Combining lyophilization and aseptic filling processes presents some design challenges, regardless of the integration of one or more equipment manufacturers. Some of the most intuitive points can be: working heights, transitions, vial conveying methods, control panels, utilities, maintenances access, alarms, pausing the line, etc… but there are some others to consider during the engineering phase:
Loading and unloading method (automatic, manual, pizza door, isolator integration)
Automatic loading system: row by row or flexible loading
Filling line filling speed for different vial sizes
Loading and unloading speeds for different vial sizes
Speed limitations due to vials stability in movement
Multiple or single lyophilizer loading and unloading system
Layout design: filling and capper location respect the lyophilizer
Layout considerations for future expansions with new lyophilizers
Lyophilizer unloading side
Single or multiple floor installation
Side mounted condenser
Vertical or horizontal condenser
Single skid or multiple skidded system
Determining conveying method for vials with liquid fill products: Bypassing lyophilizer for liquid filling
Integration of vial rejection system according to parameters: stopper position, missing stopper, color variation and sampling.
Lyophilizer CIP system
Bridge plate design for loading and unloading vials into the lyophilizer chamber
Provisions for the stoppering/shelf movement system ram assembly removal
Protection of vacuum system of contamination
Sterilization process (door seals, ram bellows, chamber and condenser)
Vent filter automatic or manual integrity test
Maintenance door side
Nitrogen blanketing (chamber and heat transfer fluid expansion tank)
Cold shelf loading
Integration of 100% headspace analysis to eliminate the risk of faulty vials
Maintenance access plan for all components
A specific section should be dedicated when the lyophilizer and the aseptic filling line are integrated with an isolator. In this case, it is important to underline a new list of points to consider.
Determine all gloved operations
Ergonomic considerations: Isolator mock-up
Isolators modules interconnection (mouse hole)
Sealing mechanism
Cleaning and decontamination
RTP ports
Filling stopper and capper feed bowls
Isolator sterilization (VHP)
Decontamination method (deactivation/biowaste system or process waste)
Air handling system and filtering system
Negative or positive pressure in isolator
Glove breach system
Isolator CIP
Inert atmosphere in isolator
Oxygen detection
Temperature control