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Impact on Quality during In-Use Preparation of an Antibody Drug Conjugate with Eight Different Closed System Transfer Device Brands

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Abstract

The aim of this study was to investigate the in-use compatibility of eight commercially available closed system transfer device brands (CSTDs) with a formulated model antibody drug conjugate (ADC). Overall, in-use simulated dosing preparation applying the CSTD systems investigated raised concerns for several product quality attributes. The incompatibilities observed were mainly associated with increased visible and subvisible particles formation as well as significant changes in holdup volumes. Visible and subvisible particles contained heterogeneous mixtures of particle classes, with the majority of subvisible particles associated with silicone oil leaching from CSTD systems during simulated dose preparation upon contact with the ADC formulation. These observations demonstrate that CSTD use may adversely impact product quality and delivered dose which could potentially lead to safety and efficacy concerns during administration. Other product quality attributes measured including turbidity, color, ADC recovery, and purity by size exclusion HPLC, did not show relevant changes. It is therefore strongly recommended to test and screen the compatibility of CSTDs with the respective ADC, in a representative in-use simulated administration setting, during early CMC development, i.e., well before the start of clinical studies, to include information about compatibility and to ensure that the CSTD listed in the manuals of preparation for clinical handling has been thoroughly assessed before human use.

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Acknowledgements

We would like to thank Ahmed Besheer for all his support in coordination of the collaboration between Merck Healthcare KGaA, Darmstadt, Germany and LONZA AG, Drug Product Services, Basel, Switzerland.

Funding

This work was funded by Merck Healthcare KGaA Darmstadt/Germany Dept. Pharmaceutical Technologies and was conducted with a model ADC drug (provided by sponsor, not commercially available) at LONZA AG, Drug Product Services.

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Authors and Affiliations

  1. Lonza AG, Drug Product Services, Hochbergerstrasse 60G, 4057, Basel, Switzerland

    Léa Sorret, Wei Han Tan, Patrick Favrod & Pascal Chalus

  2. Merck Healthcare KGaA, 64293, Darmstadt, Germany

    Senta Voss & Matthias Winzer

Authors
  1. Léa Sorret
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  2. Wei Han Tan
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  3. Senta Voss
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  4. Patrick Favrod
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  5. Pascal Chalus
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  6. Matthias Winzer
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Contributions

Matthias Winzer and Senta Voss were accountable for all aspects of the work on the sponsor side in collaboration with LONZA AG, Drug Product Services drug product service provider. Wei Han Tan conducted the experimental work at LONZA AG, Drug Product Services in accordance with the experimental designs and procedures predefined with Merck Healthcare KGaA, Darmstadt/Germany. Wei Han Tan, Pascal Chalus, Patrick Favrod, Léa Sorret, and Senta Voss contributed to the manuscript and data interpretation. Matthias Winzer is corresponding author.

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Correspondence to Léa Sorret.

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Conflict of Interest

Matthias Winzer and Senta Voss are employees of Merck Healthcare KGaA Darmstadt/Germany Dept. Pharmaceutical Technologies and supervised the studies from sponsor side at the time of the study. Wei Han Tan, Léa Sorret, Pascal Chalus, Patrick Favrod are employed at Lonza AG, Drug Product Services, Basel, Switzerland. The study was conducted to identify general trends and pitfalls in the application of CSTDs in hazardous drug handling such as ADCs, as such to avoid any business impact on commercial CSTDs, the study was blinded. A non-commercial model ADC was used to avoid any potential conflict of interest.

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Sorret, L., Tan, W.H., Voss, S. et al. Impact on Quality during In-Use Preparation of an Antibody Drug Conjugate with Eight Different Closed System Transfer Device Brands. AAPS J 26, 61 (2024). https://doi.org/10.1208/s12248-024-00931-9

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  • DOI: https://doi.org/10.1208/s12248-024-00931-9

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