The bio-pharmaceutical industry demands exacting detail in design, development,
operation, quality, and just about every other aspect of the business.
As such, there is a degree of specialty in most every field of endeavor
in this industry. This book was developed to try to accelerate the learning
process for the application of automation in bio-pharmaceuticals. The
authors' hope is that the content of this book will help scientists and engineers
continue to contribute to the manufacture of high-quality medicines
via improving process control and on-line availability of information
while reducing costs, cycle time, and process variability.
Some readers may come into this industry with previous automation
experience. Others may be in the bio-pharmaceutical industry, but have
limited automation knowledge. In either case, the authors strived to bring
the reader to a more thorough understanding of the topics.
This book is supplemented by a wealth of reference materials in the industry.
Each chapter contains a list of recommended reference materials.
TABLE OF CONTENTS Chapter 3.3 - Clean-In-Place: CIP
Process Description and Challenges
The Clean-In-Place (CIP) system is responsible for supplying cleaning
solutions to various parts of the process. Typically, this includes the
supply of both acidic and basic cleaning fluids, hi-purity water and/or
lower purity water. [3.7]
All cleaning solutions must be supplied at appropriate temperatures and
pressures to allow for rigorous cleaning action within the piping and vessels
being cleaned. The piping being cleaned may range from small chemical
addition lines up to large vessel flow paths. Spray balls are often used
to provide full coverage of vessel internals.
Temperature, pressure, and flow setpoints may change throughout the
cleaning cycle. For example, some biological processes may leave proteinaceous
residues. Attempting to clean these materials with hot cleaning
fluids may result in "baking" of the proteins, leaving a deposit that is difficult
or impossible to remove by the CIP system.
A typical CIP cleaning cycle may contain one or more of the following
steps:
- Preliminary flush with water
- Caustic cleaning
- Hot water flush
- Acid flush
- Final rinse
These steps are typically applied to each flow path within the equipment
being cleaned. They may be used in combination to provide the most
effective cleaning for a system. Figure 3-1 shows a flowchart of a typical
CIP cycle.
Cleaning fluids must be prepared to appropriate concentrations, stored at
specific conditions, and then distributed, as needed, to the process.
In some cases, cleaning fluids are recycled to reduce costs. In these cases,
the return fluid flows must be balanced with the supply, to avoid pooling
of fluids at any point in the process. Proper maintenance of the material
mass balance during the CIP cycle is critically important. A "balance tank"
may be used to keep an adequate supply of materials during the re-cycle
phase.
During system commissioning, it is typical for "Cleaning Development"
and "Cleaning Validation" activities to rigorously test the operation of the
CIP system, and establish setpoints for temperatures, flows, pressures,
conductivity/composition, and timers. It is important that the automation
system allows for this experimentation during commissioning, and
then allows for the user to "lock down" parameters to be used during routine
production.
Finally, in heavily automated systems, the CIP system may keep track of
equipment status (clean/dirty), acceptable "clean hold time" and may be
required to print cleaning reports.
