Cleaning Validation – Comparative Analysis

1. Test Description
This test is to be conducted to document the validation of a TOC analysis method for use in measuring
samples for cleaning validation. A parallel analysis of samples will be carried out and compared using TOC
and HPLC analysis.
2. Test Objective
To determine the linearity and precision of a series of standards measured by TOC and HPLC over a
known concentration range.
• To determine the accuracy and recovery of a series of standards measured by TOC and HPLC
over a known concentration range.
• To determine the limit of quantitation and limit of detection of a series of standards measured by
TOC and HPLC over a known concentration range.
3. Acceptance Criteria
Test Objective Measured Response Acceptance Criteria
3.1. Linearity The correlation coefficient
(R2) for the linear
concentration range.
3.1.1. HPLC: equal to or greater than 0.997
3.1.2. TOC: equal to or greater than 0.980
3.2. Accuracy % recovery of the theoretical
amount at all concentrations
tested.
3.2.1. HPLC: 90-110%
3.2.2. TOC: 85-115%
3.3. Limit of
Quantitation
% RSD and % recovery 3.3.1. HPLC: lowest concentration of the “active”
residue at which: The area %RSD of six replicate
injections is less than or equal to 10 and recovery
between 90-110% of the theoretical amount.
3.3.2. TOC: lowest concentration at which: the
area % RSD from four replicate injections is less
than or equal to 15.0% and recovery of the
“active” residue must be between 85-115% of the
theoretical amount.
3.4. Limit of
Detection
Lowest detectable standard
concentration.
3.4.1. HPLC: The lowest concentration of active
residue that can be consistently detected for four
consecutive replicate injections.
3.4.2. TOC:
• The lowest concentration of “active” residue
that can be readily detected by the instrument
in four consecutive injections.
• The determined LOD must be equal to or
greater than that carbon concentration obtained
by multiplying the standard deviation of six
injections of Type I water (18 megohms-cm