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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,
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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
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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
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and associated fittings, without major disassembly. CIP is commonly used for equipment such as piping, tanks, and fillers. CIP employs turbulent flow through piping, and/or spray balls for tanks or vessels. In some cases, CIP can also be accomplished with fill, soak and agitate.
282:). 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.).
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Up to the 1950s, closed systems were disassembled and cleaned manually. 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:
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deliver highly turbulent, high flow-rate solution to effect good cleaning (applies to pipe circuits and some filled equipment). The required flow rate can be calculated by considering fluid velocity minimum 1.5m/s. The right flow rate can be calculated by using
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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
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and specially designed spray nozzle systems. Simple, manually operated CIP systems can still be found in use today. However, fully automated CIP systems are in demand to avoid human errors, consistent results at reduced resources.
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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.
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The benefit to industries that use CIP is that the cleaning is faster, less labor-intensive and more repeatable, and poses less of a chemical exposure risk. CIP started as a manual practice involving a balance tank,
241:. 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.
293:) 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.
253:. 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.
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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 (
341:) which is performed to wet the interior surface of the tank and remove residue. It also provides a non-chemical pressure test of the CIP flow path.
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U.S. Food and Drug
Administration (1978). "Current Good Manufacturing Practice for Finished Pharmaceuticals: Equipment cleaning and maintenance."
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levels within processing equipment and systems. Residue removal is accomplished during CIP with a combination of heat, chemical action, and
247:. A concentrated cleaning solution will clean a dirty surface much better than a dilute one due to the increased surface binding capacity.
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deliver solution as a low-energy spray to fully wet the surface (applies to lightly soiled vessels where a static spray ball may be used).
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538:"Role of quality control in validation of biopharmaceutical processes: case example of clean-in-place (CIP) procedure for a bioreactor"
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deliver a high energy impinging spray (applies to highly soiled or large diameter vessels where a dynamic spray device may be used).
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Lydersen, Bjorn K.; D'Elia, Nancy A.; Nelson, Kim L., eds. (1994). "Cleaning of
Process Equipment: Design and Practice".
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disinfectant solution wash or hot water circulation to kill all microbes. The disinfectant can be cold disinfectant like
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In addition, CIP systems can be built into the borehole headworks to permit the injection of cleaning solutions (such as
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used for high end-uses such as natural mineral/spring waters, food production and carbonated soft drinks (CSD).
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Originally developed for cleaning closed systems as described above, CIP has more recently been applied to
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solution single pass flush through the vessel to drain. Caustic is the main cleaning solution.
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which is approved as no-rinse disinfectant if used as per the manufacturer recommendation.
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Depending on soil load and process geometry, the CIP design principles are as follows:
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purity of the drug product beyond the official or other established requirements."
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Elevated temperature, turbulence, circulation time and chemical detergents with
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https://www.dropbox.com/s/iu5c31em6c2juze/ISPE%20Cleaning%20Validation.pdf?dl=0
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Acid solution wash – used to remove mineral precipitates and protein residues.
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A typical CIP cycle consists of many steps which often include (in order):
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Final rinse with WFI or PW – rinses to flush out residual cleaning agents.
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Cleaning
Validation: Day 1 - Regulations, Definitions, Cleaning Processes
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Brewer/ ISPE & Quality
Executive Partners, R. (2020, September 21).
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batch components. It is used to remove in-process residues, control
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Final air blow – used to remove moisture remaining after CIP cycle.
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Chisti, Yusuf (2006), Ratledge, Colin; Kristiansen, Bjorn (eds.),
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Bioprocess engineering : systems, equipment and facilities
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382:(which shows that all cleaning chemicals have been removed).
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Geigert, J.; Klinke, R.; Carter, K.; Vahratian, A. (1994).
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Factors affecting the effectiveness of the cleaning agents
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Pressure exerted by the cleaning solution (or turbulence)
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are often employed to enhance cleaning effectiveness.
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Method of cleaning equipment without major disassembly
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Caustic solution re-circulation through the vessel.
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487:Chisti, Yusuf; Moo-Young, Murray (1994).
109:Learn how and when to remove this message
583:How to validate a pharmaceutical process
125:A clean-in-place unit on display at the
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378:chemical contact time, and final rinse
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394:(U.S. wastewater regulations)
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353:Intermediate WFI or PW rinse
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273:boreholes
174:cosmetics
99:June 2012
523:13810888
413:Washdown
386:See also
228:additive
158:beverage
562:8000897
345:Caustic
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190:sensors
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145:filters
131:Atlanta
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