Exposure Assessment of Four Pharmaceutical Powders Based on Dustiness and Evaluation of Damaged HEPA Filters

Abstract

In this study, we show the different dustiness characteristics of four molecular pharmaceutical powder candidates and evaluate the performance of HEPA filters damaged with three different pinhole sizes and exposed to dust using real industrial powders in a miniaturized EN15051 rotating drum dustiness tester. We then demonstrate the potential use of such data using first-order exposure modeling to assess the potential worker exposure and transmission of active powder ingredients into ventilation systems. The four powders had highly variable inhalable dustiness indices (1,036 – 14,501 mg/kg). Dust particle size-distributions were characterized by three peaks; the first occurred around 60–80 nm, the second around 250 nm, and the third at 2–3 μm. The second and third peaks are often observed in dustiness test studies, but peaks in the 60–80 nm range have not been previously reported. Exposure modeling in a 5 times 20 kg powder pouring scenario, suggests that excessive dust concentrations may be reached during use of powders with the highest dustiness levels. By number, filter-damage by three pinhole sizes resulted in damage-dependent penetration of 70–80 nm-size particles, but by volume and mass the penetration is still dominated by particles larger than 100 nm. Whereas the exposure potential was evident, the potential dust concentrations in air ducts following the pouring scenario above were at pg/m³ levels. Hence, filter penetration at these damage levels was assumed to be only critical, if the active ingredients were associated with high hazard or unique product purity is required.

[Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: An example of a typical particle number time-series of a complete dustiness test. It provides information on the HEPA-filter used including a scanning electron microscopy image of it. It also provides APS-measurements of particles penetrating the damaged HEPA-filter.]

Keywords:

• pharmaceuticals
• dustiness
• rotating drum
• HEPA filter
• filter damage
• exposure assessment

ACKNOWLEDGMENTS

This work was conducted as part of the Strategic Research effort at the National Research Centre for the Working Environment and the Danish Centre for Nanosafety (20110092173/3) from the Danish Working Environment Research Foundation. For the experimental part we gratefully acknowledge constructive discussion and access to sample material from an anonymous industrial partner and the skilled assistance from our technician S.H. Nielsen. We also thank Dr. K.I. Kling (NRCWE) for SEM-imaging of the HEPA filter.