Cleaning-In-Place systems

Pretreatment (e.g., filters, softeners, or antiscalents) and posttreatment (permeate flush and clean-in-place systems)... 

Closed manufacturing systems Closed transfer systems Clean-in-place systems Containment boxes or isolators... 

Sanitary Design. Pipelines and equipment should be easy to clean and sterilize. Clean-in-place systems are recommended wherever possible. Use signs to constantly remind personnel about personal cleanliness and work habits. 

To attain a high degree of cleaning, the four T Principles [Wolpers, Frank Clean-in-Place Systems for the Pharmaceutical Industry VDMA Seminar, Interphex 2001, Philadelphia] must be taken into account ... 

Figure 34 Freeze-drying plant condenser and shelves cooled with LN2. Clean-in-place system in chamber and condenser. 1, LN2 inlet to condenser and heat exchanger 2, N2 outlet from the condenser and heat exchanger 3, heat exchanger for the brine in shelves 4, brine to and from shelves 5, pressure plate for stoppering of vials 6, piston rod with bellows 7, hydraulic piston for 5 and 6 8, hydraulically operated valve 9, hydraulic system 10 and 13, water and steam inlet 11, pumping system 12, water outlet. (AMSCO Finn-Aqua GmbH, D-50354 Hiirth, Germany.)...

Circulation. The vessel is filled with cleaning solution and allowed to stand for a short time, after which the solution is either agitated to increase internal circulation, or circulated through an auxiliary system (called a clean-in-place system, as discussed later). FVesh makeup solution can be pumped in if used solution is withdrawn. In boilers, nitrogen can provide agitation for more-effective scale removal. 

Support systems (such as water for injection, air handling systems, compressed gases, vacuum, clean-in-place systems, and others) are likewise maintained in a qualified state. 

Normally only procedures for the cleaning of surfaces of the equipment that come into contact with the product need to be validated. Consideration should be given to non-contact parts of the equipment into which product or any process material may migrate. Critical areas should be identified (independently from method of cleaning), particularly in large systems employing semi-automatic or frilly automatic clean-in-place systems. 

Critical areas, i.e. those hardest to clean, should be identified, particularly in large systems that employ semi-automatic or fully automatic clean-in-place systems. 

Figure 3 shows a more detailed schematic of a TFF System in a cell harvesting application. In this particular set up, the system is designed for extracellular product processing but the principal components would also be used for intracellular products. It shows the plumbing of a clean-in-place system and a tank for collecting waste. The system is closed, in that all waste solutions existing the system enter a kill tank for sterilization. 

Cleaning procedures should be detailed and provide specific understandable instructions. The procedure should identify equipment, cleaning methods, solvents and detergents approved for use, inspection and release mechanisms, and documentation. For some of the more complex systems, such as clean-in-place systems, it is usually necessary both to provide a level of detail that includes drawings and to provide provision to label valves. The time that may elapse from completion of a manufacturing operation to initiation of equipment cleaning should also be stated where excessive delay may affect the adequacy of the established cleaning procedure. For example, residual product may dry and become more difficult to clean. 

Figure 10 J Valve manifold with hygienic mix-proof valves used in a Cleaning-In-Place system.

Chisti, Y., Moo-Young, M. (1994). Clean-in-place systems for industrial bioreactors design, validation and operation. Journal of Industrial Microbiology, 13, 201-207. http //dx.doi.org/10.1007/BF01569748. 

Maxcy, R.B. 1969. Residual microorganism in cleaned-in-place systems for handling milk./. Milk and Food Tech. 32 140-43. 

Figure 22 Example of a SCADA (Supervision, Control, and Data Acquisition) solution for several freeze-dryers (1,2,. ..,X), one loading and unloading system (ALUS), built into an isolator. Furthermore, a CIP (Clean in Place) system is controlled and monitored, (Steris GmbH, D-50354 Hurth, Germany).

R Cully. Refrigerants, the environment and the liquid nitrogen option. International Society of Pharmaceutical Engineering (ISPE), Antwerp, 1994 F Wolpers. Cleaning in place systems for the pharmaceutical industry. VDMA Seminar, Interphex, Philadelphia, 2001. 

Franks JW, Seiberling DA, inventors Electrol Specialities Company, assignee. Portable clean-in-place system for batch processing equipment. US patent 6,161,558. December 19, 2000. 

Sizing devices are now trimly fitted to the compactor body and controlled by variable speed drives. Most compacters no longer require a separate milling machine in tandem to size compacts as required by slugging technology. Roller compactors have clean-in-place systems that offer environmental and safety features. These systems minimize human exposure to chemicals. See Roller Compaction Technology for the Pharmaceutical Industry for additional information (23). 

A nice case study of an evaluation of a clean-in-place system on a pilot-scale single-pot processor is given in Ref (3). In this study it was proved that a complete changeover from one product to the next can take place in <2 hr. 

Decanters in casein production will often have a centripetal pump discharge to combat foam, and axial flow, as well as clean-in-place systems. Lactose production uses a double-lead conveyor, with on-the-beach rinsing, and a reslurry rinse solids collector, as well, again, as CIP. 

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