Pharmaceutical Industry at a Glance Comparison of New Drug Approval Status and Examination Periods in Japan, the U.S. and Europe

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The Office of Pharmaceutical Industry Research Chie Yoshiura, Senior Researcher
The Office of Pharmaceutical Industry Research Hiroshi Azuma, Senior Researcher

Summary

The number of new drug items approved in Japan, the U.S., and Europe in 2022 and their review periods were investigated, taking into account the impact of special measures on pharmaceutical affairs in each region. 174 new drugs were approved in Japan in 2022, with 52 NMEs, the largest number of all approved products in Japan. The median review period was 9.4 months for all approved products and 10.8 months for NMEs, which was similar to that of previous years, but Japan had the smallest median review period compared to the U.S. and Europe. The number of approvals for regenerative medicine products has been increasing in Japan, the U.S., and Europe in recent years, and the number of global products has also been increasing.

1. Introduction

The Office of Pharmaceutical Industry Research In the following section, we will provide a continuous review of the approval information and review periods for pharmaceutical products in Japan, the U.S., and Europe based on the information published by the Pharmaceuticals and Medical Devices Agency (PMDA), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA), respectively, on their respective websites. The PMDA, U.S. Food and Drug Administration (FDA), and European Medicines Agency (EMA) have been continuously collecting and analyzing the information published on their respective ^websites1). OPIR Views and ActionsIn Issue No. 67 ⁽²⁾, we reported a comparison of new drug approval status and review periods in Japan, the U.S., and Europe, focusing on actual approvals in 2021. OPIR Views and ActionsIn Issue No. 68 ^{(3), we} reported the results of our analysis of information on drugs approved in Japan in 2022. In this newsletter, we report on the number of new drugs approved in Japan, the U.S., and Europe in 2022, as well as their review periods.

Survey Methodology

The information published on the respective websites of the PMDA, FDA, and EMA was used to calculate the review period as the period from the date of application for approval 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 for approval to the date of approval. Since there are items with significantly long periods and items with short 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.

In Japan, as in No. 68 ( OPIR Views and Actions), the target drugs were those listed in the "List of New Drugs Approved " ⁴⁾ on the PMDA website, and the number of items was counted for each review report. New Molecular Entity (NME) was counted only if the application was classified as a drug containing a new active ingredient.

In the U.S., New Drug Application (NDA) and Biologic License Application (BLA) listed in "CDER Drug and Biologic Approvals for Calendar Year " ⁵⁾ approved by the FDA Center for Drug Evaluation and Research (CDER) were used. NMEs were included in the "CDER New Molecular Entity (NME) and Original Biologic Approvals Calendar Year". The NMEs included drugs listed in the CDER New Molecular Entity (NME) and Original Biologic Approvals Calendar Year.

The NMEs were those classified as "New active substance".

In addition, as special regulatory measures, priority review, expedited review, orphan drug, pioneer review designation ^system7), and conditional accelerated approval system were applied in Japan, Priority Review, Accelerated Approval, Orphan, Fast Track, and Breakthrough Therapy were applied in the U.S., and Priority Review, Accelerated Approval, Orphan, Fast Track, and Breakthrough Therapy in the U.S., and Accelerated Assessment, Orphan, Conditional Approval, Exceptional Circumstances, and Priority Medicine (PRIME) in Europe. The details of each special regulatory action are summarized in the Supplement.

Results

(1) 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 eight years (2015-2022). In Japan, 174 new drugs were approved in 2022, of which 52 were NMEs. This was the highest number of approvals in the past eight years. In the U.S., 112 products were approved in 2022, including 37 NMEs. In Europe, 164 products were approved in 2022, of which 56 were NMEs. The Office of Pharmaceutical Industry ResearchThe number of NMEs approved in Europe was the second highest after 2021, and the highest number of NMEs ever approved in Europe since the start of the data collection in the U.S. and Japan (see Fig. 1).

(2) Number of approved items that received special measures in pharmaceutical affairs (NME)

We examined the number and percentage of NMEs approved in Japan, the U.S., and Europe over the past five years (2018-2022) that received special regulatory treatment in each region (Figure 2).

OPIR Views and Actions As mentioned in Issue No. 68, of the 52 NMEs approved in Japan in 2022, 21 (40.4%) received priority review (including orphan drugs and the pioneer review designation system), 0 received expedited review (excluding priority review), and 18 (34.6%) received orphan drugs (including the pioneer review designation system), The number of items designated under the Pioneer Review Designation System was 1 (1.9%), and the number of items subject to the Conditional Accelerated Approval System was 0. The percentages of NMEs for priority review and orphan drugs were the same as last year and at the highest level ever. In addition, 7 items (including 2 NMEs) were granted special approval in response to COVID-19, and 1 item was granted emergency approval.

