Interactions between Therapeutic Proteins and Acrylic Acid Leachable.
Leachables are chemical compounds that migrate from manufacturing equipment, primary containers and closure systems, and packaging components into biopharmaceutical and pharmaceutical products. Acrylic acid (at concentration around 5 μg/mL) was detected as leachable in syringes from one of the potential vendors (X syringes). In order to evaluate the potential impact of acrylic acid on therapeutic proteins, an IgG 2 molecule was filled into a sterilized X syringe and then incubated at 45 °C for 45 days in a pH 5 acetate buffer. We discovered that acrylic acid can interact with proteins at three different sites: (1) the lysine side chain, (2) the N-terminus, and (3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed. Even thought a small amount (from 0.02% to 0.3%) of protein was found to be modified by acrylic acid, the modified protein can potentially be harmful due to the toxicity of acrylic acid. After being modified by acrylic acid, the properties of the therapeutic protein may change due to charge and hydrophobicity variations.
Acrylic acid was detected to migrate from syringes (Vendor X) into a therapeutic protein solution (at a concentration around 5 μg/mL). In this study, we discovered that acrylic acid can modify proteins at three different sites: (1) the lysine side chain, 2) the N-terminus, and 3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed.
Process & Product Development, Amgen Inc., Thousand Oaks, CA.
Dengfeng
D
Liu
Yasser
Y
Nashed-Samuel
Pavel V
PV
Bondarenko
David N
DN
Brems
Da
D
Ren
D004349:Drug Packaging; D006639:Histidine; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine; D004364:Pharmaceutical Preparations; D011506:Proteins; D013242:Sterilization; D013594:Syringes
D004364:Pharmaceutical Preparations; D011506:Proteins; D006639:Histidine; D008239:Lysine