ABSTRACT
Background: Current guidelines for sterile compounding require that single dose vials of pharmaceuticals must be discarded after 6 hours when accessed in an ISO Class 5 environment. At this time, no studies have evaluated the sterility of single dose vials at any time after opening. Objective: The purpose of this study is to evaluate the sterility of single dose vials attached to an automated compounding device for up to 24 hours and accessed and maintained within a cleanroom environment. Methods: This is a prospective, observational study evaluating the sterility of 32 pooled samples of manufactured single dose injectable drugs attached to an automated compounding device for up to 24 hours and maintained within an ISO Class 5 environment in an ISO Class 7 buffer area. Each pooled sample was comprised of the remaining contents of 10 single dose vial additives that were used for total parenteral nutrition (TPN) and attached to the compounder within the previous 24 hours. Samples were evaluated using membrane filtration sterility testing and incubated for 14 days per USP <71> requirements. Results: The results revealed zero failed sterility samples. Single dose vials remained attached to the compounder for an average of 23.8 hours (±0.1 hours). The average volume per sample was 879 mL (±105.1 mL). Manipulation of vials during the compounding process included an average of 20.4 manipulations (±1.4). Conclusions: Single dose injectable drugs attached to an automated compounding device within an ISO Class 5 cleanroom environment may remain sterile for up to 24 hours. Future studies are needed with a larger sample size and under continued dynamic working conditions to provide further evidence to extend the beyond use date within USP <797>.
ABSTRACT
PURPOSE: The stability of extemporaneously compounded diltiazem hydrochloride infusions stored in polyolefin bags was studied. METHODS: Sterile preparations of diltiazem hydrochloride were compounded to a concentration of 1 mg/mL in 5% dextrose solutions in accordance with United States Pharmacopeia chapter 797. The infusions were stored at -20 °C, 2-6 °C, and 22-25 °C. Three samples from each temperature were withdrawn and assessed for stability immediately after preparation (day 0) and on days 7, 15, 21, and 30 using a high-performance liquid chromatography (HPLC) assay. The physical stability of diltiazem samples was assessed by visual examination. Infusions were evaluated against black and white backgrounds for evidence of visible particulate matter, cloudiness, and color changes. The concentration of diltiazem hydrochloride in all samples was examined using a stability-indicating HPLC method at each time point. Diltiazem was considered stable if the solution retained over 90% of the initial concentration. RESULTS: No precipitation, cloudiness, or color change was observed at any of the temperatures studied. pH did not significantly increase or decrease among the samples, regardless of temperature, over the study period. The diltiazem hydrochloride infusions retained greater than 90% of the initial concentrations for at least 30 days. CONCLUSION: Diltiazem hydrochloride diluted to 1 mg/mL in 5% dextrose injection was stable for 30 days when stored at -20 °C, 2-6 °C, and 22-25 °C.
