An Intercompany Perspective on Compatibility and In-Use Stability Studies to Enable Administration of Biopharmaceutical Drug Products.

ABSTRACT In-use stability and compatibility studies are often used in biotherapeutic development to assess stability and compatibility of biologic drugs with diluents and/or administration components at relevant conditions for the target route of administration (commonly intravenous, subcutaneous or intramuscular), to assure that patient safety and product efficacy are maintained during clinical use. To gain an understanding of current industry, the Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, conducted an inter-company collaboration exercise, which included five bench-marking surveys around in-use stability and compatibility studies of biologic drugs. The results of this industry collaboration provide insights into the practicalities of these studies and how they are being used to support administration of biologics from early clinical programs to marketed products. The surveys queried topics including regulatory strategies and feedback; clinical in-use formulation, patient and site considerations; clinical blinding, masking and placebo approaches; study setup, execution and reporting; and clinical and in-use stability testing to provide a comprehensive picture of the range of common industry practices. This paper discusses the survey results and presents various approaches which can be used to guide the strategy and design of an in-use stability and compatibility program based on clinical and biomolecule needs.