3 Identifying and Measuring Critical Quality Attributes | Navigating the Manufacturing Process and Ensuring the Quality of Regenerative Medicine Therapies: Proceedings of a Workshop |The National Acad

develop products that are both safe and effective at treating disease. Gaps in fundamental knowledge about biology are partly to blame for this situation, she said, but so too is the fact that there are many variables in the analytical assays and in the differences between the samples harvested from the patients who will receive these therapies. Because there are so many assay and sample variables, it is difficult to design experiments and measurement methods that can get a handle on all of these things simultaneously, Plant said. To complicate the situation even more, the cells and tissues under study are dynamic, living entities that are growing and possibly even changing.

Defining CQAs for a particular product is challenging without accurately measuring endpoints. It is important to ensure correct measurements, Plant said, but it is also important to take measurements that are meaningful to the clinical outcome. Ensuring the comparability of measurements is another major challenge for researchers and product manufacturers in this area, she said. Given the complexity of the measurements needed to characterize these products, she continued, it is important to have confidence that measurements can be compared. Comparability is especially important because there may be many changes to how a material is handled as a process moves from the research laboratory to the manufacturing setting, Plant said. Changes during the scale-up process can include new raw materials, new suppliers, new storage conditions, and even new technicians. Therefore, she added, product characterization is needed as the manufacturing process changes to make sure that the product generated in the manufacturing pipeline has the desired characteristics. If manufacturers are unable to demonstrate that a product has the same characteristics as it did in the past, they may be asked to perform additional experiments or even perform another clinical trial, Plant said. She noted that there is FDA guidance about how to qualify and validate measurements.1

Characterizing an assay’s precision, reproducibility, accuracy, robustness, sensitivity, specificity, dynamic range, response function, and limit of detection can lead to confidence that measurements are yielding data that can support good decision making, Plant said. Knowing these variables can help manufacturers draw comparisons during the process of scaling up and allows them to have confidence that when they get an answer that is unexpected, it is due to changes in the product and not the assay.

FDA requires validated assays for registration-enabling clinical trials. However, Plant said, validating assays as early as possible leads to better decision making at each step along the translation process and to more

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