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

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Innovations for Next-Generation Antibody-Drug Conjugates

Part of the book series: Cancer Drug Discovery and Development ((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.

Content herein does not necessarily reflect the positions of Astellas and its affiliate Agensys.

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Notes

  1. 1.

    While we tried to support comments and positions with literature or conference reports, publications on ADC process development are scarce and some considerations are based on the author’s experience and assessment.

  2. 2.

    Marcq O, Tawfiq Z, Parker R, Tomas F, Zhu M (2017 - Unpublished Data).

  3. 3.

    Marcq O, Schwartz I, Tawfiq Z, Tomas F, Zhu M (2016 – Unpublished Data).

  4. 4.

    Hippach M, Kyung S Y, Kikuchi T, Kawai Y, Huynh J, Gredder J, Zhu M (2017 – Unpublished Data). Enhancing Production of an Engineered Antibody Containing Non-native Amino Acid for Site-Specific Conjugation: Considerations for Early and Late Stage Development.

  5. 5.

    As of June 19, 2017, based on public information releases from Seattle Genetics.

  6. 6.

    Marcq O, Tawfiq Z, Parker R, Tomas F, Zhu M (2017 - Unpublished Data)

  7. 7.

    Sandeep Kumar, Pfizer (2017 – Personal Communication).

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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    Olivier Marcq

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    Olivier Marcq

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    Marc Damelin

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Marcq, O. (2018). Outlook on Next Generation Technologies and Strategy Considerations for ADC Process Development and Manufacturing. In: Damelin, M. (eds) Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78154-9_6

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