---
_id: '11428'
abstract:
- lang: eng
  text: Systems that place high demands on availability are typically modular in design.
    However, a modular design also offers potential for optimized operation under
    norma requirements. In this paper we present an approach to find optimal operating
    points from the characteristic fields of individual modules. Our approach consists
    of a two-step procedure. In the first stage, Pareto sets are calculated using
    the NSGA-II genetic algorithm. The second stage contains a heuristic that finds
    situationally optimal operating points using a defined operating strategy.
author:
- first_name: Maximilian
  full_name: Lammersen, Maximilian
  id: '81623'
  last_name: Lammersen
  orcid: 0009-0001-9092-9088
- first_name: Rainer
  full_name: Rasche, Rainer
  id: '74574'
  last_name: Rasche
citation:
  ama: Lammersen M, Rasche R. <i>Optimized Operating Points for Power Electronic Building
    Blocks</i>. *
  apa: Lammersen, M., &#38; Rasche, R. (n.d.). Optimized Operating Points for Power
    Electronic Building Blocks. In <i>Conference proceedings of Mecatronics &#38;
    AISM 2023</i>. Mecatronics &#38; AISM2023, Yokohama. *.
  bjps: <b>Lammersen M and Rasche R</b> (n.d.) <i>Optimized Operating Points for Power
    Electronic Building Blocks</i>. *.
  chicago: Lammersen, Maximilian, and Rainer Rasche. <i>Optimized Operating Points
    for Power Electronic Building Blocks</i>. <i>Conference Proceedings of Mecatronics
    &#38; AISM 2023</i>. *, n.d.
  chicago-de: Lammersen, Maximilian und Rainer Rasche. <i>Optimized Operating Points
    for Power Electronic Building Blocks</i>. <i>Conference proceedings of Mecatronics
    &#38; AISM 2023</i>. *.
  din1505-2-1: '<span style="font-variant:small-caps;">Lammersen, Maximilian</span>
    ; <span style="font-variant:small-caps;">Rasche, Rainer</span>: <i>Optimized Operating
    Points for Power Electronic Building Blocks</i> : *'
  havard: M. Lammersen, R. Rasche, Optimized Operating Points for Power Electronic
    Building Blocks, *, n.d.
  ieee: M. Lammersen and R. Rasche, <i>Optimized Operating Points for Power Electronic
    Building Blocks</i>. *.
  mla: Lammersen, Maximilian, and Rainer Rasche. “Optimized Operating Points for Power
    Electronic Building Blocks.” <i>Conference Proceedings of Mecatronics &#38; AISM
    2023</i>, *.
  short: M. Lammersen, R. Rasche, Optimized Operating Points for Power Electronic
    Building Blocks, *, n.d.
  ufg: '<b>Lammersen, Maximilian/Rasche, Rainer</b>: Optimized Operating Points for
    Power Electronic Building Blocks, o. O. u. J. .'
  van: Lammersen M, Rasche R. Optimized Operating Points for Power Electronic Building
    Blocks. Conference proceedings of Mecatronics &#38; AISM 2023. *;
conference:
  end_date: 2023-09-11
  location: Yokohama
  name: Mecatronics & AISM2023
  start_date: 2023-09-09
date_created: 2024-05-02T09:25:01Z
date_updated: 2024-05-15T07:21:59Z
department:
- _id: DEP5026
- _id: DEP6020
keyword:
- modularity
- optimization
- PEBB
- operating strategy
- genetic algorithm
- Pareto
language:
- iso: eng
publication: Conference proceedings of Mecatronics & AISM 2023
publication_status: accepted
publisher: '*'
quality_controlled: '1'
status: public
title: Optimized Operating Points for Power Electronic Building Blocks
type: conference_editor_article
user_id: '83781'
year: '2023'
...
