Sterile transfer of components and other materials from one confined space to another has always been a concern in pharmaceutical production. A solution lies with isolation technology, which allows materials to be transferred between two closed chambers, or for two chambers of like ambiance to be connected without altering their environmental and containment properties. These exchanges use rapid transfer port (RTP) systems installed on enclosures such as isolators or production lines. Getinge-La Calhene’s DPTE system, the precursor in sterile transfer systems, has become an industry standard.
|Figure 1. Operating principle of the DPTE sterile-transfer system.|
Designing an isolator should start with an analysis both of the end-user’s needs and of the manufacturing process requiring protection, particularly in terms of ergonomics and functional features. The ensuing design solution should be validated by the construction of a full-scale mock-up that is tested by the client and the end-users (see Figure 2). This design process, which has been applied for more than 30 years by Getinge-La Calhène, has provided substantial feedback on recurring ergonomics issues encountered by isolator users.
Feedback analysis shows that repetitive sterile transfers can become an issue for the end-user even though the system has been designed with simple operating principles for ease of use. Productivity has risen, with a consequent increase in the number of transfer operations, from one per day in the 1990's to as many as six per hour today. Clearly, the ergonomics and security issues posed by transfer systems are becoming a challenge to pharmaceutical production industries, and transfer system manufacturers will have to address these new concerns.
|Figure 2. Full-scale wooden mock-up of isolator with DPTE sterile-transfer system undergoing validation in Getinge-La Calhene’s workshop.|
Positioning and accessibility of the transfer system on the isolator wall are two major factors that are taken into account when improving working conditions for operators. The Beta part must be correctly positioned to connect to the Alpha part; this first phase of the sterile transfer operation often requires the Beta part to be lifted into position then connected by rotation onto the Alpha part. This may be particularly onerous when the Beta part is voluminous or heavy, or when the Alpha door is poorly positioned on the isolator wall; it may be too high or it may interfere with other items of equipment. Getinge-La Calhène's standard is to place sterile transfer ports 1.2 m high. In production units, footstools may be positioned to assist some end-users. New, 3D design tools will enable clients to experience working with their chosen layout and revise it as required to avoid interference with other equipment in use. Although reducing the weight of the Beta part is not an option in most cases, mechanical or hydraulic lifting systems may be installed for large containers and presterilized bags of components.
Once the container has been attached, the two doors (now a double door) are opened to connect both chambers. This is done manually via a manipulation system (glove and glove port) which must be positioned close to the sterile transfer port and within the operator’s reach (see Figure 3). The standard position for two glove ports, based on experience and user feedback, is to have a 600-mm distance between the ports.
|Figure 3. Manual manipulation for sterile transfer using a DPTE system, as viewed from inside the isolator.|
Some systems, in which the Alpha part is rotated and/or the system is automated, have been devised to solve some of the issues raised by the rotation of the Beta part and the manual intervention required to complete the connection. These systems are, at present, limited in use because of issues with maintenance, cleanability, and footprint. New concepts, however, are being designed and developed by isolator manufacturers to overcome these limitations.
Manipulation inside the isolator using glove ports raises the risk of breaking confinement, which could cause costly and lengthy delays or could contaminate the operator if toxic products are involved. The protective sleeves and gloves can hamper the user’s movements and may reduce their field of vision or break their concentration. In the future, however, mechanized systems will make glove ports next to sterile transfer systems obsolete.
Christophe Dufour is Transfer Systems product manager and Chloé Guilmet is Innovation manager, both with Getinge-La Calhène, Vendôme France.