Sterile isolator for PilotMill-6

Process:

The multi-chamber isolator is designed to guarantee a sterile environment for the micronization of up to 20kg of API with a PilotMill-6 spiral jet mill.

Process steps:

• Introduce material in the micronization chamber
• Run a decontamination cycle for the working chambers and a sterilization cycle for the micronization unit
• Open the bags and charge the feeder
• Micronize the API
• Collect and weigh the micronized API in the pack-off chamber at the bottom of the cyclone filter
• Remove the micronized API from the isolator through a continuous liner installed on a rapid transfer port

What are the issues?

• The API need to be handles in sterile conditions
• The isolator and the jet mill are classified as per ATEX directive (II 3GD)
• All components of the jet mill must be accessed inside the isolator for operations and maintenance
• The micronization unit can’t be decontaminated with the vaporized hydrogen peroxide system of the isolator
• The micronization process gas must be sterile

Benefits of FPS Solution:

• FPS provides both the containment system and the micronization unit
• All components of the micronization units are designed to be connected to the Sterilization In Place line
• Decontamination cycles specifically developed to guarantee an aseptic environment in the working chambers
• The separation cyclone filter is installed in a dedicated chamber where it can be easily accessed through the gloves
• A separated pack-off chamber is installed underneath the separation cyclone for product weight and removal from the isolator
• Rapid transfer ports are provided for material introduction and product removal without breaching the sterility conditions

Description of FPS custom solution:

The rigid wall isolator is composed of a micronization chamber where the volumetric feeding unit and the spiral jet mill are installed. The product is introduced through a rapid transfer port. Before starting the operations, a decontamination cycle is executed to guarantee an aseptic environment inside the chambers. The micronization unit is connected to the SIP line for sterilization of the product contact lines. When the sterilization and decontamination cycles are completed, the product bags are opened and the API is fed in the feeder. The micronized product is collected at the bottom of the separation cyclone, in a dedicated pack-off chamber, where a weight scale is provided. The API bags are then removed from the isolator through a continuous liner installed on  a rapid transfer port on the side of the pack-off chamber. The product-gas separation filter is installed in a dedicated chamber to be easily accessed by the operators.

Custom solution highlights:

• The volumetric feeder is PED rated to be connected to the SIP line. Special caps are provided to be connected to the top and the bottom of the separation cyclone when the SIP cycle is executed
• The process gas line are sterilized during the initial SIP cycle. Special HEPA filters are provided to guarantee the sterility of the process gas during operations
• Glove bars are provided to prevent operators from accessing all chambers when the SIP cycle is being executed. The separation cyclone chamber can’t be accessed also during operations because of the pneumatic filter declogging device
• Hooks are provided inside the micronization chamber to hang the product bags for optimal decontamination
• A weight scale is installed in the pack-off chamber and a butterfly valve is installed for manual dispensing of the micronized product
• The continuous liner of the pack-off chamber is installed on a rapid transfer port to protect sterility inside the chamber
• The micronization unit is automated and controlled through the HMI of the isolator