The Pharmaceutical Industry at a Glance Comparison of New Drug Approval Status in Japan, the U.S., and Europe (2024)

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Mariko Togashi, Senior Researcher, Pharmaceutical Industry Policy 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 information published by the U.S. Food and Drug Administration (FDA) and European MedicinesAgency (EMA) on their ^websites1). Policy Research Institute News No. 68 ⁽²⁾ provides an analysis of information on drugs approved in Japan in 2022, Policy Research Institute News No. 70 ^{(3) provides} a comparative analysis of the approval status and review period of new drugs in Japan, the U.S., and Europe, focusing on the approval results in 2022, and Policy Research Institute News No. 73 ^{(4) provides a} comparative analysis of the number of new drugs approved in Japan, the U.S., and Europe in 2023. The number of new drug approvals, the number of special regulatory actions, and the review period for new drugs approved in Japan, the U.S., and Europe in 2023 were reported in the Policy Research Institute News No. 73 (4). In this report, we report on the status of new drug approvals in Japan, the U.S., and Europe in 2024 as a continuation of the survey.

Survey Methodology

In Japan, the survey covered drugs listed in the "List of New Drugs Approved " ⁵⁾ on the PMDA website. The number of items was counted for each review report, and when multiple companies simultaneously submitted applications for the same drug or multiple ingredients were approved for combination drug therapy, the number of items was counted as one. New Molecular Entity (NME) for items approved in Japan were counted if the application was classified as a drug containing a new active ingredient. 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 " ⁶⁾ on the FDA website. NMEs were counted for drugs listed in the "CDER New Molecular Entity (NME) and Original Biologic Approvals Calendar Year " ^7). 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 approval date 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 submission of the application form 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 Japan, Priority Review, Orphan, Fast Track, and Accelerated Approval in the U.S., and Priority Review, Orphan, Fast Track, Breakthrough Therapy, and Accelerated Approval in Europe, Accelerated Approval in the U.S. and Accelerated Assessment, Orphan, Priority Medicine (PRIME), Conditional Approval, and Exceptional Circumstances in Europe. The review period was based on the standard statistics.

The review period was calculated using standard statistical analysis software Stata/IC 14.2 for Windows (Stata Corp LP, College Station, TX, USA), and the "review period" was defined as the period from the date of application to the date of approval. 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, and standard deviation are also shown.

The number of approvals in Japan and the U.S. in this report is as shown above, and does not include regenerative medical products. On the other hand, the European count includes items corresponding to regenerative medical products. In order to see the trend in the number of approvals for regenerative medical products, the number of newly approved regenerative medical products was separately tabulated for the following countries. For Japan, items listed as "Approved (including approval with conditions and expiration date)" or "New" by approval/revision among the items listed in the "List of Newly Approved Regenerative Medicine Products " ⁹⁾ on the PMDA website were included. In the U.S., the year of first approval was used as the approval year for items listed in "Approved Cellular and Gene Therapy Products " ¹⁰⁾ on the FDA's website. For Europe, items approved under ^the ATMP (Advanced therapy medicinal products) ^{designation11)} were included, as well as items falling under the above tally for Japan and the U.S.

Results

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

(1) Number and breakdown of new drug approvals (by year of approval; 2015-2024)

Table 1 shows the annual number of new drugs approved in Japan between 2015 and 2024, as well as a breakdown of the items. 153 items were approved in 2024, of which 63 were drugs containing new active ingredients, the highest number ever.

In the breakdown by application category other than drugs with new active ingredients, there were 62 new indications, 18 new doses, 3 new medical combination products, 2 each of new dosage forms, follow-on biologics, and similar prescription medical combination products, and 1 new route-of-administration product.

By examination category, 106 items were under normal review and 47 items were under priority review. Of the priority review items, 41 items were orphan drugs, which accounted for the majority of the total, and although a decrease was observed in 2022 and 2023, the number turned to increase in 2024, surpassing the 40 items approved in 2021, which was the highest number of items approved so far in the period covered by this report. One product was approved under the Pioneer Drug Designation System, valementostat tosylate, which was approved under the Pioneer Drug Designation System in 2019 for the expected indication of "relapsed or refractory obliterating T-cell lymphoma: Relapsed or refractory peripheral T-cell against esalmia 50 mg tablets and 100 mg tablets. The approval was for an additional indication of relapsed or refractory peripheral T-cell lymphoma for viremetostat tosylate: esalmia tablets 50 mg and 100 mg. The number of Conditional Approval Program items was 0. The number of expedited approvals was 15, of which 7 were pre-evaluated public knowledge applications.

