Omontys® – a brand name peginesatide injectable – was voluntarily withdrawn from the market less than a year after the product launch. Clinical trials had demonstrated the drug to be safe and efficacious using data obtained by light obscuration particle testing (LO), but over 40 cases of anaphylaxis, and 7 fatalities were reported soon after the product was introduced to the market.
Peginesatide, a man-made form of erythropoietin, is used to treat anemia in people with chronic kidney disease treated with dialysis. Those suffering from kidney failure may have reduced amounts of erythropoietin in their body.
A recent article in the Journal of Pharmaceutical Sciences (JPS)1 discussed how the U.S. Food and Drug Administration (FDA) task force investigated the Omontys events with several particle analyzers, including FlowCam.
Pictured above: representative FlowCam images of particles in a sample of a protein therapeutic.
Omontys was manufactured and approved as both a single-use vial (SUV) and a multiuse vial (MUV), which differed in their formulation. Clinical trials primarily used the SUV formulation, but only the MUV formulation was marketed.
FlowCam was used during the FDA's investigation to evaluate the particle profile of SUV and MUV samples with both visual and numerical data. The investigation revealed a significantly higher concentration of subvisible particles in the MUV presentation which correlates to the cases of anaphylaxis. Although we cannot confirm whether the elevated particulate content is the cause of these serious adverse events of the drug, the report illustrates the importance of characterizing and mitigating subvisible particulates in injectable drugs.
During formulation development, the peginesatide samples passed USP <788> limits for particulates using LO, but the data presented by the FDA investigation suggest that FlowCam detected and characterized protein aggregates and other particles that went undetected using light obscuration alone.
Since the tragic events of Omontys recall, FlowCam LO has been introduced to allow users to simultaneously collect FIM and LO data from a single aliquot of sample, allowing you to meet USP particle monitoring requirements with light obscuration, while also collecting high-resolution images and morphology data with flow imaging microscopy.
In our white paper, Measuring Subvisible Particles and Aggregates using FlowCam LO, we use FlowCam LO to directly compare the particle size distributions of aqueous samples containing Polystyrene Latex calibration beads, ETFE particles, and IgG aggregates obtained from both LO and FIM analyses. The results highlight how a combined LO-FIM approach using FlowCam LO can help researchers accurately detect, count, and analyze particles in biotherapeutic samples to ensure the safety and efficacy of their products.
References
1. Subvisible Particle Content, Formulation,and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events
Kotarek, Joseph et al. Journal of Pharmaceutical Sciences 2016, Volume 0, Issue 0, DOI:10.1016/S0022-3549
http://jpharmsci.org/article/S0022-3549(15)00180-X/abstract
