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 (v1.0), a recombinant human growth hormone (rHGH) therapeutic, underwent a manufacturing update (v1.1).
The immunogenicity of somatropin v1.1 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 hGH deficiency for 1 year. The primary endpoint was the proportion of patients who developed anti‐drug 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 3 patients with ADA‐positive samples. Two patients (2.6%) had growth attenuation, but they were not ADA‐positive. The manufacturing changes for somatropin v1.1 resulted in a similar safety and efficacy profile compared with somatropin v1.0, and a different immunogenicity profile with a lower incidence of ADAs.
Vanderlaan M, Maniatis A, Olney R, et al. Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product. Clinical Pharmacology & Therapeutics 2019;0. https://doi.org/10.1002/cpt.1694
Manufacturing process changes may alter the characteristics of a protein therapeutic. In 2009, somatropin (v1.0), a recombinant human growth hormone (rHGH) therapeutic, underwent a manufacturing update (v1.1).
The immunogenicity of somatropin v1.1 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 hGH deficiency for 1 year. The primary endpoint was the proportion of patients who developed anti‐drug 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 3 patients with ADA‐positive samples. Two patients (2.6%) had growth attenuation, but they were not ADA‐positive. The manufacturing changes for somatropin v1.1 resulted in a similar safety and efficacy profile compared with somatropin v1.0, and a different immunogenicity profile with a lower incidence of ADAs.
Vanderlaan M, Maniatis A, Olney R, et al. Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product. Clinical Pharmacology & Therapeutics 2019;0. https://doi.org/10.1002/cpt.1694
