Sterile chromatography and manufacturing processes

An integrated, closed, and continuous process for manufacturing of a purified recombinant protein comprising:

• (a) providing a liquid culture medium comprising a recombinant protein that is substantially free of cells;
• and
• (b) continuously feeding the liquid culture medium into a multi-column chromatography system (MCCS) comprising at least one chromatography column containing gamma-irradiated chromatography resin, wherein the chromatography resin is exposed during each cycle to denaturing buffer;
• wherein the process utilizes reduced bioburden buffer, is integrated, and runs continuously from the liquid culture medium to an eluate from the MCCS that is the purified recombinant protein.

An integrated, closed, and continuous process for manufacturing of a recombinant protein comprising:

• (a) providing a liquid culture medium comprising a recombinant protein that is substantially free of cells;
• (b) continuously feeding the liquid culture medium into a first multi-column chromatography system (MCCS1);
• (c) capturing the recombinant protein from the liquid culture medium using the MCCS1;
• (d) producing an eluate from the MCCS1 that comprises the recombinant protein and continuously feeding the eluate into a second multi-column chromatography system (MCCS2);
• (e) continuously feeding the recombinant protein from the eluate into the MCCS2 and subsequently eluting the recombinant protein to thereby produce the purified recombinant protein, wherein:
• the process utilizes reduced bioburden buffer, is integrated, and runs continuously from the liquid culture medium to the purified recombinant protein, and
• at least one column in the MCCS1 and/or MCCS2 is a chromatography column containing gamma-irradiated chromatography resin and the chromatography resin is exposed to denaturing buffer during each cycle in the process.