ReviewPost screenContainment challenges in HPAPI manufacture for ADC generation

•Safe HPAPI manufacture requires protection of both workers and the environment.•There are 5 key aspects to a successful HPAPI plant.•Different containment strategies are reviewed.•Various containment options include isolators, different pressure gradients and PPE.

Antibody-drug conjugates (ADCs) are emerging as an impactful class of therapeutics for the treatment of cancer because of their ability to harness the specificity of an antibody and the cytotoxic potential of the payload to target and destroy cancer cells. However, the potent nature of the cytotoxic payload creates associated manufacturing challenges for active pharmaceutical ingredient (API) manufacturers, because huge investment in containment technology is required to ensure the protection of operators and the environment. Here, we examine the differing attitudes to high-potency categorisation and levels of containment control. We also provide an overview of the most widely used containment strategies for facility design, powder handling, purification, analysis, and cleaning. Finally, we briefly consider the health and safety regulatory challenges associated with the manufacture of cytotoxic payloads for use in antibody-drug conjugates.