Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis

Abstract

The Pharmaceuticals and Medical Devices Agency (PMDA) has approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the first tertile (2008-2011), 1.5 and 2.6 in the second tertile (2012-2015), and reduced to 1.3 and 2.2 in the third tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

Figure 1

Regions of the first approval among new drugs approved in Japan between 2008 and 2019. Among 400 new drugs approved in Japan, 80 (20.0%) were first approved in Japan (Japan‐first, red), and 320 (80.0%) were outside Japan (global‐first, green). The number of first‐in‐world approvals were the largest in United States (202 items, 50.5%), followed by Europe (82 items, 20.5%), Japan, and the others regions (36 items, 9.0%). The Japan‐first drugs included 45 drugs that have not yet been approved in the other regions (local approval, orange). The remaining 355 drugs have been approved in Japan and overseas (global approval, purple).

Figure 2

Change of the number of new drugs approved in Japan between 2008 and 2019. There was no specific trend in the number of new drugs with (a) global approvals and (b) local approvals. Dark and light blue bars indicate the number of Japan‐first and global‐first products with global approvals, respectively. Green bars indicate the number of new drugs with local approvals that is Japan‐first products.

Figure 3

Therapeutic areas among new drugs approved in Japan between 2008 and 2019. Top three active therapeutic areas for new drugs with (a) global approvals and (b) local approvals were oncology, metabolic/endocrine, and infectious diseases, and infection, metabolic/endocrine, and oncology, respectively. Among those three major therapeutic areas, the number of Japan‐first products were relatively large. Among therapeutic areas with ≥ 20 items in total, the number of new drugs with local approvals was low in neurology and psychiatry. Dark and light blue bars indicate the number of Japan‐first and global‐first products with global approvals, respectively. Green bars indicate the number of new drugs with local approvals that is Japan‐first products.

Figure 4

Drug lag among new drugs approved in Japan between 2008 and 2019. Shown are the median drug lag (year) for new drugs approved in Japan calculated on all new drugs (399 items, circles with a red line) and on the new drugs with global approvals (354 items, triangles with a blue line). The analysis of all new drugs is a sum of the new drugs with global approvals and local approvals, in which drug lag is zero for local approvals. A 3‐year moving average of the median drug lag (year) are shown as a dot line for each color. The median drug lag peaked in around 2011–2012, and continuously decreased since 2013. Benzoyl peroxide (Bepio) is excluded from the analysis due to no data are available on the international birth date.

Figure 5

Change of drug lag in each therapeutic area among new drugs approved in Japan. Data are described as median years (number of items). Red, orange, yellow, and green cells indicate ≥ 5 years of drug lag, 3 years ≤ drug lag < 5 years, 1 year ≤ drug lag < 3 years, and < 1 year of drug lag, respectively. NA, not available. ^aSum of the new drugs with global approvals and local approvals, in which drug lag is zero for local approvals. ^bBenzoyl peroxide (Bepio) is excluded due to no data are a vailable on the international birth date.