What are the virtues of automated cleaning systems? How do they work? Why are they so important in the pharmaceutical sector?
CIP/SIP (clean-in-place and sterilization-in-place) are systems designed for automatic washing and sterilization of systems.
These systems allow setting specific washing procedures and conditions and assure the user that these will always be the same (non-modifiable recipe), giving reproducibility to the process and allowing validation (although they may have various washing recipes, one for each type of wash). product, which will be used as appropriate). Furthermore, the fact that the systems do not have to be dismantled to carry out cleaning saves a lot of time, facilitates this process and prevents assembly errors.
It is very important to ensure that the cleaning agent reaches all points of the installation (reactors, buffer tanks, transfer lines and their elements such as pumps, valves and instruments) to guarantee that no dirty parts remain. In the specific case of guiding and lung tanks, their morphology, the range and number of cleaning balls (specifically designed to launch the cleaning solution with the appropriate pressure at all points of the tanks), as well as the flow rate and pressure of the cleaning solution define the choice. Very important is the choice of the type of ball to use. We find:
- Fixed ball: its water consumption is very high, but its assembly is easy and its price is low.
- Rotating ball: its water consumption is lower, but it requires maintenance and its price is high.
- Jet: gives the greatest possible range, which translates into better cleaning, but requires very high fluid pressure and is expensive.
Do we use detergent? Is just water enough?
- Initially, there will always be a rinsing stage done with water only. This water must be of sanitary quality or softened, if costs are to be reduced. This will start the washing, beginning to eliminate the largest fractions of dirt.
- The cleaning agents used for washing will depend on the products handled in the systems or equipment being cleaned. The most determining factor in this case is the solubility of these components in water. If a component is hydrophilic, it will be enough to use hot water for washing. If, on the other hand, it is hydrophobic, it will be necessary to use detergents or other products, in addition to water. Whatever the case, the user will not have to directly touch the product with their hands, giving more security to the process. In addition, the cleaning agent will have to be allowed to act under certain conditions of temperature and pressure, for an adequate time so that it can remove all the dirt.
- Another critical point in the use of a CIP/SIP system is the elimination of all the agents that have been used for cleaning, so that no remains remain in the equipment causing cross contamination. It is recommended to avoid the use of detergents, acids or bases, because they are more difficult to remove than water. The last rinsing stage should be done with the quality water used to manufacture the product, whether purified water or injectable quality water. In many cases, cleaning (rinsing) is carried out based on a validated time, but it is a good recommendation to use an end-point detection system with, for example, a conductivity meter of the outlet effluents.
- Finally, we proceed to sterilization (SIP stage), where any microorganisms that could remain in the equipment are eliminated, and end up causing the contamination of a batch. This sterilization can be done using heat (high temperatures kill microorganisms), through pure steam at a temperature equal to or greater than 121ºC, or using chemicals that are lethal to contaminants. Once again, we always try to avoid the use of chemicals because they must then be completely eliminated from the system. On the other hand, if sterilization is done using heat, this step will not be necessary. Good design will be key, as it must be guaranteed that the desired temperature is reached and maintained at all points in the system. To do this, a validation is carried out using temperature probes and bioindicators distributed at the points defined as most critical.
- Furthermore, if the components being washed have an activity that means they cannot be disposed of conventionally (for example, an oncology drug), a downstream inactivation step will have to be incorporated before discarding the waste to stop said activity and that are not dangerous when discarded. In a future article we will discuss biological deactivation systems.
Although the use of detergents and other chemical substances may be necessary in certain cases, at Klinea we recommend that whenever possible only water and heat inactivation be used. Since when you use a chemical, you have to make sure that once the cleaning is finished there are no traces of it on the equipment and that, in the end, makes the process more expensive and difficult.
If you are interested in learning more about CIP/SIP systems and how we can help you, contact us: klinea@klinea.es
