Navigating The Analytical Challenges Of Complex ADCs

Antibody-drug conjugates (ADCs) are expanding beyond traditional oncology applications to incorporate non-cytotoxic small molecules, peptides, and oligonucleotides. This evolution requires updated analytical strategies that build on monoclonal antibody testing. Critical quality attribute (CQA) assessments evaluate baseline attributes such as biosafety, purity, and potency, while also examining conjugate-specific parameters like linkers, drug-to-antibody ratios, unconjugated payload levels, and stability across drug substance and drug product stages. Because developing complex cell-based potency assays poses challenges, many developers outsource these tests.

To support expanding payloads and new modalities like antibody-oligonucleotide conjugates, specialized testing facilities are adapting their containment and contamination controls. MilliporeSigma addresses these needs through its integrated BioReliance testing network, including facilities in Rockville, Maryland, and Darmstadt, Germany. These hubs combine biosafety, analytical development, and release testing under enhanced safety measures. By using glove boxes, specialized biosafety cabinets, and redundant containment workflows, the company safely manages highly potent materials (OEB 4) to support ADC development from initial characterization through commercial release.