METHODS FOR MANUFACTURING A POLYCLONAL PROTEIN

摘要

Disclosed is a method for manufacturing a drug product comprising at least two distinct protein members of a polyclonal protein, said method comprising the steps of: a) providing at least two populations of cells, wherein each population encodes one distinct member of the polyclonal protein and is enclosed in a physically separate container comprising culture medium and cells expressing the protein, wherein the method comprises an upstream part comprising the steps of: i) expanding the at least two populations of cells in one or more steps of a seed train in separate containers; ii) expanding cells from the seed train in one or more steps of an inoculum train; iii) culturing cells from the inoculum train in a production phase under conditions favoring expression of the protein members so as to express the at least two distinct protein members; b) harvesting the expressed protein; c) performing at least one downstream purification step on the harvested protein; d) obtaining purified drug substance; and e) formulating purified drug substance into a polyclonal drug product; wherein the at least two populations of cells are kept separate at least during the seed train, and wherein at least part of the downstream purification is carried out on a mixture comprising the individual members of the polyclonal protein.