PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 212

predetermined thresholds, leading to review periods of 1-5 years. For example, a
risk score above 12 (out of 16) would be reviewed annually, intermediate scores
6-9 would be reviewed every two years and no periodic review is required for
scores < 6.

8.10 CLEANING VALIDATION AND CROSS CONTAMINATION RISKS

CV is establishing documented evidence through a collection and evaluation of
data that will provide a high degree of assurance that a specific cleaning process
will produce cleaning results that are consistent and reproducible, meeting its
predetermined level [29]. The purpose of CV is to:

• ensure that cleaning procedures are adequate for cleaning new products
and/or new equipment;
• ensure that residues after cleaning of equipment are reduced to an acceptable
level before the manufacture of the next batch and/or the next product in
the same equipment;
• assess a new product and/or new equipment for cleanability before GMP
production;
• provide ongoing assurance of a state of control of validated cleaning proce-
dures through monitoring and periodic revalidation; and
• evaluate changes to cleaning processes, other manufacturing processes, and
equipment to maintain these validated cleaning processes in a state of

control.

The design and cycle development for an automated cleaning process is con-
sidered a prerequisite for CV. Maximum allowable time intervals for dirty or
noncleaned hold times (time between equipment use and cleaning or steriliza-
tion) and clean hold times (time elapsed between cleaning and equipment use)
should be established [7,14]. The dirty and clean hold times should be reasonable
and not excessive and lengthy; risk-based approaches may be used to determine
the extent of validation of these parameters.
According to the ICH Q9 Guide, risk-based approaches are acceptable in
differentiating efforts in cleaning of equipment based on intended use [11]. A
risk-based approach could be used to determine validation strategy, sample sites
and testing, acceptance criteria, small-scale study, number of commercial-scale
experiments, and appropriate control to prevent cleaning failures [30]. There are
several elements of cleaning process development, control, and validation includ-
ing but not limited to cleaning solution, cycle parameters, equipment type, hold
times, sampling techniques, analytical assays, and acceptance criteria [31,32].
Small-scale cleaning studies may provide a useful model to evaluate cleanabiltiy
of new products relative to the worst case and determine the need to perform