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26 BioPharm International eBook October 2020 www.biopharminternational.com Regulatory Sourcebook Data Integrity Figure 6. Application of ALCOA+ requirements to a United States Pharmacopeia (USP) <731> Loss on Drying analysis. ALCOA is attributable (A), legible (L), contemporaneous (C), original (O), and accurate (A), and ALCOA+ adds complete (C), consistent (C), enduring (E), and available (A). Step # Analytical Procedure Description Documented evidence A L C O A C C E A 1 Interpreted procedure of USP monograph test requirement Authorised analytical procedure ü ü ü ü ü ü 2 Obtain uniquely number approved blank worksheet from the Quality function Traceable paper record issued ü ü ü ü 3 Analyst 1 adds the batch specific information and identity Record on the worksheet ü ü ü ü 4 Identify balance and oven to be used Record on the worksheet ü ü ü ü 5 Check balance calibration and oven information Record on the worksheet ü ü ü ü 6 Tare balance and weigh two dried glass weighing bottles with stoppers and print values Attach and initial the annotated balance print out to the work sheet ü ü ü ü 7 Dispense two sample amounts of between 1.5 to 2.0 g into the dried glass weighing bottles ü ü ü 8 Tare balance and re weigh the two dried glass weighing bottles and print values ü ü ü 9 Calculate the accurate weight of the samples and compare with the acceptance criterion Calculation record on worksheet ü ü ü ü 10 Record the oven temperature before placing the weighing bottles and stoppers in to it Record on the worksheet ü ü ü ü ü 11 Record time weighing bottles and stoppers placed into the oven Record on the worksheet ü ü ü ü ü 12 After 3 hours record, the oven temperature and the time Record on the worksheet ü ü ü ü ü 13 Remove weighing bottles from the oven and place into a desiccator to cool recording the time Record the time on the worksheet ü ü ü ü ü 14 Are both before and after oven temperatures in the range 105±2°C? If so initial acceptance ü ü ü 15 Calculate the drying time in the oven (must be greater than or equal to 180 minutes) Calculation record on worksheet ü ü ü 16 Record the time taken out of the dessicator Record the time taken out of the dessicator on the worksheet ü ü ü ü 17 Calculate the cooling time. The time in the desiccator must be at least 45 minutes Calculation record on worksheet ü ü ü ü ü 18 Tare balance and reweigh the two stoppered glass weighing bottles containing the samples and print values Attach and initial the annotated balance print out to the work sheet ü ü ü ü 19 Calculate the loss in weight for each sample and calculate the % LOD for each sample to 3 significant figures Calculation record on worksheet ü ü ü ü ü 20 Calculate the difference beween the two individual results Calculation record on worksheet ü ü ü ü ü 21 Compare with the defined acceptance criterion Initial acceptance or not ü ü ü 22 If acceptable, calculate the mean value which is then rounded to the number of significant figures in the standard as the reportable result Calculation record on worksheet ü ü ü ü ü 23 Compare the reportable result is in accordance with the Pharmacopeial standard Record decision and initial ü ü ü ü ü 24 Conduct a full second person (Analyst 2) review in accordance with the standard procedure Record review decision and initial ü ü ü ü ü 25 Return the uniquely number completed and reviewed worksheet to the Quality function Traceable paper record returned and reconciled ü ü Attach and initial the annotated balance print out to the work sheet üü Figure 5. Detail of the Loss on Drying analytical procedure. Analytical Record (on uniquely numbered approved blank worksheet) Steps 3 to 5; Handwritten entry Steps 6 to 8; Printouts attached Steps 10 to 12; Handwritten entry Calculation & acceptance of sample amount Step 9; Handwritten entry Steps 13, 16; Handwritten entry Acceptance of drying temperatures and calculated drying time Steps 14 & 15; Handwritten entry Calculation & Acceptance of cooling time Step 17; Handwritten entry Step 18; Printouts attached Steps 19 to 23; Handwritten entry Step 24; Handwritten entry Analytical Test Procedure Record test specific information Sample amount to be dried in weighing bottles Oven drying Cooling in desiccator Sample dried amount in weighing bottles Second Person Review Calculation of % LOD and comparison with standard