title: Bioavailability of therapeutic proteins by inhalation--worker safety aspects.
abstract: A literature review and analysis of inhalation bioavailability data for large therapeutic proteins was conducted 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 biopharmaceutical 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 ≥ 40kDa). 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.
authors: 1.F. Hoffmann - La Roche Ltd, Group Safety, Security, Health and Environmental Protection, CH-4070, Basel, Switzerland thomas.pfister.tp1@roche.com.
authors: Thomas
authors: T
authors: Pfister
authors: 2.Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors: David
authors: D
authors: Dolan
authors: 2.Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors: Joel
authors: J
authors: Bercu
authors: 3.Bristol-Myers Squibb Company New Brunswick, NJ 08903 , USA.
authors: Janet
authors: J
authors: Gould
authors: 3.Bristol-Myers Squibb Company New Brunswick, NJ 08903 , USA.
authors: Bonnie
authors: B
authors: Wang
authors: 4.Novartis Pharma AG, CH-4002, Basel, Switzerland.
authors: Rudolf
authors: R
authors: Bechter
authors: 4.Novartis Pharma AG, CH-4002, Basel, Switzerland.
authors: Ester Lovsin
authors: EL
authors: Barle
authors: 5.Roche Pharma Research and Early Development Department, Roche Innovation Center Basel, CH-4070 Basel, Switzerland.
authors: Friedlieb
authors: F
authors: Pfannkuch
authors: 1.F. Hoffmann - La Roche Ltd, Group Safety, Security, Health and Environmental Protection, CH-4070, Basel, Switzerland.
authors: Andreas
authors: A
authors: Flueckiger
mesh_terms: D001682:Biological Availability; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism*; D008452:Maximum Allowable Concentration; D016273:Occupational Exposure / Q000032:analysis / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000032:analysis; D011506:Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012449:Safety; D020711:Threshold Limit Values; D017132:Workplace
chemical_list: D007074:Immunoglobulin G; D004364:Pharmaceutical Preparations; D011506:Proteins
keywords: OEL; inhalation bioavailability; occupational exposure limit; therapeutic proteins