Diluted trastuzumab deruxtecan stable for 28 days in the fridge
GERPAC Congress 2026 highlights
Trastuzumab deruxtecan (Enhertu®) diluted in 5% glucose keeps its physicochemical, structural and functional characteristics for at least 28 days at 2–8°C when protected from light, according to Yara Bendiab (Pitié-Salpêtrière University Hospital, AP-HP, Paris). This is a major improvement on the 24 hours stated in the Summary of Product Characteristics (SmPC). At room temperature, however, glycation and oxidation gradually reduce the drug’s biological activity.
Trastuzumab deruxtecan (T-DXd) is a third-generation antibody-drug conjugate used in HER2-positive breast cancer. It consists of an anti-HER2 antibody linked to about eight molecules of deruxtecan. Its short post-dilution shelf-life prevents advance preparation and limits flexibility for outpatient and home care. It also leads to waste: the hospital’s losses on this drug came to more than €74,000 in 2024.
In this study, three batches of T-DXd at 1 mg/mL and 4 mg/mL were prepared in 5% glucose in multilayer polypropylene bags. The bags were stored for 28 days at 2–8°C or at 25°C. Forced degradation studies (heat, pH, light, agitation, oxidation and freeze–thaw cycles) were also carried out. The team used a wide range of complementary analytical methods covering colloidal stability, aggregation and fragmentation, hydrophobicity, glycosylation, charge variants and structural modifications. Biological activity was assessed by HER2 ELISA and Fc receptor affinity. They also checked the integrity of the drug–antibody linkage.
Under refrigeration, all the parameters remained essentially unchanged. The pH stayed at 5.4–5.5 and no visible particles appeared. Antibody concentrations varied by less than 5%, regardless of concentration, temperature or batch. There was no aggregation, fragmentation, change in glycosylation or loss of the drug payload. HER2-binding activity was 94% of the initial value after 28 days.
At 25°C, mass spectrometry detected glycation and oxidation of the antibody after one to two weeks. An increase in acidic variants followed from day 21. By day 28, HER2-binding activity had fallen to 78%.
The authors concluded that diluted T-DXd preparations can be stored for at least 28 days under refrigeration and protected from light. This would allow doses to be prepared in advance, with benefits for patients, hospitals and the environment. The bags should not be stored at room temperature for prolonged periods.
Juul C, Bendiab YM, Hindès E et al. Glycation and oxidation: key determinants of the physicochemical behaviour of trastuzumab deruxtecan (Enhertu®) in a glucose infusion solution. Short communication. GERPAC Congress 2026
Image: Yara Bendiab
