May 6-11, 2018
According to authority guidelines, process understanding is considered the key factor for a successful control strategy in submissions for biopharmaceutical production processes. This knowledge is usually gained in scale down model (SDM) experiments and therefore is subject to the ability of the SDM to reliably predict behavior of cell culture processes in manufacturing scale. In order to prove predictability, SDM runs at target conditions are typically compared to manufacturing scale target runs only. At the same time, predictability is also assumed within the whole design space described or even beyond as evaluated in process design studies. The proof at off-target conditions, however, is rarely provided. In this presentation, the author will exhibit an example where a well-established scale down model was used to determine off-target conditions to manufacture clinical material of a marketed product in 10,000 L scale with a deliberately deviant from target but nevertheless well-defined product quality profile. The desired quality attribute profile was achieved in two manufacturing runs with remarkable accuracy providing additional evidence of the SDM predictability. Hence, confidence is increased in the capability of the resultant control system which has been submitted to authorities for a post licensure manufacturing change.
Markus Emmler, Stefanie Menrad, and Yosuke Watanabe, "Off-target at-scale Scale Down Model verification of a marketed biopharmaceutical" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). https://dc.engconfintl.org/ccexvi/13