Raw materials (also sometimes known as ancillary materials) are reagents, culture media, process buffers, product-contacting components, etc., that are needed to carry out the manufacture of a biopharmaceutical—but are not part of the manufactured product. Many different types of raw materials are needed to manufacture the biopharmaceutical drug substance (DS), not only during the upstream production stage (e.g., the numerous cell culture media components) but also during the purification stage (e.g., column resins, process buffers). Biopharmaceutical manufacturers in their selection of raw materials must address “fit-for-use”—the impact that the selected raw material and its quality grade might have on either (a) the consistent performance of the biopharmaceutical manufacturing process, and/or (b) the quality of the manufactured biopharmaceutical drug product, and/or (c) potential patient safety concerns. The focus of this chapter is on the steps that the biopharmaceutical drug substance manufacturer can take to address these fit-for-use concerns.