Fluid Dynamic Sampling Site Characterization Improves Process Correlation During Continuous Online Sampling
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ORIGINAL ARTICLE
Fluid Dynamic Sampling Site Characterization Improves Process Correlation During Continuous Online Sampling Benedikt Scheidecker 1 & Reinhard Braaz 2 & Josef Vinnemeier 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Implementation of Process Analytical Technologies (PAT) is an important consideration to increase process knowledge during pharmaceutical manufacturing. Currently used batch sampling methods, however, are limited in terms of temporal resolution when compared with continuous process sampling. Here, we show the importance of fluid dynamic characterization when repurposing available batch sampling sites comprising needle insertion mechanisms to generate continuous sample streams. Methods Rheological flow profiles in a needle-based sampling site were characterized by computational fluid dynamics. Observed characteristics were confirmed with a NovaSeptum sample system in reenacted sampling situations, and correlation of sample and system flow was achieved by simultaneous measurement of an acetone gradient. Results As a result of the sampling mechanism causing distinct flow patterns around the needle body, velocity fields are shown to generate orientation-dependent sample flow. Due to the inherent relationship between flow detachment and turbulent flows, extracted sample flow depends on system flow profiles, affecting sample correlation. A combination of active sample extraction, check valve addition, and geometrical changes in sampling site design is shown to reduce sample efflux variability, allowing for system parameter-independent sample generation. The resulting sample flow has been correlated to a simulated process flow, enabling a continuous representation of at-scale systems. Conclusions Repurposing existing sampling sites requires fluid dynamic characterization in order to generate representative sample streams, which allows the exchangeable inclusion of process analytics otherwise not compatible with at-scale systems. Resulting time-dependent, discrete samples can then be utilized for on- and off-line analysis to provide additional process knowledge according to the PAT initiative. Keywords Process analytical technology . Continuous sampling . CFD . Flow detachment
Introduction Quality assurance of pharmaceutical drug products is a central part of industrial drug manufacturing, with product quality being assessed by tightly controlled process parameters and
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12247-020-09458-w) contains supplementary material, which is available to authorized users. * Benedikt Scheidecker [email protected] 1
Department of Chemical System Engineering, University of Tokyo, Tokyo 113-8654, Japan
2
Clinical Supply Center Downstream Processing, Roche Diagnostics GmbH, 82377 Penzberg, Germany
batch sampling for detailed biochemical analysis [1]. While pharmaceutical processes are extensively validated [2], direct data from at-scale manufacturing i
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