In the U.S., 6 (16.2%) of the 37 NMEs approved in 2022 received Accelerated approval, down from 14 last year, the highest number since 2011. 24 (64.9%) received Priority review and 20 (54.9%) received Orphan designation. The number of Fast Track designated items was 12 (32.4%), and the number of Breakthrough Therapy designated items was 13 (35.1%), the same level as last year.

In Europe, of the 56 NMEs approved in 2022, 5 (8.9%) received Accelerated Assessment, 21 (37.5%) received Orphan designation, and 8 (14.3%) received Conditional approval, Exceptional Circumstances were 7 (12.5%), and 8 (14.3%) were designated PRIME. Last year, the number of Conditional approvals was the highest since 2014, but this number decreased in 2022, while the number of Exceptional Circumstances was the highest since 2014, and the number of PRIME-designated items was the second highest after the nine items in 2020.

(3) Comparison of review periods for new drugs between Japan, the U.S. and Europe

Table 1 compares the review period (in months) of new drugs approved in 2022 in Japan, the U.S., and Europe with that of last year, The median review time for each of the NMEs approved in 2022 was 10.8 months in Japan, 11.0 months in the U.S., and 14.0 months in Europe, with similar median review times in Japan and the U.S.

(4) Review period for items that received special measures by the pharmaceutical affairs bodies

Of the products approved in 2022, those that received special regulatory measures (Japan: Priority Review, Pioneer Review Designation System; the U.S.: Priority Review, Breakthrough Therapy; Europe: Accelerated Assessment, PRIME) aimed at shortening the review period are shown in Table 2. Table 2 shows the items that received priority review (Japan: Priority Review System, USA: Priority Review, Breakthrough Therapy, Europe: Accelerated Assessment, PRIME). In particular, the Priority Review and Designation System, Breakthrough Therapy, and PRIME are systems that aim to further shorten the review period for new drugs with high potential for breakthrough, and to obtain prior intervention from the reviewing authorities on a priority basis. (Supplemental)

In 2022, the number of approved priority review items in Japan was all approved (37 items) and NME (21 items), with a median review period of 8.4 months and 9.1 months, respectively. 31 of the 37 items were approved within 9 months, as per the target set by ^PMDA8). In addition, one NME was approved as a designated product under the Pioneer Review Designation System, achieving the PMDA's target of 6 months for the review period. OPIR Views and ActionsAs mentioned in No. 68, the number of approvals of items under routine review increased in 2022 compared to 2021 due to many approvals of items under public knowledge, but the median review period for routine review was similar to that in 2021.

Regarding the number of approved Priority review-designated products in the U.S. in 2022, the number of all approved products (40) was lower than in 2021, along with NMEs (24). The median and median review times were 8.0 and 8.0 months, respectively, the same as in 2021. The mean review time was 14.5 months and 16.9 months, respectively, an increase from 2021, and the variation in review time (standard deviation) was also large. The review period defined in this paper is from the date of initial application to the date of approval, which is the total period including the time required for resubmission of data by the applicant in addition to the FDA's review period. For 20 of the Priority Review-designated products, the applicant resubmitted data after the start of the review, which is longer than the review period defined in this report (the time required from submission to approval). For Therapy-designated products, 16 products (including 13 NMEs) were approved, with median review times of 11.5 months and 11.0 months, respectively. As in the previous year, the number of designated items was higher compared to the number of items designated for pioneering review in Japan.

In Europe, there were five Accelerated Assessment-designated products (all NMEs) among all approved products, and although the percentage of products that received priority review was smaller than in Japan and the U.S., the median review period for Accelerated Assessment-designated products in 2022 was 8.3 months and The median review time for Accelerated Assessment-designated products in 2022 was 8.3 months, more than four months shorter than that for products that did not receive priority review.

(5) Annual median review period (Japan, US, EU)

Table 3 shows the review period (in months) by year of approval (2000-2022) for drugs approved in Japan, the U.S., and Europe, and Figure 3 shows the annual changes in median review period. For NMEs, the period from 2013 to 2022, after the Japanese review period was significantly shortened, is included in the survey.

