The Pharmaceutical Industry at a Glance Comparison of New Drug Approval Status in Japan, U.S. and Europe (2023)

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Chie Yoshiura, Senior Researcher, Pharmaceuticals and Industrial Policy Research Institute
Mariko Togashi, Senior Researcher, Pharmaceuticals and Industrial Policy Research Institute

SUMMARY

1. Introduction

The Pharmaceuticals and Medical Devices Agency (PMDA), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA) publish information on drug approvals in Japan, the United States, and Europe. The PMDA continuously collects and analyzes the information published by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on their ^websites1). In Policy Research Institute News No. 68 ⁽²⁾, we reported the results of our analysis of information on drugs approved in Japan in 2022, and in Policy Research Institute News No. 70 ^{(3), we} reported the results of our comparative analysis of new drug approval status and review periods in Japan, the United States, and Europe, focusing on actual approvals in 2022. This paper reports on the number of new drug approvals, the number of special regulatory actions, and the review periods for new drugs approved in Japan, the U.S., and Europe in 2023.

Survey Methodology

The number of items was counted by review report, and when multiple companies simultaneously submitted applications for the same drug or multiple ingredients were approved for concomitant therapy, the number of items was counted as one item. New Molecular Entity (NME) for items approved in Japan were counted if the application was classified as a drug containing a new active ingredient. The approval information for each item was extracted from the review report, package insert, "List of Approved New Drugs" and the Pharmaceutical Affairs Bulletin. The date of application was the date of submission as stated in the review report, and the date of approval was the date of approval as stated in the "List of New Drugs Approved for Human Use.

The survey targets in the U.S. were drugs that were applicable to the New Drug Application (NDA) and Biologic License Application (BLA) listed in the "CDER Drug and Biologic Approvals for Calendar Year " ⁵⁾ on the FDA's website. NMEs were counted for drugs listed in the "CDER New Molecular Entity (NME) and Original Biologic Approvals Calendar Year " ⁶⁾. Approval information for each item was extracted from each item information in the FDA website. The date of application was the date of submission as indicated in the Approval Letter for each item, and the date of approval was the Approval Date as indicated in the information for each item.

The NMEs were those classified as "New Active Substance". The approval information for each item was extracted from the information on each item in the EMA website. The date of application was the date of application submission as indicated in the Assessment Report for each item, and the date of approval was the date of marketing authorization issued as indicated in the information for each item.

Special regulatory measures include Priority Review, Orphan, Fast Track, Breakthrough Therapy, and Accelerated Approval in the U.S., and Priority Review, Orphan, Fast Track, Breakthrough Therapy, and Accelerated In the U.S., Priority Review, Orphan, Fast Track, Breakthrough Therapy, and Accelerated Approval were counted, and in Europe, Accelerated Assessment, Orphan, Priority Medicine (PRIME), Conditional Approval, and Exceptional Circumstances were counted. The details of each special regulatory action are summarized in Supplement 1.

The review period was calculated as the period from the date of application to the date of approval using standard statistical analysis software Stata/IC 14.2 for Windows (Stata Corp LP, College Station, TX, USA). The "review period" was calculated as the period from the date of application to the date of approval. Since there are some items with significantly longer periods and some with shorter periods due to special exceptions, the main basic statistic is the median value, and the number of samples, mean values, and standard deviations are also shown (Supplements 2-4).

The number of approvals in Japan and the U.S. in this report is as described above, and does not include regenerative medical products. On the other hand, the European count includes items corresponding to regenerative medical products. The number of newly approved regenerative medical products was calculated separately for the following countries in order to see the trend in the number of approvals for regenerative medical products. For Japan, the data covers the products listed as "Approved" or "New" by the approval/revision category among the products listed in the "List of Newly Approved Regenerative Medicine Products " ¹⁰⁾ on the PMDA website. In the U.S., items listed in "Approved Cellular and Gene Therapy Products" on the FDA ^website11) were counted as the year of first approval. In Europe, products approved ^{under the} ATMP (Advanced therapy medicinal products) ¹²⁾ designation as well as products that fall under the above tabulation for Japan and the U.S. were included.

Results

(1) Number and Breakdown of New Drugs Approved in Japan

Table 1 shows the annual number of new drugs approved in Japan between 2010 and 2023, and a breakdown of the items. 106 items were approved in 2023, of which 30 were drugs containing new active ingredients.

In terms of application categories other than drugs containing new active ingredients, there were 52 new indications, 15 new doses, 5 new routes of administration, 1 new dosage form, and 3 follow-on biologics.

By review category, 75 items were under normal review and 27 items were under priority review. Of the priority review items, 22 were orphan drugs. The number of approved orphan drugs was 40 in 2021, the largest number in the period under review, but in 2023, the number of approved orphan drugs was 22, about half the number in 2021, and 9 fewer than in 2022. The number of items subject to the pioneering review designation system (currently the pioneering drug designation system) and the conditional approval system was 0 each. The number of fast-track approvals was 13, of which 7 were pre-evaluated public knowledge applications. 4 special approvals were granted in 2023, all for the prevention of infections caused by the new coronavirus (SARS-CoV-2).

