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19 Cleaning Validation Strategies
Charles Lankford
PharmaSys, Inc., Cary, North Carolina, U.S.A.
OVERVIEW OF CLEANING VALIDATION STRATEGIES AND METHODS
This chapter is an overview of cleaning validation strategies and methods.
Principles and concepts employed in the design and implementation of an effective
cleaning validation program will include cleaning validation study design and
implementation, analytical techniques, establishment of acceptance criteria, and
single versus multi-product issues.
It is impossible to provide athorough in-depth dissertation of the cleaning
validation process within the confines of this chapter as it is acomplex subject
and quite specific to the product or products that are being manufactured. Volumes
have been written on the subject. There are, however, common principles and
industry accepted techniques involved and this chapter will focus on the basic
principles of validating the cleaning process for clean-in-place (CIP) systems which
translates to validation of manual cleaning procedures as well.
Cleaning validation is uncomplicated in concept. Simply put, it is proving
that aspecific cleaning process adequately cleans the contact surfaces of aspecific
equipment train configuration of aspecific substance to apredetermined acceptable
limit; and further that the cleaning agent is adequately removed from the
contact surfaces of the equipment train to apredetermined acceptable limit. To be
valid, acleaning process must also be consistent and reproducible.
Many factors are taken into consideration when designing a cleaning
validation study program. These factors include physical product characteristics,
the toxicity of the product and the cleaning agent, the dirty/clean hold times for the
equipment, the sample/recovery techniques and locations, and the analytical
techniques used to evaluate the effectiveness of the cleaning process. All of these
factors are highly specific to agiven substance and therein constitutes the problem
with asingle source reference on the subject.
CLEANING VS. SANITIZATION VS. STERILIZATION
To start with, let’s contrast the following terms to clarify what we are talking
about:
& Cleaning is the process of removing particulates and residue from asurface.
Aclean surface is free of dirt, grime, or other residue. It is easy to clean a
surface but cleaning doesn’t mean sanitizing.
& Sanitization is generally thought of as killing the more sensitive vegetative
cells but not heat-resistant spores. Sanitization does not necessarily include
sterilization, although some processes of sanitization accomplish sterilization.
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