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Prolonged In-use Stability of Reconstituted Herceptin in Commercial Intravenous Bags

Author(s):  Nalenz Heiko, Köpf Ellen, Dietel Elke

Issue:  Sep/Oct 2018 - Volume 22, Number 5
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Abstract:  Herceptin is a humanized monoclonal antibody that selectively binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2). Herceptin has an important role in the treatment of HER2-positive breast cancer when used in the neoadjuvant, adjuvant, and metastatic settings, and in the treatment of HER2-positive metastatic gastric cancer, and gastroesophageal junction adenocarcinoma. Prior to intravenous infusion, Herceptin must be reconstituted with sterile water for injection and then diluted in intravenous bags with normal saline. The objective of this study was to test the in-use physicochemical stability of the Herceptin drug product after dilution in 0.9% sodium chloride in commercial polyvinylchloride, and polyolefin/ polyethylene/polypropylene infusion bags over the course of a 7-day storage at 2°C to 8°C followed by 24 hours of storage at 30°C with ambient light exposure. Three batches of Herceptin were reconstituted to yield a 21-mg/mL solution that was stored for 48 hours at 2°C to 8°C prior to dilution with 0.9% sodium chloride to create low (0.24-mg/mL) and high (3.84-mg/mL) concentration solutions that were then tested in simulated infusions with a polyvinylchloride or polyolefin/polyethylene/polypropylene infusion bag. Samples for analysis were obtained immediately after dilution of the reconstituted solution (T0), after 7 days of storage at 5°C (T7), after 1 further day of storage at 30°C (T7+1), and after administration through intravenous tubing (Tend). Control samples were obtained from bags containing only 0.9% sodium chloride at each time point. For experiments with both infusion bags, all samples were practically free from particles, were colorless, and had low numbers of subvisible particles with no differences between control and experimental samples. No change in turbidity was detected between T0 and Tend for low and high-concentration samples for each batch. The pH values remained consistent between T0 and T7+1, and osmolality values were consistent across low-concentration and high-concentration samples. Protein content, size, and potency remained consistent throughout storage and simulated infusion. In conclusion, Herceptin remains physicochemically stable for 7 days when stored at 2°C to 8°C, followed by an additional 24 hours at 30°C when diluted in 0.9% sodium chloride and stored in commercially available polyvinylchloride or polyolefin/polyethylene/polypropylene infusion bags.

Related Keywords: Heiko Nalenz, PhD, Ellen Köpf, PhD, Elke Dietel, PhD, herceptin, human epidermal growth factor receptor 2, HER2 antibody, HER2-positive breast cancer, HER2-positive gastric cancer, gastroesophageal junction adenocarcinoma, polyvinylchloride infusion bags, polyolefin/polyethylene/polypropylene infusion bags, compatability, physical stability, chemical stability


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