Outlook on Next Generation Technologies and Strategy Considerations for ADC Process Development and Manufacturing

  • Olivier MarcqEmail author
Part of the Cancer Drug Discovery and Development book series (CDD&D)


In the chapter, we review new conjugation technologies from the standpoints of process development and manufacturability and identify potential process hotspots. We briefly review recent progress in conventional conjugation methods and assess, for instance, how new linkers impact process. We also consider antibody modeling and its untapped potential to help design ADCs. We address outsourcing options and trends and provide an overview of single use technologies. Finally, strategies for efficient early process development to ensure CMC consistency across clinical phases and manufacturing scales and ensure readiness for accelerated regulatory approval paths are discussed.


ADC Process development Analytical development Scale-up Manufacturing GMP Drug substance Drug product Bulk drug substance DS DP BDS Conjugation technologies Site specific Bridging Thiobridge Conventional cysteine Engineered cysteine Lysine Serine Unnatural amino acid Non-natural amino acid Maleimide Valine-citruline Maleimidocaproyl Thiosuccinimide Haloacetamide Click chemistry Azide Cyclooctyne Glycan Enzyme Enzymatic ligation Transglutaminase Seleno mAb AmbrX Eucode Xpress THIOMAB Glycoconnect Fleximer Hydraspace Auristatin Ozogamicin Talirine Maystantin Quaternary amine Glucuronide Linker Payload Aggregate Aggregation Stability Hydrophobicity DAR Drug antibody ratio Modeling Antibody Probody Extracellular Bispecific TFF HIC Chromatography Tangential flow filtration Regulatory approval CMC Accelerated approval Single use Outsourcing CMO CQA Critical quality attribute Toxicity Cytotoxicity MTD MED Therapeutic index PK PD 



Antibody Drug Conjugate


Antibody Drug Conjugate


Bulk Drug Subtance


Bulk Drug Subtance


Biologics License Application


Biologics License Application




Contract Manufacturing Organization


Critical Quality Attribute




Drug Antibody Ratio


Drug Linker


Design of Experiments


Drug Product


Drug Substance


Drug Substance Intermediate


First In Patient




Minimum Effective Dose




Maximum Tolerated Dose


Non-Natural Amino Acid




Polyethylene Glycol




Proof Of Concept


Personal Protection Equipment


Quality Attribute


Quality by Design


Subject Matter Expert


Strain promoted azide–alkyne cycloaddition


Single Use Technology


Tangential Flow Filtration


Therapeutic Index


Un-natural Amino Acid




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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Agensys, an affiliate of Astellas PharmaSanta MonicaUSA
  2. 2.SutroVaxFoster CityUSA

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