Data Support Advanced Preparation of Reconstituted and Diluted Biosimilar Trastuzumab, SB3

Samsung Bioepis’ SB3, approved under the name Ontruzant in the United States and European Union, is a biosimilar trastuzumab referencing Herceptin.

Like that of its reference, SB3’s product information highlights the need for aseptic conditions during handling, as the product is for a single use and does not contain a preservative. Under aseptic conditions, SB3, like Herceptin, is physically and chemically stable for 48 hours after reconstitution with sterile water and stored at 2°C to 8°C. Diluted SB3 is also physically and chemically stable for 24 hours up to 30°C when stored in in polyvinylchloride, polyethylene, or polypropylene bags containing 0.9% normal saline.

Extended stability data for the reference Herceptin have been published, supporting advanced preparation and dose banding. Given stability data for SB3 are limited, a new study, published in Advances in Therapy, sought to assess the extended physiochemical stability and bioactivity of the biosimilar and to evaluate the advanced preparation of the reconstituted and diluted product.

Under controlled, aseptic conditions, researchers assessed the stability of reconstituted and diluted SB3 according to UK National Health Service guidance, then stored the reconstituted product at 25°C  (± 2°C) with 60% (±5%) relative humidity for 3 days. Next, diluted SB3 was stored in an infusion bags in the absence of light at 25°C  (±2°C) with 60% (±5%) relative humidity for 28 days, and 5°C (±3°C) for 28 days, respectively.

Then, physiochemical stability, biological activity, and properties that could impact safety—such as subvisible particulates or submicronic aggregation) were determined.

The investigators found no signs of physiochemical instability or any changes in biological activity for either reconstituted or diluted biosimilar up to day 28. No major change was observed in the proportion of molecular weight variants or relative percentages of acidic, main, and basic charge isoforms of the protein. No increases in particulate or aggregates that could impact safety were noted.

Furthermore, the study included an evaluation of samples at 1 time point beyond the proposed storage period of 28 days; at 33 days of additional storage, the proportion of high molecular weight impurity was not changed.

These findings, write the researchers, further support the physicochemical stability and maintained biological activity of reconstituted SB3 under proper storage conditions, and may help reduce the need to discard unused SB3 doses and to allow for advanced preparation without impacting the quality or biological activity of the product.

Reference

Yun J, Kim J, Chung J, Hwang SJ, Park SJ. Extended stability of reconstituted and diluted SB3 (trastuzumab biosimilar) assessed by physiochemical and biological properties [published online May 17, 2019]. Adv Ther. doi: 10.1007/s12325-019-00973-y.