title: In vitro considerations to support bioequivalence of locally acting drugs in dry powder inhalers for lung diseases.
abstract: Dry powder inhalers (DPIs) are used to deliver locally acting drugs (e.g., bronchodilators and corticosteroids) for treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Demonstrating bioequivalence (BE) for DPI products is challenging, primarily due to an incomplete understanding of the relevance of drug concentrations in blood or plasma to equivalence in drug delivery to the local site(s) of action. Thus, BE of these drug/device combination products is established based on an aggregate weight of evidence, which utilizes in vitro studies to demonstrate equivalence of in vitro performance, pharmacokinetic or pharmacodynamic studies to demonstrate equivalence of systemic exposure, and pharmacodynamic and clinical endpoint studies to demonstrate equivalence in local action. This review discusses key aspects of in vitro studies in supporting the establishment of BE for generic locally acting DPI products. These aspects include comparability in device resistance and equivalence in in vitro testing for single inhalation (actuation) content and aerodynamic particle size distribution.
authors.affiliation: Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, MD 20855, USA. sau.lee@fda.hhs.gov
authors.forename: Sau Lawrence
authors.initials: SL
authors.lastname: Lee
authors.forename: Wallace P
authors.initials: WP
authors.lastname: Adams
authors.forename: Bing V
authors.initials: BV
authors.lastname: Li
authors.forename: Dale P
authors.initials: DP
authors.lastname: Conner
authors.forename: Badrul A
authors.initials: BA
authors.lastname: Chowdhury
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D009330:Nebulizers and Vaporizers; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D013810:Therapeutic Equivalency
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D011208:Powders