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

  • Olivier Marcq
Chapter
First Online:
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

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.

Keywords

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 

Abbreviations

ADC

Antibody Drug Conjugate

ADC

Antibody Drug Conjugate

BDS

Bulk Drug Subtance

BDS

Bulk Drug Subtance

BLA

Biologics License Application

BLA

Biologics License Application

Cit

Citruline

CMO

Contract Manufacturing Organization

CQA

Critical Quality Attribute

Cys

Cysteine

DAR

Drug Antibody Ratio

DL

Drug Linker

DoE

Design of Experiments

DP

Drug Product

DS

Drug Substance

DSI

Drug Substance Intermediate

FIP

First In Patient

HIPS

Hydrazino-Pictet-Spengler

MED

Minimum Effective Dose

MFG

Manufacturing

MTD

Maximum Tolerated Dose

NNAA

Non-Natural Amino Acid

PBD

Pyrrolobenzodiazepine

PEG

Polyethylene Glycol

PK

Pharmacokinetics

POC

Proof Of Concept

PPE

Personal Protection Equipment

QA

Quality Attribute

QbD

Quality by Design

SME

Subject Matter Expert

SPAAC

Strain promoted azide–alkyne cycloaddition

SUT

Single Use Technology

TFF

Tangential Flow Filtration

TI

Therapeutic Index

UAA

Un-natural Amino Acid

UF/DF

Ultrafiltration/Diafiltration

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© 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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