Bioavailability of Therapeutic Proteins by Inhalation—Worker Safety Aspects

Abstract

A literature review and analysis of inhalation bioavailability data for large therapeutic proteins was con-ducted in order to develop a practical estimate of the inhalation bioavailability of these drugs. This value is incorporated into equations used to derive occupational exposure limits(OELs) to protect biophar-maceutical manufacturing workers from systemic effects. Descriptive statistics implies that a value of 0.05, or 5 % is an accurate estimate for large therapeutic proteins (molecular weight ≥ 40 kDa). This estimate is confirmed by pharmacokinetic modeling of data from a human daily repeat-dose inhalation study of immunoglobulin G. In conclusion, we recommend using 5 % bioavailability by inhalation when developing OELs for large therapeutic proteins. K e y w o r d s: inhalation bioavailability; occupational exposure limit; OEL; therapeutic proteins I n t r o d u c t I o n Biologics constituted>30 % of approved pharmaceu-ticals, with 179 new biologics (that are not vaccines or blood products) approved between 1993 and early 2013 (Sathish et  al., 2013; U. S.  FDA, 2013). These drugs have offered novel and effective treatment