Abstract
Demonstrating bioequivalence (BE) for nasal spray/aerosol products for local action has been very challenging because the relationship between the drug in systemic circulation and the drug reaching the nasal site of action has not been well established. Thus, the current BE standard for these drug/device combination products is based on a weight-of-evidence approach, which contains three major elements: equivalent in vitro performance, equivalent systemic exposure, and equivalent local delivery. In addition, formulation sameness and device similarity are evidences to support BE. This paper presents a comprehensive review of the scientific rationale of the current BE standard and their development history for nasal spray/aerosol products, as well as the Food and Drug Administration’s review and approval status of generic nasal sprays/aerosols with the application of these BE standard.
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Notes
Per Approved Drug Products with Therapeutic Equivalence Evaluations, 32th Edition, “Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s), are of the same dosage form, route of administration and are identical in strength or concentration (e.g., chlordiazepoxide hydrochloride, 5mg capsules). Pharmaceutically equivalent drug products are formulated to contain the same amount of active ingredient in the same dosage form and to meet the same or compendial or other applicable standards (i.e., strength, quality, purity, and identity), but they may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (including colors, flavors, preservatives), expiration time, and, within certain limits, labeling.” (http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/UCM071436.pdf. Last access: 27 Jan 2013)
Per Approved Drug Products with Therapeutic Equivalence Evaluations, 32th Edition, “Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety, but are different salts, esters, or complexes of that moiety, or are different dosage forms or strengths (e.g., tetracycline hydrochloride, 250 mg capsules vs. tetracycline phosphate complex, 250 mg capsules; quinidine sulfate, 200 mg tablets vs. quinidine sulfate, 200 mg capsules). Data are generally not available for FDA to make the determination of tablet to capsule bioequivalence. Different dosage forms and strengths within a product line by a single manufacturer are thus pharmaceutical alternatives, as are extended-release products when compared with immediate-release or standard-release formulations of the same active ingredient.” (http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/UCM071436.pdf. Last access: 27 Jan 2013)
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This article reflects the views of the author and should not be construed to represent the Food and Drug Administration’s views or policies.
Bing V. Li and Feiyan Jin equally contributed to this work.
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Li, B.V., Jin, F., Lee, S.L. et al. Bioequivalence for Locally Acting Nasal Spray and Nasal Aerosol Products: Standard Development and Generic Approval. AAPS J 15, 875–883 (2013). https://doi.org/10.1208/s12248-013-9494-2
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DOI: https://doi.org/10.1208/s12248-013-9494-2