By: Richalle Ritts, Manager Process Engineering
What is the future of clean-in-place (CIP) technology as we remove human interaction to achieve 4.0 CIP processes? CIP processes are a considerable component of the cost of goods in bioprocesses. Therefore, addressing CIP processes has a big pay-off.
Before we rush to adopt new technologies, we must first consider the problems we are trying to solve and the goals we are trying to achieve as our technology advances to 4.0. The baseline CGMP requirements from 21 CFR 211 Subpart D require equipment to be cleaned, as to not alter the safety, identity, strength, quality or purity of the drug. Our goals are quality, flexibility, improved uptime, improved turn-around times and reduced cycle times.
How do we lower the cost of goods while achieving our goals? There are some solid approaches when looking at the Time Action Concentration Temperature, or TACT, of CIP. One such approach is to reduce overall water usage by optimizing cycle times and volumes, greatly impacting the support systems. Optimizing proper CIP solution action or flow in all areas is important so additional wash times and rinse times can be reduced. Just one area where a valve is improperly oriented can add significant rinse time and water usage.
The overdesigning of processes and padding rinse and wash times to give the illusion of meeting regulatory requirements must also be kept in check. Less water means reducing the pure water generation volume and reducing distribution size and complexity. If we find ways to improve rinsibility of our CIP solutions, we lower the wash temperatures. Lower wash temperatures reduce the size of boilers and cost of capital to install heat exchangers. This impacts overall energy usage for the plant as a whole, ultimately lowering the cost of goods. Improved material handling at the skid for closed dosing processes improves productivity and ensures consistent quality. Performing coupon testing to select proper chemistry and minding which water you use for initial rinses and washes will go a long way to reducing chemical and water usage.
The problem with doing CIP the way it has always been done is that it leaves us with high water and energy usage. Identifying critical process control parameters coupled with accurate and real-time measurements of critical process parameters is necessary to re. This level of thought should be incorporated into the master planning stages to ensure facilities are on track to achieve 4.0 processes. Improving sensor reliability and advanced process control strategies deliver the quality we need. Current sensor technologies require off-line calibration and require redundancy to overcome reliability issues. Online TOC analyzers technology is improving. Without wasting water you can quickly take reading. TOC measurements are required to ensure you are removing product that is not conductive.
I do not foresee a disruptive 4.0 CIP technology coming up, so we must continuously improve on what we have. Single-use eliminates the need for CIP; however, large-scale bioprocess and blood fractionation facilities will continue to require CIP.