastomer System, Newport, UK) thermoplastic elastomer is overmolded on the connector cover. This seal ensures the quality of the system's closure integrity.
The connector device must be subjected to at least 25 kGy of gamma irradiation to ensure its sterility. The device was validated at 45 kGy to ensure that the entire radiation range was validated. The connector should be irradiated alone if it will be attached to a nonirradiated container such as a stainless steel vessel. If it will be used with a stainless steel vessel, the connector can be sterilized by autoclaving. High- and low-pressure cycles should be used to push water vapor into the connector and dry it. Preliminary tests performed with 106 biological indicators located in the assembled connector have shown total kill. If the connector will be used with containers such as plastic pouches, it should be irradiated after assembly.