Alternative Method: H˛O˛ more effective than Steam for Sterilisation of Freeze Dryers
Why?
The production of many pharmaceuticals requires sterile conditions. Therefore freeze dryers are equipped with SIP-Systems (Sterilisation-in-Place) working with steam, which means that the freeze dryers are exposed to different stresses and strains. During a freeze drying process the plants undergo pressures of 5 x 10-3 mbar up to 2,5 bar and temperatures ranging from -80 degree Celsius to 121 degree Celsius. Consequently the chamber, condenser and the related piping have to be built pressure proof making those freeze dryers much more expensive than the non-steam sterilisable executions.
The Alternative Technology GEA Lypohil has looked for a less expensive solution and found a way to sterilise freeze dryers at vacuum and at room temperature: The H
˛O
˛ –Sterilisation. We developed the VAPOVAC H
˛O
˛ –Steriliser which at the same time reduces the investment costs and furthermore the sterilisation cycle time. GEA Lyophil is the only manufacturer that offers this technology.
The H
˛O
˛ – Sterilisation is faster, safer, more efficient and more environmentally friendly than using steam. This technology is available for new plants and as a retrofit option to existing installations.
The VAPOVAC steriliser from GEA Lyophil uses VHP technology to sterilise equipment under vacuum at room temperature. Only a very small quantity of hydrogen peroxide is used to penetrate the freeze dryer vessels and all associated piping of the equipment. This method effectively eliminates all residual contamination. The freeze dryer is then fully vented, leaving no harmful residues.
The Process
This consists of five steps:
- Drying: The freeze drying chamber and condenser are dried before feeding hydrogen peroxide into the equipment.
- Evacuation: The freeze dryer is evacuated to a very low pressure.
- Injection: When the injection set pressure is reached, the H˛O˛ –solution is lead into the freeze dryer.
- Residence Time: After injection the residence time of the hydrogen peroxide is monitored and can be adjusted to ensure effective sterilisation.
- Removal of H˛O˛: After sterilisation, the hydrogen peroxide is completely and safely removed from the chamber.
Benefits
The VHP systems have many advantages over other sterilisation methods:
- Shorter sterilising times
- Lower investment costs
- No complex pressurized vessel needed
- Simplified piping systems
- Less energy consumption
- Longer service intervals
- No cooling needed before re-use.
Increased plant availability
The faster turnaround results in greater efficiency. The entire sterilization operation takes place at room temperature – meaning that sterilization can be performed in approximately 3 hours for an average production freeze dryer, compared with approximately 8 hours for steam sterilization. This allows the plant operators to increase productivity and make the whole system more efficient.
Low cost and kind to the environment
Very little energy is needed to operate the VAPOVAC steriliser, making it cheaper and, therefore, kinder to the environment. The chamber, condenser and connecting pipes are used at atmospheric pressure, which makes them less expensive and easier to install. The elimination of high-pressure hoses also makes the process safer and reduces operational wear – meaning that plant system lifetimes are extended.
Increased safety
The H˛O˛-system meets GAMP, cGMP, FDA, DIN, ISO and all other European and US codes.
The residence time of the hydrogen peroxide can be varied as the system is monitored and can be adjusted to ensure effective sterilisation. After sterilisation, the hydrogen peroxide is completely and safely removed from the chamber – the operator having to positively confirm to the control system that H˛O˛ evacuation has been achieved successfully in order to complete the sterilisation process.
Retrofit maximization and application support
Retrofitting a freeze dryer with the H˛O˛-sterilisation system offers operators a way to increase the lifespan of existing equipment. In addition to gaining a highly efficient and cost-effective method of sterilisation, GEA Lyophil can, at the same time, enhance plant performance through a range of new systems, in addition to the H˛O˛-system.
GEA Lyophil’s experts can recommend various methods and equipment in increase productivity of existing plant. For example, new shelf packages and GEA Lyophil’s ALUS (automated loading/unloading system) give plant a new lease of life and extend the operational usefulness of the entire plant.
FAQ (Frequently Asked Questions) for H˛O˛ -Sterilization for Freeze Dryers (Lyophilizers)
Can our freeze dryer be equipped with the VAPOVAC sterilizer?
New built freeze dryers are available having the VAPOVAC sterilizer incorporated.
Old existing freeze dryers which are not steam sterilizable can be retrofitted with the VAPOVAC sterilizer as well at a reasonable price and with reasonable effort. Therefore an expert of GEA-Lyophil will evaluate your freeze dryer on site to determine the neccessary changes.
Up to which freeze dryer volume can be sterilized ?
Up to 30 cubic meter freeze dryer volume.
How does the VAPOVAC sterilizer communicate with our freeze dryer ?
Dry contacts when retrofitted to older freeze dryers.
Bussystem when integrated in new built freeze dryers.
Except for the freeze dryer, can H˛O˛ sterilize the tanks or pipes?
Any vacuum vessel and associated piping can be sterilized. We only support the sterilization of freeze dryer at this time.
What freeze dryer conditions are required for the VAPOVAC sterilization ?
The freeze dryer must be defrosted and dry and at ambient temperature.
How can we remove residual moisture from our freeze dryer ?
Water droplets will be dried off by the drying phase of the VAPOVAC cycle.
What vacuum level is required for VAPOVAC sterilization ?
About 0,02 mbar before injection.
How long does a VAPOVAC sterilization take ?
An average cycle takes less than 3 hours total cycle time (basis: average production size freeze dryer).
- The better the vacuum pump set capacity,
- The dryer the freeze dryer vessels,
- The smaller the freeze dryer volume
- The smaller existing dead ends
the shorter is the sterilization cycle.
What is the H2O2 consumption during a VAPOVAC sterilization cycle ?
An average cycle takes total 25 to 100 ml H˛O˛ (basis: average production size freeze dryer).
- The smaller the freeze dryer volume
- The smaller existing dead ends
the smaller the amount of H˛O˛ required for the VAPOVAC sterilization.
How do you protect the operator ?
The last action of the aeration phase is the H˛O˛ -residual check. The MAK-level of 1ppm should not be exceeded before door opening is released. The operator can check the H˛O˛ residual manually using an indicator tube and hand pump or the system can be equipped optionally with an automatic H˛O˛ -residual-sensor.
What SAL (sterility assurance level) is possible with VAPOVAC sterilization ?
6 log reduction
Is there a difference in validation when changing from steam sterilization to H˛O˛ – sterilization?
No, the procedure is the same. Chemical and biological indicators especially designed for vaporized hydrogen are required.
Can we sterilize the cold trap (condenser) as well?
The condenser and the chamber and associated piping will be sterilized.
How is validation performed ?
You pick the spots of assumed worst access for the gas to reach and place your biological indicators and run a validation cycle. This is exactly the same procedure as using steam only that you use biological indicators which are designed for H˛O˛ -gas. The BI's are transferred and evaluated the same way in the laboratory as you would do with steam bioindicators.