A comparative approach of pharmaceutical regulation in Europe and Japan

Abstract

Japan and EU regulatory bodies historically have in principle mutually agreed on the requirements and regulatory processes to provide drugs in a timely manner while ensuring safety, quality, and efficacy. However, there are still a number of pharmaceutical regulations in Japan and the EU which are different. The aims of the study were (i) to compare pharmaceutical regulations in Japan and those in the EU and identify differences and similarities and (ii) to identify perceptions of healthcare professionals (HCPs) about Japanese and European regulations. The study focused on Japanese and European regulations applied in: (i) research and development (R&D), (ii) application for marketing authorization (MA), (iii) manufacturing, (iv) distribution, (v) post-marketing, and (vi) clinical use. The regulations were obtained from websites of regulatory bodies, official websites (such as the Organization for Economic Co-operation and Development), laws, and journals. Perceptions of HCPs were evaluated through a focus group discussion consisting of doctors and pharmacists from Japan and Malta. Regulatory harmonization between Japan and the EU was identified in the R&D, MA application, and manufacturing phase. In the R&D phase, the data obtained under Good Laboratory Practice (GLP) is mutually accepted, and clinical trials are conducted by referring to the same guidelines. The Common Technical Document (CTD) used for the MA application is in common for Japan and the EU. Products manufactured under Good Manufacturing Practice are mutually accepted. Regulatory differences were also identified. The GLP inspection fees in Japan are based on the category of the test facilities and products, while in Malta, fees are based on the number of inspectors and location of the inspected site. Fees for GCP inspections in Japan are based on inspection types, while those in the EU are based on clinical trial activities. Module 1 of the CTD is region-specific. The Japanese CTD focuses on product-development history while, the EU CTD focuses on product information and environmental risk assessment. Japan categorizes over-the-counter (OTC) drugs according to their risk-based classification which enables non-pharmacist personnel and non-pharmacy outlets to sell a particular category of OTC products. In Malta, all medicinal products must be dispensed from pharmacies. Supplying emergency contraception (EC) requires a prescription in Japan, while EC can be purchased directly from a pharmacy without a prescription in Malta. The principles underlying regulations in the post-marketing phase were similar between Japan and the EU. Japan does not have a system to promote public reporting of adverse drug reactions (ADRs). Two types of drug information documents are used in Japan and the EU. The Japanese Drug Information Sheet (DIS) and European Patient Information Leaflet (PIL) are intended for patient use. The Japanese Package Insert and European Summary of Product Characteristics are used by HCPs. A total of eighteen HCPs took part in the FGD. Fourteen participants considered that the DIS is personalized, which is deemed to be effective to increase adherence (n=10). Fifteen participants agreed that the PIL contains plentiful information which can be counterproductive (n=13). Ten HCPs agreed that accessibility is an advantage in the Japanese OTC distribution system, and 11 HCPs perceived that pharmacist intervention in OTC sales is necessary for patient safety. Six out of 9 Maltese HCPs perceived that there is an ethical dilemma in the EC supply in Malta. Regulatory harmonization between Japan and the EU did not cover regulations related to the ADR reporting system, the public distribution of non-prescription medicines, and drug information documents. The use of personalized drug information would benefit patients by facilitating the understanding of presented information. It is envisioned that it is possible with discussion and allowance for some cultural differences for harmonization to be achieved between Japan and the EU.