What is the speed of the listing application review?

Analysis of the implementation of 21 Category 1 new drugs included in the priority review and approval process: What factors depend on the speed?

Recently, the Center for Drug Evaluation of the State Drug Administration has publicly solicited opinions on the "Center for Drug Evaluation to Accelerate the Review of Marketing Applications for Innovative Drugs (Trial)" (hereinafter referred to as the "Working Procedures")
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This "Working Procedure" is mainly applicable to innovative drugs included in the breakthrough therapy drug program, and makes relevant requirements for the review time limit, working procedures and working requirements of innovative drugs within the scope of application

According to the "Administrative Measures for Drug Registration", the breakthrough therapy drug procedure is one of the procedures for accelerated marketing registration of drugs, but there is no clear time limit for review
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The consultation draft of the "Working Procedures" proposes that the review time limit shall be set at 130 working days with reference to the time limit for priority review varieties

Accelerating the review of innovative drug marketing applications is key to encouraging research and creation of new drugs and meeting clinical needs
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At present, on the CDE official website, a total of 93 varieties have been included in the list of breakthrough therapy varieties, all of which are still in the clinical stage
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Therefore, there is no practice data for "marketing application review" for innovative drugs under the breakthrough therapy drug program

So, what is the equivalent speed of the 130-working-day time limit set in the "Working Procedures" draft for comments? Let's take a look at the implementation of another drug accelerated marketing registration process - the priority review and approval process
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The fastest time to complete the certification is less than 200 days, where is the "fast"?

In 2021, a total of 21 Class 1 new drugs will be included in the priority review and approval process.

Let’s take a look at how long the marketing application review and approval process of these drugs took

On the whole, from the time when the marketing application "entered the CDE review center" to the "certificate preparation - approval has been issued", the shortest review and approval process was CStone's pratinib capsules, which only took 198 days
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Where is Pratinib Capsule Fast? Although it is not clear about the communication between CStone and CDE, only from the records of key time points in its review and approval process, its "fastness" is at least reflected in the following aspects:

① Fast approval of applications included in the priority review and approval process

First of all, the application for pratinib to be included in the priority review and approval process was passed quickly, and it entered the CDE review center earlier than the marketing application
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The application date of the priority review and approval process for pratinib capsules was August 21, 2020, and the announcement was made five days later, that is, August 26, 2020

Of course, there are many people who go early and fast at this level, such as Shunjian Bio's Orebatinib Tablets
.

② did not enter the supplementary information task sequence

Secondly, among these 21 drugs, only 2 drugs did not enter the task sequence of supplementary information, and pratinib capsule is one of them
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Pratinib capsules soon entered the NMPA approval process after the three major professional reviews of pharmacology and toxicology, clinical and pharmacy of the new report task were completed

"Slow" reason? Supplementary information is an important "threshold"

Looking at the 21 class 1 new drugs that have been included in the priority review and approval process, no one has gone more smoothly than pratinib capsules
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So, where are other new drugs "slow"?

Supplementary information is definitely one of the most important "thresholds"
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As mentioned earlier, only 2 of the 21 drugs did not enter the task sequence of supplementary information, except for Pratinib Capsules, which is the second domestic CAR-T product, Ruiki Aurenzai Injection
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However, because the drug regulatory authorities are still very cautious about cellular immunotherapy products, Ruiki Orenza injection, like the first domestic CAR-T product Akirenza injection, has completed the pharmacology and toxicology, clinical, After the review of the three majors of pharmacy, it took several months to enter the NMPA approval process

The other 19 drugs have all gone through the process of re-evaluation after supplementary information
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Once additional information is needed, it is difficult to get up quickly
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Of course, due to the different difficulty and difficulty of the materials that need to be supplemented, the time required for each drug to complete the supplementation of these materials and re-enter the review is different
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Among these 19 drugs, in terms of the time interval from completing the first round of three major professional reviews to entering the task sequence for supplementary information, the shortest is vedicitumab for injection, which takes about one month, and the longest is about 17 Months, most medicines this process takes 2 to 3 months
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The difference in review time after entering the supplementary information task sequence is larger than that of the first round of review
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The short time is 1-2 months to complete the review, and the slow one takes about a year (from the perspective of the status change time, it may have experienced more than one supplementary information)
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Is it really fast to be included in priority review and approval?

For this issue, the author did not do a large range of statistics
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However, judging from the category 1 new drugs approved for marketing in 2021, the final marketing application for drugs included in the priority review and approval process is not necessarily faster than that for drugs that have not entered this process
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Among the 33 Class 1 new drugs approved for marketing in 2021, the 21 drugs included in the priority review and approval process have experienced an average of 528 days, while the other 12 drugs experienced an average of 459 days
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If only the first round of review is counted, the 21 drugs included in the priority review and approval process have experienced an average of 149 working days from the time of “entering the new reporting task sequence” to the completion of the three major professional reviews, while the other 12 drugs It took an average of 146 working days
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It is worth noting that not all of the 21 drugs were included in the priority review and approval process as soon as they entered the CDE
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Some drugs start to apply for inclusion in the priority review and approval process before the marketing application has entered the CDE, and some are applied for a long time after the marketing application has entered the CDE review center
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The time interval from application to inclusion also has a length
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Therefore, if these drugs were included in the priority review and approval process, the first round of review took an average of 101 working days to the latest completion time of the three major professional reviews
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But even so, inclusion in the priority review approval process is really not necessarily faster than not inclusion
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Although there are pratinib capsules that complete the whole process in 198 days, there are also many drugs that require repeated communication with CDE, supplementary information, or even secondary supplemental information
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Those who were not included in the priority review and approval process also passed the review quickly
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Among the 12 new drugs approved in 2021 that were not included in the priority review and approval process, half of them completed the entire review and approval process in about a year, and only 2 drugs took more than 2 years
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After the listing application has been reviewed, how can I get up quickly?

So, how can the listing application be reviewed quickly? The answer to this question may be in the drafting instructions of the "Working Procedures" draft for comments - "early intervention, research and review linkage, rolling submission, inspection and inspection first"!

This is not only for the review team, but also for the applicant
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The research and clinical practice are solid, the early communication is thorough, and the materials are well prepared, and there is less possibility of "rework"
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That's how it really speeds up!

This content is original for the media platform of "Medical Economic News"
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