Follow
1.0 OBJECTIVE
To lay down a procedure for determination of chromatographic peaks as extraneous to determine and evaluate apparently extraneous peaks in chromatographic data obtained from analytical testing and review of chromatography.
2.0 SCOPE
This procedure is applicable to the evaluation of chromatographic data generated in the analysis of swab-samples used in cleaning verification. However, the general principles discussed in the SOP may be applied to the review of any chromatographic data, especially those involving chemistry for trace level detection and quantitation.
3.0 RESPONSIBILITY
3.1 Designated officer/ Sr. officer/ Assistant manager shall be responsible to develop and validated the excel worksheet.
3.2 All analysts shall be responsible for following the procedure as described in this SOP.
3.3 Overall responsibility for training, implementation and follow-up with the QC Manager or his/her nominee.
4.0 ACCOUNTABILITY
4.1 Head of Quality.
5.0 PRECAUTION
5.1 Chromatographic analysis should be conducted following all applicable laboratory SOPs, policies, practices and training.
5.2 The Analyst or Data Reviewer should follow this SOP whenever reviewing chromatographic data.
5.3 Extraneous peaks should be investigated in accordance with all applicable laboratory SOPs, policies, and practices.
6.0 PROCEDURE
6.1 Extraneous Peak – A peak response in the sample’s chromatogram above the analytical method’s validated Limit of quantitation not readily attributable as a characteristic of the injection profiles of the blank, mobile phase, diluting solvent, standard, or other preparation other than the sample, which requires determination of identity through investigation.
6.2 Noise – A peak response in the sample’s chromatogram below the analytical method’s validated Limit of quantitation. Noise is not considered to be extraneous, and therefore does not require analytical investigation for identification.
6.3 Review each chromatogram for the entire chromatographic run.
6.3.1 Chromatograms of the injections of blank, mobile phase, diluting solvent, gloves, vials/caps, laboratory glassware exposed to diluting solvent/extraction solvent/mobile phase, cleaning detergent (when applicable) extraction solvent, any other solutions/solvents, (or combination of any of the former), the sample would contain in its preparation or analysis, or any other injections indicated by the analytical method should be reviewed to establish the retention times of any components that may generate an absorbance signal.
6.3.2 Chromatograms of each injection of the system suitability standard should be evaluated for uniformity of profile. Each chromatogram should appear as identical to the others as possible; the only differences between them being characteristic of the RSD determination.
6.3.3 Chromatograms of Samples should not contain any peak that was not detected in any of the chromatograms from injections from 6.3.1 and 6.3.2.
6.3.4 Chromatograms of Samples may not contain all peaks detected in injections from 6.3.1 and 6.3.2.
6.4 If a peak is detected that cannot be readily attributed to any of the profiles of the injections cited in 6.3.1 and 6.3.2, the following will apply:
6.4.1 Determine the percent peak area of the extraneous peak versus that of the quantitation standard at the specification limit. If the percent area is greater than 10% of the peak area of the quantitation standard at the specification limit, proceed as indicated in 6.6.1. Note that the quantitation standard in the analytical method may not be at the specification limit. If the result is less than 10%, proceed as indicated in 6.7, skipping 6.5 and 6.6.
6.4.2 Determine the sum of the percent peak areas of the extraneous peaks versus that of the quantitation standard at the specification limit. Note that the quantitation standard in the analytical method may not be at the specification limit. If the sum of the percent areas is greater than 40% of the peak area of the quantitation standard at the specification limit, proceed as indicated in 6.5. If the result is less than 40%, proceed as indicated in 6.7, skipping 6.5 and 6.6.
6.5 If the percent area is greater than 10% of the peak area of the quantitation standard at the specification limit, and/or if the percent area is greater than 40% of the peak area of the quantitation standard at the specification limit, this peak, or peaks should be considered extraneous and a laboratory investigation should be initiated.
6.5.1 Determination of the identity of the extraneous peak (s) through appropriate protocol-driven experimentation, should be made considering that the extraneous peak may be the result or by-product of factors such as, but not limited to, the following:
6.5.1.1 Reaction of the active pharmaceutical ingredient (or product, including its excipients) with the cleaning agent under the conditions of the cleaning process, i.e. exposed to hot water, etc.
6.5.1.2 A product previously runs on that manufacturing equipment, i.e. residue of an active pharmaceutical ingredient from the previous manufacturing campaign.
6.5.1.3 A reaction between active pharmaceutical ingredients from previous manufacturing campaigns, or combination thereof, which has produced a unique peak.
6.5.1.4 Lubricants or grease from the manufacturing process.
6.5.1.5 Other components or materials involved in the process.
6.6 The investigation into the determination of the identity of the extraneous peak may require analysis by analytical techniques other than UV with photo-diode array. For example, mass spec analysis or other such technique/instrumentation may be necessary.
6.7 If the percent area of the peak is greater than the analytical method’s validated Limit of quantitation, but less than 10% of the peak area of the quantitation standard at the specification limit, and/or if the sum of the percent areas of all peaks greater than the analytical method’s validated Limit of quantitation is less than 40% of the peak area of the quantitation standard at the specification limit, this peak, or peaks are not considered extraneous and no investigation is required.
