title: Paving the Way for Dose Banding of Chemotherapy: An Analytical Approach.
abstract: Background:In an interdepartmental cooperation, we investigated the feasibility and benefits of implementing dose banding of chemotherapy at our medical center. Based on this concept, chemotherapy doses are clustered into bands of similar dosage levels, thereby allowing the preproduction of frequently used standard doses of drugs, with sufficient physicochemical stability. Although established practice in the United Kingdom, there is little published evidence of its introduction elsewhere.Methods:We performed an analysis of local prescribing practice (22,310 chemotherapies) and identified gemcitabine, 5-fluorouracil, and carboplatin, among various others, as cytotoxic drugs suitable for dose banding.Results:First, we determined the physicochemical stability of the selected chemotherapy drugs during 12-weeks' storage by performing pH analysis and visual examination for color change or particles. No relevant changes were identified. Gemcitabine was selected for quantitative high-performance liquid chromatography analysis and we were able to show that ≥95% remained after 12 weeks' storage, in accordance with international guidelines. To simulate a worst case scenario, we performed microbiological stability testing of simulated cytotoxic compounding by replacing the cytotoxic drug with liquid media. Samples were incubated over defined storage time points (3, 6, and 12 weeks) and evaluated using the direct inoculation method. For the container integrity test, we deposited the samples into highly contaminated broth for 1 hour. Microbiological stability was demonstrated in both tests for the full storage period.Conclusions:Our data show that 12-weeks' storage of selected cytotoxic products is feasible from a microbiological perspective. Sterility of prepared products was maintained under extreme storage conditions. Gemcitabine content was in accordance with international guidelines after 12-weeks' storage. These results support the introduction of dose-banded gemcitabine products with the predicted advantages of optimized pharmacy workflow and reduced patient waiting times. We highlight the need for further research and consensus on the performance of purity analyses in dose-banded drug products.
authors.affiliation: University Medical Center Freiburg, Department of Hematology and Oncology, Freiburg, Germany
authors.forename: Heike
authors.initials: H
authors.lastname: Reinhardt
authors.affiliation: University Medical Center Freiburg, Pharmacy, Freiburg, Germany
authors.forename: Rainer
authors.initials: R
authors.lastname: Trittler
authors.affiliation: Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Pharmacy Department, Cambridge, United Kingdom
authors.forename: Alison G
authors.initials: AG
authors.lastname: Eggleton
authors.affiliation: University Medical Center Freiburg, Pharmacy, Freiburg, Germany
authors.forename: Stefan
authors.initials: S
authors.lastname: Wöhrl
authors.affiliation: University Medical Center Freiburg, Department of Clinical Chemistry, Freiburg, Germany
authors.forename: Thomas
authors.initials: T
authors.lastname: Epting
authors.affiliation: University Medical Center Freiburg, Environmental Health Sciences and Hospital Infection Control, Freiburg, Germany
authors.forename: Marion
authors.initials: M
authors.lastname: Buck
authors.affiliation: University Medical Center Freiburg, Environmental Health Sciences and Hospital Infection Control, Freiburg, Germany
authors.forename: Sabine
authors.initials: S
authors.lastname: Kaiser
authors.affiliation: University Medical Center Freiburg, Environmental Health Sciences and Hospital Infection Control, Freiburg, Germany
authors.forename: Daniel
authors.initials: D
authors.lastname: Jonas
authors.affiliation: University Medical Center Freiburg, Department of Hematology and Oncology, Freiburg, Germany|Comprehensive Cancer Center Freiburg, Freiburg, Germany
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.affiliation: Comprehensive Cancer Center Freiburg, Freiburg, Germany|Albert-Ludwigs-University Freiburg, Institute of Pharmaceutical Sciences, Freiburg, Germany; and hGerman Cancer Consortium (DKTK), Freiburg, Germany
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.affiliation: University Medical Center Freiburg, Pharmacy, Freiburg, Germany
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hug
authors.affiliation: University Medical Center Freiburg, Department of Hematology and Oncology, Freiburg, Germany
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000592:standards; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004340:Drug Contamination; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D010818:Practice Patterns, Physicians'; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents