Evaluation of copolymer diethylamide

摘要

Methods of analyzing glatiramer acetate (GA) or a polymeric precursor thereof are provided. The methods can include determining a level of one or more diethylamide-modified amino acids in a sample comprising GA or a polymeric precursor thereof, and selecting at least a portion of the sample based on the assessment of the one or more diethylamide-modified amino acids in the sample.

主权项

1. A method of manufacturing glatiramer acetate drug product, the method comprising:
manufacturing an amino acid copolymer of L-glutamic acid, L-alanine, L-Lysine, and L-tyrosine; detecting, in at least one sample of the manufactured copolymer, the levels of at least two, three, or four diethylamide-modified fragments selected from the group consisting of: fragments having a diethylamide-modified alanine, fragments having a diethylamide-modified lysine, fragments having a diethylamide-modified glutamic acid, and fragments having a diethylamide-modified tyrosine; and processing the copolymer to manufacture a glatiramer acetate drug product if the detected level of at least one of the at least two, three, or four diethylamide-modified fragments meets commercial release specification (i), (ii), (iii), or (iv): (i) the level of fragments having a diethylamide-modified alanine in the sample is 59.5-76.1% of the total diethylamide-modified fragments in the sample on a mol percent basis; (ii) the level of fragments having a diethylamide-modified lysine detected in the sample is 11.3-17.3% of the total diethylamide-modified fragments in the sample on a mol percent basis; (iii) the level of fragments having a diethylamide-modified glutamic acid detected in the sample is 9.9-15.0% of the total diethylamide-modified fragments in the sample on a mol percent basis; or (iv) the level of fragments having a diethylamide-modified tyrosine detected in the sample is 4.8-7.2% of the total diethylamide-modified fragments in the sample on a mol percent basis, thereby manufacturing glatiramer acetate drug product.