A process for producing insulin or insulin analog, wherein the process has a digestion step in which pre-proinsulin or pre-proinsulin analog is digested with one or more proteolytic enzymes to produce an aqueous solution of insulin or insulin analog, digestion byproducts, and host cell impurities and a downstream purification or chromatography step, in which the insulin or insulin analog is separated from the digestion byproducts, and host cell impurities, wherein the process comprises performing two tandem microfiltration steps subsequent to the digestion step and prior to the downstream purification or chromatography step, wherein the microfiltration step comprises (a) adjusting the pH of the aqueous solution from the digestion step to a pH sufficient to precipitate the insulin or insulin analog from the aqueous solution to provide an aqueous mixture comprising precipitated insulin or insulin analog and soluble and precipitated digest related impurities and host-cell impurities; (b) applying the aqueous mixture to a surface of a micro filter having a pore exclusion size sufficient to retain the precipitated insulin or insulin analog thereto to provide a first retentate pool; (c) permeating the soluble impurities that are smaller than the exclusion pore size of the micro filter through the micro filter while washing the first retentate pool with water or a first aqueous solution at a pH that is at or within 1.5 pH units of the pH of the pH-adjusted aqueous mixture for a time sufficient to substantially remove the soluble impurities from the first retentate pool to provide a second retentate pool; and (d) adding a second aqueous solution to the second retentate pool and adjusting the pH to a pH sufficient to solubilize the precipitated insulin or insulin analog to provide a third retentate pool and permeating the third retentate pool comprising the solubilized insulin or insulin analog through the microfilter wherein insoluble impurities and impurities larger than the exclusion pore size of the microfilter are retained by the microfilter and a permeate pool comprising the solubilized insulin or insulin analog is collected to produce the insulin or insulin analog. (a) adjusting the pH of the aqueous solution from the digestion step to a pH sufficient to precipitate the insulin or insulin analog from the aqueous solution to provide an aqueous mixture comprising precipitated insulin or insulin analog and soluble and precipitated digest related impurities and host-cell impurities; (b) applying the aqueous mixture to a surface of a micro filter having a pore exclusion size sufficient to retain the precipitated insulin or insulin analog thereto to provide a first retentate pool; (c) permeating the soluble impurities that are smaller than the exclusion pore size of the micro filter through the micro filter while washing the first retentate pool with water or a first aqueous solution at a pH that is at or within 1.5 pH units of the pH of the pH-adjusted aqueous mixture for a time sufficient to substantially remove the soluble impurities from the first retentate pool to provide a second retentate pool; and (d) adding a second aqueous solution to the second retentate pool and adjusting the pH to a pH sufficient to solubilize the precipitated insulin or insulin analog to provide a third retentate pool and permeating the third retentate pool comprising the solubilized insulin or insulin analog through the microfilter wherein insoluble impurities and impurities larger than the exclusion pore size of the microfilter are retained by the microfilter and a permeate pool comprising the solubilized insulin or insulin analog is collected to produce the insulin or insulin analog. <EOS>