In biopharmaceutical and many pharmaceutical operations, post-production residues are primarily removed by chemical, rather
than physical, means. Chemical cleaning is typically the most efficient mechanism for removing in-process material. Chemical
cleaning methods rely on fully developed turbulent flow in pipelines and spray devices (often non-rotating sprayballs) in
vessels and other processing equipment to supply rinsing and washing solutions to surfaces being cleaned. Cleaning is a mass
transfer process that relies on good mixing and strong convection to produce turbulence. Turbulent flow promotes efficient
mass transfer and thus is a key factor in optimizing cleaning cycles.
Clean-in-place (CIP) systems generate and deliver cleaning solutions to process equipment. Controlling the generation of specific
concentrations, the distribution of consistent quantities, and the temperatures of rinse waters and cleaning solutions is
automated. These rinsing waters and cleaning solutions are typically returned to the CIP system where they are either sent
to drain or recirculated.
Advances in the application of cleaning technology to biopharmaceutical process systems have resulted in a new focus on the
optimization of cleaning processes as a means to increase productive capacity. This article examines cleaning processes and
theory and addresses how to reduce cleaning run times and increase capacity.
Figure 1. ESC CIP System - ESC, an Entegris Company
PROCESS SYSTEM DESIGN FOR CIP
CIP engineering begins with the overall definition of cleaning circuit and cycle strategy, continues with design and build
of the manufacturing facility, and culminates in the development of optimized and validated cleaning circuits. For the purposes
of this discussion, a CIP circuit includes the CIP skid, CIP supply piping, the process equipment being cleaned (including
its interconnecting process piping), and the CIP return piping (Figures 1 and 2).
For the most effective use of CIP technology, cleaning circuits must be designed into the facility from the beginning. In
many facilities, cleaning operations are designed as an afterthought. Design starts with process flow diagrams and continues
in detail with piping and instrument drawings. The best time to incorporate CIP design is during these early design stages
because the CIP and process piping are closely integrated and interdependent — although this is not always acknowledged.
Figure 2. Typical CIP Circuit Schematic
If the integration of CIP and process piping is not addressed during plant design, it will ultimately be handled in the facility
— either during or following plant construction. Design features that could have been perfected with "pencil and eraser" must
be addressed with "hacksaw and torch," which is extremely inefficient.
Specify new equipment designs so they are suitable for CIP. Ensure that vendors have experience with CIP operations and vendors
and mechanical contractors comply with the guidelines of the American Society of Mechanical Engineers Biopharmaceutical Process
Committee (ASME-BPE). Finally, always specify disc-type vortex breakers to ensure proper vessel drainage. The vortex breaker
will help to assure adequate vessel drainage while it is being cleaned, eliminating residue and cleaning agent carry-over.