Analysis of amino acid copolymer compositions

A method for manufacturing a pharmaceutical composition comprising glatiramer acetate, the method comprising:

• preparing an amino acid copolymer of L-glutamic acid, L-alanine, L-lysine, and L-tyrosine, wherein the preparing step comprises co-polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA)-protected L-lysine, and L-tyrosine to generate a first material;
• treating the first material to deprotect the benzyl-protected L-glutamic acid therein and to partially depolymerize the first material, thereby generating a second material;
• purifying and drying the second material to produce a purified and dried second material;
• treating the purified and dried second material to deprotect the TFA-protected L-lysine to produce a third material;
• and purifying the third material, to thereby produce the copolymer of L-glutamic acid, L-alanine, L-lysine, and L-tyrosine;
• measuring pyro-glutamate content of the copolymer in a sample of the copolymer;
• processing the copolymer to produce a pharmaceutical composition comprising glatiramer acetate only if the measured pyro-glutamate content of the copolymer in the sample is within 2000-7000 parts per million (ppm) on a dry weight/dry weight basis, thereby producing a pharmaceutical composition comprising glatiramer acetate.