---
_id: '11377'
abstract:
- lang: eng
  text: <jats:p>consuming and often performed rather empirically. Efficient optimization
    of multiple objectives such as process time, viable cell density, number of operating
    steps &amp; cultivation scales, required medium, amount of product as well as
    product quality depicts a promising approach. This contribution presents a workflow
    which couples uncertainty-based upstream simulation and Bayes optimization using
    Gaussian processes. Its application is demonstrated in a simulation case study
    for a relevant industrial task in process development, the design of a robust
    cell culture expansion process (seed train), meaning that despite uncertainties
    and variabilities concerning cell growth, low variations of viable cell density
    during the seed train are obtained. Compared to a non-optimized reference seed
    train, the optimized process showed much lower deviation rates regarding viable
    cell densities (&lt;10% instead of 41.7%) using five or four shake flask scales
    and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall,
    it is shown that applying Bayes optimization allows for optimization of a multi-objective
    optimization function with several optimizable input variables and under a considerable
    amount of constraints with a low computational effort. This approach provides
    the potential to be used in the form of a decision tool, e.g., for the choice
    of an optimal and robust seed train design or for further optimization tasks within
    process development.
article_number: '883'
author:
- first_name: Tanja
  full_name: Hernández Rodriguez, Tanja
  id: '52466'
  last_name: Hernández Rodriguez
- first_name: Anton
  full_name: Sekulic, Anton
  last_name: Sekulic
- first_name: Markus
  full_name: Lange-Hegermann, Markus
  id: '71761'
  last_name: Lange-Hegermann
- first_name: Björn
  full_name: Frahm, Björn
  id: '45666'
  last_name: Frahm
citation:
  ama: Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing Robust
    Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization
    Applied to a Biopharmaceutical Seed Train Design. <i>Processes</i>. 2022;10(5).
    doi:<a href="https://doi.org/10.3390/pr10050883">10.3390/pr10050883</a>
  apa: Hernández Rodriguez, T., Sekulic, A., Lange-Hegermann, M., &#38; Frahm, B.
    (2022). Designing Robust Biotechnological Processes Regarding Variabilities Using
    Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.
    <i>Processes</i>, <i>10</i>(5), Article 883. <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>
  bjps: <b>Hernández Rodriguez T <i>et al.</i></b> (2022) Designing Robust Biotechnological
    Processes Regarding Variabilities Using Multi-Objective Optimization Applied to
    a Biopharmaceutical Seed Train Design. <i>Processes</i> <b>10</b>.
  chicago: Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann, and
    Björn Frahm. “Designing Robust Biotechnological Processes Regarding Variabilities
    Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.”
    <i>Processes</i> 10, no. 5 (2022). <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>.
  chicago-de: Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann und
    Björn Frahm. 2022. Designing Robust Biotechnological Processes Regarding Variabilities
    Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.
    <i>Processes</i> 10, Nr. 5. doi:<a href="https://doi.org/10.3390/pr10050883">10.3390/pr10050883</a>,
    .
  din1505-2-1: '<span style="font-variant:small-caps;">Hernández Rodriguez, Tanja</span>
    ; <span style="font-variant:small-caps;">Sekulic, Anton</span> ; <span style="font-variant:small-caps;">Lange-Hegermann,
    Markus</span> ; <span style="font-variant:small-caps;">Frahm, Björn</span>: Designing
    Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective
    Optimization Applied to a Biopharmaceutical Seed Train Design. In: <i>Processes</i>
    Bd. 10. Basel, MDPI AG (2022), Nr. 5'
  havard: T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Designing
    Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective
    Optimization Applied to a Biopharmaceutical Seed Train Design, Processes. 10 (2022).
  ieee: 'T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, and B. Frahm, “Designing
    Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective
    Optimization Applied to a Biopharmaceutical Seed Train Design,” <i>Processes</i>,
    vol. 10, no. 5, Art. no. 883, 2022, doi: <a href="https://doi.org/10.3390/pr10050883">10.3390/pr10050883</a>.'
  mla: Hernández Rodriguez, Tanja, et al. “Designing Robust Biotechnological Processes
    Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical
    Seed Train Design.” <i>Processes</i>, vol. 10, no. 5, 883, 2022, <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>.
  short: T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Processes
    10 (2022).
  ufg: '<b>Hernández Rodriguez, Tanja u. a.</b>: Designing Robust Biotechnological
    Processes Regarding Variabilities Using Multi-Objective Optimization Applied to
    a Biopharmaceutical Seed Train Design, in: <i>Processes</i> 10 (2022), H. 5.'
  van: Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing Robust
    Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization
    Applied to a Biopharmaceutical Seed Train Design. Processes. 2022;10(5).
