(b)(4).Investigation: per the customer, the units were processed and the alleged hemolysis was observed in the plasma post centrifugation.The disposable sets were not returned for evaluation.The manufacturing records, test records and inspection records were reviewed for this lot.No anomalies were noted and the product conformed to current established specifications.No similar reports have been received regarding this lot number.Three retention samples from this production number were visually examined.One bag was tested for solution volume and the other two were tested for the composition of the solution.There were no abnormalities in appearance and measured values conformed to in-house standards.Investigation of the manufacturing change control history for the past two years, confirmed that the specification for the cationizing agent had been increased.This change had been implemented, to allow greater stability in production.Hemolysis testing was performed to investigate the impact of the cationizing agent.Investigation results indicate that the cationization level of the filter which was integrated into the sterilized product increased and the concentration of free hemoglobin in whole blood increased.The distribution width of the cationization level of actual filters were reviewed and found that it was possible that the width of the cationization level of actual filters is causing the hemolysis the control method of the average cationization level was changed to a new control method.Root cause:the following root causes were determined:-as a result of the increase in the amount of the cationizing agent, the cationization level of the filter which was integrated into the sterilized product, increased.-the distribution width of the average cationization level of the combination of filter membranes was wide and showed some filter membranes of which the average cationization level was high.Corrective action:the following corrective actions were implemented:-the amount of the cationizing agent was restored to the previous manufacturing specifications.-a new filter control method was created, and the control criteria of the average cationization levels was reduced.
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