TY - JOUR T1 - Assessment of sensor concepts for a 100% in-process control of low volume aseptic fill finish processes JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2019.011270 SP - pdajpst.2019.011270 AU - Tim Dreckmann AU - Imke Sonja Ludwig AU - Joerg Luemkemann AU - Andreas Ernst AU - Wolfgang Aipperspach AU - Tim Dreckmann AU - Joerg Huwyler AU - Julien Troendle Y1 - 2020/01/01 UR - http://journal.pda.org/content/early/2020/07/16/pdajpst.2019.011270.abstract N2 - Pharmaceutical industry is being confronted with new and complex challenges when it comes to aseptic filling of parenterals, in particular monoclonal antibodies. One challenge to point out are fill volumes < 200 μL which become increasingly important with the development of more and more intravitreal drugs and high concentrated formulations. Not only the filling itself poses new challenges to aseptic manufacturing but also the suitable in-process control which ensures a reliable and robust filling process. In particular, the established method of gravimetric fill volume control reaches the limits of accuracy and robustness when it comes to fill volumes < 200 μL It was therefore the aim of the present work, to evaluate and test novel sensors, which allow an accurate and precise 100% contact-free measurement of drug-product formulation with respect to fill volumes. These sensors were designed to be less influenced by inevitable noise factors like unidirectional air flow and vibrations. We set up a study with five different sensor concepts, to screen and identify suitable alternatives to the gravimetric fill volume control. Sensor concepts are based on airflow, capacitive pressure, light obscuration and capacitive measurement. Our results demonstrate that all sensor types tested worked in the desired low-volume range of 10 − 150 μL and showed remarkable results in terms of accuracy and precision against a high precision gravimetric balance. A sensor based on capacitance measurement was identified as the most promising candidate in view of a future sensor implementation into an aseptic filling line. This sensor design proved to be superior in terms of high sensitivity and precision. We conclude, that this technology is able to allow the pharmaceutical industry to overcome challenges with respect to reliable measuring of fill volumes < 200 μL during aseptic filling. This technology has the potential to fundamentally change the way pharmaceutical industry confirms correct dosing by allowing a 100% in-process control even at high machine speeds. ER -