II. Quality findings Introduction Structure Elotuzumab consists of the complementarity determining regions (CDRs) of the antibody, MuLuc63, grafted onto human IgG1 heavy and kappa light chain framework regions. The predominant molecular isoform, heavy chain without C-terminal lysine and with the G0F/G0F glycoform, has an empirical formula of C6576H10142N1718O2092S42 with a calculated molecular mass of 148087 Daltons. Charge variant forms of the elotuzumab heavy chain exist with and without the C-terminal lysine residue. In heavy chain lacking a C-terminal lysine, glycine is the terminal residue. Physical and chemical properties Elotuzumab is a to very opalescent, colourless to slightly yellow liquid, pH 6.0, in an aqueous buffer. Based on the amino acid sequence defined by the nucleotide sequence, elotuzumab has an isoelectric point of 7.9 for the predominant charge variant, and a theoretical extinction coefficient of 1.61 mL mg-1 cm-1. Elotuzumab is produced from cell culture using an NS0 mouse myeloma-based cell line. The manufacturing process is initiated by thawing a vial of the working cell bank (WCB). The cell culture is expanded using a series of shake flasks, a cell bag bioreactor, and seed bioreactors to generate a sufficient amount of viable cells to inoculate the production bioreactor. Elotuzumab is purified using a series of chromatographic and filtration steps. The drug substance in filled bags is frozen and stored at -35°C. ≤ Stability Drug substance The sponsor proposed a shelf life of 36 months at -35°C for the drug substance. Stability data have been generated real time and stressed conditions. Stability data were generated under real time conditions to characterise the stability profile of the substance and to establish a shelf life. The real time data submitted support a shelf life of 36 months when stored at -35oC. ≤ Drug product Stability data have been generated under stressed and real time conditions to characterise the stability profile of the product. The product is not photostable. The proposed trial life is 36 months when stored at 5°C. Stability studies have been conducted in accordance with relevant ICH guidelines.
II. Quality findings Introduction Structure Elotuzumab consists of the complementarity determining regions (CDRs) of the antibody, MuLuc63, grafted onto human IgG1 heavy and kappa light chain framework regions. The predominant molecular isoform, heavy chain without C-terminal lysine and with the G0F/G0F glycoform, has an empirical formula of C6576H10142N1718O2092S42 with a calculated molecular mass of 148087 Daltons. Charge variant forms of the elotuzumab heavy chain exist with and without the C-terminal lysine residue. In heavy chain lacking a C-terminal lysine, glycine is the terminal residue. Physical and chemical properties Elotuzumab is a to very opalescent, colourless to slightly yellow liquid, pH 6.0, in an aqueous buffer. Based on the amino acid sequence defined by the nucleotide sequence, elotuzumab has an isoelectric point of 7.9 for the predominant charge variant, and a theoretical extinction coefficient of 1.61 mL mg-1 cm-1. Elotuzumab is produced from cell culture using an NS0 mouse myeloma-based cell line. The manufacturing process is initiated by thawing a vial of the working cell bank (WCB). The cell culture is expanded using a series of shake flasks, a cell bag bioreactor, and seed bioreactors to generate a sufficient amount of viable cells to inoculate the production bioreactor. Elotuzumab is purified using a series of chromatographic and filtration steps. The drug substance in filled bags is frozen and stored at ≤ -35°C. Stability Drug substance The sponsor proposed a shelf life of 36 months at -35°C for the drug substance. Stability data have been generated real time and stressed conditions. Stability data were generated under real time conditions to characterise the stability profile of the substance and to establish a shelf life. The real time data submitted support a shelf life of 36 months when stored at ≤ -35oC. Drug product Stability data have been generated under stressed and real time conditions to characterise the stability profile of the product. The product is not photostable. The proposed life is 36 months when stored at 5°C. Stability studies have been conducted in accordance with relevant ICH guidelines. trial
auspar-elotuzumab-171009.docx