Trend Analysis of Regulatory Approvals for Generics and Biosimilars in Japan: 15 Years of PMDA During Fiscal Years 2009-2023.

Generics and biosimilars play an important role in sustaining the universal healthcare insurance systems in Japan. The Pharmaceuticals and Medical Devices Agency (PMDA) reviews the quality, efficacy, and safety of generics and biosimilars for marketing authorization in Japan. Trend analyses of generics and biosimilars in terms of regulatory science have rarely been published.

Revisions to the requirement of the Japanese clinical study data for biosimilar developments in Japan.

Background: The 'Questions and Answers (Q&A)' document regarding Japanese biosimilar guideline elucidated that Japanese participant enrollment in at least one comparative clinical study was required for the marketing authorization application (MAA) of biosimilars in Japan.

Research Design And Methods: To discuss the requirement of Japanese clinical study data for biosimilar development, the trend in comparative clinical studies conducted for approved biosimilars of monoclonal antibodies and fusion proteins was analyzed, and the consistency of the results between the overall population and the Japanese population according to the publicly available information was reviewed.

Results: The number of comparative clinical studies enrolling Japanese participants was 25 cases, and the type and percentage were 13 (52%) and 12 (48%) cases of comparative pharmacokinetic study and comparative efficacy study, respectively.

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as an enantioseparation enhancer for fluorescence chiral derivatization-liquid chromatographic analysis of dl-lactic acid.

This paper reports a novel fluorescence chiral derivatization-liquid chromatography (LC) method for the analysis of d- and l-lactic acids (LAs) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an enantioseparation enhancer. In this method, the dl-LAs were fluorescently derivatized with (S)-(+)-4-(N,N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole [(S)-(+)-DBD-APy] in the presence of DMT-MM as a condensing agent. These conditions resulted in the hydroxyl group of the LA derivative being etherified by the triazine unit of DMT-MM, producing sterically bulky diastereoisomers.

Automatic analyzer for highly polar carboxylic acids based on fluorescence derivatization-liquid chromatography.

A sensitive, versatile, and reproducible automatic analyzer for highly polar carboxylic acids based on a fluorescence derivatization-liquid chromatography (LC) method was developed. In this method, carboxylic acids were automatically and fluorescently derivatized with 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ) in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride by adopting a pretreatment program installed in an LC autosampler. All of the DBD-PZ-carboxylic acid derivatives were separated on the ODS column within 30 min by gradient elution.