Clean-in-place

Clean-in-place (CIP) is a method of automated cleaning the interior surfaces of pipes, vessels, equipments, filters and associated fittings, without major disassembly. CIP is commonly used for equipment such as piping, tanks, and fillers. CIP employs turbulent flow through piping, or sprayballs for large surfaces. In some cases, CIP can also be accomplished with fill, soak and agitate. 
Up to the 1950s, closed systems were disassembled and cleaned manually. (Lydersen et al., 1994, p. 487) The advent of CIP was a boon to industries that needed frequent internal cleaning of their processes. Industries that rely heavily on CIP are those requiring high levels of hygiene, and include: dairy, beverage, brewing, processed foods, pharmaceutical, and cosmetics.
The benefit to industries that use CIP as a cleaning methodology include the following:
Since the 1950s, CIP has evolved to include fully automated systems with programmable logic controllers, multiple balance tanks, sensors, valves, heat exchangers, data acquisition and specially designed spray nozzle systems. Simple, manually operated CIP systems can still be found in use today.
Depending on soil load and process geometry, the CIP design principle is one of the following:
Elevated temperature and chemical detergents are often employed to enhance cleaning effectiveness.
Factors affecting the effectiveness of the cleaning agents.
Temperature of the cleaning solution. Elevating the temperature of a cleaning solution increases its dirt removal efficiency. Molecules with high kinetic energy dislodge dirt faster than the slow moving molecules of a cold solution.
Concentration of the cleaning agent. A concentrated cleaning solution will clean a dirty surface much better than a dilute one due to the increased surface binding capacity.
Contact time of the cleaning solution. The longer the detergent contact period, the higher the cleaning efficiency. After some time, the detergent eventually dissolves the hard stains/soil from the dirty surface.
Pressure exerted by the cleaning solution (or turbulence). The turbulence creates an abrasive force that dislodges stubborn soil from the dirty surface.
Groundwater sources.
Originally developed for cleaning closed systems as described above, CIP has more recently been applied to groundwater source boreholes used for high end-uses such as natural mineral / spring waters, food production and carbonated soft drinks (CSD).
Boreholes that are open to the atmosphere are prone to a number of chemical and microbiological problems, so sources for high end-use are often sealed at the surface (headworks). An air filter is built into the headworks to permit the borehole to inhale and exhale when the water level rises and falls quickly (usually due to the pump being turned on and off) without drawing in airborne particles or contaminants (spores, molds, fungi, bacteria, etc.).
In addition, CIP systems can be built into the borehole headworks to permit the injection of cleaning solutions (such as sodium hypochlorite or other sanitizers) and the subsequent recirculation of the mix of these chemicals and the groundwater. This process cleans the borehole interior and equipment without any invasive maintenance being required.
Bioreactors, fermentors, and mix vessels.
CIP is commonly used for cleaning bioreactors, fermenters, mix vessels, and other equipment used in biotech manufacturing, pharmaceutical manufacturing and food and beverage manufacturing. CIP is performed to remove or obliterate previous mammalian cell culture batch components. It is used to remove in-process residues, control bioburden, and reduce endotoxin levels within processing equipment and systems. Residue removal is accomplished during CIP with a combination of heat, chemical action, and turbulent flow.
The U.S. Food and Drug Administration published a CIP regulation in 1978 applicable to pharmaceutical manufacturing. The regulation states, “Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements.”
Repeatable, reliable, and effective cleaning is of the utmost importance in a manufacturing facility. Cleaning procedures are validated to demonstrate that they are effective, reproducible, and under control. In order to adequately clean processing equipment, the equipment must be designed with smooth stainless steel surfaces and interconnecting piping that has cleanable joints. The chemical properties of the cleaning agents must properly interact with the chemical and physical properties of the residues being removed.
A typical CIP cycle consists of many steps which often include (in order):
Critical parameters must be met and remain within the specification for the duration of the cycle. If the specification is not reached or maintained, cleaning will not be ensured and will have to be repeated. Critical parameters include temperature, flow rate/supply pressure, chemical concentration, chemical contact time, and final rinse conductivity (which shows that all cleaning chemicals have been removed).