Check list for the Integration of Lyophilization and Aseptic Filling Equipment

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