Evaluation of the Exposure Risk to Thiotepa from the Preparation and Administration Process of RETHIO^® Injection 100 mg

Abstract

Injection 100 mg is currently marketed as a medicinal drug composed of thiotepa, 1,1',1''-phosphorothioyltriaziridine, for the pretreatment of autologous hematopoietic stem cell transplantation in pediatric malignant solid tumors. Thiotepa is an antineoplastic alkylating agent and categorized as a highly potent compound. Also, since thiotepa is potentially carcinogenic and volatile, it is noti ed in the package insert that RETHIO should be handled carefully using containment systems and protective equipment to avoid exposure to the hazardous product. In Japan, closed system drug transfer devices; CSTDs have been gradually introduced for the preparation of anticancer injections since 2016, when the MHLW revised the medical fees for the application of CSTDs. One purpose of this study was to investigate the exposure to RETHIO by monitoring spilled and volatilized thiotepa from preparation of infusion bags using a CSTD to administration with tubing and a vent lter. As a result, no thiotepa was detected in the preparation process performed in accordance with an appropriate guideline and using CSTD, and the safety was also con rmed for the administration process. The other purpose was to assess whether representative materials used in the preparation and administration were compatible with macrogol 400, the solvent of RETHIO. No issues for appearance and functionality were observed in the materials in contact with macrogol. In conclusion, no exposure risk to thiotepa was veri ed by appropriate operation of CSTDs from preparation to the administration process. Also, the functionality of apparatuses for preparation and administration for RETHIO was maintained for the expected operation time.