Cleaning cycles vary by industry; however, they are based on the same principles of relying on TACT. Various water- soluble solutions with different properties are used in sequence to obtain the desired cleaning effect. For example, alkaline solutions may be useful to break down proteins and fats, while acid solutions help to neutralize alkaline conditions and remove mineral deposits. The development of cleaning cycles takes into consideration the residue characterization information to decide the most effective combination of conditions and parameters.
CIP units are usually optimized to avoid unnecessary waste of utilities and chemicals and to achieve cleaning in the shortest time possible. In-process instruments can measure solution pH, volume flow rate, turbidity levels, temperature, time, and pressure. These parameters can be used to define the start and end point of different cycles. The cycle development will select and justify the optimum sequence and combination of cleaning steps to achieve a consistent, robust, and validatable cleaning process.
The following CIP Cycle example is typical of aqueous-based cleaning used for biological type process residues that primarily consist of proteins, carbohydrates, lipids and water-soluble salts. CIP cycles for nonbiological, chemically synthesized process residues requiring solvent-based cleaning may vary greatly from the following example in that the cycle may consist partially or entirely of contacting and solubilizing the residue with one or more nonaqueous solvents.
Water used for CIP cycle Rinse and Wash Phases can be of the most available in the process area that is designated as suitable for use on product contact surfaces for cleaning procedures. Water used in the Final Rinse Phase should be of equivalent quality to that used in the subsequent process.
Example CIP Cycle
Pre-CIP Activities
Residual product material is removed from process equipment to the greatest extent possible, for example by draining in the case of liquids or dumping in the case of dry solids.
Process system components that are not suitable for CIP cleaning are removed for COP and taken for cleaning either manually or in a parts washer. If the location of the removed component leaves an opening where CIP solution would escape, the location is sealed or capped using in a CIP-cleanable method of closure.
Any manual connections that are necessary for completing the CIP supply and return flow path are completed using components such as hoses, piping spool pieces, and U-bend transfer panel jumpers. Manual valves are set to the necessary position required during CIP.
Start of CIP Cycle
The automated CIP Cycle should start following the end of production at a time not exceeding the validated DHT. First Rinse or Initial Rinse Phase
During the initial rinse, easily detached soils are removed from the equipment surfaces. Frequently, the vast majority of active and chemicals are removed in this first step. For actives or chemicals containing proteins, the initial rinse water is typically at ambient temperature, to reduce the chance of denaturing the protein causing adhesion to the equipment surface. Conversely, for residues with a high lipid composition, a heated initial rinse may be advantageous to prevent congealing.
For spray-device contact circuits, a starting point for cycle development is on the order of three successive Rinse- Drain burst combinations of 30 s surface rinse contact time followed by complete vessel drain. Successive Rinse- Drain combinations help ensure that as non-soluble material rinses from the equipment, it is carried down the outlet to the CIP return. For process lines, a continuous initial rinse volume on the order of two times the total line volume is a typical starting point. Initial rinse duration is adjusted during cycle development based on achieving a balance of optimizing removal of easily detached residue against required cycle time duration and water consumption.
System Drain Phase
A Drain Phase allows for solution to drain completely from vessels and/or lines through the CIP return, improving the cleaning effectiveness of the subsequent step.
Alkali Detergent Wash Phase
The Alkali Detergent Wash is an alkaline aqueous-based solution alone or in combination with wetting agents and other additives. The Alkali Detergent Wash duration timer starts when the equipment surface is contacted by solution meeting the action (flow rate and pressure), chemical concentration, and temperature criteria of the TACT principle.
For spray-device contact circuits, a starting point for Alkali Detergent Wash cycle development is on the order of 10 min contact time. For process lines, a continuous detergent wash volume on the order of five times the total line volume is a typical starting point. The TACT parameters of the Detergent Wash are adjusted based on the recommendations of the cleaning compound manufacturer to achieve the requisite surface cleaning.
This step may be a single pass or recirculated where the cleaning agent is delivered to the equipment from the CIP system recirculation/wash tank and either is directed to drain or recirculated through the equipment and back to the CIP system recirculation/wash tank.
Gas Purge (Air Blowdown) and Drain Phase
The Gas Purge utilizes clean process air or nitrogen to clear the CIP supply lines and process piping of residual solution prior to supplying fresh solution in the next phase. A Drain Phase follows the Gas Purge Phase to allow the pressure to dissipate and for the solution to drain.
Intermediate Rinse Phase
An Intermediate Rinse is used to remove residual detergent wash solution from the equipment surfaces before proceeding with subsequent cycle phases.
For spray-device contact circuits, a starting point is on the order of two successive Rinse-Drain burst combinations of 30 s surface rinse contact time followed by complete vessel drain. For process lines, a continuous Intermediate Rinse volume is on the order of one time the total line volume.
Acid Detergent Wash Phase
The Acid Detergent Wash is an acidic aqueous-based solution alone or in combination with wetting agents and other additives. The Acid Detergent Wash helps to neutralize residual caustic, remove mineral salts and oxides, and establish a free-rinsing surface. The Acid Detergent Wash duration timer starts when the equipment surface is contacted by solution meeting the action (flow rate and pressure), chemical concentration, and temperature criteria of the TACT principle.
For spray-device contact circuits, a starting point for Acid Detergent Wash cycle development is on the order of 5 min contact time. For process lines, a continuous detergent wash volume on the order of two times the total line volume is a typical starting point. The TACT parameters of the Detergent Wash are adjusted based on the recommendations of the cleaning compound manufacturer to achieve the requisite surface cleaning.
Gas Purge (Air Blowdown) and Drain Phase
The Gas Purge utilizes clean process air or nitrogen to clear the CIP supply lines and process piping of residual solution prior to supplying fresh solution in the next phase. A Drain Phase follows the Gas Purge Phase to allow the pressure to dissipate and for solution draining.
Final Rinse Phase
During the Final Rinse Phase, process equipment surfaces are flushed free of process and chemical detergent residue along with lower quality water that may have been used in the preceding phases. For spray-device contact circuits, a starting point for cycle development is on the order of three successive Rinse-Drain burst combinations of 30 s surface rinse contact time followed by complete vessel drain. For process lines, a continuous Final Rinse volume on the order of two times the total line volume is a typical starting point. Final Rinse duration is adjusted to achieve the final validated state for cleaning, frequently based on an online rinse water solution resistivity and/or TOC criteria.
Final Gas Purge and Drain Phase
The Gas Purge utilizes clean process air or nitrogen to clear the CIP supply lines and process piping of residual solution prior to supplying fresh solution in the next phase. A Final Drain Phase follows the Gas Purge Phase to allow the pressure to dissipate and for a complete draining of the process equipment, process lines, CIP system, and CIP supply/return lines.
Post-CIP Activities
Process system components that have been removed for COP are reinstalled in their use location.
Any manual connections that are necessary for returning to subsequent process conditions are completed using components such as hoses, piping spool pieces, and U-bend transfer panel jumpers. Manual valves are set to the necessary position for subsequent process conditions.
Process sanitization or sterilization procedures follow if applicable. Clean Hold Time (CHT)
The process CHT starts at the end of CIP or at the conclusion of sanitization or sterilization. Use of the process equipment in subsequent production should start prior to expiration of the CHT.
Related: Cleaning Validation Fundamentals