PDE/OEL setting in the pharmaceutical company

<p>At pharmaceutical manufacturing sites, it is necessary to set residual or worker exposure limits for each pharmaceutical product from the viewpoint of preventing contamination (cross-contamination) in the next pharmaceutical product and protecting workers from exposure to manufactured substances. In addition, it is necessary to set a limit value for worker exposure from the viewpoint of occupational health and safety for experimenters.</p><p>In 2021, the domestic GMP Ministerial Ordinance was amended to require the setting of limits for PDEs based on toxicological evidence. Therefore, there are more opportunities for toxicology researchers to be involved in setting limits.</p><p>As a method for setting PDEs based on toxicological evidence, the guidelines for setting health-based exposure limits (HBEL) which came into effect from the PIC/S (Pharmaceutical Inspection Agreement and Pharmaceutical Inspection Cooperative Scheme) in 2018 and the guidelines for residual solvents for ICH Q3C can be used as references. However, since each drug has different types of studies and data, it is necessary to select PODs and adjustment factors on a case-by-case basis based on a wide range of data, and experience in PDE setting as well as knowledge of pharmacology and toxicology is important.</p><p>Among them, one of the points that toxicology researchers at pharmaceutical companies should keep in mind when setting PDEs is that pharmacological effects are also regarded as adverse effects, unlike toxicity evaluation in drug development. The reason for this is that the possibility of unintentional intake of the pharmaceutical product by patients with other diseases and workers must be considered, whether it is cross-contamination or worker exposure.</p><p>In this presentation, I will explain the typical flow of setting PDEs and difficulties for the person in charge of setting PDEs. In addition, from the perspective of drug development, we will introduce the setting of limit values according to each stage and how toxicology researchers should be involved in this process.</p>