Development and Qualification of Analytical Methods to Support Low Concentration Drug Product in-use Studies

•Analytical method development and suitability assessments with pre-defined acceptance criteria in accordance with regulatory and ICH guidelines were completed for protein concentration, size and charge variants and relative binding to support low concentration and low dose in-use studies.•The devel...

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Veröffentlicht in:Journal of pharmaceutical sciences 2024-03, Vol.113 (3), p.604-615
Hauptverfasser: Zheng, Laura, Console, Gary, Wang, Christopher, Whang, Kevin, Ting, Hau-Ping, Torres, Yazmin M., Rude, Erina, Smithson, David C., Stella, Cinzia, Bhargava, Adithi C.
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Sprache:eng
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Zusammenfassung:•Analytical method development and suitability assessments with pre-defined acceptance criteria in accordance with regulatory and ICH guidelines were completed for protein concentration, size and charge variants and relative binding to support low concentration and low dose in-use studies.•The developed methods are reliable, well-documented and indicate potential platform use with a variety of mAbs and proteins for in-use studies.•Method modifications and sample matrices do not significantly affect reported results, ensuring these methods can be used across a wide range of protein concentrations. The emergence of highly potent therapeutics with low expected clinical doses creates a challenge for analytical characterization of simulated drug product in-use samples. The low expected protein concentration (often µg/mL) and highly charged and sub-optimal sample matrices like 0.9% saline or 5% dextrose make ensuring dose solution stability and characterizing product quality changes difficult. Health authority expectations require analysis of low concentration in-use samples to be completed with suitable assays to ensure little to no changes are occurring during drug product dose preparation and administration, thus ensuring patient safety. However, characterization of these samples for protein concentration, size variants, charge variants and potency often necessitates additional analytical method development to improve sensitivity and compatibility with in-use samples. Here we report the development and qualification of reliable in-use methods to characterize simulated in-use samples to assist during drug product development.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2023.09.011