Monitoring Cleaning Cycles

Temperature, flow, pressure, fluid level, drainage, conductivity and pH may play a role in monitoring
the cleaning program.

The nature of the cleaning method will determine the critical parameters to
be monitored during cleaning. Critical operating parameter ranges should be established during cycle development and cleaning validation studies.

Instrumentation for monitoring critical parameters should be accurate and subject to a routine
calibration program.

Instrumentation may be placed directly in the process/cleaning stream or off-line for monitoring purposes. In-line instrumentation should be of appropriate sanitary design to prevent product or cleaning agent build-up and prevent "dead legs."

Post-Cleaning Equipment Storage

 

After cleaning the equipment should be well protected from the environment to avoid cross contamination of other products.

The  protection can be done by covering the equipment as soon as it is cleaned.

Before using the equipment a visual inspection is must be  carried out. Every cleaning should be identified using number system

Record must be kept and the cleaning details such as equipment number, date of cleaning, person name who cleaned and the inspection .

Cleaning Frequency

The frequency and rigor of cleaning is usually determined by the nature of the changeover process.
For example, the frequency will depend upon whether the manufacturing involves many different
products or several batches of the same product.

Between batches of different products
When equipment is changed over from one product to another, cleaning must take place to
prevent product cross-contamination.

Between batches of the same product (campaign)
The cleaning frequency within batches of the same product should be determined as part of
the process development. In some cases, it is possible to show that cleaning between batches
may be reduced or eliminated.

Validation should be accomplished to determine the number of lots of the same product that may be consecutively manufactured before a more rigorous cleaning is necessary.

Equipment Design Considerations

Equipment Design Considerations

Equipment Design Considerations
Equipment cleanability and function must be considered during equipment design. In order to
minimize the risks of cross-contamination, microbial or endotoxin contributions to equipment, the
system must be designed with care.

This applies to process equipment and the cleaning process itself. Ideally, the equipment should be constructed of non-reactive, non-additive, non-adsorptive, nonporous
materials. A review of the materials of construction may be warranted based upon the action
of the cleaning agents to be used; if the cleaning agents are corrosive or are likely to react with such components as sealants, plastics or filters, care should be taken when specifying design requirements and preventative maintenance procedures.

Equipment should be free-draining and have limited intricate or complex parts. Sanitary designs
employing principles such as appropriately finished surfaces, lack of crevices, absence of dead legs and suitable construction materials are recommended.

Cleaning equipment should be designed to ensure adequate coverage of all process equipment
surfaces to be cleaned. In tankage and enclosed piping systems, the volume of cleaning solution
available must be sufficient to clean all interior surfaces of the pipe. For spray ball or nozzle spray
apparatus, all equipment surfaces should be available for contact with the spray.

Residue Removal and Cleaning Methods

As identified previously, cleaning relies upon the solubilization, chemical reaction and physical action for removal of residuals.

Some of the methods for achieving residue removal in these categories include: dissolving, suspending, emulsifying, sequestering, wetting, saponifying, and scraping, brushing and scrubbing.

The effectiveness of a cleaning agent when in contact with the residue that is to be removed may be dependent upon such parameters as the cleaning agent concentration, exposure time, pressure, temperature or pH.

Often the interactions of the cleaning agent and the process residue are not enough to result in
effective cleaning. In these instances, additional techniques such as agitation, direct impingement,
and disruption by ultrasonic vibration have proven useful to facilitate residue removal.

The determination of the cleaning cycle will depend upon equipment design criteria, surface
characteristics, geometry and composition.

The equipment design criteria will affect the amount of residual remaining on equipment surfaces and the ease with which such residuals are removed.

In most types of cleaning, some disassembly of the equipment may be required. Disassembly is critical in providing access to previously inaccessible areas of the equipment as well as providing the opportunity to visually examine the internal surfaces to verify that they have been effectively cleaned by the cleaning process.

It is important to include disassembly directions in the cleaning SOP and training activities to ensure reproducibility of cleaning.

Placebo Batches as a Cleaning Method

Disposable Equipment

Cleaning Porous Equipment

Equipment