title: Challenges in inhaled product development and opportunities for open innovation.
abstract: Dosimetry, safety and the efficacy of drugs in the lungs are critical factors in the development of inhaled medicines. This article considers the challenges in each of these areas with reference to current industry practices for developing inhaled products, and suggests collaborative scientific approaches to address these challenges. The portfolio of molecules requiring delivery by inhalation has expanded rapidly to include novel drugs for lung disease, combination therapies, biopharmaceuticals and candidates for systemic delivery via the lung. For these drugs to be developed as inhaled medicines, a better understanding of their fate in the lungs and how this might be modified is required. Harmonized approaches based on 'best practice' are advocated for dosimetry and safety studies; this would provide coherent data to help product developers and regulatory agencies differentiate new inhaled drug products. To date, there are limited reports describing full temporal relationships between pharmacokinetic (PK) and pharmacodynamic (PD) measurements. A better understanding of pulmonary PK and PK/PD relationships would help mitigate the risk of not engaging successfully or persistently with the drug target as well as identifying the potential for drug accumulation in the lung or excessive systemic exposure. Recommendations are made for (i) better industry-academia-regulatory co-operation, (ii) sharing of pre-competitive data, and (iii) open innovation through collaborative research in key topics such as lung deposition, drug solubility and dissolution in lung fluid, adaptive responses in safety studies, biomarker development and validation, the role of transporters in pulmonary drug disposition, target localisation within the lung and the determinants of local efficacy following inhaled drug administration.
authors.affiliation: King's College London, Pharmaceutical Science Division, 150 Stamford St, London SE19NH, UK. ben.forbes@kcl.ac.uk
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
authors.forename: Bahman
authors.initials: B
authors.lastname: Asgharian
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
authors.forename: Douglas
authors.initials: D
authors.lastname: Ferguson
authors.forename: Per
authors.initials: P
authors.lastname: Gerde
authors.forename: Mark
authors.initials: M
authors.lastname: Gumbleton
authors.forename: Lena
authors.initials: L
authors.lastname: Gustavsson
authors.forename: Colin
authors.initials: C
authors.lastname: Hardy
authors.forename: David
authors.initials: D
authors.lastname: Hassall
authors.forename: Rhys
authors.initials: R
authors.lastname: Jones
authors.forename: Ruth
authors.initials: R
authors.lastname: Lock
authors.forename: Janet
authors.initials: J
authors.lastname: Maas
authors.forename: Tim
authors.initials: T
authors.lastname: McGovern
authors.forename: Gary R
authors.initials: GR
authors.lastname: Pitcairn
authors.forename: Graham
authors.initials: G
authors.lastname: Somers
authors.forename: Ron K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008168:Lung / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
chemical_list: D004364:Pharmaceutical Preparations