How Does “Regulatory Practice” Create Discrepancies in Drug Label Information Between Asian and Western Countries? Different Label Information for Direct Oral Anticoagulants Approved in the United States,Europe,Korea,and Japan

Abstract

Globalization of the pharmaceutical industry has continued over the past few decades, and various regulatory authorities have put considerable effort into harmonizing and standardizing drug regulations. However, the regulatory practices of each regulatory authority, in addition to local differences in ethnic, social, and cultural backgrounds, create discrepancies in risk/benefit assessments, regulatory decisions, and drug label information in various countries. This study examines discrepancies in the label information for direct oral anticoagulants approved in the US, Europe, Korea, and Japan and reviews the causes of those discrepancies, focusing on regulatory practices. Although the label information for each direct oral anticoagulant in all 4 regions was supported by the same global, pivotal clinical data, it differed depending on regulatory authorities’ judgments about the risk/benefit balance, which were based on their own requirements, regulations, perspectives on making regulatory decisions, and regulatory approval experiences, in addition to their review of the scientific data. In particular, the Korean Ministry of Food and Drug Safety and Japanese Pharmaceuticals and Medical Devices Agency have taken a comparatively conservative stance, with more emphasis on safety than on efficacy compared with regulatory authorities in western countries, because of the double threshold in their regulatory practice. Our findings suggest that drug label information in various regions will not be equal as long as differences in regulatory practice and non-regulatory factors exist among regulatory authorities. Also, those differences should be considered in order to streamline global drug discovery, development, and approval.