Mylan (United Kingdom)

583Background: Myl-1401O is a proposed trastuzumab biosimilar. The biosimilarity of Myl-1401O to EU-Herceptin has been demonstrated in physicochemical analyses, nonclinical studies, and one previous PK study. Methods: This single-center, randomized, double-blind, three-arm, parallel-group, Phase I study was conducted in healthy adult male volunteers. The primary objective of this study was to establish PK similarity of A to B and C. The subjects were randomized to receive either A, B or C as 8 mg/kg over 90 minutes as an intravenous infusion. For the primary endpoint, the bioequivalence criterion was that the 90% confidence intervals (CI) of the mean ratios of AUC0-∞ , AUC0-last , and Cmax were bounded within 80.00% - 125.00% calculated using natural log-transformed data. As secondary endpoints, λz, tmax and t1/2 along with assessment of safety (including immunogenicity) was performed. Results: A total of 132 subjects (44/treatment) were enrolled and 120 [42 (A), 41(B), 37(C)] subjects were included in an...

The purpose of this article is to review the suitability of the analytical and statistical techniques that have thus far been developed to assess the dissolution behavior of particles in the respirable aerodynamic size range, as generated by orally inhaled products (OIPs) such as metered-dose inhalers and dry powder inhalers. The review encompasses all analytical techniques publicized to date, namely, those using paddle-over-disk USP 2 dissolution apparatus, flow-through cell dissolution apparatus, and diffusion cell apparatus. The available techniques may have research value for both industry and academia, especially when developing modified-release formulations. The choice of a method should be guided by the question(s) that the research strives to answer, as well as by the strengths and weaknesses of the available techniques. There is still insufficient knowledge, however, for translating the dissolution data into statements about quality, performance, safety, or efficacy of OIPs in general. Any attempts to standardize a dissolution method for compendial inclusion or compendial use would therefore be premature. This review reinforces and expands on the 2008 stimulus article of the USP Inhalation Ad Hoc Advisory Panel, which "could not find compelling evidence suggesting that such dissolution testing is kinetically and/or clinically crucial for currently approved inhalation drug products."