Starting materials (also referred to as source materials) are the materials used during the manufacture of the biopharmaceutical drug substance that become part of the drug substance. Introduction of the starting materials into the manufacturing process is the point at which cGMP is applied. A problem with a starting material can create problems all the way through the entire manufacturing process, even to the final drug product. Some of the key attributes desired for any starting material are as follows: homogeneous, fully characterized, free of adventitious agents, free of undesired impurities or contaminants, readily available for manufacturing, and, of course, fit-for-use. The focus of this chapter is on both general and specific issues for starting materials: the single starting material for the protein-based biopharmaceuticals (i.e., the recombinant cell bank) and the numerous starting materials for the gene-based biopharmaceuticals (i.e., recombinant cell banks, cell banks, DNA plasmids, viral vectors, patient cells). The level of GMP control necessary in the manufacture of the starting materials, which varies across the different types of starting materials, will be discussed. Regulatory authorities understand the critical importance of starting materials and have high expectations and major requirements for the biopharmaceutical manufacturer, which will be examined in this chapter.