Investigation on the stability of a monoclonal antibody

• Authors: Aser Zidan, FDA/CDER (Student), George Liang, FDA/CDER (Student), Chikkathur Madhavarao FDA/CDER (Mentor)

• Center: Center for Drug Evaluation and Research

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Abstract

Monoclonal antibodies (mAbs) form a major component of therapeutic proteins produced mostly by mammalian cell culture, for the treatment of various human diseases. The efficacy of the mAb drugs suffers if mAbs are not able to retain their native and effective physico-chemical state. Loss of native and effective physico-chemical state of the mAbs can also lead to aggregation, particulate formation, and immunogenic responses in patients, leading to withdrawal from treatment. Therefore, retention of active physico-chemical state of an mAbs is essential, which depends on how the mAb drug is formulated. Here we investigate the integrity and stability of a mAb biosimilar to Humira in aqueous solution phase by using three buffers under three pH conditions- 5.5, 6.0 and 7.0. In each buffer, 7 different cosolutes and a surfactant are prepared separately providing a set of 24 aqueous test solutions. The mAb samples in these 24 test solutions are tested for retaining physico-chemical integrity against 4 test conditions- (i) 2 cycles of freeze thaw; (ii) storage in a refrigerator (0-4 C); (iii) storage at room temperature for 1 h, and (iv) storage at 50 C for 1 h. The mAb integrity is evaluated by SDS-PAGE analysis under non-reducing native conditions to observe for loss of integrity and appearance of aggregation. Preliminary data indicate that specific buffer and solute combinations afford

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