Cleaning Validation – Swab Test

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					                                                                             TEM-015
                                                                             Issue date
                            Cleaning Validation – Swab Test
                                           (Ref. VAL-020)



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SWABBING RECOVERY STUDIES

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 swab samples will be
         carried out and compared using TOC and HPLC analysis. Standard solutions will be
         applied to stainless steel plates, dried and the residue removed by swabbing using the
         Texwipe TX761 swab. Assessment of Linearity, Accuracy (recovery), LOQ, LOD and
         precision of the swabbing method will be determined.

2.       Test Objective
         1. Determine the linearity and precision of a series of standards swabbed from a
            stainless steel plate and measured by TOC and HPLC over a known concentration
            range.
         2. Determine the accuracy (recovery) of a series of standards swabbed from a stainless
            steel plate and measured by TOC and HPLC over a known concentration range.
         3. Determine the Limit of quantitation and limit of detection of a series of standards
            measured by TOC and HPLC over a known concentration range.
         4. Determine correlation between HPLC and TOC analysis.
         5. Determine the visually clean limit.
         6. Determine the final HPLC and TOC swabbing limits based on recovery studies.

3.       Acceptance Criteria
          Test              Measured Response                Acceptance Criteria
          Objective
          3.1. Linearity    The correlation coefficient      3.1.1. HPLC: equal to or greater than 0.997
                              2
                            (r )   for     the   linear
                                                             3.1.2. TOC: equal to or greater than 0.980
                            concentration range.
          3.2. Precision    % RSD                            3.2.1. HPLC: The recovery %RSD less than or equal
                                                             to 10.0%.
                                                             3.2.2. TOC: The recovery %RSD less than or equal
                                                             to 15.0%.




File Location:                               Date Printed:                                Page 1 of 7
                                                                               TEM-015
                                                                               Issue date
                             Cleaning Validation – Swab Test
                                          (Ref. VAL-020)

                    important that all the alcohol has evaporated from the surface prior to
                    swabbing).
                 4.2.2. Place the required number of swabs into the established volume of
                    extraction solvent. Remove swab(s) and swab the designated area according
                    to the established procedure outlined in the Cleaning Validation SOP G 1.7 or
                    as outlined in the modified analysis method. Place the swab(s) back into the
                    extraction solvent and vortex for 1 minute. Remove swabs from vial. Analyse
                    the        resultant      extracts       by       HPLC         and      TOC.

                    Residue        recovery        will       be      calculated     as        follows:

                           where % recovery =        result found   x 100
                                                    result expected


                 4.2.3. Determine the visually clean limit while performing the swabbing studies
                    by observing the minimum concentration at which the active residue is visible
                    on the surface of the stainless steel test plate to the human eye.
                 4.2.4. Tabulate results as detailed in results section and plot linear regression
                    and document results of linear regression analysis for both HPLC and TOC
                    analysis.

5.       Results
         3.1. Linearity - Swabbing Active Residue
                 3.1.1. HPLC Analysis
                   Active     Concentration      Peak Area of Active
                   (ug/mL)
                   (50%)
                   (100%)
                   (400%)
                 • Plot Concentration vs Peak Area (calculate linear regression)
                                                     2
                 • Coefficient of Determination (R ) =
                 3.1.2 TOC Analysis
                   Actual Total Organic          Measured Total Organic
                   Carbon Concentration          Carbon Response (ppm)
                   (ppm)
                   (50%)
                   (100%)
                   (400%)
                 • Plot Actual TOC Concentration (ppm) vs Measured TOC Response (ppm)
                                                     2
                 • Coefficient of Determination (R ) =
         3.2 Accuracy - Swabbing active residue / Precision
                For each measured response over the concentration range examined in the
                Linearity test calculate % recovery and % RSD for each of the triplicate samples.
                 • where % recovery = result found            x 100


File Location:                                Date Printed:                                 Page 3 of 7
                                                                          TEM-015
                                                                          Issue date
                           Cleaning Validation – Swab Test
                                         (Ref. VAL-020)


                       2
          MAC per cm level            Average        Recovery      Average         recovery
                                      (Budesonide) ppm             (Pulmicort carbon) ppm
                                      HPLC                         TOC
          (50%)
          (100%)
          (400%)
                  • Plot Average Recovery Active 1 ppm HPLC vs Average recovery Active 2 ppm
                     TOC
                  Linear regression line             =
                  Correlation coefficient (R)        =
                                                 2
                  Coefficient of determination (R )  =
         5.2. Visually Clean Limit
                 The Visually clean Limit must be determined while performing the swab recovery
                 studies. This is done by visually inspecting the surface and determining the
                 highest concentration of active residue that is not easily detectable by visual
                 inspection. This concentration is then recorded as the Visually clean limit.
                 Visually Clean Limit = _________________
         5.3. Determining Final HPLC and TOC Swabbing Limits Based on Recovery
         Studies
                HPLC Swabbing Limits
                Determine the lowest and most conservative active recovery value obtained
                during the method validation study for HPLC analysis.
                Lowest HPLC swab recovery value = ____________
                Calculate the final HPLC swabbing limit for the surface tested:
                                      2
                Active MAC per cm of total surface area x swabbing area x lowest swab
                recovery
                            average recovery from swabbing material
                = “X” mg per swab
                divide by extraction volume and multiply by 1000 to give ppm limit per swab
                HPLC Swabbing Limit = __________________________________= ________
                mg per swab
                HPLC Swabbing Limit (ppm) = ________________________= __________
                ppm per swab
                Example Calculation:
                                  2         2
                0.000417 mg/cm x 100 cm x 0.6864 = 0.02898 mg per swab
                             0.9877
                If each swab is extracted using 25.0 mL of water, the limit becomes:
                  →0.02898mg/25mL x 1000 µg/mL = 1.16 µg/mL or 1.16ppm per swab.
         5.4. TOC Swabbing Limits
         Determine the lowest and most conservative active recovery value obtained during the
         method validation study for TOC analysis.
                Lowest TOC swab recovery value = ____________


File Location:                            Date Printed:                                Page 5 of 7
                                                             TEM-015
                                                             Issue date
                           Cleaning Validation – Swab Test
                                        (Ref. VAL-020)

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