Ten-year road—from 2011 to 2021, the trend analysis of new drug review and approval in China

● 2.
1 Comparison of the review and approval time of all new drugs

As shown in Figure 2, the NDA review and approval time from 2017 to 2021 was the shortest (median time 15.
4 months), compared with 2011-2013 (median time 22.
1 months) and 2014-2016 (median time 31.
5 months), the speed of review and approval was significantly accelerated and the approval time was significantly shortened
.
From 2017 to 2021, the median NDA review and approval time for small molecule drugs, biological products and vaccines was 15.
7, 14.
2 and 22.
0 months, respectively, and all of them were shorter than the time required for review and approval from 2011 to 2016, and the difference was statistically significant
.
The shortened approval time provides direct evidence
of the initial positive impact of regulatory policy reform.
Under the new regulatory system, with the approval of more new drugs, it is expected that the NDA review time limit in China will be further shortened
.

Figure 2 Time required for approval of new drugs approved in China from 2011 to 2021 (time from new drug application to approval of the first indication)

**p<0.
01；***p<0.
001

● 2.
2 Comparison of the review and approval time of imported and domestic products

As shown in Figure 3, in the above three time periods, the median NDA review and approval time of imported drugs is shorter than that of domestic drugs
.
In 2011-2013 and 2014-2016, 19.
9 vs.
respectively 32.
5 months (< 0.
001) and 10.
0 vs 34.
1 months (p<0.
01), the difference was statistically significant, but in 2017-2021, the difference was no longer statistically significant (14.
5 vs="" p="">0.
05）
。 Although the NDA review and approval time of domestic and imported drugs has been shortened in recent years, the time limit for domestic drugs has been shortened even more
.
From 2017 to 2021, the difference between domestic drugs and imported drugs in NDA review and approval was only 2.
2 months
.
This also provides additional evidence
of the positive impact of optimizing the evaluation process.

Figure 3 From 2011 to 2021, the time required for NDA review and approval of domestic drugs and imported drugs

**p<0.
01；***p<0.
001

● 2.
3 The impact of the number of supplements on the time limit for review and approval

Studies have shown that the more supplements are issued, the longer it takes for review and approval (11.
7, one round vs 20.
6 months, two or more rounds, p<0.
001).

However, in the near future from 2017 to 2021, the time required for review and approval has become less
affected by the number of supplementary issuances.

● 2.
4 Analysis of the review and approval time limit of priority review (PR) and clinical urgent overseas new drugs (UNOD).

Excluding deviating varieties, 257 were included in the analysis, including 156 PR, 25 UNOD, 9 PR/UNOD dual designations and 67 non-certifications
.
From 2017 to 2021, the median time required for review and approval of varieties included in PR, UNOD and not included in PR and UNOD was 14.
4 months, 9.
6 months and 22.
1 months, respectively (Figure 4).

Compared with the standard review time, the review and approval time of varieties incorporating PR and UNOD was significantly shortened, and the median NDA approval time of UNOD was also statistically shorter than that of PR (p<0.
01).

PR、 Accelerated pathways such as conditional approval and breakthrough therapy are important regulatory pathways to bring drugs for the treatment of serious life-threatening diseases to patients as soon as possible, and China first implemented a clear PR procedure in 2016, and then gradually improved, together with conditional approval, breakthrough therapy and special approval, it has become a formal accelerated channel
.
With the exception of the special approval process, the other three accelerated procedures are very similar to
the FDA's accelerated pathway.
The key feature of PR is the reduction of the NDA review time limit to 155 working days
.

The UNOD approval process is a unique policy formulated in November 2018 in China, which designates new drugs approved in the United States, the European Union and Japan in the past 10 years, and is considered to be urgently needed for clinical purposes in China, and these drugs may be quickly approved
based on foreign clinical data.
From November 2018 to November 2020, the Center for Drug Review designated 81, of which 51 drugs had been approved
by the end of 2021.

● 2.
5 Analysis of the review and approval time limit of antitumor drugs and non-tumor drugs

Studies have shown that for antineoplastic drugs included in the PR program, the time required for NDA review and approval is significantly shorter than that for non-oncology drugs included in the PR program (12.
8 months vs 16.
2 months), and the antineoplastic drugs that obtained UNOD were not significantly different but shortened compared with non-antineoplastic drugs for UNOD (see Figure 5).

Cancer is a disease that affects millions of lives, the timely approval of new anti-tumor drugs can provide patients with new therapeutic hope, and regulatory authorities continue to strive to quickly approve new anti-tumor drugs
.
In November 2021, the Center for Drug Review issued the Guidelines for Clinical R&D of Antitumor Drugs Guided by Clinical Value, which is the first patient-centered drug R&D guideline in China, and also reflects the efforts
of regulatory agencies to accelerate review and improve access to oncology patients.

Figure 4 Comparison of the time required for accelerated review approval and routine procedures in China from 2017 to 2021

Figure 5 From 2017 to 2021, the time required for NDA review and approval of anti-tumor new drugs and non-anti-tumor new drugs obtained PR or UNOD was compared

● 2.
6 Miscellaneous

2.
6.
1 There was no significant difference
in the time limit for review and approval of rare disease drugs and non-rare disease drugs.

2.
6.
2 The trend of imported new drugs lagging behind in China

The analysis results show that in 2011-2013, 2014-2016 and 2017-2021, compared with the time when the imported drug was first approved overseas, the median lag time of imported new drugs approved in China was 5.
1 years, 7.
2 years and 5.
0 years, respectively, with no significant difference, but the lag time tended to
shorten 。 In 2018, the 60-day tacit consent system was adopted for clinical trial applications, and the State Medical Products Administration organized the formulation of the Technical Guidelines for Accepting Overseas Clinical Trial Data of Drugs, and in 2019, ICH E17 was officially adopted in China, and these changes in the regulatory environment have led more multinational pharmaceutical companies to include China in international multi-center trials
.
However, in order to fully solve the problem of China's drug lagging on the market, it still takes a lot of time and effort
.
China's new regulatory environment after reform and the emergence of Chinese regulatory bodies as ICH members provide opportunities
for the simultaneous global development of drugs and the convergence of regulatory environments.
Multinational pharmaceutical companies will benefit from the inclusion of China in their early-stage global development strategies that can shorten the late-stage clinical development time and will have the opportunity to file marketing applications simultaneously in multiple countries, including China
.

Summary and outlook