(2) Number and Breakdown of Orphan Drugs (by Approval Year; 2015-2024) (3) Number of Approved Drugs by Therapeutic Category

Figure 1 shows the annual trend in the number of orphan drugs among new drugs approved in Japan between 2015 and 2024. The number of orphan drugs approved in 2024 was 41 (including 18 NMEs), the highest ever. The percentage of NMEs increased or decreased in the range of 17.8% to 29.6% during the period, and no certain bias or trend was observed between the percentages of NMEs and others.

(3) Ratio of Approved Drugs by Therapeutic Category

Figure 2 shows the number of new drugs approved in Japan in 2024 by drug class. Oncology drugs accounted for the largest number of approved drugs at 19 (30.2%), followed by biologics at 12 (19.0%). This was followed by other metabolic drugs with 6 (9.5%), chemotherapeutic agents and CNS drugs with 4 (6.3%) each.

(2) Comparison of the number of new drug approvals between Japan, the U.S. and Europe

(i) Number of approved drugs in Japan, U.S. and Europe

Figure 3 shows the number of new drugs approved in Japan, the U.S., and Europe over the past 10 years (2015-2024). The number of new drugs approved in Japan is as shown in (1) Number and Breakdown of New Drugs Approved in Japan. In the U.S., 107 new drugs were approved in 2024, of which 49 were NMEs. In Europe, 161 items were approved, of which 37 were NMEs. The number of NMEs in the U.S. in 2024 decreased by 6 and the total number of approved NMEs decreased compared to 2023, while the number of NMEs in Japan and Europe increased by 33 and 1, respectively, and the total number of approved NMEs increased compared to 2023.

(ii) Number of NMEs approved under special regulatory measures

Figure 4 shows the number of NMEs approved in Japan, the U.S., and Europe over the past five years (2020-2024) that received special regulatory treatment in each region.

Of the 63 NMEs approved in Japan in 2024, 20 (31.7%) received priority review (including orphan drugs) and 18 (28.6%) received orphan drugs, perhaps in conjunction with the increase in the number of NMEs in 2024 from 2023, the number of NMEs that received priority review and orphan drugs The number of NMEs that fall under priority review and orphan drugs also turned to increase compared to 2023. Three NMEs were also approved for expedited review (excluding priority review), compared to zero in the previous four years.

In the U.S., of the 49 NMEs approved in 2024, 29 (59.2%) were Priority review, 25 (51.0%) Orphan, 22 (44.9%) Fast Track, 18 (36.7%) Breakthrough Therapy, and 18 (36.7%) Accelerated Review. The number of NMEs in the U.S. in 2024 decreased from 2023, and the number of NMEs receiving special regulatory action also decreased for most measures, while Breakthrough Therapy showed an increase from 2023. Breakthrough Therapy was found to have increased from 2023.

In Europe, of the 37 NMEs approved in 2024, 1 (2.7%) had Accelerated Assessment, 15 (40.5%) had Orphan designation, 6 (16.2%) had PRIME designation, 6 (16.2%) had Conditional Approval, and 2 (5.4%) had Exceptional Circumstances. The number of NMEs in Europe in 2024 was 15 (40.5%), 6 (16.2%) for PRIME, 6 (16.2%) for Conditional Approval, and 2 (5.4%) for Exceptional Circumstances. The number of NMEs in Europe in 2024 increased by only one from 2023, while the number of NMEs that received special regulatory action increased for Orphan, PRIME, and Exceptional Circumstances designated products, and decreased for Accelerated Assessment and A decrease was observed for Accelerated Assessment and Conditional Approval.

Annual change in median duration of review (all approved items)

The median, mean, and standard deviation of the review period for NMEs are shown in Table 2, and the median, mean, and standard deviation of the review period for NMEs are shown in Table 3. The review periods of NMEs that received special regulatory measures (Japan: Priority Review, Pioneer Drug Designation System; U.S.: Priority Review, Breakthrough Therapy; Europe: Accelerated Assess- ment, PRIME) to shorten the review period are shown in Table 4.

The median review period for the entire period covered by the survey was 10.0 months in Japan, 10.0 months in the U.S., and 12.3 months in Europe. 2024 was 9.9 months in Japan, 10.0 months in the U.S., and 12.6 months in Europe, and the mean values were 9.8 months in Japan, 16.0 months in the U.S., and 13.0 months in Europe, with Japan having the lowest values. The mean values were 9.8 months in Japan, 16.0 months in the U.S., and 13.0 months in Europe, with Japan having the smallest mean value (Table 2). The median review period in Japan was approximately 10 months, which was maintained at the same level as that in the U.S. The median review period for NMEs in Japan was approximately 10 months, which was maintained at the same level as that in the U.S. (Figure 5).

