RTP extracted from the 2023 version of GMP Guidelines - Sterile Preparations (Volume 1) (2)
GI/D sterile preparations undergo corresponding disinfection/sterilization treatments and are transmitted through equipment and facilities such as transfer chambers, airlocks, RTP, etc. There are three common types of transmission equipment and facilities with sterilization/decontamination functions.
The de heating tunnel oven is used for continuous sterilization/de heating of packaging materials such as bulk penicillin bottles, and is connected to filling equipment to enter an A-level environment.
Electron beam sterilization system (E-Beam) and pulse strong light sterilization system are used for continuous sterilization of surfaces of items that are intolerant to high temperatures, such as pre filled slot box packaging surfaces, and are connected to subsequent unpacking equipment.
Vaporize hydrogen peroxide to contaminate the transfer chamber, which is used to remove contamination from the surface of smooth, regular non-contact product components or sterilized packaged materials before transferring them into the core area. This type of transmission cabin is usually docked with the core area. A. The Rapid Transfer Interface (RTP) is a closed and sterile docking interface structure designed to control extremely low contamination risks, allowing two sterile environments to connect and achieve aseptic transfer. Figure 17-6 shows a schematic diagram of using RTP to transfer items into the isolator. A set of RTP that can be used for docking is divided into alpha valve and beta valve. Generally, the beta valve is installed on the wall of the barrier system cabin, while the alpha valve is installed on various containers that need to be transmitted through it, such as stainless steel barrels, soft bags, etc. By locking the docking of the alpha and beta valves, open the locked alpha and beta valves from one side of the isolation system to connect the container and the interior of the isolation system. Use gloves to transfer items to the isolation system.
RTP applications mainly have the following forms:
Packaging of ready to use consumables with RTP pre sterile, such as washable and non extinguishing stoppers with RTP interface, culture media, etc; Figure 17-6 Schematic diagram of RTP usage
Containers with RTP sterilization/decontamination capabilities, after sterilization/decontamination, are connected to the RTP interface in the core area for material transfer. For example, vaporization of hydrogen peroxide with RTP to contaminate the transfer chamber; Barrel with RTP for moist heat sterilization; Rubber stopper cleaning and sterilization system with RTP, etc;
A barrier system with RTP interface is configured in front of the sterilization cabinet to transfer sterile items into the core production area through barrels with RTP interface. In addition, there is a continuous bag integrated with RTP interface, which is generally used for the transfer of items, such as waste, isolation devices, and culture dishes sampled by 617 17 barrier technology on the background environment side inside the isolator.
According to its design principles, the use of RTP requires regular testing of its integrity to ensure good sealing performance. Corresponding seals also need to be inspected regularly, and their replacement cycle should be evaluated based on the application.
B. Transfer of sterile drugs and clean pipeline docking: Generally, buffer tanks are installed inside the barrier system, and clean pipeline interfaces are welded and docked on the barrier system barrier through pipelines with CIP/SIP functions. This design should be noted that when using an isolator to vaporize hydrogen peroxide for decontamination, local high temperatures on the surfaces of pipelines and buffer tanks CIP/SIP can affect decontamination, and should be avoided during process scheduling. ·Using RTP bags or barrels for docking: Place the tubing, needles, and other components used for drug docking into RTP barrels or customized bags with RTP, pre sterilize them, and dock them with barrier systems before transferring them to the core area for use.
The sterile transfer interface for disposable applications is a docking method similar to the RTP principle, which can achieve sterile transfer of medication. C. When considering the transfer method of RTU (ready to use) ready to use needle packaging slot boxes, the first thing to do is to clarify whether to choose double-layer packaging or single-layer packaging slot boxes. Before entering the core production area after unpacking, the surface of the packaging material of the single-layer packaging trough box needs to be disinfected/sterilized, generally requiring a decrease of 6 logarithmic values in the biological indicator. There are various methods in the industry, such as E-beam, strong light irradiation, vaporization of hydrogen peroxide to remove pollution, and NO ₂. Among them, E-beam and strong light irradiation can meet the continuous pollution reduction needs of high-speed production lines. By using conventional methods such as vaporized hydrogen peroxide to remove pollution and NO ₂, batch surface disinfection is carried out, which is suitable for the production of small and medium-sized batches. At present, single-layer packaging trough boxes are also used in the industry for non-contact transfer after unpacking, but corresponding consideration needs to be given to surface disinfection or decontamination of the packaging surface during the transfer process. When using a double layered packaging box, it is possible to consider choosing a contactless unpacking process, which can be achieved manually or automatically. However, corresponding pollution control measures and verification are needed to prove that there is no risk of contamination of small bottles or syringes during this process.