TEM-015 Issue date

Cleaning Validation – Swab Test
(Ref. VAL-020)

Project number: Protocol Number: Product/Active: Process Line:

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 Objective 3.1. Linearity Measured Response The correlation coefficient 2 (r ) for the linear concentration range. % RSD Acceptance Criteria 3.1.1. HPLC: equal to or greater than 0.997 3.1.2. TOC: equal to or greater than 0.980 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%.

3.2. Precision

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Analyse the resultant extracts by HPLC and TOC.TEM-015 Issue date Cleaning Validation – Swab Test (Ref. 4. Results 3. Residue recovery will be calculated as follows: where % recovery = result found x 100 result expected 4. 4.2. Remove swab(s) and swab the designated area according to the established procedure outlined in the Cleaning Validation SOP G 1.1. Remove swabs from vial. Place the required number of swabs into the established volume of extraction solvent.1.2.2.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.4. VAL-020) important that all the alcohol has evaporated from the surface prior to swabbing).2. Place the swab(s) back into the extraction solvent and vortex for 1 minute.2 Accuracy .Swabbing Active Residue 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. 5. Tabulate results as detailed in results section and plot linear regression and document results of linear regression analysis for both HPLC and TOC analysis.3.7 or as outlined in the modified analysis method. Linearity .2 TOC Analysis Actual Total Organic Carbon Concentration (ppm) (50%) (100%) (400%) • Plot Actual TOC Concentration (ppm) vs Measured TOC Response (ppm) • Coefficient of Determination (R ) = 3. • where % recovery = result found x 100 2 2 Concentration Peak Area of Active Measured Total Organic Carbon Response (ppm) File Location: Date Printed: Page 3 of 7 . HPLC Analysis Active (ug/mL) (50%) (100%) (400%) • Plot Concentration vs Peak Area (calculate linear regression) • Coefficient of Determination (R ) = 3.1.1.

TOC Swabbing Limits Determine the lowest and most conservative active recovery value obtained during the method validation study for TOC analysis.0 mL of water. Visually Clean Limit The Visually clean Limit must be determined while performing the swab recovery studies. VAL-020) MAC per cm level 2 Average Recovery (Budesonide) ppm HPLC Average recovery (Pulmicort carbon) ppm 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. the limit becomes: →0.02898 mg per swab 0.6864 = 0.3. 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.4. 5. 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 0.16 µg/mL or 1. This concentration is then recorded as the Visually clean limit.16ppm per swab.9877 If each swab is extracted using 25. Lowest TOC swab recovery value = ____________ File Location: Date Printed: Page 5 of 7 . This is done by visually inspecting the surface and determining the highest concentration of active residue that is not easily detectable by visual inspection.02898mg/25mL x 1000 µg/mL = 1.000417 mg/cm x 100 cm x 0.2.TEM-015 Issue date Cleaning Validation – Swab Test (Ref. Visually Clean Limit = _________________ 5.

VAL-020) DOCUMENT REVISION HISTORY Revision # Date Reason for Revision Author Initial for Retrieval of Outdated Documents File Location: Date Printed: Page 7 of 7 .TEM-015 Issue date Cleaning Validation – Swab Test (Ref.

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