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Approach for Multicriteria Equipment Redesign in Sterile Manufacturing of Biopharmaceuticals

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Journal of Pharmaceutical Innovation Aims and scope Submit manuscript

Abstract

Purpose

There is a continuous search for efficient optimization methods in the production of biopharmaceuticals, with a special focus on reducing production time and costs. Pharmaceutical production is currently dominated by batch production processes that have a relatively long downtime for cleaning and reconfiguration of the plant equipment when the product or its format size is changed. The geometry and design of the equipment can strongly affect process performance. This work presents an approach for generating and assessing design alternatives for process equipment used in the sterile filling of biopharmaceutical drug products.

Methods

A case study is presented based on background information provided by Hoffmann-La Roche for a surge tank used in the filling of liquid vials. Three criteria—namely equipment cleanability, production efficiency, and flexibility—are used to evaluate the proposed shape alternatives for the surge tank. Computational fluid dynamics (CFD) was applied to investigate the flow behavior of cleaning water inside the tank.

Results

A trade-off in the results was observed between the different evaluation criteria for the investigated basic shapes. However, it was found that a different part of the tank controls the results obtained for each criterion. An alternative tank design is presented that combines the optimal features to achieve the best possible performance for all assessment criteria.

Conclusion

The transfer and application of the established CFD technique to the field of sterile manufacturing of biopharmaceuticals were demonstrated and facilitated by the introduction of appropriate model simplifications. Valuable insights on equipment cleanability and on the measures required to achieve cleanliness were obtained, which proves the importance of the application of such techniques. Redesigning equipment and applying geometrical changes were shown to be effective measures for process performance optimization.

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Abbreviations

alt.:

Alternative

CAD:

Computer-aided design

CFD:

Computational fluid dynamics

CIP:

Cleaning-in-place

FVM:

Finite volume method

OpenFOAM :

Open source field operation and manipulation

PSE:

Process system engineering

RANS:

Reynolds-averaged Navier–Stokes equation

RAS:

Reynolds-averaged simulation

SIP:

Sterilization-in-place

SST:

Shear stress transport

VOF:

Volume of fluid

WFI:

Water-for-injection

ε :

Turbulent dissipation (m2·s−3)

k :

Turbulent kinetic energy (m2·s−2)

Γ :

Percentage of wetting (−)

ω :

Specific turbulence dissipation rate (s−1)

P loss :

Product loss (m3/batch)

t :

Time (s)

u :

Velocity vector in (x, y, z)-direction (m·s−1)

u’ :

Small oscillations in (x, y, z)-direction (m·s−1)

U :

Time-averaged velocity vector in (x, y, z)-direction (m·s−1)

V flex :

Volume representing the production flexibility (m3)

V max :

Volume up to the maximum liquid level (m3)

V min :

Volume up to the minimum liquid level (m3)

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Acknowledgments

The authors would like to thank the many collaborators from F. Hoffmann–La Roche Ltd for providing necessary information and resources for this study. The authors also acknowledge financial support from a Grant-in-Aid for Young Scientists (A) No. 17H04964 from the Japan Society for the Promotion of Science, and a Research Grant 2017 from the Nagai Foundation Tokyo. The Top Global University Project of the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT), and Japan Student Services Organization (JASSO) are also gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Anicia Zeberli, Gioele Casola, Sara Badr & Hirokazu Sugiyama

  2. Sterile Manufacturing, F. Hoffmann–La Roche Ltd, Wurmisweg, 4303, Kaiseraugst, Switzerland

    Christian Siegmund & Markus Mattern

Authors
  1. Anicia Zeberli
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  2. Gioele Casola
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  3. Sara Badr
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  4. Christian Siegmund
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  5. Markus Mattern
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  6. Hirokazu Sugiyama
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Corresponding author

Correspondence to Hirokazu Sugiyama.

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Teaser

The work presents an approach to redesign equipment in the filling step of biopharmaceutical drug product manufacturing. It investigates the effect of the shape of the equipment on process performance and introduces an application of computational fluid dynamics to simulate the cleaning-in-place process.

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Zeberli, A., Casola, G., Badr, S. et al. Approach for Multicriteria Equipment Redesign in Sterile Manufacturing of Biopharmaceuticals. J Pharm Innov 15, 15–25 (2020). https://doi.org/10.1007/s12247-018-9355-8

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  • DOI: https://doi.org/10.1007/s12247-018-9355-8

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