Designing a Clean-in-Place System

November 21, 2012
Cody Shrader

Andrew Wong

Equipment and Processing Report

Equipment and Processing Report, Equipment and Processing Report-11-21-2012, Volume 0, Issue 0

An efficient cleaning cycle begins with equipment and automation-system design.

Clean-in-place (CIP) technologies improve cleaning processes and increase critical equipment uptime. An efficient cleaning cycle begins with equipment and automation systems designed to ensure successful cleaning.

Equipment design
Tank and piping design should be reviewed for sanitary cleanability, as described in section SD-3.1 of the American Society of Mechancial Engineers Bioprocessing Equipment standard (1). This design may include: minimizing deadlegs; verifying pipes are sloped toward a drain; checking for low-point drains, sanitary connections, and valves; and verifying that all product-contact surfaces are accessible to cleaning solutions.

The next step in the cleanability review is to create a preliminary design of flow paths for CIP circuits. Segments of equipment and piping should be properly separated and/or combined into different cleaning circuits as part of a preliminary design. Important considerations include process and schedule requirements, potential residues, and piping design.

Process and schedule. Knowledge of the equipment’s use can provide insight on process hold or transfer times. Transfer lines and tanks may need to be chained together into a single CIP circuit for quick equipment turnaround to meet these demands. Clean and dirty hold times may also affect equipment scheduling and cleaning requirements.

Residues. Characterizing residues through cleaning studies and identifying associated product-contact surfaces aid in parameter development. Certain residues may require different cleaning solutions, concentrations, and temperatures for suitable cleaning to occur. This analysis can help organize circuits by common cleaning parameters.

Piping design. Available transfer panel connections may limit the combination of certain transfer lines and tanks. The user should account for line sizes and lengths as major pressure drops may decrease flow and turbulence within the pipe. Additional pumps and other spool pieces may be required within the system. Caution should be exercised in these cases to minimize manual configuration steps and reduce the risk of setup errors. Finally, the user should consider the availability of low-point gravity drains throughout the CIP circuit. Gravity drains remain critical for efficient CIP cycles.

Automation-system design
The cleaning automation design should also be reviewed for efficient cleaning characteristics. Developing cycles and sequences that complement a particular automation-control system greatly reduces long-term operating costs. For instance, a fast response, direct-action, process-logic controller (PLC) may minimize rinse times and water consumption by toggling through every auxiliary path on a complex bioreactor quickly enough in parallel with the sprayballs while not extending sprayball coverage test durations. In contrast, the path-transition time within a distributed-control system (DCS) depends on its programming style and may require several layers of equipment module (EM) and sub-EM commands before finally reaching the target control modules (CMs). Only after waiting for valve and state confirmations can the next step begin. Here, creating a cycle that combines multiple transitions into a single grouping will result in the shortest and most cost-efficient cycle possible. Combining cleaning actions (e.g., rinse, drain, and air blow) within phases also reduces the cycle duration. In contrast, a strategy of using more modular, individual phases may elongate the cycle.

Various time and cost-reducing methods must be balanced with skid equipment capability. For example, one may be able to take advantage of integrated PLC capabilities of equipment (e.g., vendor-provided PLC-based centrifuges). These design considerations must be identified early in the project to ensure that quality and validation procedures can be developed to address the sampling, instrumentation, and verification requirements being built into the CIP and recipient systems.

For the CIP cycle itself, the automated step sequencing, step-transition criteria, and parameter values must be well defined and documented to optimize utility usage while providing sufficient process control.

Sequence. Typically, a cleaning cycle should start with water rinses followed by detergent cleaning and post-detergent rinses. In between any rinse or detergent wash, the system should be drained completely to prevent dilution or chemical reaction with the next cycle step. An air-blow step, placed before the drain, can greatly decrease the gravity drain time and thus decrease the overall cycle time.

Transition criteria. Defining step-transition criteria provides a way to control the critical cleaning-cycle parameters. For example, the chemical-wash duration, minimum temperature set point, and concentration target can all be set as requirements before the wash step transitions to the next step.

Parameter values. Laboratory-scale process residue cleaning studies can provide an excellent starting point for CIP cycle parameters. Scalable attributes such as cleaning-agent concentration, process temperature, exposure time, and external energy can be explored within the cleaning design space to isolate the most critical parameter(s). Combined with an evaluation of the most effective cleaning agent and identification of worst-case residues in the process, these laboratory-scale efforts can dramatically reduce the number of cycle iterations that must be performed during commissioning and allow for a focus on improving efficiency.


  • The American Society of Mechanical Engineers, ASME BPE-2009, Bioprocessing Equipment. (New York, NY, 2009).

Andrew Wong and Cody Shrader are senior engineers at Hyde Engineering + Consulting, Boulder, CO,