351. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events.
- Author
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Kotarek J, Stuart C, De Paoli SH, Simak J, Lin TL, Gao Y, Ovanesov M, Liang Y, Scott D, Brown J, Bai Y, Metcalfe DD, Marszal E, and Ragheb JA
- Subjects
- Cells, Cultured, Chemistry, Pharmaceutical methods, Clinical Trials, Phase III as Topic, Drug Hypersensitivity, Humans, Nanoparticles administration & dosage, Nanoparticles adverse effects, Product Surveillance, Postmarketing, Drug-Related Side Effects and Adverse Reactions etiology, Erythropoietin administration & dosage, Erythropoietin adverse effects, Particulate Matter administration & dosage, Particulate Matter adverse effects, Peptides administration & dosage, Peptides adverse effects
- Abstract
Peginesatide (Omontys(®); Affymax, Inc., Cupertino, CA) was voluntarily withdrawn from the market less than a year after the product launch. Although clinical trials had demonstrated the drug to be safe and efficacious, 49 cases of anaphylaxis, including 7 fatalities, were reported not long after market introduction. Commercialization was initiated with a multiuse vial presentation, which differs in formulation from the single-use vial presentation used in phase 3 studies. Standard physical and chemical testing did not indicate any deviation from product specifications in either formulation. However, an analysis of subvisible particulates using nanoparticle tracking analysis and flow imaging revealed a significantly higher concentration of subvisible particles in the multiuse vial presentation linked to the hypersensitivity cases. Although it is unknown whether the elevated particulate content is causally related to these serious adverse events, this report illustrates the utility of characterizing subvisible particulates not captured by conventional light obscuration., (Copyright © 2016. Published by Elsevier Inc.) more...
- Published
- 2016
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