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Updated: Jan 5, 2026
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Quantification of Metal Leaching in Immobilized Metal Affinity Chromatography
Published on: January 17, 2020
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Quantitative characterization of leachables sinks in biopharmaceutical downstream processing
Kushal Paudel1, Armin Hauk1, Tanja Verena Maier1
1Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany.
Summary
Biopharmaceutical manufacturing processes significantly reduce leachables using downstream steps like filtration. Hydrophobic leachables model compounds were effectively removed, enhancing product safety and quality.
Area of Science:
- Biopharmaceutical Manufacturing
- Process Chemistry
- Analytical Chemistry
Background:
- Leachables can accumulate during biopharmaceutical manufacturing.
- Controlling leachables is critical for drug safety and quality.
Purpose of the Study:
- To quantitatively assess the removal of leachables during key downstream processing steps.
- To evaluate the effectiveness of centrifugation, depth filtration, sterile filtration, and virus filtration in reducing leachables.
Main Methods:
- Eight common leachables model compounds (LMCs) were spiked into protein-containing feed solutions.
- Analysis of LMCs was performed using High-Performance Liquid Chromatography with Ultraviolet detection (HPLC-UV).
- Clearance rates were calculated based on the reduction in LMC concentration post-processing.
Main Results:
- Downstream processing steps significantly reduced LMCs, particularly hydrophobic compounds.
- Cell removal via centrifugation or depth filtration nearly eliminated LMCs.
- Sterile and virus filtration demonstrated high scavenging effects for most LMCs.
- One hydrophilic acid showed limited removal by the investigated processes.
Conclusions:
- Key downstream processing steps are effective in reducing leachables in biopharmaceutical manufacturing.
- Hydrophobic leachables are efficiently removed, contributing to process safety.
- The findings support the integration of leachables control into process qualification and risk mitigation strategies.
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