Although a biosimilar should mimic a biological drug as closely as possible, changes in manufacturing can alter the drug. For example, “biosimilar products inherently have quality differences in comparison to [the] innovator molecule which may be related to size, charge, and glycosylation,” wrote Tarun Gupta, senior general manager at India-based Kashiv BioSciences, and Sriram Seshadri, PhD, associate professor in the Institute of Science at Nirma University in Gujarat, India. “Despite these differences, they are supposed to demonstrate similar behavior in safety and efficacy profile[s] to the reference product and these differences should not be clinically meaningful.”
When asked how often charge variants are found in biosimilars, Seshadri says, “Charge variants are an inherent property of biologics expressed in a mammalian host and are due to post-translational modifications.” Plus, charge variants can have “a potential influence on the stability and biological activities of a biologic molecule,” he adds.
So, Gupta and Seshadri studied the impact of charge variants on omalizumab, a biosimilar monoclonal antibody used to treat asthma. To do this, these scientists made highly purified charge variants of this drug. Then, they analyzed the impact of a range of temperatures on these charge variants and used an ELISA method to estimate their in vitro potency.
From this work, Seshadri says that “highly purified charge variants are very much stable at different thermal stress conditions up to a week.” In addition, this work showed that “there are no significant differences on in vitro potency with highly purified—greater than 90%—charge variants.”
Although charge variants did not impact the stability or potency of omalizumab in these tests, bioprocessors should not expect comparable results with charge variants in other biosimilars. As Seshadri concludes: “Monoclonal antibody biosimilarity needs to be demonstrated and depends on the biological molecule.”
