A process for making a biological composition for use as a blood serum reference composition in diagnostic analysis. The process comprises:(a) adding calcium to citrated plasma and mixing well to form decitrated plasma;(b) adding thrombin to the decitrated plasma and mixing well to form a clot of fibrin;(c) performing at least one freeze-thaw routine on the clot to cause the fibrin to contract;(d) removing the fibrin to thereby obtain serum;(e) molecular washing and ultrafiltering the serum and thereby obtaining concentrated serum; and(f) adding to the concentrated serum at least one alkylene polyol having from 2-5 carbon atoms in an amount such that said composition's non-biological component comprises from about 40 to about 85 weight percent water and from about 15 to about 60 weight percent of said alkylene polyol.