LAUSR

In May 2019, the Food and Drug Administration (FDA) proposed a quality range (QR) method for the comparative analytical assessment in biosimilar studies. In this process, several reference product lots are necessary, selected from a wide period of manufacturing dates with different shelf lives, to calculate the total variability expressed as the standard deviation of reference product lots. This one depends on the between-lots variation and analytic method uncertainty (i.e., within-lots variation). During this time, the analytical method must be in control and stable but with an appropriate accuracy and precision. In such a situation, various control charts were used to fix the method requirements and detect small changes in the process. The results indicate that the method is indeed in control and stable, but does not meet the requirements of the Analytical Target Profile (ATP) approach, independently of the established uncertainty range. However, it does satisfy the traditional approach for an uncertainty range of ±2%. The application of this new QR approach shows that the selection of reference lots has an impact on the estimated standard deviation of the reference product, and consequently on the QR, penalizing good test products. The contribution of the analytic method error is known and in-control through the validation process. However, the between-lots variation requires a higher attention and control by the manufacturer. All these aspects were analyzed, using simulation and real-data from various bevacizumab lots.