Manufacture of the biopharmaceutical drug product from the manufactured biopharmaceutical drug substance is the common pathway for biopharmaceuticals. However, sometimes with protein-based biopharmaceuticals, the purified drug substance is bioconjugated before manufacture into the drug product. Bioconjugation is an effective strategy for forming a stable covalent linkage between a biomolecule (e.g., recombinant protein, monoclonal antibody) and a chemical entity (e.g., small molecules such as a chemical drug, radioisotope). The steps of the bioconjugation manufacturing process add additional complexity to the existing biopharmaceutical manufacturing process, and these additional steps are examined in this chapter. The concerns of CMC regulatory compliance for both the biopharmaceutical and the chemical entity in the manufacture of various bioconjugated drug substances will be addressed—antibody–drug conjugates (ADCs), PEGylated protein-based biopharmaceuticals, antibody–radionuclide conjugates (ARCs), and antibody–oligonucleotide conjugates (AOCs).