Antibody-drug Conjugate (ADC) Standards and Materials

Antibody–drug conjugates (ADCs) represent an innovative class of biopharmaceutical drugs specifically engineered for targeted cancer therapy. ADCs leverage the targeted specificity of antibodies to deliver potent cytotoxic agents directly to cancer cells while minimizing damage to healthy tissues. ADCs work like traditional monoclonal antibodies (mAbs) by binding a targeted antigen on a cell that then gets internalized through receptor-mediated endocytosis, which facilitates the release of the cytotoxic drug and induces target cell death. Only ~2% of the administered dose of tumor-targeted ADCs reach the tumor tissue, therefore highly potent payloads are required to achieve therapeutic efficacy.

An ADC comprises three main components: the antibody, the linker, and the cytotoxic payload. Each component must be meticulously characterized to ensure the efficacy and safety of the final ADC product.

The manufacturing process for critical starting materials, intermediates, and the final conjugated product must be governed by a science-based process control strategy and defined product release specifications - including in-process controls - to ensure a robust, consistent process that delivers ADC products of consistent quality:

1. Starting materials: Antibody | Linker | Payload
2. Intermediate conjugation product: Antibody-Linker or Linker-Payload intermediates
3. ADC (Final drug substance): Antibody-Linker-Payload