An investigation of the quality and in-use stability of diluted trastuzumab biosimilar Kanjinti (also known as ABP 980) versus the reference trastuzumab demonstrated no clinically meaningful differences in stability and activity over extended storage periods, according to Crampton et al. [1].
Trastuzumab is a monoclonal antibody treatment for breast and gastric cancer that is HER2 receptor positive*. It was developed by Roche/Genentech and sold under the brand name Herceptin. Patents on Herceptin expired in 2014 in Europe and in 2019 in the US.
Several biosimilars have since been developed and approved. ABP 980 (trade name Kanjinti) is a trastuzumab biosimilar developed by Amgen. It was approved by the European Medicines Agency in March 2018 and by the US Food and Drug Administration in June 2019.
ABP 980 has the same amino acid sequence and similar post-translational modifications, product-related variants, and protein content as the reference trastuzumab and clinical tests have shown no significant differences in pharmacokinetics, safety and tolerability.
A study [1] recently published in GaBI Journal investigated the quality and in-use stability of diluted ABP 980 versus reference trastuzumab.
Often, centralized pharmacies prepare trastuzumab which is then transported to clinical sites for administration to patients. This requires holding the prepared solutions for longer durations, making the in-use stability of trastuzumab important.
The authors of the study used various assays to investigate the quality and in-use stability of diluted intravenous (IV) formulations of ABP 980 compared with the reference product to mimic dosing in IV bags, transportation and extended storage prior to infusion. These included simulated transportation by a steel spring truck and extended storage (35 days at 2°C–8°C or 30°C, followed by 30°C for 48 hours).
Assessments included protein concentration, pH, aggregation of the solution, purity and potency. Assessments were made pre- and post-transportation simulation, at Weeks 1, 2, 4, and 5; and at Week 5+ following 48 hours at 30°C pre-infusion, and post-infusion.
The findings show consistent quality between ABP 980 and the reference trastuzumab. ABP 980 did have a higher initial level of high molecular weight species than the reference trastuzumab, but rates of aggregation were similar for both products.
Although storage at 30°C led to changes in both products, these changes did not appear to affect biological activity. On the basis of these data, a National Health Service (NHS) Foundation Trust in England recommended extended storage of 28 days in a refrigerator for dilutions of 0.3 mg/mL–3.8 mg/mL in saline solution.
Overall, the findings support advance preparation of ABP 980 infusion bags at dosages of 0.3 mg/mL–3.8 mg/mL in saline solution and storage for 35 days at 2°C–8°C.
Storage of this kind could reduce workload for pharmacies and nurses, provide dose-banding flexibility, reduce drug wastage, and improve patient management. For example, the ability to transport ABP 980 to satellite clinics or pharmacies could enable patients to be treated closer to their home.
Although sterility was not evaluated by this study, high and low dose dilutions were prepared under aseptic conditions and no bacterial or fungal contamination had been reported in a similar study of the trastuzumab biosimilar CT-P6.
*Human epidermal growth factor receptor 2 positive
Conflict of interest
All authors of the research paper [1] are employees of Amgen and hold Amgen stock.
Editor’s comment
Readers interested to learn more about trastuzumab biosimilars are invited to visit www.gabi-journal.net to view the following manuscripts published in GaBI Journal:
Clinical trials for trastuzumab biosimilars
Extended stability of a biosimilar of trastuzumab (CT-P6) after reconstitution in vials, dilution in polyolefin bags and storage at various temperatures
Biosimilar trastuzumab similar to Herceptin in non-clinical study
Readers interested in contributing a research or perspective paper to GaBI Journal – an independent, peer reviewed academic journal – please send us your submission here.
Related articles
Scientific evidence in development of trastuzumab biosimilar ABP 980
FDA approves trastuzumab biosimilar Kanjinti
Biosimilars of trastuzumab
Reference
1. Crampton S, Polozova A, Asbury D, et al. Stability of the trastuzumab biosimilar ABP 980 compared to reference product after intravenous bag preparation, transport and storage at various temperatures, concentrations and stress conditions. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;9(1):5-12. doi:10.5639/gabij.2020.0901.002
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