Aseptic isolation process
for filling and sealing of pre filled syringes

Traditional aseptic processes mainly use PVC curtains and walls for isolation. Clean air is supplied and recirculated through an HVAC system, and a laminar flow is added around the A-grade area for protection. Product protection relies on limited pressure differentials. This process is suitable for aseptic production and manufacturing.

Subsequently, Restricted Access Barrier Systems (RABS) were developed, which provide more comprehensive isolation of the environment and personnel compared to traditional aseptic processes, and can be intervened and operated through gloves. RABS can be categorized as open (O-RABS) or closed (C-RABS), and can be further classified as active or passive based on the clean air supply method.

Passive O-RABS mainly use glass doors as the main means of isolation. Clean air is supplied and recirculated through HVAC, and it is connected to the environment. Operation is mainly carried out through RABS and doors, and material transfer is done through small doors or buffer airlocks. The RABS maintains limited positive pressure during operation and is suitable for aseptic production and manufacturing.

Active O-RABS, compared to passive O-RABS, use independent fan units for the supply and recirculation of clean air. This allows for easier control of airflow velocity, maintaining relative positive pressure in the RABS during operation.

Passive C-RABS systems use glass doors and walls as the main means of isolation, with the glass doors connecting to the equipment surface to separate the aseptic area from the clean area. Clean air is supplied and recirculated through HVAC, and operation is mainly done through RABS gloves. Material transfer is done through mouse holes, RTP interfaces, or buffer airlocks. The RABS maintains limited positive pressure during operation and is suitable for the protection of closed products.

Active C-RABS systems use a closed modular design, with the supply and exhaust of clean air forming a closed recirculation system, isolating the aseptic area from the cleanroom. Different areas can be maintained with varying levels of positive or negative pressure. Clean air supply in the active system is achieved through independent fan units, and operation is done through sealed gloves. Material transfer is done through mouse holes, RTP interfaces, or buffer airlocks. This system is suitable for injection products, especially powder filling.

Compared to RABS systems, isolators provide safer and more reliable aseptic process operations and isolation performance. Isolators provide a closed environment with measurable pressure, using validated and monitored disinfection modes to consistently deliver sterilizing agents. Aseptic operations are conducted under positive pressure inside the isolator, making it the preferred filling method for products with cytotoxic properties.

Process design in production refers to the methods and processes used by pharmaceutical manufacturers to add value to raw materials and semi-finished products, ultimately turning them into finished pharmaceutical products. Pre-filled syringe production lines are an improvement over traditional aseptic production lines, focusing primarily on the filling system. The process flow of pre-filled syringe production lines includes pre-cleaning and disinfection of pre-filled syringes, disinfection of outer bags, tearing of outer bags, removal of nest trays, tearing of inner packaging, filling and stoppering, and placement of syringes in nest trays.

The improvement in pre-filled syringe production lines mainly lies in the filling system, using aseptic syringes for sterile filling and improving auxiliary systems. Depending on the specific process flow, different system designs can be used, such as O-RABS systems, C-RABS systems, and isolator systems. The use of terminal sterilizers allows some products to be filled in a final sterile form, reducing the background requirements of the filling area.

With the widespread application of pre-filled syringes in biological or vaccine products, in addition to ensuring that the products are kept away from environmental contamination, the safety of operators also needs to be guaranteed, especially for live virus vaccines. Isolators have stronger sealing and reliable aseptic process operations and isolation performance compared to RABS systems, and have lower requirements for the background environment.

In summary, aseptic isolation processes and production process designs are measures taken to reduce the risk of microbial contamination in the production of aseptic products. By designing the process flow reasonably and introducing appropriate isolation equipment, product sterility can be effectively protected, and operator safety can be ensured. The application of these technical measures is of great significance for improving the quality and safety of pharmaceutical production.