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ADC Downstream Purification Technologyhttps://adc.bocsci.com/services/adc-analys

For any given ADCs, the chemical property of cytotoxins and linkers, as well as the choice of attachment sites, will greatly affect the physicochemical properties. Thus, different ADCs may utilize different analytical assessment methods according to their unique properties. <br>

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ADC Downstream Purification Technologyhttps://adc.bocsci.com/services/adc-analys

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  1. ADC Downstream Purification Technology Tel: 1-631-504-6093 Email: info@bocsci.com

  2. Contents 01 02 03 04 05 06 07 08 09 Basic Composition of ADC Drug ADC Analysis and Characterization Methods ADC Drug Production Process Tangential Flow Filtration (TFF) Size Exclusion Chromatography (SEC) Hydrophobic Interaction Chromatography (HIC) Ion Exchange Chromatography (IEC) Hydroxyapatite Chromatography (HA) Membrane Chromatography (MC) Copyright © 2022 BOC Sciences. All rights reserved. www.adc.bocsci.com

  3. Basic Composition of ADC Drug • Attachment • Maleimide, disulfide, amide or other biorthogonal groups • Stable in plasma • (Ideally) hydrophilic • Conjugation Site • No interruption of antigen binding • No interruption of FcRn binding • Stochastic or site-specific • Payload • Sub-nanomolar toxicity • Stable in target cells • (Ideally) by-stander effect Attachment Linker • Linker • Cleavable or non-cleavable • Stable in plasma • Degradation after internalization • (Ideally) hydrophilic • Monoclonal Antibody • Target antigen selectively • No immunogenicity • Stable in plasma • Internalizable

  4. ADC Analysis Characterization ADC Analysis and Characterization Methods Chromatographic Analysis Of Drug Distribution Size Exclusion Chromatography Analysis Antibody Drug Conjugation Ratio (DAR) Drug Distribution For any given ADCs, the chemical property of cytotoxins and linkers, as well as the choice of attachment sites, will greatly affect the physicochemical properties. Thus, different ADCs may utilize different analytical assessment methods according to their unique properties. Biological Analysis Free Small Molecule Analysis Charge Variant Separation Peptide Mapping

  5. mAb ADC Drug Production Process Dilution/ Bulfer Exchange by TFF Reaction mixture mAb Modfication(ex. TCEP Reduction) In the past 20 years, the research and development of ADC drugs have become a hot spot of competition among major pharmaceutical companies. Currently, the FDA has approved more than 10 ADC drugs, and more than 100 ADC drugs are under clinical trials or pharmaceutical research and development stages. Therefore, major pharmaceutical companies must develop a stable ADC platform-based production process. mAb intermediate Payood Conjugation Crude ADC Chromatography (SEC, HIC membrane etc.) Purifcaton by TFF Purified ADC Purified ADC Bufler Exchange/ Formulation by TFF Butler Exchange/ Formulation by TFF Final ADC composition

  6. Tangential Flow Filtration (TFF) Tangential flow filtration is a pressure-driven membrane purification technique based on molecular size. In tangential flow filtration, the sample mixture is not forced through a single passageway membrane as in direct flow filtration but is recirculated tangentially across the membrane surface through multiple cycles. Materials Science in Semiconductor Processing. 2022, 145: 106618.

  7. Size Exclusion Chromatography (SEC) • Buffer Exchange • Aggregate Removal • Non-protein Impurity Removal • Small Molecular Impurity Removal Journal of Pharmaceutical and Biomedical Analysis.2014,101:161-173.

  8. Hydrophobic Interaction Chromatography (HIC) ADC drugs are covalently coupled with hydrophobic drug linkers, toxins, monoclonal antibodies, and impurities that reveal different drug-to-antibody ratios, and hydrophobic chromatography is used according to the hydrophobic differences for removal. Journal of Pharmaceutical and Biomedical Analysis. 2020, 186: 113313.

  9. Ion Exchange Chromatography (IEC) Ion exchange chromatography involves protein analysis, such as charge variant analysis and glycoform analysis, to elucidate the structural changes of proteins. Ion exchange chromatography generally yields high recovery and removes non-antibody-related compounds, including small molecules and endotoxins. Therefore, ion exchange chromatography is a promising method of ADC purification. • Small Molecule Impurities • Host DNA Impurities • Endotoxin Impurities • Charge Variant Impurities

  10. Hydroxyapatite Chromatography (HA) • Hydroxyapatite chromatography is a useful method for monoclonal antibody purification. • Hydroxyapatite chromatography utilizes calcium and phosphate minerals, which bind to antibodies through the interaction of calcium metal affinity and phosphate-based cation exchange. • The use of hydroxyapatite chromatography can reduce antibody aggregates from 60% to 0.1%. The Crystalline Structure of HA Ceramics, 2021, 4(4): 542-563.

  11. Membrane Chromatography (MC) J. Clin. Med. 2021, 10, 552.

  12. Tel: 1-631-504-6093 Email: info@bocsci.com Address: 45-16 Ramsey Road, Shirley, NY 11967, USA

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