3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans and test procedures designed to assure that components, drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
Your firm failed to validate the Excel spreadsheet used to perform the assay calculation for your “[redacted].” Your procedures lacked guidance on how to check and manually verify the calculation sheets. During the inspection, our investigator identified a calculation error within the spreadsheet. The incorrect formula for averaging the Internal Standard peak area was used.
There is no assurance that the associated assay results recorded are reliable and accurate.
In your response, you stated that you have retrospectively tested products in the market using correct procedures and will update the validation master plan to ensure that spreadsheets are included within the scope of validation efforts. You created a new procedure which details the approach for validating spreadsheets as well as protecting the file from accidental changes. You also stated all Excel spreadsheet calculations for your [redacted] batches have been retrospectively reviewed.
During the review, you identified another error within your Excel spreadsheets. The assay test result for [redacted] batch [redacted] was incorrect due to a transcription entry error for active peak area. Your firm used a new spreadsheet and entered the correct active peak area. The result was recalculated, and the final result was reported. The product had already been released with test results using the incorrect calculation, although the recalculated test result was still within specification. You have committed to manually check calculations until the spreadsheet has been validated.
Your firm relied on Excel spreadsheets to calculate assay and determine the reportable result for final batch release. Your computerized systems must perform their functions satisfactorily and that your firm establish a written program to ensure ongoing proper system performance.
Your response is inadequate. You have not fully assessed the potential impact of using data from unvalidated, unsecured spreadsheets for critical CGMP functions.Excel spreadsheets are so useful, and who knew they had to be validated? (answer: lots of people)