The median review period for NMEs during the entire survey period was 10.2 months in Japan, 9.9 months in the U.S., and 14.0 months in Europe. The average values were 10.2 months in Japan, 14.7 months in the U.S., and 15.3 months in Europe, with Japan showing the smallest value for NMEs and a stable review period with a small standard deviation, with almost no difference between all approved items and NMEs (Table 3). As shown in Figure 6, there were no significant fluctuations in the annual trends during the survey period in Japan, the U.S., and Europe, but the review period in Japan for the most recent three years was shorter than that in the U.S.

As shown in Table 4, the number of NME approvals for priority review in Japan in 2024 was 20, an increase from 2023. The median and mean review periods were 8.1 and 8.7 months, respectively, both the shortest in the last three years, indicating a steady reduction. In addition, the standard deviation of the review period was very small and stable. There were no NME approvals in the last two years for items designated under the Priority Drug Designation System. The number of NME approvals for Priority Review-designated products in the U.S. in 2024 was 29, a decrease from 2023. The median review period (8.0 months) remained unchanged over the last three years. 18 products were designated for Breakthrough Therapy and 7 products were designated for Accelerated Approval, both with a median review period (8.0 months) similar to that of Priority review. The median review time for both was 8.0 months, similar to the Priority review. In Europe, there was one Accelerated Assessment-designated product in 2024 with a median review time of 8.1 months, which was approximately 6 months shorter than that for the product that had not received designation. In addition, six items were designated for PRIME, with a median review time of 13.1 months. The review period for items that received special regulatory measures was significantly shorter than that for items under normal review.

(3) Comparison of the number of approved regenerative medical products between Japan, the U.S. and Europe

The number of new approvals of products equivalent to regenerative medicine products approved in Japan, the U.S., and Europe (2015-2024) is shown in Figure 7. In Japan, one new product was approved in 2024, Sanbio's Acugo Intracerebroventricular Transplantation Injection (traumatic brain injury), which was the first product approved in Japan in the Japan-US-EU comparison, and was subject to conditional and time-limited approval. In addition, two items were approved in Europe, but they were items that had already been approved in the US. In the U.S., the number of new approvals was prominent with 10 new products approved in 2024. Of these, one was approved in Japan, two were already approved in Europe, and seven others were approved in the U.S. first.

In 2024, however, there was no clear increase in Japan and Europe, while the number of newly approved products in the U.S. exceeded last year's record number by a wide margin.

Summary and Discussion

This report compiles and compares the number of new drug approvals, special regulatory actions, and review periods for new drugs approved in Japan, the U.S., and Europe in 2024, based on information published by the regulatory authorities of each country.

The number of new drugs approved in 2024 in Japan was lower than the number in 2022, which was the highest number in the past 10 years, but the number of NMEs was the highest ever (63). The number of approved drugs for rare diseases also reached a record high (41 drugs, including 18 NMEs). In the report of Policy Research Institute News No. 75, it was confirmed that the number of domestic approvals of new drugs for pediatric indications is also expected to increase significantly by ^202412). The future development of NME products in Japan will be closely watched.

Looking at the classification of NME products in Japan, 19 (30.2%) were oncology drugs. Cancer remains a major cause of death in ^Japan13), indicating the high level of unmet medical needs. In addition, many of the drugs were tailored to the characteristics of the patients, reflecting the influence of the recent progress in personalized medicine. Next in number were 12 biologics (19.0%), of which 8 were vaccines, indicating the growing interest in various infectious diseases or preventive medicine since the COVID-19 pandemic.

Regarding the number of approvals in the U.S. and Europe, Europe saw an increase of one product from last year, while for the U.S., both the total number of approved products and the number of NMEs were below the 2023 level. As for the number of NMEs that received special regulatory action, similar to the trend in the overall number of NMEs, the overall number of NMEs in Japan and Europe increased compared to 2023, while the number of NMEs in the U.S. decreased. In Japan, while the number of NMEs approved under priority review (including orphan drugs) was 20, the number of NMEs under expedited review was 3, and the number of NMEs under the pioneer drug designation system and the conditional approval system were both zero, continuing from the previous year. The ratio of items receiving special measures indicates that a large proportion of items in the U.S. are designated, while a wide range of systems are utilized in Europe. In Japan, while various special measures comparable to those in Europe and the U.S. have been designed and implemented, the number of designated products indicates that the systems are not being fully utilized.

