Starting Materials for Manufacturing the Biopharmaceutical Drug Substance

Starting materials (also referred to as source materials) are the starting point for cGMP manufacturing of the biopharmaceutical drug substance. Some of the key attributes desired for any starting material are to be homogeneous, fully characterized, free of adventitious agents, free of undesired impurities, and readily available for manufacturing. Problems with the starting material can create problems all the way through the manufacturing process to the finished biopharmaceutical drug product. The focus of this chapter is on the typical single starting material for the protein-based biopharmaceuticals (i.e., the recombinant cell bank) and on the numerous starting materials for the gene therapy-based biopharmaceuticals (i.e., the cell banks, plasmids, viral vectors, patient cells, etc.). Regulatory authorities understand the critical importance of the starting materials and have high expectations, as well as major requirements, for the biopharmaceutical manufacturer's control over and use of these starting materials, which will be examined in this chapter. Misunderstandings about starting materials will also need to be corrected.