Development of an analytical method to assess the occupational health risk of therapeutic monoclonal antibodies using LC-HRMS

Abstract

Monoclonal antibodies are a group of commonly used therapeutics, whose occupational health risk is still discussed controversially. The long-term low-dose exposure side effects are insufficiently evaluated; hence, discussions are often based on a theoretical level or extrapolating side effects from therapeutic dosages. While some research groups recommend applying the precautionary principle for monoclonal antibodies, others consider the exposure risk too low for measures taken towards occupational health and safety. However, both groups agree that airborne monoclonal antibodies have the biggest risk potential. Therefore, we developed a peptide-based analytical method for occupational exposure monitoring of airborne monoclonal antibodies. The method will allow collecting data about the occupational exposure to monoclonal antibodies. Thus, the mean daily intake for personnel in pharmacies and the pharmaceutical industry can be determined for the first time and will help to substantiate the risk assessment by relevant data. The introduced monitoring method includes air sampling, sample preparation and detection by liquid chromatography coupled with high-resolution mass spectrometry of individual monoclonal antibodies as well as sum parameter. For method development and validation, a chimeric (rituximab), humanised (trastuzumab) and a fully humanised (daratumumab) monoclonal antibody are used. A limit of detection between 1 μg per sample for daratumumab and 25 μg per sample for the collective peptide is achieved. Graphical abstract Demonstration of the analytical workflow, from the release of monoclonal antibodies to the detection as single substances as well as sum parameter.

Clinical Oncology Society of Australia Position Statement: 2022 update to the safe handling of monoclonal antibodies in healthcare settings

“…The recommendations are underpinned by the assumption that PPE is being correctly worn, and that repeated accidental exposure does not occur due to rigorous training around the safe handling of mABs 7 . Finally, an analytical method to detect airborne antibodies has been described in the literature; however, its application in practice is unclear as there is no defined occupational exposure limit for each mAB 33 …”

“…7 Finally, an analytical method to detect airborne antibodies has been described in the literature; however, its application in practice is unclear as there is no defined occupational exposure limit for each mAB. 33 Based on the risk exposure routes and risk assessment information above, recommendations for the safe handling of mABs are described below.…”