The median review period for the entire period covered by the survey was 10.9 months in Japan, 10.1 months in the U.S., and 13.2 months in Europe (Table 3). 2022 maintains the same review period as last year with 9.4 months in Japan, 11.0 months in the U.S., and 12.4 months in Europe, with Japan having the lowest median value. In terms of annual changes, since the significant reduction of the examination period in Japan in 2011, the median examination period has been about 10 months, comparable to that of the U.S. Europe has also shortened its examination period (about 12 months) since 2015.

The median review period for NMEs for the entire survey period was 10.3 months in Japan, 9.7 months in the U.S., and 14.1 months in Europe (Table 4). Although the median review time in the U.S. increased by 3 months compared to 2021, the review times in Japan and Europe remained at the same level as last year (Figure 4).

(6) Comparison of review periods for biopharmaceuticals between Japan, the U.S., and Europe

In recent years, the presence of biopharmaceuticals has been increasing compared to small molecule drugs, and it was reported in the previous report that biopharmaceuticals account for more than half of the top 100 drugs in the pharmaceutical market in terms of percentage of global ^sales10). OPIR Views and ActionsIn Issue No. 67, a comparison of regions was attempted in terms of approval periods and special measures for biopharmaceuticals, based on the hypothesis that biopharmaceuticals are expected to have high efficacy and breakthrough potential due to their high directivity, and that as a result, they are more likely to receive special measures under the Pharmaceutical Affairs Law, and the review period tends to be shorter. The same analysis was conducted for this news.

Table 5 shows the review periods (in months) of biopharmaceuticals approved in Japan, the U.S., and Europe by year of approval (2013-2022) in the NME, and Figure 5 shows the annual changes in median review periods. In Japan, 137 biopharmaceuticals were approved as NMEs in the aggregate year, and the overall median review period was 10.3 months. In particular, 23 items were approved in 2022, following a record high of 24 items in 2021. In the U.S., 115 drugs were approved, and the median review time for the entire aggregate year was 10.1 months. In Europe, 160 products were approved, with a median review time of 13.6 months for the total year. As a comparative reference, Table 6 shows the review period (in months) for non-biopharmaceuticals by year of approval (2013-2022) in the NME. Comparing the median review periods for biopharmaceuticals and non-biopharmaceuticals, the median review periods for biopharmaceuticals in 2022 were similar in Japan (11.4 months and 10.4 months, respectively) and shorter in the US and Europe. The impact of biopharmaceuticals on the review period was small, similar to the results of the previous survey. It can be said that the review period for biopharmaceuticals is expected to be at least as long as that for non-biopharmaceuticals in both Japan, the U.S., and Europe.

(7) Comparison of the number of approvals for regenerative medicine products between Japan, the U.S. and Europe

OPIR Views and Actions In Issue No. 68, we reported on the six regenerative medicine products newly approved in Japan in 2022. As mentioned in the survey methodology, the number of approvals in this report does not include regenerative medicine products, since the Japanese survey covered drugs listed in the "List of New Drugs Approved" on the PMDA's website. In the U.S., the data for drugs listed in the FDA's "CDER Drug and Biologic Approvals for the Calendar Year" were used, so products that are equivalent to regenerative medical products were not included in the scope of this report. On the other hand, for Europe, the data covers drugs approved by the EMA through the central review system and listed in the "European Medicines Agency Annual Reports," and products that are equivalent to regenerative medicine products are also included.

This section reports on the number of approvals in Japan, the U.S., and Europe in recent years for products that are equivalent to regenerative medicine products in Japan. The number of items includes those listed as "approved" by approval/revision, and does not include those listed as "single revision". The period covered was 2015 and after the enforcement of the current Pharmaceutical Affairs Law, which newly defines regenerative medical products. In the U.S., the data were collected for drugs listed in "Approved Cellular and Gene Therapy Products" on the FDA ^website12) in the year when the product was first approved. In Europe, drugs approved by the EMA under the central review system and listed in the "European Medicines Agency Annual Reports" were included, and those with ATMP (Advanced therapy medicinal products) ¹³⁾ designation were included. The data were collected from the "European Medicines Agency Annual Reports".

Figure 6 shows the number of new approvals (2015-2022) for products equivalent to regenerative medicinal products approved in Japan, the U.S., and Europe, and the number of products approved in Japan, the U.S., or Europe in two or more regions as of the end of 2022. In Japan, 15 products were newly approved from 2015 to 2022, including 7 products that were approved in either or both the US and Europe. The product names, year of approval and review period in each pole are shown in Table 7.

Nineteen and 20 products were newly approved in the U.S. and Europe, respectively, from 2015 to 2022, and 12 and 13 products were approved in two or more regions by the end of 2022, respectively. The number of newly approved products in both Japan, the U.S., and Europe is increasing, and the number of global products approved in more than one of the two regions is also increasing. Figure 7 shows the classification of diseases for which regenerative medical products were approved. Antineoplastic agents are the most common, and several products targeting the sensory organs and nervous system have received approval in Japan.

