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A decision-support model for evaluating changes in biopharmaceutical manufacturing processes

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Abstract

A simulation is described that evaluates the impacts of altering bio-manufacturing processes. Modifications designed to improve production levels, times and costs were assessed, including increasing feed volumes/titres, replacing initial downstream stages with packed or expanded bed affinity steps and removing ion exchange steps. Options were evaluated for manufactured product mass, COG, batch times and development costs and timescales. Metrics were combined using multi-attribute-decision-making techniques generating a single assessment metric for each option. The utility of this approach was illustrated by application to an FDA-approved process manufacturing rattlesnake anti-venom (Protherics U.K.). Currently, ovine serum containing anti-venom IgG is purified by precipitation/centrifugation, prior to antibody proteolysis by papain. An ion exchanger removes FC, before affinity chromatography yields the final anti-venom. An expanded bed affinity column operating with an 80% higher IgG titre, 66% higher feed volume and without the ion exchanger delivered the best multi-attribute-decision-making value, potentially providing the most desirable alternative.

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Abbreviations

M A :

Actual product mass (g FAB)

M 0 :

Lowest product mass set to represent the zero bound in normalisation (g FAB)

M 1 :

Highest product mass set to represent the one bound in normalisation (g FAB)

N i :

Normalised value of the ith performance metric (–)

OR:

Overall Rank (–)

w i :

Weighting of the ith performance metric (–)

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Acknowledgements

The support of the Engineering and Physical Sciences Research Council and Protherics U.K. Limited is acknowledged gratefully. The advice of Dr. Suzanne Farid (UCL) is acknowledged gratefully.

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Authors and Affiliations

  1. The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK

    S. Chhatre, N. J. Titchener-Hooker & E. Keshavarz-Moore

  2. Process Development Group, Protherics U.K. Limited, Blaenwaun, Ffostrasol, Llandysul, Wales, SA44 5JT, UK

    R. Francis, K. O’Donovan & A. R. Newcombe

Authors
  1. S. Chhatre
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  2. R. Francis
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  3. K. O’Donovan
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  4. N. J. Titchener-Hooker
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  5. A. R. Newcombe
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  6. E. Keshavarz-Moore
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Corresponding author

Correspondence to E. Keshavarz-Moore.

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Chhatre, S., Francis, R., O’Donovan, K. et al. A decision-support model for evaluating changes in biopharmaceutical manufacturing processes. Bioprocess Biosyst Eng 30, 1–11 (2007). https://doi.org/10.1007/s00449-006-0086-8

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  • DOI: https://doi.org/10.1007/s00449-006-0086-8

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