date_created: 2024-04-25T13:35:04Z
date_updated: 2024-05-21T09:30:15Z
department:
- _id: DEP4000
doi: 10.3390/pr10050883
intvolume: '        10'
issue: '5'
keyword:
- Gaussian processes
- Bayes optimization
- Pareto optimization
- multi-objective
- cell culture
- seed train
language:
- iso: eng
place: Basel
publication: Processes
publication_identifier:
  eissn:
  - 2227-9717
publication_status: published
publisher: MDPI AG
status: public
title: Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective
  Optimization Applied to a Biopharmaceutical Seed Train Design
type: scientific_journal_article
user_id: '83781'
volume: 10
year: '2022'
...
---
_id: '10193'
abstract:
- lang: eng
  text: Development and optimization of biopharmaceutical production processes with
    cell cultures is cost- and time-consuming and often performed rather empirically.
    Efficient optimization of multiple objectives such as process time, viable cell
    density, number of operating steps & cultivation scales, required medium, amount
    of product as well as product quality depicts a promising approach. This contribution
    presents a workflow which couples uncertainty-based upstream simulation and Bayes
    optimization using Gaussian processes. Its application is demonstrated in a simulation
    case study for a relevant industrial task in process development, the design of
    a robust cell culture expansion process (seed train), meaning that despite uncertainties
    and variabilities concerning cell growth, low variations of viable cell density
    during the seed train are obtained. Compared to a non-optimized reference seed
    train, the optimized process showed much lower deviation rates regarding viable
    cell densities (<10% instead of 41.7%) using five or four shake flask scales and
    seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it
    is shown that applying Bayes optimization allows for optimization of a multi-objective
    optimization function with several optimizable input variables and under a considerable
    amount of constraints with a low computational effort. This approach provides
    the potential to be used in the form of a decision tool, e.g., for the choice
    of an optimal and robust seed train design or for further optimization tasks within
    process development.
author:
- first_name: Tanja
  full_name: Hernández Rodriguez, Tanja
  id: '52466'
  last_name: Hernández Rodriguez
- first_name: Anton
  full_name: Sekulic, Anton
  last_name: Sekulic
- first_name: Markus
  full_name: Lange-Hegermann, Markus
  id: '71761'
  last_name: Lange-Hegermann
- first_name: Björn
  full_name: Frahm, Björn
  id: '45666'
  last_name: Frahm
citation:
  ama: 'Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing robust
    biotechnological processes regarding variabilities using multi-objective optimization
    applied to a biopharmaceutical seed train design. In: Pörtner R, Möller J, eds.
    <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>.
    Vol special issue. Processes : open access journal. MDPI; 2022:21-48. doi:<a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>'
  apa: 'Hernández Rodriguez, T., Sekulic, A., Lange-Hegermann, M., &#38; Frahm, B.
    (2022). Designing robust biotechnological processes regarding variabilities using
    multi-objective optimization applied to a biopharmaceutical seed train design.
    In R. Pörtner &#38; J. Möller (Eds.), <i>Bioprocess Systems Engineering Applications
    in Pharmaceutical Manufacturing: Vol. special issue</i> (pp. 21–48). MDPI. <a
    href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>'
  bjps: '<b>Hernández Rodriguez T <i>et al.</i></b> (2022) Designing Robust Biotechnological
    Processes Regarding Variabilities Using Multi-Objective Optimization Applied to
    a Biopharmaceutical Seed Train Design. In Pörtner R and Möller J (eds), <i>Bioprocess
    Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special
    issue. Basel: MDPI, pp. 21–48.'
  chicago: 'Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann, and
    Björn Frahm. “Designing Robust Biotechnological Processes Regarding Variabilities
    Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design.”
    In <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>,
    edited by Ralf Pörtner and Johannes Möller, special issue:21–48. Processes : Open
    Access Journal. Basel: MDPI, 2022. <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>.'
  chicago-de: 'Hernández Rodriguez, Tanja, Anton Sekulic, Markus Lange-Hegermann und
    Björn Frahm. 2022. Designing robust biotechnological processes regarding variabilities
    using multi-objective optimization applied to a biopharmaceutical seed train design.
