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Lankford
acleaning validation protocol has been initiated for aspecific product, the next two
batches of the same product should be used for the process. By skipping abatch, it
will call into question the validity of the study.
Analytical Techniques
The analytical methods used for cleaning validation vary according to the
characteristics of the potential contaminants thus making it impossible to specify
one preferred analytical method in this dissertation. Abrief survey of methods
currently utilized and factors that should be considered when selecting cleaning
validation methods will be discussed.
The basic considerations for use of analytical methods for cleaning validation
are the ability of the method to detect the target substance(s) at levels consistent
with the acceptance criteria and the ability to detect the target substance(s) in the
presence of other materials that may also be present in the sample (8,9).
Regardless of the method(s) utilized, they should be validated for the specific
application. Method validation is beyond the scope of this dissertation; however,
each method should be validated for specificity, linearity, precision, accuracy, limit
of detection (LOD), and limit of quantitation (LOQ) (10). Validated analytical
techniques utilized in evaluating residues in cleaning validation are critical to the
success of the programand each substance may require differentmethods. Method
validation is beyond the scope of this chapter.
Analytical methods can be grouped into two categories, specific and nonspecific.
Each category has advantages and disadvantages which will be covered
later in the text. Regardless of the analytical method utilized for cleaning validation,
it must be scientifically applicable and validated for its intended application.
Care should be taken when using analytical methods to test for acceptable
residual amounts of active material. Several opportunities exist to introduce
unknown material into the sample. Acommon occurrence is the introduction of
leached material into the sample by rinsing or swabbing agents. Plastic and rubber
material from tubing, seals, and components are often the source of these
unknowns. Asound investigation and reporting procedure covering unknown
material in samples should be developed. Atypical investigation path would be to
check the unknowns against the two previous active materials and the detergent(s)
used for cleaning.
Specific or Selective Methods
An analytical method that is specific will provide aquantitative assessment of a
particular target contaminant. The primary advantage of using aspecific method is
the fact that the target contaminant can be detected and measured.
The use of specific methods is traditionally considered the conservative
approach for testing for active contaminants and cleaning agents during cleaning
validation. Health Canada and PIC/S recommend that specific methods be used in
cleaning validation (6,2). However, the FDA, the European Community Working
Party on Control of Medicines and Inspections, and Active Pharmaceutical
Ingredients Committee (APIC) do not require aspecific method to be used for
cleaning validation analysis (8,11,12). Indeed APIC directly addresses that nonspecific
methods are acceptable for cleaning validation.
In most cases, companies will already have analytical methods to detect active
products as part of their stability and/or product release program. It should be