The Use of Amplified ATP Bioluminescence for Rapid Sterility Testing of Drug Product Formulations

Abstract

The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development. However, sterile material manufactured under Good Manufacturing Practice (GMP) conditions may not always be available, for example, during studies to understand the bacterial retention of sterilizing grade filters. In cases of bactericidal products, the use of surrogates may be justified if they are suitably representative of the final drug product formulation. It may not be possible to secure GMP facility access to prepare such surrogate formulations; in those cases, the principles of GMP may be applied in a controlled laboratory setting. The rapid sterility test was used to provide the sterility assurance of the prepared surrogate material. In this case study, the application of amplified ATP bioluminescence sterility testing enabled a fast response to ensure mitigations could be executed in a timely manner. This meant that overarching project plans could be met. The case study also provides information on the rapid identification technique used to identify the slow growing and difficult to recover organism, which allowed faster indication of a nonsterile material. The example also highlights some of the aspects of the challenges of culturing microorganisms and the value of modern techniques in their ability to indicate a quality drift. Dermacoccus nishinomiyaensis was isolated from the test article, and throughout the investigation, it was not possible to culture this organism on standard tryptic soya agar.