Revolution Is Progress
Suitability of static spray balls in validated cleaning processes of biopharmaceutical plants is not unlimited. Bioengineering's RotaCIP is a CIP-lance equipped with spray ball which rotates by the force of the CIP-fluid. Rotation and thus cleaning intensity can be verified by sensors. The dynamic of the lance renders the CIP-process more efficiently, faster, and safer than the static of old fashioned spay balls.
Cleaning of a biopharmaceutical plant is not merely a necessary duty for which no thoughts are wasted. It is an integral part of the process. During cleaning not only media components and cell debris, but also residues of the produced active ingredient, metabolites and auxiliary substances are removed. In multipurpose plants every contamination of a previous batch can make the entire product of the current batch unusable. Cross contaminations especially with active ingredients and allergens must be avoided at all costs to ensure product safety.
Developing the Cleaning Process
Validation has top priority during the development of the cleaning process in biopharmaceutical plants. For this purpose hard to clean areas in the reactor have to be identified. Cleaning agents must be tested for their suitability to remove all residues of the production process. Removability of cleaning agents is also an important factor. Complete cleanness is verified with swab-tests and rinse tests.
Environmental compatibility increasingly gains in importance not only for ecological but also for economical reasons. Toxicity, environmental impact, water consumption and heating expenses have to be evaluated in this context. Generation of detailed risk analysis is advisable at this stage.
Not only the nature of the cleaning agents has to be considered, but also equipment and process management. Fully automated CIP-systems are expensive initial investments, but have comparatively low operational costs due to low chemical and water consumption. Time expenditure is much lower in automated than in other cleaning systems because all components have already been mounted to the plant and the cleaning process can seamlessly follow the production process. An automated CIP-system consists of mixing tanks for cleaning agents, probes, pumps, elaborate piping systems, valves, a complex controller and various other components.
The spray ball as a technically not very advanced component is necessary for automated and manual CIP-systems. But it is often viewed as a matter of course and its suitability for the process is not evaluated intensively.
Spray Balls Required
Even simple bioreactors for standard fermentations are equipped with many built-in components. Among them are baffles, aeration tube, agitator, and probes. If these are sprayed during cleaning only from above with a simple spray ball, spray shadows may form. The affected areas of the vessel are insufficiently cleaned. Product carry-over and contamination with media components are the result. In severe cases pockets of dirt may form, where microorganisms survive sterilization. These externally acquired microorganisms start to grow during cultivation, contaminate the fermenter and waste the entire production.
This problem is eliminated when two or - depending on vessel size - more static spray balls are used. Especially in combination with a CIP-valve which sprays the built-in components from below, there will be no problems in respect to spray shadows.
Two or more static spray balls could, however, bring about an entirely different set of problems. They must not be used if the water pressure of the cleaning and rinse solutions is not sufficiently high, since the pressure is evenly distributed to all spray balls during the cleaning process. Insufficient pressure of the CIP-solutions decreases the range of each spray ball and the complete cleanness cannot be ensured.
Even if the CIP-system can be supplied with adequate water pressure, it must be evaluated if several spray balls are the optimum equipment for the process, or if they use too much space, resources and energy.
Limits of Static Spray Balls
The fermenter lid is always fitted with dosing systems for media and corrective agents, inlet and exhaust air filters, and probes. The space for additional components is limited and is further decreased if the reactor is equipped with a top drive or a foamkill system. Often the available space in the fermenter lid is insufficient for several spray balls. Equipment must be removed before every cleaning process to provide space for the spray balls. This may even involve opening of the fermenter lid. Time and work invested for this - a lifting device or with large reactors even a crane is required - annihilates all advantages of the CIP-process, endangers the personnel and is costly.
Static spray balls further have spray characteristics which could be a risk for the entire cleaning process. The cleaning solution hits the vessel interior with the intended pressure only through the bore holes of the spray balls. Since the spray balls are static the punctual impacts of cleaning solution are always on the same places. The areas in between are merely rinsed and not actively cleaned with mechanical force. Therefore cleaning with static spray balls is very time consuming. If all areas of the vessel interior and especially the hard to clean areas would be sprayed actively, application times of cleaning agents and rinse times could be drastically reduced.
The bore holes of the spray balls are relatively small and can be obstructed by insufficiently dissolved particles of the cleaning agent. If bore holes are clogged, the vessel is not adequately cleaned in the respective areas. There is no way to determine when exactly the bore holes clogged and when the cleaning process became irregular.
Rotation As Solution
If the spray ball rotates on a static lance the problem of punctual spraying is reduced but the problem of spray shadows remains. If spray ball and lance are in motion both problems are overcome. The spray ceases to hit the vessel in the same tiny distinct areas. The range of the cleaning agent is enlarged and all areas within are actively sprayed. An additional mechanical component is added to the cleaning process by the rotation itself. This shortens the cleaning time, reduces the consumption of chemicals and eliminates spray shadows. Only one spray ball instead of several is required.
Bioengineering has developed the CIP-lance RotaCIP with rotating spray ball to render the cleaning process safer, faster and more environmentally compatible. The lance is mounted into the reactor lid or a side port to effectively support the cleaning process. It remains in the reactor during cultivation and can be fully integrated into an automated cleaning process.
The spray ball which is located at the end of a curved pipe is driven by the force of the CIP-solution and rotates along a horizontal plane. This ensures evenly spraying of the reactor interior. Spray shadows do not form.
The lance has a modular construction and can be individually adapted to the vessel geometry. Material and design comply with established sterile and hygienic regulations. Rotation is put into effect via bearings and is therefore not only hygienic, but also low maintenance.
Common spray balls have no means to survey whether they perform faultlessly or whether they function at all. The rotation of the CIP-lance can be monitored by a sensor. With this it can be documented at any time during the CIP-process that the spray ball rotates correctly and sprays the vessel interior with sufficient water pressure.
Validation and environmental compatibility, automation and documentation, speed and efficiency, hi-tech and economy, these are the keywords for developments not only in the biopharmaceutical industry. All-too often during the design of an entity such as the CIP-process it is not considered that the desired properties can only be achieved with the interplay of all components. A spray ball might seem trivial. The lance is not, because it significantly increases efficiency and safety of the CIP-process with sophisticated design, love for detail, and innovative force.