The review period for all approved items and NMEs was similar to the average, ranging from 10 to 15 months in each region. The review period analyzed in this report is 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 Japanese, US, and European regulatory authorities, and includes the time required to respond to inquiries from the authorities. In the analysis of this report, the standard deviation of the review period in Japan in 2024 is very small, and the median review period is the smallest among Japan, the U.S., and Europe. In the U.S., where many cases receive first-in-the-world approval, the time from application to approval may be longer, but the review period in Japan was shorter than that in Europe and Japan, where many cases are filed in the second or third position. Looking at the review period for NME items that received special regulatory measures, it can be said that the review period for priority review items in Japan was reduced to the same level as the period for special measures items in the U.S. and Europe (about 8 months). On the other hand, the review period for NMEs in Japan also differed from that for priority review items by about 2 to 3 months, and in comparison with the review periods for NMEs in the U.S. and Europe, the approval period was about 1 to 3 months shorter. In addition, despite the fact that the number of NMEs in 2024 was the highest in the past 10 years, the period of the study, there was no impact in the direction of extending the review period. In Japan, the review period for special measures is becoming shorter than that in the U.S. and Europe. In addition, the fact that the review period for regular review is shorter than that in the U.S. and Europe, and is expected to be completed within the target period set by the ^{authorities14)}, increases the predictability of the development timeline for the launch of a new drug. This is an excellent feature of Japan's review system, as it increases the predictability of the development timeline for new drug launches.

In the U.S., the number of newly approved regenerative medicine products in 2024 was 10, a sharp increase from the previous year. On the other hand, Japan has one product and Europe has two products, which raises concerns about the delay in development in Japan. The regulation stipulates that a person who intends to conduct a clinical trial on processed cells that are expected to become a regenerative medicine product must submit a notification of the clinical trial ^plan15).

Figure 8 shows the annual trend of notifications of clinical trial plans. Although the meaning of this trend is not beyond the realm of speculation, it can be said to indicate the severity of regenerative medicine product development in Japan. It is hoped that measures will be taken to resolve various issues specific to regenerative medical products.

The products approved in Japan in 2024 are those to which the conditional and time-limited approval for regenerative medical products applies, bringing the total number of products to which conditional and time-limited approval has been applied to date to five. The conditional and time-limited approval system for regenerative medical products is an approval ^system16) established for the purpose of early delivery of products to patients awaiting treatment, whereby approval is granted to regenerative medical products whose safety has been confirmed and efficacy is "presumed", subject to certain conditions such as post-marketing surveillance and a time limit of up to seven years in principle. The approval is granted to regenerative medical products for which safety has been confirmed and efficacy is "presumed. In 2024, the withdrawal of approval was approved for two of the products under this system. Although formal applications for approval were filed for both products when they reached the expiration date, approval was withdrawn for one product ^{due to the} fact that the domestic Phase III clinical trial results could not be reproduced in the post-marketing ^{surveillance17)}, and for the other product, as a result of deliberations by the Regenerative Medicine Product and Biologic Technology Subcommittee on the results of the drug use-results survey, etc., the conditions and the As a result, it was determined that the product did not meet the performance criteria set at the time of approval with conditions ^and time limits, and that it was not appropriate to formally approve the ^{product18, 19) ,} leading to the withdrawal of approval. While these cases demonstrated that the "approval system with conditions and time limits" was functioning properly, they also highlighted multiple practical issues in the social implementation of innovative technologies, including case collection, study design, efficacy verification, accountability to the medical community, etc., and insurance coverage. In response to this case, the MHLW issued the "Guidance on Conditional and Expiration Date Approval for Regenerative Medicine Products and Subsequent Efficacy Evaluation Plans," with the aim of enhancing predictability in the application of the conditional and expiration date approval system and contributing to further promotion of development of regenerative medicine ^products20). The guidance also indicates the direction to deepen the discussion on how the insurance coverage should be toward the next revision of ^{reimbursement21)}.

This experience reaffirms the importance of efficacy verification and provides important suggestions for reconsidering ethical considerations and information disclosure in the future development and approval process. However, this case should not be used as a reason to avoid the use of special measures in Japan. Rather, the lessons learned should be appropriately reflected in the design and operation of the system. In other words, a major challenge for the future is to refine the design of the system to enable both the early provision of innovative medical care and the assurance of public trust.

Conclusion

In 2024, Japan recorded the highest number of NME approvals ever, especially in the areas of rare diseases and pediatric indications. In addition, the review period remained the shortest and most stable in Japan, the U.S., and Europe, confirming that the environment is becoming more predictable for new drug development. On the other hand, the limited use of the special measures system and the cases of withdrawal of approval for regenerative medicine products revealed issues in the operation of the system. However, these are not negatives of the system itself, but rather valuable experiences that will lead to improvements in the future. In order to achieve both early provision of innovative medical care and scientific and ethical relevance, industry, government, and academia must work together to refine the design of the system and promote its transparent operation. In order for Japan to continue to be an important center for international new drug development, we hope that the findings of this paper will be applied to future discussions and initiatives.

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