Table 7 compares the approval year and review period of regenerative medical products in Japan with those of the same products in Europe and the United States.

Four of the seven products listed in Table 7 were approved in Japan within one year of the initial approval in the U.S. and Europe. In addition, five of the seven products received approval within 10 months, indicating that the review period for these products can be expected to be completed in a shorter time than in the U.S. and Europe.

Summary and Discussion

This report compiles and compares the number of new drugs approved in Japan, the U.S., and Europe in 2022 and their review periods, based on information published by their respective regulatory authorities.

For the past eight years, the number of approved items in 2022 was high in Japan, the U.S., and Europe, both in terms of the number of all approved items and the number of NMEs. The number of special regulatory actions was also at the same level as last year. In both Japan, the U.S. and Europe, the median review period (median) for items that received special regulatory measures was shorter than the median review period (median) for items that received regular review, indicating that the measures were effective.

The median review period for all items approved in Japan in 2022 was 9.4 months as shown in Table 3, which was the smallest in Japan compared to Europe and the U.S. The standard deviation was also small at 3.6 months. The fact that the review period to obtain approval in Japan is at least as long as that in Europe and the U.S. is considered to be a very important factor in achieving rapid access to new drugs, and we hope that the same level of review time will be maintained in the future. In addition, there were nine special approvals in 2021 in response to COVID-19, and seven special approvals and one emergency approval were also approved in 2022, indicating that the response to the COVID-19 epidemic has become more active and expedited.

^On the other hand, as shown in Table 1, the median review period for products approved in the U.S. in 2022 was 11.0 months for all approved products, which was similar to the average year, but the mean was 19.5 months, with a large standard deviation.) Of the 112 products approved in the U.S. in 2022, 63 (56.3%) were from companies with 10 or fewer products already on the market14) , an increase from 55 (48.2%) of the 114 products approved in 2021. The median and average review periods for products by companies with 10 or fewer products already on the market were 12.0 months and 20.0 months, respectively, which were longer than the median and average review periods for products by other companies (10.0 months and 18.8 months, respectively), suggesting that the large number of approvals by companies with fewer products already on the market may have affected the review period in 2022. In Europe, there is a regulatory support system for small companies, and the success rate of approval applications by these companies more than doubled between 2016 and 2020. ¹⁵⁾ In addition to conventional face-to-face advice and pre-interviews, the PMDA also provides regulatory support mainly to universities, research institutions, and venture companies. The PMDA also provides comprehensive regulatory science consultation and regulatory science strategy consultation services mainly for universities, research institutes, and venture ^companies16).

In the area of special measures for pharmaceutical affairs, there are the Pioneer Review Designation System, Breakthrough Therapy, and PRIME for drugs that are expected to be highly effective against serious diseases, but compared to the number of Breakthrough Therapy and PRIME cases in Europe and the U.S., the number of cases approved under Japan's Pioneer Review Designation System is small. However, the number of approvals under Japan's Pioneer Review Program is small compared to the number of Breakthrough Therapy and PRIME approvals in Europe and the United States. The impact of this on access to highly innovative drugs in Japan has not yet been analyzed, but further efforts may be needed to maintain and improve access to drugs at the same level as in Europe and the U.S., in addition to making maximum use of the current special measures in the pharmaceutical affairs.

Following last year's OPIR Views and ActionsNo. 67, we conducted a survey of biopharmaceuticals by category, and found that the number of items was at a record high level in Japan, the U.S., and Europe, as in the previous year, and the review period was the same regardless of whether a biopharmaceutical was applicable or not. In addition, a comparison was made between Japan, the U.S., and Europe in terms of the approval status of regenerative medical products, as described in OPIR Views and ActionsNo. 68. The number of approvals of regenerative medicine products has been increasing in Japan, the U.S., and Europe in recent years, and the number of global products approved in two or more regions has also been increasing. As shown in Table 7, the review period for each product varied, but there was a trend for the review period in Japan to converge around 10 months. The fact that a certain review period can be expected for biopharmaceuticals, regenerative medicines, and other products, regardless of modality, is considered important in lowering the hurdles to the early launch of innovative drugs. In addition to maintaining the same or faster review process as in the U.S. and Europe, we hope to continue our analysis of this paper in anticipation of more flexible responses to innovative technologies and unforeseen circumstances, such as COVID-19.

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