Small Molecule Impurities Represent A Key Challenge When Designing Control Systems For ADC Therapeutic Manufacture

Antibody-drug conjugates (ADCs) harness the specificity of an antibody to the cytotoxic potency of a small molecule drug to achieve targeted cell death. An important, emerging class of biopharmaceuticals, ADCs have proven efficacy in cancer treatment. Within the past decade, four ADC drugs have been granted approval for oncology indications, and many more such therapeutics are currently in pre-clinical or clinical development. The ADC market is predicted to be worth approximately $10 billion by 2025.

Although ICH guidelines clearly define acceptable levels of drug-related impurities for small molecule new chemical entities (NCEs), there are currently no established rules for ADCs. Composed of both antibody and small molecule elements, ADCs have a complex structure from which many different impurities can arise. Drawing on existing ICH guidelines, a recent publication co-authored by AbbVie suggests a science-based approach that can be applied to the design of an effective control strategy for small molecule impurities in ADC therapeutics.