A study on the stability of the adalimumab biosimilar candidate TUR01, a tumor necrosis factor-α inhibitor, found long-term stability of the drug substance and drug product were maintained under different temperatures.
A study of the stability of the adalimumab biosimilar candidate TUR01 (Turgut İlaçları), a monoclonal antibody to tumor necrosis factor-α by its manufacturer, found long-term stability of both the drug substance and drug product were maintained under different temperatures.
Changes in temperature and other conditions during storage, transport, and administration of monoclonal antibodies can affect the quality, efficacy, and safety of the molecule. In addition to the required clinical trial comparing safety and efficacy of a candidate biosimilar to its originator, stability studies are also required by regulatory agencies, “since different modifications can be observed on the biosimilar molecule due to the variability of the cell line, cell culture conditions, passage number of the cells, and post-translational modifications,” the researchers said.
The authors, from biosimilar’s manufacturer Turgut İlaçları, assessed the stability of TUR01 using analytical methods at 2 different temperatures based on International Conference on Harmonisation of Technical Requirements guidelines: at or below –65°C and 5°C for the drug substance and 5°C and 25°C with 60% relative humidity for the drug product. The drug substance was stored in polyethylene terephthalate copolyester, glycol modified bottles, and the drug product was stored in glass pre-filled syringes.
The candidate biosimilar drug substance was stable at both temperatures for 18 months
The authors assessed appearance, acidic and basic variants, protein content, biological activity, monomers and aggregates, bioburden, and endotoxin in the drug substance for 18 months at the 2 temperatures. Over the 18-month study, the authors said there was no change in appearance, isoform profile, protein content, biological activity, and microbiological results. At 18 months, by chromatography-size exclusion chromatography, the monomer percentage was 99% at the lower temperature and 98% at 5°C. Regarding acidic and basic variants, the lowest main peak across the duration of the study was 73.34% at 6 months and -65°C, and 71.95% 12 months at 5°C, compared to 74.44% at baseline. The researchers noted this “slight” change in the main peak was in the acceptable range of critical quality attributes determined based on the properties of the originator.
The drug product was stable refrigerated for 24 months, and at room temperature for 2 months
To assess the shelf-life of the TUR01 monoclonal antibody stored in pre-filled syringes at a typical refrigerated storage temperature, protein content, appearance, color, opalescence, sub-visible particulates, pH, osmolality, extractable volume, acidic and basic variants, biological activity, monomers and aggregates, low molecular fragments, sterility, and endotoxin were monitored at 5°C for 24 months. The authors found a “slight” decrease in the main peak, accompanied by an increase in the acidic peak after the first 6 months. They also noted a slight increase in aggregates and low molecular weight. However, all of these results were in their acceptable range of critical quality attributes.
The drug product was also monitored at 25°C with 60% relative humidity for 6 months to assess stability during room temperature storage. Although protein content, opalescence, pH, and osmolality did not change over that time, the authors began to see other changes at 3 months at room temperature, which they said were expected. Specifically, they noted a reduction in monomers from 97.4% to 96.2%, and an increase in aggregates and low molecular weight fragments. There was also a decrease in the main peak after 2 months. According to the researchers, TUR01 can be safely refrigerated at 5 +/– 3°C for 24 months, and if the cold chain is broken, the product will remain stable at room temperature for 2 months.
Demirhan D. Stability evaluation of the biosimilar monoclonal antibody using analytical techniques. Turk J Pharm Sci. 2023;20(1):48-57. doi:10.4274/tjps.galenos.2022.47690