(2) Comparison of the number of new drugs approved in Japan, the U.S., and Europe

Figure 1 shows the number of new drugs approved in Japan, the U.S., and Europe over the past 10 years (2014-2023). In the U.S., 128 new drugs were approved in 2023, of which 55 were NMEs. In Europe, 140 new drugs were approved in 2023, of which 36 were NMEs. In the U.S., the number of NMEs in 2023 increased by 18 compared to 2022, and the total number of approved NMEs also increased, while in Japan and Europe, the number of NMEs decreased by 22 and 20, respectively, compared to 2022, and the total number of approved NMEs also decreased.

(3) Number of NMEs approved under special regulatory measures

Figure 2 shows the number of NMEs approved in Japan, the U.S., and Europe over the past five years (2019-2023) that received special regulatory treatment in each region.

Of the 30 NMEs approved in Japan in 2023, 10 (33.3%) received priority review (including orphan drugs), 7 (23.3%) received orphan drugs, and none were subject to the pioneer review designation system, conditional approval system, or expedited review. The number of NMEs that qualified for Priority Review and Orphan Drug Status also decreased in 2023 compared to 2022.

In the U.S., of the 55 NMEs approved in 2023, 33 (60.0%) were Priority review, 28 (50.9%) were Orphan, 25 (45.5%) were Fast Track, 9 (16.4%) were Breakthrough Therapy, and 9 (16.4%) were Orphan. The number of NMEs in the U.S. in 2023 increased from 2022, and the number of NMEs that received special regulatory action also increased from 2022, except for Breakthrough Therapy.

In Europe, of the 36 NMEs approved in 2023, 3 (8.3%) were Accelerated Assessment, 10 (27.8%) were Orphan Designated, 3 (8.3%) were PRIME Designated, 7 (19.4%) were Conditional Approval The number of PRIME-designated products was 3 (8.3%), Conditional Approval was 7 (19.4%), and Exceptional Circumstances was 1 (2.8%). In Europe, the number of NMEs in 2023 was lower than in 2022, and the number of NMEs that received special regulatory action was also lower.

(4) Annual changes in median review period

Annual changes in median review duration by year of approval (2000-2023) for drugs approved in Japan, the U.S., and Europe are shown in Figure 3, and for NMEs, the period from 2013 to 2023, after the Japanese review period was significantly reduced, is included in the study, and annual changes in median review duration are shown in Figure 4. The review periods, medians, means, and standard deviations are shown in Supplement 2 and Supplement 3, respectively, for NMEs that received special regulatory measures (Japan: Priority Review, U.S.: Priority Review, Europe: Accelerated Assessment) to shorten the review period. Supplement 4.

The median examination periods for the entire period covered by the survey were 10.9 months in Japan, 10.2 months in the U.S., and 13.2 months in Europe. 2023 was 10.3 months in Japan, 10.8 months in the U.S., and 12.2 months in Europe, with Japan having the smallest median (Supplement 2). As shown in Figure 3, the median examination period for Japan has generally remained at around 10 months since 2011, when the examination period was significantly shortened.

The median examination periods for NMEs for the entire survey period were 10.3 months in Japan, 9.9 months in the U.S., and 14.1 months in Europe; the median examination periods in 2023 were 10.9 months in Japan, 11.0 months in the U.S., and 14.7 months in Europe, with Japan also having the smallest median for NMEs (Supplemental 3). Supplement 3). In terms of annual trends, as shown in Figure 4, there were no significant changes within the aggregation period in Japan, the U.S., and Europe. In addition, the number of NME approvals by review period is shown in Figure 5. The largest number of NMEs in Japan and the U.S. were approved for a review period of 6 to 12 months, while the largest number of NMEs in Europe were approved for a review period of 12 to 18 months.

(5) Comparison of the number of NMEs approved in Japan, the U.S. and Europe

Figure 6 shows the number of new approvals (2015-2023) for items equivalent to regenerative medical products approved in Japan, the U.S., and Europe, and the number of items approved in Japan, the U.S., or Europe in two or more regions as of the end of 2023. In Japan, 18 products were newly approved from 2015 to 2023, 8 of which were approved in either or both the US and Europe. In the U.S. and Europe, 25 and 21 new drugs were approved from 2015 to 2023, respectively, and 13 and 14 drugs were approved in two or more regions by the end of 2023, respectively.

In recent years, the number of newly approved products has been increasing in both Japan, the U.S., and Europe. In 2023, the U.S. had a record number of 6 products approved, while Japan had 3 products approved, the same number as in 2022, and Europe had 1 product approved, a decrease.

Summary and Discussion

This report compiles and compares the number of new drugs approved in Japan, the U.S., and Europe in 2023, the number of special regulatory actions, and the review periods based on information published by the respective regulatory authorities.

