Cleaning Validation – Rinsate and Swab Sample,Test Method Development and Validation

If a specific method is being validated, then specificity studies need to be performed for
the analyte of interest. The potential for interference from the following should be
considered:
o Swab extractables
o Cleaning agents
o Sample containers and lids
o Excipients and other compounds potential present
􀂇 If a specific method is being validated for a cleaning agent, the only specificity
experiment typically executed is specificity from swab extractables.
Range
The equipment cleaning analytical method should be validated around the calculated RAL for the
material. The method is considered valid for any RAL within the validated recovery range. If the
RAL falls outside the validated recovery range, the method should be revalidated with respect to
the affected elements (e.g. range, linearity).
Linearity
Linearity should at a minimum cover the expected analyte RAL and encompass the levels
included in repeatability and recovery studies. The lower end of the linearity study shall take into
consideration the correction factor for sampling recovery, if applicable (e.g. if the RALs have a
range of 4-6 ug/cm2 and the recovery is 50 percent, the linearity study should include levels of
2-6 ug/cm2 ).
Intermediate Precision
Intermediate precision is the study of the effects of random events (e.g. days, analysts, equipment
etc.) on the precision of the analytical procedure. A method intermediate precision experiment
should be conducted unless there is a documented rationale otherwise (e.g. a reliable and robust
swabbing verification program is implemented). Method intermediate precision should include
use of a second Lab Analyst, on a different day, using different solutions and different analytical
equipment, if possible.
System Suitability
System suitability should be conducted for systems such as HPLC and TOC. Although nonspecific
methods like UV, pH etc. may be used; the ability of the selected method to detect the
residue shall be demonstrated (for example UV absorbance at the residue maximum wavelength
and non-interference of the rinse solution).
Recovery Studies
Analyte residue recovery shall be challenged as part of the analytical method validation. The
recoveries of each material (product or cleaning agent) from the different process-contact surfaces
that constitute the major portions of equipment􀂶s surface area are typically demonstrated.
Alternatively, the recovery value of a worst case material could be substituted for all the materials
sampled with the same rinse solvent. Typical surfaces may include hastelloy, stainless steel,
glass/glass lined carbon steel and PTFE (polytetrafluoroethylene).
The solvent used in the recovery study should be the same as is used for routine sampling.