title: Containment challenges in HPAPI manufacture for ADC generation.
abstract: 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.
authors.affiliation: The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, A94 X099, Ireland. Electronic address: elizabeth.dunny@nibrt.ie.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dunny
authors.affiliation: Pfizer Ireland Pharmaceuticals, Ringaskiddy, Co. Cork, P43 X336, Ireland.
authors.forename: Imelda
authors.initials: I
authors.lastname: O'Connor
authors.affiliation: The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, A94 X099, Ireland; School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, D04 V1W8, Ireland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bones
mesh_terms: D003603:Cytotoxins; D004345:Drug Industry; D006801:Humans; D018796:Immunoconjugates; D016273:Occupational Exposure / Q000517:prevention & control* / Q000592:standards; D016272:Occupational Health
chemical_list: D003603:Cytotoxins; D018796:Immunoconjugates