On April 12, 2020, a new drug declared by Sinopharm, novel coronavirus inactivated vaccine, was granted the clinical trial approval by the China National Medical Products Administration (NMPA). This is the world's first inactivated novel coronavirus vaccine that has been approved for clinical trials.
In this production line, Tofflon isolation technology is applied to the core process, including virus inoculation, dispensing, testing and culture, to provide a sterile environment for virus culture, dispensing and related operations, while guaranteeing the safety of operators and the environment at the same time. What are the technologies behind such an isolation system?
The isolator mainly consists of two spatial parts: a pass box, and a process operating chamber. The operating chamber is equipped with the interfaces required by the process, which can integrate the equipment or instruments required for the virus production process to form a “full station” system. Since all production operations are performed by operators wearing gloves, the isolator needs to be ergonomically designed to ensure that the operators have sufficient vision and space to operate. Mock-up test is often conducted before the isolator design. A wooden mold is fabricated to simulate the actual production space, and the critical dimensions of the isolator are designed during this phase. Currently, we are using visual reality (VR) technology to perform the digital design of equipment.
Equipped with an RTP (Rapid Thermal Processing) valve for material transfer, it can also be connected to the incubator equipped with RTP interface, and directly docked with the isolator to achieve continuous sealing in the whole culture process.The isolator chamber is controlled to negative pressure relative to the background environment. The discharge of air generated inside the isolator is discharged through the Bag-in/Bag-out (BIBO) mechanism with full supply and exhaust design. The inlet/exhaust air of the isolator is handled by an independent AHU to avoid cross-contamination with the background environment. BIBO is a mechanism that allows safe replacement of the filter. In the filter replacement process, the filter element with hazardous substances is enclosed in a bag to ensure that those substances will not be exposed to the background environment.
The leak rate of the isolator is strictly controlled. Before use, the system automatically performs a leak test. If the test fails, the system will not be able to initiate the production mode. The standard at which the isolator leak rate should be controlled can be calculated theoretically through the working conditions. The working condition model of the isolator is established, including the background room space, the air exchange rates, etc., to calculate the acceptable leak rate level.
Decontamination with Vapor Phase Hydrogen Peroxide (VPHP)
The built-in VPHP decontamination function can kill bacteria and viruses completely, with > 6log reduction in the biological indicators. We have tested and analyzed the most prominent factors affecting the sterilization effect and taken control measures in the sterilization development process to ensure the sterilization effect and reproducibility.
The high-performance hydrogen peroxide decomposition module can quickly degrade high-concentration hydrogen peroxide after decontamination to ensure that the concentration of hydrogen peroxide in the air exhausted to outside reaches a safe level.
The components and equipment installed in the isolator will be exposed to hydrogen peroxide. The hydrogen peroxide adsorption and tolerance of these materials will affect the sterilization effect and system reliability. Hence, long-term testing of various materials is required.
The isolator is not just a stainless-steel box, but an environment created by mechanical automation technology, materials science, microbiology, HVAC engineering, and other technologies. The concept with QbD (Quality by Design) as the basis of quality management will become the key to the application and development of isolation technology in the future.
Committed to providing professional technical services in the pharmaceutical industry, Tofflon will continuously strive for the early launch of the vaccine to market!