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    Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions
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    • Nicole M. Ralbovsky*
      Nicole M. Ralbovsky
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
      *Email: [email protected]. Tel.: (215) 652-5614.
      More by Nicole M. Ralbovsky
      Orcidhttps://orcid.org/0000-0002-4498-6567
    • Gunjan Dixit
      Gunjan Dixit
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Justin P. Lomont
      Justin P. Lomont
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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      Orcidhttps://orcid.org/0000-0003-1106-3683
    • Jay Desai
      Jay Desai
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Cristina Butu
      Cristina Butu
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Anumita Saha-Shah
      Anumita Saha-Shah
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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      Orcidhttps://orcid.org/0000-0002-5047-6870
    • Emily Costello
      Emily Costello
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Janelle Lukens
      Janelle Lukens
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Michael Mazur
      Michael Mazur
      Global Vaccines and Biologics Commercialization, MMD, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Patrick M. McHugh
      Patrick M. McHugh
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Rodell C. Barrientos
      Rodell C. Barrientos
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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      Orcidhttps://orcid.org/0000-0002-6006-5047
    • Andrew Semple
      Andrew Semple
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Gregory J. Hughes
      Gregory J. Hughes
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Rebecca Chmielowski
      Rebecca Chmielowski
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Sheng-Ching Wang
      Sheng-Ching Wang
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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    • Bhumit A. Patel
      Bhumit A. Patel
      Analytical Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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      Orcidhttps://orcid.org/0000-0002-7970-7759
    • Joseph P. Smith
      Joseph P. Smith
      Process Research & Development, MRL, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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      Orcidhttps://orcid.org/0000-0002-0062-2534
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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2025, 29, 2, 353–362
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    https://doi.org/10.1021/acs.oprd.4c00399
    Published January 22, 2025
    Copyright © 2025 American Chemical Society
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    Abstract

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    Process analytical technology (PAT) is increasingly being explored within pharmaceutical production and process development, with a particular emphasis in the vaccine and biologics space. PAT aims to provide increased process understanding and control through real-time monitoring of critical quality attributes and key process parameters as well as detection of process deviations. Downstream purification in pharmaceutical manufacturing processes can be complex and requires copious analytical characterization. Herein, we showcase the successful implementation of PAT for monitoring bioconjugation reactions related to both vaccine and biologic pharmaceutical manufacturing processes. Specifically, we explore a variety of PAT-based techniques and their utility for monitoring polysaccharide–protein and protein–small molecule bioconjugation reactions. PAT applications using at-line multiangle light scattering, in situ fluorescence spectroscopy, in situ viscosity, and at-line hydrophobic interaction chromatography are shown to each provide distinct, real-time analytical information to enhance the understanding and characterization of bioconjugation reactions.

    Copyright © 2025 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.oprd.4c00399.

    • Process information and general schematic of the protein–polysaccharide bioconjugation; experimental information and general schematic of the at-line MALS setup for protein–polysaccharide bioconjugation (PDF)

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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2025, 29, 2, 353–362
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.oprd.4c00399
    Published January 22, 2025
    Copyright © 2025 American Chemical Society
    Request reuse permissions

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