One-month stability study of a biosimilar of infliximab (Remsima^®) after dilution and storage at 4 °C and 25 °C

详细信息    查看全文

• 作者：V. Vieillard ; ^{victoire.vieillard@aphp.fr} ; A. Astier ; C. Sauzay ; M. Paul
• 关键词：Monocolonal antibody ; Biosimilar ; Physical stabililty ; Chemical stability ; &ldquo ; In-use&rdquo ; conditions
• 刊名：Annales Pharmaceutiques Françaises
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：75
• 期：1
• 页码：17-29
• 全文大小：1696 K
• 卷排序：75

文摘

There is currently only one monoclonal antibody for which there is a biosimilar: infliximab, which was released onto the French market in 2015. The SPC for the biosimilar (Remsima®) are superimposable on those of the original, including 24-hour stability at both 4 and 25 °C. The aim of our study was to determine the stability of this biosimilar during one month at 4 and 25 °C. Three different batches at two concentrations (0.7 mg/mL or 1.6 mg/mL) were used. Physicochemical stability was evaluated by the following methods: turbidity, UV spectrometry, DLS, ion chromatography (CEX), gel exclusion chromatography (SEC), and light microscopy. The analyses were performed in triplicate. All methods used have been demonstrated to be valid for measuring antibody stability. There were no signs of physicochemical instability after seven days (on D7) of storage at 4 or 25 °C. From D15, we observed slight changes by ion (percentage distribution of the different isoforms) and gel exclusion chromatography (percentage distribution of different polymers, i.e. dimers, oligomers). However, the areas under the curves were unchanged, and the proportions of polymers remained lower than 0.5%. Tertiary structure analysis also showed a change from D15. All observed changes are consistent with progressive oligomerization by hydrophobic interactions. In conclusion, the reconstituted biosimilar is stable for seven days at 4 and 25 °C. Gradual oligomerization is observed from D15 but appears to be less than 0.5%, suggesting instability, albeit very limited, in the longer term; the practical consequences of this remain to be evaluated.