A filling line for aseptic products in isolation technology offers a wide number of advantages with respect to a similar line installed in a conventional clean-room or with an open RABS.
We can summarize these benefits in the following topics:
increased product safety (that results in an increased product quality)
higher operator protection (in case of toxic product)
production area in class C or D, instead of class A or B
possibility to frequently perform cleaning and sterilization cycles…
…but it is time to deeply analyze the advantages of the engineered air flow supplied within an Isolator for a filling machine.
IMA Life isolators for filling lines are equipped with a sophisticated air flow circuit that can be subdivided in three main sections:
re-circulated air flow to create the unidirectional air flow (UAF)
“make-up” air flow, to ensure an adequate amount of “new” air in the loop
extraction air flow, to have a fine pressure adjustment inside each isolator chamber.
These air flow systems allow a drastic cost reduction related to the HVAC handling costs, recycling up to 90% of the air needed by the system, just adding what is required to avoid the temperature drift due to thermal dissipation of the fans and the friction of the filters.
A filling machine 2 meters wide and 1 meter deep, that needs an unidirectional air flow (UAF) all over its surface, needs 3.240 m3 of air per hour.(2m x 1m x 0,45m/s x 3600s= 3.240 m3/h).
This is the total amount of air handled by the circuit “a”.
It is a closed loop composed by inlet fans and inlet filters (HEPA H14) in charge of the generation of the unidirectional air flow (UAF) inside the isolator. At the bottom of each isolator section, all the air is extracted by the fans in charge of the recirculation, and re-introduced in the isolator chamber via the filtration stage.
In case a toxic product is manipulated, the extracted air is filtered with HEPA H14 filters before the re-circulating fans. These exhaust filters are installed in a special container that allows a safe replacement procedure called bag-in/bag-out (BIBO).
The Isolator control unit (PLC) receives a continuous information by the anemometers installed in each isolator section, and drives the fan speeds in order to achieve a stable air speed of 0.45m/s (± 20%). In that case each chamber results independent and the air speed finely controlled.
If we re-circulate 90% of this air, we just need to supply 324 m3 of “new conditioned air” per hour. In some defined applications also this air can be re-circulated through the same HVAC system that was generating this flow . See circuit “b”.
It is a good practice to install a centralized HVAC system equipped with a 3-stage filtration with increasing efficiency G4, F9 and finally H14. Supplying well filtered and conditioned air to the isolator will increase the life of the filters in charge of the unidirectional air flow (LAF) generation, decreasing the interventions in classified areas to replace the filters on board of the isolators and therefore costs.
This small amount of air (10 to 20% of the total air needed) can be exhausted or recycled through the HVAC. The choice depends on many factors such as: presence of solvents in the products, external temperature, external humidity, etc.
Also the extraction unit, in charge of the extraction of the portion of air to be re-conditioned, should be equipped with HEPA H14 filters in order to prevent any contamination of the HVAC and of the environment in case this portion of air will be exhausted in the environment.
The circuit “c” is in charge of the “fine pressure control”. Big HVACs have a high response time when a modification in the air flow (pressure, speed, etc.) is required, due to its size and related inertia.
Through this extraction pipe, the main control system is able to ensure a very fast and precise pressure control for each single section.
The isolator control system receives a continuous information by the pressure gauge installed in each isolator section, and drives the exhaust fan speeds in order to achieve the required pressure value.
In that case, each chamber results independent and the pressure inside the chamber finely controlled.
Typically, when an aseptic nontoxic product is manipulated, the pressure inside the isolator chambers should be higher than the external surrounding (+50/75 Pa).
If the product is toxic but not aseptic, the pressure inside the isolator chambers should be lower than the external surrounding (-50/75 Pa).
Many of the new generation anti-cancer products are aseptic and toxic, in this case the pressure inside the isolator chambers is suggested to be slightly higher than the external surrounding (+20/30 Pa).
Isolators should be routinely leak checked, applying a test procedure in according with the ISO 10648-2. If the system must be decontaminated with VHP (Vaporized Hydrogen Peroxide) the leak check routine becomes a compulsory step prior to sterilization.
Conclusions: A modern isolated filling line should be supplied with its dedicated HVAC system.
A well-engineered project that integrates a sophisticated air flow circuit and pharmaceutical grade HVAC systems will increase the performances of your installation, focusing in the following topics: