CIP-100 : CLEAN IN PLACE

Various cleaning solutions are used in the pharmaceutical industry to wash reactor chambers in between production batches. Obtaining instantaneous measurement of the active ingredients concentration in the cleaning solution is of great importance.

The washing process consists of several cycles, in each a certain amount of methanol (or any other cleaning material) is recycled through the system. For maximum efficiency the cycling of methanol should be stopped when the concentration of the active ingredient reaches steady state.

Validation of cleaning procedures are of utmost importance to the pharmaceutical, food and specialty chemicals industry. The OMA-517, an industrial spectrophotometer is utilized to monitor traces of active material in the development stages, validation routines and to the control of a Clean In Place (CIP) process.

Effective cleaning strategies

The washing process consists of several cycles, in each a certain amount of methanol or other rinsing material is recycled through the chamber, pumps, valves and flow system, during which the concentration of the active material in the methanol increases until a steady state is reached and the wash cycle is considered to be complete. A new batch of clean methanol is then loaded and the same process is repeated. For maximum efficiency, the cycling of methanol should be stopped when the concentration of the active material reaches a plateau. Or alternatively, the time derivative could be monitored to maximize sensitivity to the zero change state. Continuing the wash past this point is ineffective.

The Method

Most active materials have a distinct UV or SWNIR absorbance spectra, and therefore can be monitored spectroscopically. The OMA-517, an industrial spectrophotometer, may be installed on-line and programmed to measure trace impurities in the methanol washing cycle 

Benefits in continuous monitoring:

• Validation of cleaning and final purity level.
• Greater availability of reactor volume
• Detect possible faulty valves & pipes in the flow system.

 

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Washing cycle - setup

Some of the recycled solvent is diverted to a small by-pass flowing through the spectrometer. After reaching a steady state a new batch of cleaning solvent is loaded and the process is repeated until the concentration of impurities reaches a pre-set threshold value.

The concentration of the active ingredient in the methanol increases until it reaches a plateau. The same occurs for each wash. The 1st derivative of the concentration with time (dc/dt) approaches zero when the process reaches steady state. The UCL (Upper Control Limit) is also shown.

UV absorbance spectrum of several active materials: The absorbance spectrum of some active materials are shown above, note the low detection levels of the method.

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