Devices and methods for integrated continuous manufacturing of biological molecules

An apparatus for separating a protein of interest from a heterogenous tissue culture fluid mixture, comprising:

• (a) a continuous perfusion fermentation system adapted to continuously produce a tissue culture fluid containing a protein of interest at a substantially constant volumetric flow rate;
• (b) a continuous particle removal system integrated with and adapted to continuously receive the tissue culture fluid from the perfusion fermentation system and continuously produce a clarified tissue culture fluid;
• and
• (c) a continuous purification system integrated with and adapted to continuously receive the clarified tissue culture fluid from the particle removal system and continuously produce a product isolate containing the protein of interest;
• wherein the continuous purification system is an ultrafiltration system, wherein the ultrafiltration system comprises an ultrafiltration membrane having an area in square meters equal to a range of between 0.1 to 2 times the volumetric flow rate of the continuous perfusion fermentation in liters/hour and wherein the apparatus is maintained under sterile conditions.