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End-to-End Approach to Surfactant Selection, Risk Mitigation, and Control Strategies for Protein-Based Therapeutics

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A Correction to this article was published on 11 January 2023

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Abstract

A survey performed by the AAPS Drug Product Handling community revealed a general, mostly consensus, approach to the strategy for the selection of surfactant type and level for biopharmaceutical products. Discussing and building on the survey results, this article describes the common approach for surfactant selection and control strategy for protein-based therapeutics and focuses on key studies, common issues, mitigations, and rationale. Where relevant, each section is prefaced by survey responses from the 22 anonymized respondents. The article format consists of an overview of surfactant stabilization, followed by a strategy for the selection of surfactant level, and then discussions regarding risk identification, mitigation, and control strategy. Since surfactants that are commonly used in biologic formulations are known to undergo various forms of degradation, an effective control strategy for the chosen surfactant focuses on understanding and controlling the design space of the surfactant material attributes to ensure that the desired material quality is used consistently in DS/DP manufacturing. The material attributes of a surfactant added in the final DP formulation can influence DP performance (e.g., protein stability). Mitigation strategies are described that encompass risks from host cell proteins (HCP), DS/DP manufacturing processes, long-term storage, as well as during in-use conditions.

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Acknowledgements

The authors would like to acknowledge the AAPS Communities for providing the DP Handling Community with a space to meet and engage in scientific discussions. In addition, we want to thank Maria Nadeau from AAPS for setting up the electronic survey and providing the team with the responses.

Author information

Authors and Affiliations

  1. Dosage Form Design and Development, BioPharmaceuticals Development, R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, Maryland, 20878, USA

    Annette Medina Morales & Indira Prajapati

  2. Genentech, Pharmaceutical Development, South San Francisco, California, 94080, USA

    Alavattam Sreedhara & Isabella de Jong

  3. Technical Research and Development, Novartis Pharma AG, 4002, Basel, Switzerland

    Jakob Buecheler & Sebastian Brosig

  4. Compassion BioSolution, LLC, Lomita, California, 90717, USA

    Danny Chou

  5. Amgen, Process Development, Thousand Oaks, California, 91320, USA

    Twinkle Christian & Bharat Jagannathan

  6. Analytical Development and Attribute Sciences, Bristol Myers Squibb, New Brunswick, New Jersey, USA

    Tapan Das

  7. Pharmaceutical Development, F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland

    Jonas Fast

  8. Drug Product Development, AbbVie, North Chicago, Illinios, 60064, USA

    Ehab M. Moussa

  9. Department of Pharmaceutical Sciences & Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA

    M. Reza Nejadnik & Yusra Rahman

  10. Symbiotix, New York City, New York, 10016, USA

    Allison Radwick

  11. GlaxoSmithKline R&D, Biopharmaceutical Product Sciences, Collegeville, Philadelphia, Pennsylvania, 19426, USA

    Shubhadra Singh

Authors
  1. Annette Medina Morales
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  2. Alavattam Sreedhara
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  3. Jakob Buecheler
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  4. Sebastian Brosig
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  5. Danny Chou
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  6. Twinkle Christian
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  7. Tapan Das
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  8. Isabella de Jong
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  9. Jonas Fast
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  10. Bharat Jagannathan
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  11. Ehab M. Moussa
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  12. M. Reza Nejadnik
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  13. Indira Prajapati
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  14. Allison Radwick
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  15. Yusra Rahman
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  16. Shubhadra Singh
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Contributions

Annette Medina Morales and Sreedhara Alavattam designed and coordinated survey responses with AAPS, as well as collated and analyzed the responses. All of the authors contributed to the conception and design of the manuscript, as well as critical review and approval.

Corresponding author

Correspondence to Annette Medina Morales.

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The original article has been updated to correct the order of authors.

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Morales, A.M., Sreedhara, A., Buecheler, J. et al. End-to-End Approach to Surfactant Selection, Risk Mitigation, and Control Strategies for Protein-Based Therapeutics. AAPS J 25, 6 (2023). https://doi.org/10.1208/s12248-022-00773-3

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