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.
Notes
[21 CFR 320.1(e)].
Pharmaceutical equivalents means drug products in identical dosage forms that contain identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the same therapeutic moiety, or, in the case of modified release dosage forms that require a reservoir or overage or such forms as prefilled syringes where residual volume may vary, that deliver identical amounts of the active drug ingredient over the identical dosing period; do not necessarily contain the same inactive ingredients; and meet the identical compendial or other applicable standard of identity, strength, quality, and purity, including potency and, where applicable, content uniformity, disintegration times, and/or dissolution rates [21 CFR 320.1(c)].
Pharmaceutical alternatives means drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each such drug product individually meets either the identical or its own respective compendial or other applicable standard of identity, strength, quality, and purity, including potency and, where applicable, content uniformity, disintegration times and or dissolution rates [21 CFR 320.1(d)].
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The opinions expressed in this review by the authors do not necessarily reflect the views or policies of the Food and Drug Administration (FDA).
An erratum to this article is available at http://dx.doi.org/10.1208/s12248-010-9243-8.
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Lee, S.L., Adams, W.P., Li, B.V. et al. In Vitro Considerations to Support Bioequivalence of Locally Acting Drugs in Dry Powder Inhalers for Lung Diseases. AAPS J 11, 414–423 (2009). https://doi.org/10.1208/s12248-009-9121-4
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DOI: https://doi.org/10.1208/s12248-009-9121-4