In Japan, both the number of all approved items and the number of NMEs decreased in 2023 compared to 2022. The same trend was observed in Europe, while in the U.S., both the number of all approved items and the number of NMEs were higher than in 2022. Looking at the number of NMEs in the most recent years, the U.S. had 53 and 50 more NMEs in 2020 and 2021, respectively, and 37 fewer NMEs in 2022. In Japan and Europe, the number of NMEs was over 50 in 2021 and 2022, one year behind the U.S., and decreased in 2023. As reported in a previous issue of Policy Research Institute News No. 63 ⁽¹³⁾, as of 2020, the U.S. had a majority of first global launches, while Japan and Europe had a high percentage of second- or third-launched products. This behavior is thought to have affected the number of NMEs.

As for the number of NMEs that received special regulatory measures, the number of NMEs decreased overall in Japan and Europe from 2022, while it increased in the U.S., similar to the trend in the number of NMEs. In Japan, the number of NMEs approved under the Pioneer Review Designation System, the Conditional Approval System, and Expedited Review were all zero in FY2023. Although it is important for innovative drugs to be promptly introduced into Japan, even under the Pioneer Review and Designation System, which had a relatively high number of NME approvals in Figure 2, there were only 8 cases in the past 5 years, or 3.8% of the total number of NMEs. Compared to Breakthrough Therapy in the U.S. and PRIME in Europe, which are similar to the Pioneer Review Designation System in that guidance is provided by the regulatory authorities from the development stage, there were 71 NMEs (29.2% of NMEs) in Breakthrough Therapy and 27 in PRIME in the same period. The number of NMEs that fell under Breakthrough Therapy was 71 (29.2% of the total number of NMEs) and the number of NMEs that fell under PRIME was 27 (12.7% of the total number of NMEs). Figure 7 shows the number of cases newly designated as these special measures in the past five years and valid at the present time. Japan had 88 ⁾, the U.S. had ²³⁰¹⁴⁾, and Europe had ⁷⁰¹⁵⁾. Although not directly comparable to the number of approvals, the number of designations themselves was higher in the U.S. and Europe.

On the other hand, Figure 8 shows the status of introduction into Japan of NME-approved products that received U.S. Breakthrough Therapy and European PRIME designation in the past two years, and more than 80% of them have been approved or are under development in Japan. This does not mean that there is currently a significant delay in the introduction of drugs that have received special measures in the pharmaceutical affairs as breakthrough new drugs in the U.S. and Europe, but it is desirable that the pioneering drug designation system be utilized more to create new drugs that originate in Japan or that make Japan the first in the world to receive such designation. The current low number of designations compared to Europe and the U.S. may require an analysis of the causes and a review of the system.

The review period for all approved items and NMEs was similar to the normal year, ranging from 10 to 15 months in each region. The review period analyzed in this report is defined as the period from the date of submission of application materials to the date of approval, which differs in part from the review periods in various reports issued by the regulatory authorities in Japan, the U.S., and Europe, and includes the time required to respond to inquiries from the authorities. For example, the standard deviation of the review period shown in Supplemental 2 and Supplemental 3 is large because some of the items approved in the U.S. in 2023 have an old initial application date and a review period of more than 10 years. In the analysis in this paper, the standard deviation of the examination period in Japan in 2023 is relatively small, and the median examination period in Japan in 2023 is the smallest among Japan, the U.S., and Europe. As shown in Figure 5, of the 30 NMEs in Japan in 2023, only 5 (16.7%) had a review period of 12 months or longer, and 24 (80.0%) had a review period of 6 months to less than 12 months, indicating that more than 80% of them were approved in 12 months from the application date. Although the period from application to approval may be longer in the U.S., where many cases receive world-first approval, the review period in Japan was shorter than that in Europe and Japan, where many cases are filed in the second to third position. The fact that the review period is as short as or shorter than in Europe and the U.S., and that the review can be expected to be completed within the target period set by the regulatory ^{authorities16)}, is an excellent feature of the Japanese review system, as it increases predictability in the development timeline for the launch of a new drug.

The number of newly approved regenerative medicine products has been on the rise in recent years, with the United States having the highest number of six in 2023, followed by Japan with three and Europe with one, a decrease from 2022. In addition, the number of global products approved in two or more regions at the end of 2023 was one in both Japan, the U.S., and Europe. Of the 24 products approved in Europe and the U.S. shown in Figure 6, 24 products that were either approved in both Europe and the U.S. or under development in Europe and the U.S. were selected and surveyed for development information in Japan (Figure 9). 14 products (58.3%) were approved or under development in Japan, while 10 products (41.7%) had no development information available in Japan. There is concern that the development of some products, not only pharmaceuticals but also regenerative medicine products, may be delayed or not be introduced in Japan. In addition to the recent discussions on measures against drug lag and loss, such as the improvement of the clinical trial environment, it is hoped that measures will be taken to resolve various issues specific to regenerative medicine products.

Conclusion

This report compares the number of new drugs approved in Japan, the U.S., and Europe in 2023, the number of special regulatory actions, and the duration of review, The median review period was the smallest in Japan. It will be interesting to see how these characteristics of Japan compared to the U.S. and Europe will affect the number of approvals in Japan in the future, especially how quickly they will be introduced to Japan, and we will continue to investigate this issue.

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