The Center for Drug Evaluation (CDE) has released a draft set of “Guiding Principles for Pharmaceutical Research and Evaluation of Antibody Drug Conjugates” and is soliciting public feedback until July 21, 2023. The document primarily addresses the technical requirements during the market approval filing stage for antibody drug conjugate (ADC) products, providing a framework for the development and evaluation of these innovative therapies.
Focus on Technical Requirements for ADC Products
The guidelines are applicable to ADC products formed by coupling antibodies/antibody fragments with payloads through linkers, as well as other conjugated drugs such as antibody conjugated nuclide drugs, peptide conjugated drugs, and antibody oligonucleotide conjugated drugs. The document highlights that ADC products combine the attributes of both large- and small-molecule drugs, presenting unique challenges in research and control aspects that need to be analyzed based on specific circumstances.
Production Processes and Quality Attributes
ADC production processes typically involve multiple stages, including naked antibody production, payload/linker/payload linker production, ADC stock solution, and formulation. The document emphasizes the need to fully characterize not only the quality attributes of antibody drugs but also other quality attributes such as payload/linker/payload linker, coupling process, drug antibody coupling ratio (DAR), drug load distribution, molecular size variants, and charge variants.
Risk Assessment and Control Considerations
In terms of risk assessment and control, the document outlines the need to consider multiple factors, including molecular design, production process, quality control, and stability. It also sets out requirements for the various processes and quality control measures within the ADC production process, ensuring that these complex drugs meet the highest standards of safety and efficacy.-Fineline Info & Tech
