Clean-in-place (CIP) technology, the automatic, reproducible and reliable delivery of cleaning solutions and rinse water through process equipment and piping, offers significant advantages to pharmaceutical and life sciences manufacturing facilities. The ability to clean a processing system — incorporating tanks, pumps, valves, filters, heat exchange units and process piping — without having to disassemble all or part of the system is a lowercost, regulatory-compliant solution. Cleaning-in-place also increases efficiency, improves safety, avoids crosscontamination, and ultimately, provides higher assurance of product quality.
However, achieving these benefits requires tight measurement and control of the CIP process. A plant manager must use the appropriate amounts of cleaning solutions and be able to determine reliably that those solutions have been removed completely before the next processing run or campaign. Conductivity analysis can help confirm those processes. Since the various cleaning solutions are more conductive than the water used for flushing, conductivity measurement is a logical way to monitor the cleaning steps and the final rinse. This article will review the proper use of conductivity measurement in CIP systems, and discuss advances in conductivity analysis.
How CIP Works
The key objectives of an efficient CIP system are:
- Maximize safety — to avoid cross-contamination.
- Minimize CIP time — to help speed time-to-market and reduce impact on plant production.
- Optimize thermal efficiency — to avoid unnecessary heat loss and reduce energy requirements.
There are multiple configurations of CIP systems available, the two most common being single-use and multi-tank. In other industries, multi-tank systems are typically used to provide for the recycling of water and possible regeneration of cleaning chemicals. There is, however, a greater risk of cross-contamination with this configuration. Pharmaceutical and life sciences manufacturers typically employ multi-tank systems, but use them as single-use systems, with the tanks being drained between programs to minimize the potential for cross-contamination. Each of the multiple stainless steel tanks holds a different quality grade of water, such as deionized water (DI), hot or cold water for injection (WFI), and water for reverse osmosis units (RO).
The CIP process involves multiple cycles including an initial and final drain step, a pre-rinse, a sodium hydroxide wash and a post-rinse. Rinse and wash cycles vary from five minutes to one hour. The process may include a “sanitize” cycle to reduce the levels of bacterial contamination using strong oxidants such as hydrogen peroxide, ozone, chlorine dioxide or other chlorine-containing compounds. Thorough removal of these chemicals is required to prevent cross-contamination and to avoid corrosion of the stainless steel apparatus.
When the CIP process is initiated, pre-rinse water is sent through the circuit and “chases” the product. A timing sequence based on distances and flow rates will switch the valves at the proper time to minimize the interface between product and rinse water. Over 90% of the product residue is removed during pre-rinse in order to minimize the use of washing chemicals. Proper cleaning (as determined by FDA) is a function of detergent strength, cleaning time and temperature.
Figure 1: CIP equipment/process configuration.
Where Conductivity Works
Conductivity measurement plays a key role in the following CIP stages and functions:
CIP acid and caustic detergent concentrationTo provide detergent of the proper concentration for each CIP circuit and to validate that cleaning was done at the proper detergent strength, conductivity measurement is applied to the returning acid and caustic. These conductivity measurements are proportional to the concentration or solution strength (see Figure 2, below) and are recorded by control systems for validation. The fluids are often partially neutralized during the CIP process, and additional concentrate dosing is required. Conductivity indicates when sufficient concentrate has been added to the appropriate tanks. Figure 1 shows a typical configuration.
CIP/process interface and CIP completionBecause the various cleaning solutions are more conductive than the water used for flushing and final rinsing, conductivity measurement is a cost-effective way to monitor the CIP steps. It is highly effective at detecting the interface between cleaning solutions and the product so that the valves can be switched at the appropriate time to minimize the interface between the two and any resulting product loss. Conductivity measurement can also determine the interface between cleaning fluids and rinse water to minimize CIP time while meeting compliance requirements. When the conductivity drops to the value of rinse water, it indicates that the water is running clear, prompting the next step or the end of the cycle.
Selecting the Right Conductivity Sensor
Conductivity sensors used in CIP applications must be of sanitary design. This means the sensor surface should not have contours or crevices that could trap residue from the product and cause decay or harbor microorganisms that would result in cross-contamination. They also must be made of FDA-approved materials.
There are two main types of sanitary conductivity sensors — contacting and inductive. Contacting sensors bring the measurement electrodes into contact with the solution to be measured. This can be a problem if the solution can foul or corrode the electrodes. Inductive sensors are non-contacting and are often called toroidal because they use toroidal transformers isolated from the process. One toroid acts as a transmitter and the other as a receiver. The transmitter toroid produces an electric current in the process solution that induces a voltage in the receiver toroid. The strength of that induced voltage is directly proportional to the conductivity of the solution.