Development and validation of a method for airborne monoclonal antibodies to quantify workplace exposure

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 221; p. 115046
• Main Authors: Reinders, Lars M.H., Noelle, Dennis, Klassen, Martin D., Jaeger, Martin, Schmidt, Torsten C., Tuerk, Jochen, Teutenberg, Thorsten
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 30-11-2022
• Subjects: Airborne; Monoclonal antibody (mAb); Occupational health and safety; Personal air sampling; Recommendation for action; Personal air sampling; CTX; DRTM; OMLZ; Airborne; Recommendation for action; Occupational health and safety; BVCZ; Monoclonal antibody (mAb); mAbs; RTX; SMEPAC; API; TTZ
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2022.115046

Modern therapy strategies are based on patient-specific treatment where the drug and dose are optimally adapted to the patient's needs. In recent drugs, monoclonal antibodies (mAbs) are increasingly used as active ingredients. Their patient-specific formulations are not part of the pharmaceutical industry’s manufacturing process but are prepared from concentrates by pharmaceutical personnel. During the manufacturing process, however, active pharmaceutical ingredients are released in trace amounts or, in the case of accidents and spills, also in high concentrations. Regardless of the source of entry, mAbs can become airborne, be inhaled, and cause undesirable side-effects such as sensitization. To assess the risk for pharmaceutical personnel, a personal air sampling method was developed and validated for bevacizumab, cetuximab, daratumumab, omalizumab, rituximab and trastuzumab. The method is based on the combination of high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The analytical method achieves a limit of detection of 0.30–8.8 ng mL−1, recoveries of 83–96 % (intra-day assay) and 75–89 % (inter-day assay), with no detectable carry-over. A polycarbonate filter proved suitable for sampling airborne monoclonal antibodies, as it achieved 80–104 % recovery across all mAbs. It also showed concentration-independent desorption efficiency. The sampling duration can be up to 480 min without negatively affecting the recovery. MAbs are stable on the polycarbonate filter at 5 °C for 3 days (recovery: 94 % ± 5 %) and at − 20 °C for 14 days (recovery: 97 % ± 4 %). Our method demonstrated that there is a potential for release when handling monoclonal antibodies. However, this can be reduced below the limit of detection by using pressure equalization systems (spikes).
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•Development of an HPLC-MS/MS method for six monoclonal antibodies.•Personal sampling of airborne monoclonal antibodies.•Evidence of a release potential when handling monoclonal antibody drugs.•Release of airborne antibodies can be reduced by pressure equalisation systems.•Improving occupational health and safety.