The following is excerpted from the chapter, “Cleaning and Sanitization Practices,” in the book, Contamination
Prevention for Nonsterile Manufacturing, by Andrew Dick. The book can be purchased at the PDA Bookstore.
- Include identification and classification of equipment (by
type) in the validation.
- Identify the strategy by which product(s) and/or equipment
are grouped in the validation. Use the hardest-to-clean products
and hardest-to-clean equipment for the validation study
and supply a rationale (e.g., why one piece of equipment is
used rather than another).
- Be prepared to demonstrate reproducibility of the resultant
cleaning; in most cases, three executions are sufficient to demonstrate
- Identify or define the specific cleaning procedure that will be used
to clean the equipment (i.e., in an SOP), including reference to a
change control document, as well as validation frequency.
- Ensure the results meet the “reasonable” industry standard of
1/1000 of the active ingredient level dose or no more than 10
ppm of any previous product.
- Conduct residue studies to ensure elimination of product,
detergent, and chemical sanitizer. The detergent manufacturer
should list the specific composition of the chemical so that the
site can test for the composition recovery after cleaning. Two
methods are commonly used:
- Direct Surface Sampling: Measures the actual equipment
surface being cleaned. Determine the type of sampling material
used and its impact on the test data as the sampling material
may interfere with the test. For example, the adhesive
used in swabs has been found to interfere with analysis of
samples. Therefore, early in the validation program, ensure
that the sampling medium and solvent (used for extraction
from the medium) are satisfactory and can be used readily.
- Rinse Samples: Tests for contaminants remaining in
rinse water. There are two advantages of using rinse samples:
a larger surface area can be sampled and inaccessible
systems, or those that cannot be routinely disassembled,
can be sampled and evaluated. One disadvantage of rinse
samples is that the residue or contaminant may not be soluble or may be physically occluded
in the equipment, giving a
false negative result. (Rinse water
samples taken may pass; however,
when opened, residue is evident
indicating that water did not rinse
- An analogy that can be used for
rinse samples is the “dirty pot.”
In evaluating the cleaning of a
dirty pot, particularly one with
dried-out residue, observe the
interior of the pot to see that it is
clean, rather than observing the
- Check to see that a direct measurement
of the residue or contaminant
has been made for the rinse water
when it is used to validate the cleaning
process. In other words, the rinse
water cannot simply be tested to see
that its quality meets pharmacopeial
standards; it must also be tested for
potential contaminates and TOC.
- Identify the times, locations, and number
of replications for equipment sampling,
including “worst-case” scenarios. Include
which equipment must be dismantled
for sampling and inspection.
- Identify the people responsible for
cleaning and sanitizing equipment.
- Provide validation activity summaries
as indicated in the validation protocol.
Testing should demonstrate the
ability of the cleaning procedure to
adequately meet the criteria for success.
Any test results exceeding the
criteria for success must be addressed,
the risk assessed, and corrective action
- Include digital photographs of the
equipment that requires cleaning and
sanitizing in the master validation
report and validation implementation.
Take photos both before cleaning and
after sanitization to demonstrate what