Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.

Methods of producing multiple protein products from blood-based materials including alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins are described herein. The inventive methods include steps of: salt fractionation, chromatography, ultrafiltration, diafiltration, solvent-detergent treatment, and sterile filtration. Advantageously, the inventive methods are simple and produce alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins in high yields. The sequence of process steps can be selected to obtain multiple products from various in-process materials, such as supernatants, pastes, chromatography flow-though, and chromatography washes.

The present invention advantages over conventional methods and products. In an aspect, a method comprises separating a mixture of allulose, fructose, glucose, and gluco-oligosaccharides, wherein the separating comprises using simulated moving bed chromatography, and recovering allulose at a high purity and yield. In an aspect, the simulated moving bed (SMB) chromatography to separate a fraction enriched with allulose from a fraction enriched with fructose and glucose, and to separate a fraction enriched with fructose from a fraction enriched with glucose. In an aspect, the method provides separation of an allulose from a mixture of allulose, fructose, and D-glucose, wherein the mixture is produced from high fructose corn syrup (HFCS) when HFCS is contacted with an allulose epimerase. In an aspect, the method produces a high quality allulose product. In an aspect, the fraction enriched with fructose can be recycled to contact the allulose epimerase.