    In: <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>,
    hg. von Ralf Pörtner und Johannes Möller, special issue:21–48. Processes : open
    access journal. Basel: MDPI. doi:<a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>,
    .'
  din1505-2-1: '<span style="font-variant:small-caps;">Hernández Rodriguez, Tanja</span>
    ; <span style="font-variant:small-caps;">Sekulic, Anton</span> ; <span style="font-variant:small-caps;">Lange-Hegermann,
    Markus</span> ; <span style="font-variant:small-caps;">Frahm, Björn</span>: Designing
    robust biotechnological processes regarding variabilities using multi-objective
    optimization applied to a biopharmaceutical seed train design. In: <span style="font-variant:small-caps;">Pörtner,
    R.</span> ; <span style="font-variant:small-caps;">Möller, J.</span> (Hrsg.):
    <i>Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing</i>,
    <i>Processes : open access journal</i>. Bd. special issue. Basel : MDPI, 2022,
    S. 21–48'
  havard: 'T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, Designing
    robust biotechnological processes regarding variabilities using multi-objective
    optimization applied to a biopharmaceutical seed train design, in: R. Pörtner,
    J. Möller (Eds.), Bioprocess Systems Engineering Applications in Pharmaceutical
    Manufacturing, MDPI, Basel, 2022: pp. 21–48.'
  ieee: 'T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, and B. Frahm, “Designing
    robust biotechnological processes regarding variabilities using multi-objective
    optimization applied to a biopharmaceutical seed train design,” in <i>Bioprocess
    Systems Engineering Applications in Pharmaceutical Manufacturing</i>, vol. special
    issue, R. Pörtner and J. Möller, Eds. Basel: MDPI, 2022, pp. 21–48. doi: <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>.'
  mla: Hernández Rodriguez, Tanja, et al. “Designing Robust Biotechnological Processes
    Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical
    Seed Train Design.” <i>Bioprocess Systems Engineering Applications in Pharmaceutical
    Manufacturing</i>, edited by Ralf Pörtner and Johannes Möller, vol. special issue,
    MDPI, 2022, pp. 21–48, <a href="https://doi.org/10.3390/pr10050883">https://doi.org/10.3390/pr10050883</a>.
  short: 'T. Hernández Rodriguez, A. Sekulic, M. Lange-Hegermann, B. Frahm, in: R.
    Pörtner, J. Möller (Eds.), Bioprocess Systems Engineering Applications in Pharmaceutical
    Manufacturing, MDPI, Basel, 2022, pp. 21–48.'
  ufg: '<b>Hernández Rodriguez, Tanja u. a.</b>: Designing robust biotechnological
    processes regarding variabilities using multi-objective optimization applied to
    a biopharmaceutical seed train design, in: <i>Pörtner, Ralf/Möller, Johannes (Hgg.)</i>:
    Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing, Band
    <i>special issue</i>, Basel 2022 (Processes : open access journal),  S. 21–48.'
  van: 'Hernández Rodriguez T, Sekulic A, Lange-Hegermann M, Frahm B. Designing robust
    biotechnological processes regarding variabilities using multi-objective optimization
    applied to a biopharmaceutical seed train design. In: Pörtner R, Möller J, editors.
    Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing. Basel:
    MDPI; 2022. p. 21–48. (Processes : open access journal; vol. special issue).'
date_created: 2023-08-08T12:58:36Z
date_updated: 2023-08-16T09:24:16Z
department:
- _id: DEP4000
doi: https://doi.org/10.3390/pr10050883
editor:
- first_name: Ralf
  full_name: Pörtner, Ralf
  last_name: Pörtner
- first_name: Johannes
  full_name: Möller, Johannes
  last_name: Möller
keyword:
- Gaussian processes
- Bayes optimization
- Pareto optimization
- multi-objective
- cell culture
- seed train
language:
- iso: eng
page: 21-48
place: Basel
publication: Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing
publication_identifier:
  eisbn:
  - 978-3-0365-5209-5
  eissn:
  - 2227-9717
  isbn:
  - 978-3-0365-5210-1
publication_status: published
publisher: MDPI
quality_controlled: '1'
series_title: 'Processes : open access journal'
status: public
title: Designing robust biotechnological processes regarding variabilities using multi-objective
  optimization applied to a biopharmaceutical seed train design
type: book_chapter
user_id: '83781'
volume: special issue
year: '2022'
...