Abstract 18P
Background
Atezolizumab (atezo) is administered by intravenous (IV) infusion after dilution in IV infusion bags containing 0.9% sodium chloride (NaCI) solution. The objective of this study was to evaluate the physicochemical stability of diluted atezo in IV infusion bags stored for an extended period of time.
Methods
Two types of IV infusion bags with product-contact surfaces comprised of polyvinyl chloride (PVC) and polyolefin were tested. Polyolefin is a copolymer of polyethylene and polypropylene, so is abbreviated as PO-PE-PP here. Under aseptic conditions, atezo was withdrawn from commercial vials (840 mg or 1200 mg) and added to 100 mL or 250 mL IV infusion bags containing 0.9% NaCl with target concentrations of 2.4, 9.6 and 16.8 mg/mL. Bags containing diluted atezo were stored at 30°C for 24 hours with exposure to ambient light, then at 2–8°C for up to 12 months, protected from light. 10 mL samples were withdrawn at selected time points and evaluated by analytical assays for colour, opalescence and clarity; visible and sub-visible particulates; pH; protein content, by UV spectrophotometric analysis; size exclusion high-performance liquid chromatography (SE-HPLC); ion exchange high-performance liquid chromatography (IE-HPLC); non reduced capillary electrophoresis-sodium dodecyl sulfate (NR-CE-SDS); and potency assays.
Results
There were no substantial changes in atezo product quality by any measure related to any analytical assay listed after storage for 24 hours at 30°C followed by 3 months at 2–8°C. No new peaks were observed on SE-HPLC, IE-HPLC or NR CE-SDS profiles of diluted atezo after the extended storage. Over 12 months of storage at 2–8°C, trends for increases in protein aggregates by SE-HPLC, increases in fragments by NR CE-SDS, and increases in acidic species by IE-HPLC were observed in some diluted samples.
Conclusions
With a comprehensive assessment of multiple atezo concentrations and storage conditions, the study demonstrates that atezo diluted in 0.9% NaCl over a concentration range of 2.4–16.8 mg/mL was physicochemically stable when stored for 24 hours at 30°C followed by 3 months at 2–8°C in both PVC and PO-PE-PP IV infusion bags.
Clinical trial identification
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Blair Jarvis, MSc, of Health Interactions, was provided by Genentech, Inc., South San Francisco, CA, USA.
Legal entity responsible for the study
Genentech, Inc.
Funding
Genentech, Inc.
Disclosure
A. Hui: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. J. Yin: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. W. Liu: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland. K. Zheng: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, F. Hoffmann-La Roche Ltd – Third-party editing assistance: F. Hoffmann-La Roche, Basel, Switzerland.