Stable Isotope-Labeled Biosimilars
Stable-Isotope Labeled Biosimilar Antibodies
Biosimilars antibodies are identical in terms of sequence and biological activity to reference therapeutic antibodies. They differ from approved biological products in terms of production – conditions, scale, cell line, or expression vector. Moreover, biosimilars lack the excipients and additives commonly found in therapeutic formulations. For this reason, these reagents have a significantly higher degree of purity, making them ideal as reference or standards for research, bioanalysis, and drug development applications.
Stable-Isotope Labeled Antibodies use
Stable-isotope labeled biosimilar antibodies incorporate 13C and 15N from arginine and lysine. These reagents are produced by growing transfected Chinese Hamster Ovary (CHO) cells in media enriched with isotope-labeled amino acids – 13C6, 15N4-labeled arginine, and 13C6, 15N2-labeled lysine. They are designed to be used as internal standards (IS) for mass spectrometry (MS) analysis allowing the absolute quantification of therapeutic antibodies in complex samples such as serum. The quantification is more accurate when combining liquid chromatography (LC) with MS and protein cleavage. Isotope-labeled biosimilars used as IS are typically used to spike serum samples prior to trypsin digestion and subsequent sample purification. The efficiency of the digestion and purification processes is highly dependent on the matrix of the sample. For this reason, the use of an IS allows the robust determination of the rate of efficiency of each step and more accurate quantification of the therapeutic antibody found in the serum after administration.
Stable-Isotope Labeled Biosimilar Antibodies for therapeutic development
This type of analysis is typically employed for pharmacokinetics studies – the fate of antibody therapies in the organism (metabolism, degradation, adsorption, etc.). These studies are vital at the preclinical and clinical stages, because they aid in the optimization of dosages and dose regimens, thus, increasing the safety and effectiveness of immunotherapies. The use of stable isotope-labeled biosimilars makes this bioanalysis more accurate and robust, significantly speeding up the clinical development process.