(762a) Process Development and Manufacturing: Single Use Versus Glass and Stainless Steel

Single-use equipments are now commonly used for process development and production activities. The advantages of these equipments have been well demonstrated over more than a decade and include absence of cleaning, no need for sterilization, easy and fast validation, reduced labor time and increased flexibility. However, only a few data on their scalability are published and most studies focus on a single type of equipment such as Single-Use Bioreactors (SUBs) or on DSP units such as clarification or chromatography skids. Few studies actually describe full USP and DSP disposable trains.

During the period 2010-2012, we performed studies in order to evaluate the performances of Single-Use equipments from early Process Development activities down to the manufactured Drug Substance after a full manufacturing process. As different formats were available, this study compared performances of several types of equipments from 3L to 1250L scale. The evaluation was performed both for Process Development applications and for clinical material production through the development of a fed-batch process and its use for clinical scale production.

The quality of the molecule together with the titer and the cell growth were measured. The process performances were compared in single use, glass and stainless steel bioreactors of different sizes including 3L, 50L, 200L and 1,250L. Several clinical runs at 200L and 1250L scale were performed to ensure a meaningful comparison. We evaluated the differences between the systems using different types of cells such as CHO and NS0 but also different molecules including several MAbs and Fc-Fusion protein. The data generated allowed to conclude on the scalability and the comparability of the different systems and technologies. Beyond the process performances and technical data we recorded timings and evaluated the cost of the different operations to complete the assessment.

This study demonstrated the benefits of using disposable equipment in several key areas. The comparison of stainless steel, glass and disposable equipment showed how comparable they are regarding titers, molecule quality…and how different they are regarding organization and financial aspects. The operator feedbacks on the ease of use and the necessary changes in the GMP area to introduce SUBs were discussed as well.