A method of refolding a protein expressed in a non-mammalian expression system and present in a volume at a concentration of 2.0 g/L or greater during refolding, wherein said protein comprises an Fc region, said method comprising: (a) contacting the protein with a refold buffer comprising a redox component comprising a final thiol-pair ratio having a range of 0.001 to 100 and a thiol-pair buffer strength of 2 mM or greater and one or more of: (i) a denaturant; (ii) an aggregation suppressor; and (iii) a protein stabilizer; to form a refold mixture; wherein the thiol-pair ratio is calculated according to Equation 1: reductant 2 oxidant; wherein the thiol-pair buffer strength is calculated according to Equation 2: 2 oxidant + reductant; wherein said thiol-pair ratio and said thiol-pair buffer strength are evaluated in a full or partial factorial matrix; and together with the parameters of incubation time, concentration of said protein and pH, with each component varied over a range of at least 3 concentration or pH levels with all other parameters kept constant; and wherein the thiol-pair ratio value and thiol-pair buffer strength value used in said refold buffer are those respective values resulting in a higher yield of the desired form of said protein than is obtained prior to said varying of said thiol-pair ratio and said thiol-pair buffer strength; (b) incubating the refold mixture; and (c) isolating the protein from the refold mixture. (a) contacting the protein with a refold buffer comprising a redox component comprising a final thiol-pair ratio having a range of 0.001 to 100 and a thiol-pair buffer strength of 2 mM or greater and one or more of: (i) a denaturant; (ii) an aggregation suppressor; and (iii) a protein stabilizer; to form a refold mixture; wherein the thiol-pair ratio is calculated according to Equation 1: reductant 2 oxidant; wherein the thiol-pair buffer strength is calculated according to Equation 2: 2 oxidant + reductant; wherein said thiol-pair ratio and said thiol-pair buffer strength are evaluated in a full or partial factorial matrix; and together with the parameters of incubation time, concentration of said protein and pH, with each component varied over a range of at least 3 concentration or pH levels with all other parameters kept constant; and wherein the thiol-pair ratio value and thiol-pair buffer strength value used in said refold buffer are those respective values resulting in a higher yield of the desired form of said protein than is obtained prior to said varying of said thiol-pair ratio and said thiol-pair buffer strength; (i) a denaturant; (ii) an aggregation suppressor; and (iii) a protein stabilizer; to form a refold mixture; wherein the thiol-pair ratio is calculated according to Equation 1: reductant 2 oxidant; wherein the thiol-pair buffer strength is calculated according to Equation 2: 2 oxidant + reductant; wherein said thiol-pair ratio and said thiol-pair buffer strength are evaluated in a full or partial factorial matrix; and together with the parameters of incubation time, concentration of said protein and pH, with each component varied over a range of at least 3 concentration or pH levels with all other parameters kept constant; and wherein the thiol-pair ratio value and thiol-pair buffer strength value used in said refold buffer are those respective values resulting in a higher yield of the desired form of said protein than is obtained prior to said varying of said thiol-pair ratio and said thiol-pair buffer strength; (b) incubating the refold mixture; and (c) isolating the protein from the refold mixture.