Disclosed are methods for testing the presence and/or activity of glutathione system components and thioredoxin system components during the manufacturing process of disulfide bond-containing proteins. Also disclosed are methods for mitigating reduction of disulfide bonds during the manufacturing process, and for lowering the reduction potential of disulfide bond-containing proteins. Provided are compositions, kits, and methods for mitigating reduction and diminishing reduction potential of disulfide bond-containing proteins during protein manufacturing processes.