Antibody-drug conjugates and the need for third-modality regulatory science

Area of Science:

• Biologics and small-molecule therapeutics
• Drug development and manufacturing
• Regulatory science

Background:

• Antibody-drug conjugates (ADCs) integrate biologics and small molecules, challenging traditional regulatory frameworks.
• ADC performance relies on complex interactions between antibody, linker, payload, and manufacturing processes.
• Existing regulations may not adequately address the unique attributes of ADCs.

Purpose of the Study:

• To propose a novel regulatory science framework for antibody-drug conjugates (ADCs).
• To support innovation, manufacturing flexibility, and patient access for ADCs.
• To enhance regulatory rigor for this emerging therapeutic modality.

Main Methods:

• Development of a risk-based, third-modality scientific approach.
• Integration of product-level assessment, component-specific scrutiny, and platform evidence.
• Emphasis on life cycle comparability for regulatory evaluation.

Main Results:

• The proposed framework offers a comprehensive strategy for ADC regulation.
• It addresses the integrated nature of ADCs, moving beyond conventional assessments.
• Facilitates a balance between scientific innovation and patient safety.

Conclusions:

• A risk-based, integrated scientific framework is essential for advancing ADC development and regulation.
• This approach supports manufacturing flexibility and broadens patient access to novel therapies.
• The proposed methodology ensures continued regulatory rigor for ADCs.