Stability of IgG1 Monoclonal Antibodies in Intravenous Infusion Bags Under Clinical In-Use Conditions

Compounding pharmacists are expected to prepare safe and efficacious doses of medication under time and economical constraints while protecting pharmacy staff and caregivers from inadvertent exposure to the drug. The pharmacist has the additional responsibility to ensure that the product is stable in the final-administrated form as the time between drug preparation and administration is considerable. Pharmacists are responsible for setting a "beyond-use" date based on United States Pharmacopeia 797, wherein the beyond-use date for the compounded sterile preparation (CSP) is defined as the time by which the compounded preparation must be used to avoid risks for product degradation, contamination, and so on. Physical and chemical stability of the CSP can be difficult to maintain over extended storage, especially since the formulation components are diluted within the intravenous (i.v.) bag contents. Recent published reports have suggested the use of extended time, beyond that recommended by the manufacturer, for the storage and administration of CSP. These recommendations were based on inadequate analytical testing of the CSP. Herein, we demonstrate that setting of the beyond-use date should be carefully assessed using the appropriate analytical methods and testing. Results from our studies clearly indicate that many of the tested IgG(1) monoclonal antibodies should not be diluted and stored in i.v. bags over extended period of time, and particularly should not be transported after dilution in the infusion bags without consulting the manufacturer. Results from this study also indicate that i.v. bag agitation studies should be performed during pharmaceutical development of protein therapeutics under clinical in-use conditions, especially when storage and transportation of i.v. bags are possible in global clinical trials and post-licensure usage.