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Cleaning cycle development may be accomplished with simulated soil or expiredor
rejected product. However, itiscritical that the simulated soils and the process
conditions are as closely matched to the actual soils and actual process conditions as
possible. The final setting of cleaning parameters (time, temperature, and concentration)
must be based on acleaning validation performance qualification with
actual product soils. Regulatory and operational requirements make it necessary to
establish robust clean and dirty hold times.
Large biopharmaceutical projects with hundreds of CIP cycles may generate
thousands of CIP samples during cycle development and validation work. Therefore,
the collection, identification, handling of the samples, analysis, recording of
data, and communication of QC data must be carefully planned. It is not unusual to
generate tens of thousands of cycle development and cleaning validation data
points. Consider the need for CIP team training in sample handling and analysis
activity, and involve your QC department as early as possible in the planning
process. Attention should also be given to special analysis requirements.
CIP CONSIDERATIONS IN OPERATIONS
CIP provides many benefits to the user in addition to providing a means of
achieving validated cleaning of all equipment, after each period of use. The
advantage of full CIP automation is the capability to monitor operations on not
only adaily but also hourly basis—program after program. The acquisition of key
information about flow,pressure, temperature, conductivity,what is being cleaned,
and who is operating the system, can all be tabulated and plotted against time. This
in turn makes it possible to create trend CIP circuit performance reports, and monitor
cleaning chemical usage and utility usage. Cleaning optimization is possible to
reduce water, chemical, and time needs even though such work will require
revalidation of each changed CIP cycle. CIP skids and circuits may also be used
to repassivate process piping and equipment on aregular basis. Finally, another
chapter in this book will suggest how CIP operational data can be used as the basis
for troubleshooting and maintenance procedures.
CIP INTEGRATION AT THE GENENTECH OCEANSIDE
PRODUCT OPERATIONS
Roebers and Seiberling
From project conception until the completion of the project, the owner emphasized
the objective of developing an appropriate CIPable facility layout and process.
Consideration of a basement was eliminated during the early stages of the
conceptual design for cost and code reasons. The three-floor manufacturing
building shown in Figure 8maintained “top-down” process flow and gravity CIP
return capability with CIP skids on the ground floor, and standard centrifugal CIP
return pumps on the ground floor for ground floor and some second floor vessels.
Most CIP equipment including skids and CIP S/R distribution valve arrays
were located in “gray space” for maintenance accessibility. During the conceptual
design phase of the project, the project team was able to reduce the amount of
transfer panels from 80 to 3. This was accomplished by reducing the degree
of desired process flexibility and by the use of valve arrays. Athorough evaluation
of transfer panels versus valve arrays by the owner’s engineering, safety, and
operation teams universally favored mix-proof valve arrays as a means of
providing CIP flow control and CIP skid redundancy.