A comparison of decision and timing of safety related labeling changes for new drugs approved both in Japan and the United States

Abstract

Purpose It is important to make the most up‐to‐date drug safety information available to the public in a timely manner so that health care professionals and patients can consider the information. The aim of the present study was to investigate the consistency and simultaneity of safety related updates in product labeling in Japan and the United States. Methods New safety label changes that were made for new drugs approved concurrently both in Japan and the United States in the recent 5 years were identified and reviewed for concordance and time lag analysis. Factors associated with the time lag were also investigated. Results Despite similar medical practices, population health and regulation in the countries, a low level of concordance (40/115, 34.8%) in the decision of labeling change was found in 31 new active substances. Only 3/40 (7.5%) of the concordant changes were made simultaneously. Labeling change orders issued by regulators and domestic postmarketing adverse event reports were associated with a significant difference in the timing of labeling change between the countries. Conclusions We found a low level of concordance between regulators in the decision of labeling changes and the timeliness of the changes. The low concordance and time lag highlighted the need for further international collaboration between regulators and industry and greater transparency in the decision‐making process for the label change.

Decision and timing of safety‐related labeling changes for new drugs in Japan: Comparison with the United States and the European Union

“…This means that the regulatory authority in each country/region often makes decisions individually. Several studies have found low concordance of safety warnings between countries, 14,[30][31][32] which is consistent with the present result. The discrepancies maybe caused by differences in data source (e.g., domestic adverse event reports), events of interest, and action thresholds.…”

“…In these cases, precautions for the events had been listed in the non‐warning sections of the Japanese labeling at the time of approval. A previous study showed that domestic adverse event reports were associated with a significant difference in the timing of labeling change between Japan and the US 14 . In the cases of linagliptin and lenvatinib, accumulation of domestic adverse event reports provided the rationale for adding the precautions to the warning section of the Japanese labeling, 22,23 which might have affected the difference in the revision dates.…”

“…A previous study showed that domestic adverse event reports were associated with a significant difference in the timing of labeling change between Japan and the US. 14 In the cases of linagliptin and lenvatinib, accumulation of domestic adverse event reports provided the rationale for adding the precautions to the warning section of the Japanese labeling, 22,23 which might have affected the difference in the revision dates. In Japan, effective evaluation of adverse event reports outside of Japan may help narrow the gap in the revision timing between countries/region; however, in order to process the vast number of adverse event reports worldwide, we believe that prioritization of evaluation is necessary, taking into account the impact on public health in terms of the degree of uncertainty and severity of the event.…”

“…A previous study showed that there was no trend of delayed safety-related labeling change in Japan compared to that in the US, although the concordance rate of the contents of labeling change between the two countries was low. 14 The PV legislation in the EU as well as the Food and Drug Administration (FDA) Amendments Act in the US have strengthened their PV system through various approaches. 15,16 In addition, as in the US, the EU guidelines allow regulators and the pharmaceutical industry to share their basic approaches to the details of the PV process.…”

A Comparison of Safety Information in Drug Labeling at the Initial Approval of New Drugs Approved Both in Japan and the United States

“…Our group previously investigated the concordance in decision and timing of safety-related labeling changes after approval in Japan and the US and reported a low level of concordance between countries [ 22 ]. In the present study, we revealed that the inconsistency existed from the time of approval even in the cohort of drugs concurrently approved in both countries in the recent 7 years.…”