Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product

Manufacturing process changes may alter the characteristics of a protein therapeutic. In 2009, somatropin (version 1.0), a recombinant human growth hormone therapeutic, underwent a manufacturing update (version 1.1). The immunogenicity of somatropin version 1.1 as a daily subcutaneous injection was evaluated in 2014 in a prospective, open‐label, single‐arm clinical study of treatment‐naive pediatric patients with idiopathic human growth hormone deficiency for 1 year. The primary end point was the proportion of patients who developed antidrug antibodies (ADAs) after treatment. Eighty‐two patients were enrolled. The mean (SD) treatment duration was 347 (53) days. The incidence of ADAs was 3.7%. No neutralizing antibodies were observed in the three patients with ADA‐positive samples. Two patients (2.6%) had growth attenuation, but they were not ADA positive. The manufacturing changes for somatropin version 1.1 resulted in a similar safety and efficacy profile compared with somatropin version 1.0 and a different immunogenicity profile with a lower incidence of ADAs.