Derivation of an occupational exposure limit (OEL) for a potent bispecific protein-Blinatumomab (BLINCYTO®)

As part of product stewardship, pharmaceutical companies generate and evaluate nonclinical and clinical data to establish safe handling practices, including safe levels of airborne drug substances [referred to as occupational exposure limits (OELs)] to protect workers. OEL setting is well-established for large molecules such as monoclonal antibodies, for which oral and dermal bioavailability are negligible. As a result, inhalation or accidental injections are the only realistic occupational exposure pathways; however, even via these routes, systemic exposure is expected to be minimal. Nonetheless, the potency and potential serious effects associated with immune-activating protein therapeutics, such as bispecific antibodies, may generate concerns among workers from even very low-level exposures. Herein, we describe a science-based approach for establishing an OEL for blinatumomab (BLINCYTO®), a potent bispecific T-cell engager (BiTE®) immuno-oncology therapeutic and illustrate its protectiveness for occupational exposures. An in vivo inhalation bioavailability study was conducted in rats to assess inhalation exposure, and clinical pharmacology pharmacokinetic (PK)/pharmacodynamic (PD) analyses were used to estimate the systemic exposure from inhalation and accidental injection relative to expected pharmacological exposures. The results indicate that potential occupational exposures are far below thresholds associated with meaningful biological activity. This assessment demonstrates that estimated systemic exposures to healthcare workers (HCWs) from a large, potent, therapeutic protein (blinatumomab) are well-below predicted effect levels.