Analysis of inline-filter blockage with trastuzumab formulation using scanning-electron microscopy

Biomedicine & Pharmacotherapy

Megumi Yatabe¹  Hiroko Gomi²  Motoki Inoue³  Shigeru Adachi⁴  Chiaki Ogawa⁴  Yutaka Yachi⁴  Kazuhiko Nakadate⁴  Tomoo Itoh⁵  Yoshiyuki Nagayama⁵ 

[1] Corresponding author at: Department of Pharmacy, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.;Corresponding author at: Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan.;Laboratory of Pharmaceutics, Kitasato University School of Pharmacy, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;Department of Pharmacy, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan;Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan;

关键词: Inline-filter;    Blockage;    Trastuzumab;    Scanning-electron microscopy;   

DOI  :  

来源: DOAJ

【 摘 要 】

The instability of pharmaceutical monoclonal antibodies are affected by physical stimuli including, temperature, denaturant, surfactant, stirring, solid phase adsorption, oxidation, and ultraviolet rays. Clinically, we frequently experience precipitation during preparation of several pharmaceutical monoclonal antibodies for cancer. Although it is possible to remove precipitates in the injection solution during the preparation procedure, potential filter blockade during administration remains a problem with adverse effects on the quality of life of patients. Therefore we sought to investigate factors contributing to this phenomenon. To closely observed the mechanisms involved in blockade of filters during trastuzumab preparation, we prepared samples under the same conditions used in clinical practice and observed them comprehensively. The precipitates that caused filter blockade were observed when the samples were vigorously shaken and left for several hours after dissolving. The precipitates were identified as proteins. The vigorous shaking caused contact between the protein and air, which induced protein precipitation caused by the surfactants derived from the foam formation. We discovered that the external stimulation may cause the instability of monoclonal antibody preparations and, so, it is important for procedures to be as rapid to avoid precipitate formation as much as possible.

【 授权许可】

Unknown