Handling the extreme: Safety & operational challenges in ADC development
Khanh Ngo Courtney of Solvias examines the infrastructure, safety, and cost considerations of handling highly potent ADC payloads
Cancer remains one of the leading global health challenges, with 20 million new cases and 9.7 million deaths reported worldwide in 2022.1 Conventional chemotherapy has long been a cornerstone of cancer care. However, its lack of selectivity often causes severe and debilitating side effects, due to damage to healthy tissues.
As oncology moves toward more targeted therapies aimed at improving efficacy while reducing systemic toxicity, antibody-drug conjugates( ADCs) have emerged as a promising therapeutic approach. By combining the targeting specificity of monoclonal antibodies, the potency of cytotoxic drugs, and the controlled stability and release provided by the linker( Figure 1), ADCs selectively deliver treatment to tumour cells while limiting off-target effects.
API OELs(µ g / m ³) Paracetamol 3,000 Metoprolol succinate 500 Paclitaxel 1 Fentanyl 0.7 Doxorubicin 0.5 Sufentanil 0.05 Oestradiol 0.04 Nafarelin acetate 0.01 Interferon( protein) 0.01 – 0.1
Table 1 – OELs of selected APIs
Figure 1- Architecture of an ADC
As of June 2025, 19 ADCs have been approved globally, and more than 400 candidates are currently in development, including over 200 in various stages of clinical trials. 2, 3
The most common ADC payloads act through one of three primary mechanisms: microtubule inhibition, immunomodulation or DNA damage, ultimately leading to cell cycle arrest and cell death.
The amount of ADC uptake by a tumour can be as low as low as 0.1 – 2 % due to several factors, including antigen density on the cell surface, the efficiency of ADC internalisation and the intracellular linker cleavage required to release the cytotoxic payload. As a result, their payloads must be 100 to 1,000 times more potent than the drugs used in traditional chemotherapy. 3, 4
While this extreme potency is essential for therapeutic efficacy, it also creates a challenge for laboratories involved in ADC development and testing. As high potency APIs( HPAPIs), ADC payloads require stringent containment strategies to protect personnel and prevent crosscontamination. Consequently, laboratories handling these compounds must operate under rigorous safety standards supported by specialised facilities, advanced engineering controls and highly trained personnel.
32 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981