Cleaning-in-place procedures

Free of hygiene risk. Must be constructed with a food-grade material of construction, permit standard clean-in-place procedures, and be free of dead flow zones. 

Optimise binding, elution, wash and cleaning-in-place procedures using unclarified sample in expanded mode at small scale (0.02 - 0.15 litres bed volume of media)... 

Effective cleaning and disinfection. A further essential pre-requisite for the production of cosmetic products is the ease with which production and ancillary equipment can be cleaned. As a rule of thumb, a production line which does not automatically empty its entire contents and, due its construction, cannot be purged in situ, has to be considered a potential source of contamination. Effective cleaning and disinfection procedures require that the plant itself is cleanable. Only production plants constructed in compliance with rules for hygiene technology (EN 1672-2) may be cleaned automatically according to Cleaning In Place procedure, without recourse to... 

Ferric ion was immobilized on a Chelating Sepharose Fast Flow column preparatory to the separation of seven enkephalin-related phosphopep-tides.17 Non-phosphorylated peptides flowed through the column, and the bound fraction contained the product. The capacity of the column was found to be 23 pmol/mL by frontal elution analysis. Cupric ion was immobilized on Chelating Superose for the isolation of bovine serum albumin.18 Cupric ion was immobilized on a Pharmacia HiTrap column for the separation of Protein C from prothrombin, a separation that was used to model the subsequent apparently successful separation of Factor IX from prothrombin Factor IX activity of the eluate was, however, not checked.19 Imidazole was used as the displacement agent to recover p-galactosidase from unclarified homogenates injected onto a nickel-loaded IMAC column.20 Pretreatment with nucleases and cleaning in place between injections were required procedures. A sixfold purification factor was observed. 

In addition, there are certain closed systems cleaned by clean in place (CIP) procedures in which the equipment is not opened and visually inspected after each cleaning event. One might question what the signature actually represents in such cases. The signature means that every phase of cleaning occurred as intended, and that is enough, providing the CIP procedure was appropriately validated prior to utilization on a commercial batch. 

Drawbacks of the RTP ports are that they cannot be hooked into the isolator clean in place (CIP) system so, they must always be considered dirty until an adequate cleaning procedure is developed. There are also size limitations to the RTP ports and their corresponding containers. Once a certain size port is selected for the isolator, this is the only diameter container that can be used, unless the isolator port is modified. The port also requires an additional penetration of the isolator wall and serves as another potential point for air leaks. In addition, the RTP containers are not amenable to the transport of flasks into and out of the isolator they require rotation and maneuvering of the RTP container to dock it into the isolator. Unless the port is mounted into the isolator floor, which will take up valuable space, the ability to transport liquids into and out of the isolator is limited to securely closed vials or bottles. The final limitation is the tendency of the seals on the mating surfaces of the RTP ports to become contaminated with potent material during transport operations. Procedures should be put in place to ensure that the mating surfaces of the RTP ports are thoroughly decontaminated as soon as the transport container is undocked from the isolator wall. 

When reusing an expanded bed one must have guarantees that it is clean and sterile. Therefore, proper sanitation is required. In most cases, treatment with 0.5 M NaOH is recommended. After a treatment for 1 hr it is regarded that any cells present have been killed. The sanitation is often carried out as a cleaning-in-place (CIP) procedure. To meet the challenges that such treatment exerts on the system, support and attached ligands as well as the coupling link must be stable to the treatment. 

Technical Procedures for Operation of Cleaning-in-Place and Sterilization-in-Place Process for Production Freeze-Drying Equipment... 

The general text in the main part of these guidelines may be applicable to validation and qualification of premises, equipment, utilities and systems, and processes and procedures. More specific principles of qualification and validation are addressed in the appendices. Semi-automatic or fully automatic clean-in-place (CIP) systems and other special cases should be treated separately. 

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. 

The prevention of bacterial or fungal infections in cell culture and recovery systems can be assured, to a high degree of confidence, by the use of a piping and vessel system which maintains absolute containment of the sterile medium fluids. The equipment used must be of a nature to allow cleaning and sterilizing by Clean in place (CIP) and Sterilize in place (SIP) procedures (usually high-quality stainless steel). Most cell culture processes require... 

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. 

In the food applications mentioned above it is impractical to remove components that could foul the membranes, because these are necessary constituents of the product. In such cases the process is operated under conditions that minimize fouling, and then the fouling that does occur is handled by cleaning in place (CIP). The CIP procedures can include soaking in brine, current reversal and washing with acid, base and nonionic surfactants. 

Procedures are the strategy for carrying out batch activities within a process cell. Procedures, such as clean in place, do not always produce a product or a product intermediate. 

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