Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies

Stable therapeutic antibody dosage forms present production technology challenges, particularly when high‐concentration formulations are needed to meet the elevated dose requirements that are generally required for successful antibody therapy. Solid dosage forms, such as lyophilized powders, are generally more stable than liquid formulations. High‐concentration drug products can be achieved by reconstitution of the lyophilisate in a smaller volume than its initial (pre‐lyophilization) volume, but requires a significant vial overfill. High‐concentration liquid formulations are becoming feasible as new techniques and technologies become available. Analytical methods to detect subtle molecular variations have been developed to demonstrate manufacturing consistency. Some molecular heterogeneity is contributed by conserved sites, such as Asn297 glycosylation and the loss of heavy chain C‐terminal Lys residues. Characteristics that affect potency, stability, or immunogenicity must be elucidated for each therapeutic antibody. Drug Dev. Res. 61:137–154, 2004. © 2004 Wiley‐Liss, Inc.