title: Considerations for toxicology studies of respiratory drug products.
abstract: The standard approaches for the preclinical development of chronically administered drugs also apply to most respiratory drugs. Modifications from the standard preclinical development plan, however, may be necessary if the drug is administered intranasally or by inhalation. Administration by these routes may result in airway toxicity and the intended patient population is often particularly susceptible. Current and former representatives of the Division of Pulmonary Drug Products (CDER, U.S. FDA) present this article to describe general principles of preclinical development for respiratory drug indications. The article addresses drugs intended for administration by the intranasal or inhalation routes. The article describes the types of studies recommended, considers the initial human dose, and discusses dose-escalation strategies in clinical trials. Other areas of special concern with intranasal or inhalation administration include immunotoxicity, reproductive toxicity, types of dosing apparatus, excipients and extractables, and formulation changes. The approaches described in this article are intended as general information and should be adapted to the scientific considerations and circumstances of a particular drug under development.
authors.affiliation: Division of Pulmonary Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: DeGeorge
authors.forename: C H
authors.initials: CH
authors.lastname: Ahn
authors.forename: P A
authors.initials: PA
authors.lastname: Andrews
authors.forename: M E
authors.initials: ME
authors.lastname: Brower
authors.forename: Y S
authors.initials: YS
authors.lastname: Choi
authors.forename: M Y
authors.initials: MY
authors.lastname: Chun
authors.forename: T
authors.initials: T
authors.lastname: Du
authors.forename: D Y
authors.initials: DY
authors.lastname: Lee-Ham
authors.forename: W D
authors.initials: WD
authors.lastname: McGuinn
authors.forename: L
authors.initials: L
authors.lastname: Pei
authors.forename: L F
authors.initials: LF
authors.lastname: Sancilio
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: H V
authors.initials: HV
authors.lastname: Sheevers
authors.forename: C J
authors.initials: CJ
authors.lastname: Sun
authors.forename: S
authors.initials: S
authors.lastname: Tripathi
authors.forename: W M
authors.initials: WM
authors.lastname: Vogel
authors.forename: V
authors.initials: V
authors.lastname: Whitehurst
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: A S
authors.initials: AS
authors.lastname: Taylor
mesh_terms: D006801:Humans; D012106:Research; D012107:Research Design; D019141:Respiratory System Agents / Q000633:toxicity*
chemical_list: D019141:Respiratory System Agents