Testing of microbial contamination during the preparation of the radiocompound [⁹⁰Y]DOTATOC for clinical trials: a process validation study by Media Fill approach.

Abstract

AimRadioisotopes used in nuclear radiopharmacy possess short half-lives, not allowing enough time to wait for completion of sterility tests. Moreover, carrying out sterility tests on highly radioactive solutions inside the hospital microbiology laboratory arises concerns about radioprotection. Therefore, the release of radiopharmaceuticals for injection is allowed in microbial analysis. For this reason, the effectiveness of the aseptic procedures has to be continuously assessed in order to guarantee the safety of the drug. The aim of this study was to validate the sterile preparation of [⁹⁰Y]DOTATOC by means of media fill test.MethodsIn order to validate the process, a simulation test was used: the media fill test. To apply this method, operators simulated each step of the process using culture medium (Triptic Soy Broth, TSB) instead of actual radiopharmaceutical product. Media fill test procedure has been subdivided into 5 phases, from the simulation of reagent preparation through the dispensing operations up to ward delivery. After every step, the processed medium was incubated at 35 °C for 14 days. If the compounding procedures are adequately performed, no growth of microorganisms will be detected.ResultsMicrobiological analyses, carried out on all vials obtained at the end of each step, showed no microbial growth. For this reason, sterility tests were considered satisfactory.ConclusionApplication of media-fill test allowed both to validate operative modality used for [⁹⁰Y]-DOTATOC handling and to attest the ability of operators who worked on it. Additionally, a correct quality control of the radiopharmaceutical i.v. preparations allows clinic infections control and prevention.