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Chapter 22: Development and Scale-Up of the Mixing Process for Biopharmaceuticals

  • Feroz JameelEmail author
  • Ann M. Czyzewski
  • Tong Zhu
  • Kushal Sinha
  • Nandkishor K. Nere
Chapter
  • 85 Downloads
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 35)

Abstract

Hydrodynamics of stirred vessels used in various biopharmaceutical processing unit operations affect many important process and product attributes. Hence, reliable process scale-up requires careful characterization of the mixing performance, which can be impacted by fluid properties, operating parameters, and geometric considerations. Here we begin with a discussion of the merits and limitations of empirical correlations and platform approaches that can be applied to traditional mixing systems. More advanced approaches including first-principle modeling coupled with model-guided experiments are then described, which are capable of providing a fundamental, process-specific understanding in more complex, shear-sensitive, or biphasic mixtures. Appropriate application of these tools in the design and scale-up of biomolecule processes enables more robust process performance and reproducible product attributes.

Keywords

Hydrodynamics Mixing Computational fluid dynamics (CFD) Scale-up Shear-sensitive biomolecules Strain rate Energy dissipation rate Gas entrainment Mass transfer 

Nomenclature

a:

Specific interfacial area [m2]

αair:

Air volume fraction

C:

Impeller clearance [m]

CL:

Gas concentration

C∗:

Equilibrium gas concentration

D:

Impeller diameter [m]

db:

Volume-averaged bubble diameter [m]

DM:

Molecular diffusivity [m2/s]

γB:

Bulk shear rate [1/s]

γI:

Impeller tip shear rate [1/s]

H:

Height of liquid [m]

J:

Baffle width [m]

KLa:

Gas-liquid mass transfer coefficient

KSL:

Solid-liquid mass transfer coefficient [1/(m2∗s)]

L:

Agitator blade length [m]

μ:

Liquid viscosity [Pa∗s]

n:

Rotational speed [1/s]

NB:

Impeller blend number

NP:

Impeller power number

NQ:

Impeller pumping number

P:

Impeller power [W/m3]

q:

Volumetric flow rate [m3/s]

Re:

Reynolds number

ρ:

Liquid density [kg/m3]

Sc:

Schmidt number

T:

Tank diameter [m]

t:

Torque

ϴ:

Theoretical mixing time [s]

W:

Agitator blade width [m]

ν:

Tangential velocity [m/s]

VB:

Bulk velocity [m/s]

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Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  • Feroz Jameel
    • 1
    Email author
  • Ann M. Czyzewski
    • 2
  • Tong Zhu
    • 1
  • Kushal Sinha
    • 2
  • Nandkishor K. Nere
    • 2
  1. 1.Formulation Development, New Biological Entities, AbbVie (United States)North ChicagoUSA
  2. 2.Process Research and Development, AbbVie Inc.North ChicagoUSA

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