Innovative drugs: Please pay attention to the ICH-E series to obtain an implied clinical license

Since China started the consistency evaluation of generic drugs and large-scale centralized procurement, innovative drugs have ushered in the catalytic development under the general environment
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The number of newly developed Class 1 chemical drugs has also increased from 100 in 2019 to nearly 250 in 2021
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After the company obtains the IND implied license, it will naturally carry out a lot of work, mainly clinical, and simultaneously carry out certain non-clinical and pharmaceutical work
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An important part "E" of ICH will be associated here, and now the "ICH-E series/E1-E18/E2/E2F" document of this chain will be interpreted and introduced
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01What is the E series file? The so-called ICH-E refers to the guiding principles related to Efficacy under the ICH system.
In addition to E ~ effectiveness, there are also Q ~ quality, S ~ safety, M ~ multi-disciplinary; the total number of guiding principles is close to 150, and China's CDE -The ICH department now has nearly 120 translations
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For details, please refer to the official website - https://
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Specifically speaking about ICH-E, the content of this part, for those engaged in the pharmaceutical industry, the degree of exposure will be much less than that of Q and
M.
Although the content of E seems to be understandable from the surface, but at the practical level, it is often confusing, especially some materials that need to be presented in front of CDE teachers
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Let’s take a closer look at the series of translations of the guidelines issued by the ICH work office on the CDE official website.
From E1 to E18 (without E13), there are 31 guidelines in total, of which the larger parts include E2 pharmacovigilance, E6 drug clinical trial management Standards, E9 statistical principles of clinical trials,
etc.
The details are shown in the following table: 02E2&E2F Specific content E2, pharmacovigilance, there are many things to be said here, the most worth mentioning is "Pharmacovigilance Quality Management Practice"
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In May 2021, the State Food and Drug Administration issued an announcement on the "Quality Management Practice for Pharmacovigilance" (No.
65 of 2021), which will be officially implemented on December 1, 2021.
The responsible persons are the drug marketing license holder and drug registration application People, so it is also closely related to the drug marketing authorization holder system
.
Further look at the ICH documents on pharmacovigilance, specifically E2A, E2B, E2C, E2D, E2E and E2F, which define safety data management, case reports, risk assessment, etc.
, and most specifically involve innovative drug IND- Documents worked during NDA and presented to CDE teachers, mainly for study and research on E2F
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What information does the 03E2F file contain? E2F, there are mainly two guidance documents, namely "E2F: Security Update Report During Research and Development" and "E2F: Example of Security Update Report During Research and Development", these two documents will be introduced below
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?"E2F: Safety Update Report During Research and Development" The safety update report during research and development, the English is Development Safety update Report, referred to as DSUR, is designed for drugs in the research and development stage in the ICH region (including drugs that have been marketed but are still under further research) ) provides a uniform standard for regular reporting; US and EU regulators believe that the DSUR submitted annually can meet existing national and regional requirements and can replace the current US IND annual report and EU annual safety report
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This shows that the DSUR report is extremely important
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The main purpose of DSUR: is to conduct a comprehensive and in-depth annual review and assessment of the safety information collected during the reporting period related to investigational drugs (whether marketed or not)
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Completed by: Checking whether the information obtained by the sponsor during the reporting period is consistent with the original safety information of the investigational drug; Describing new safety issues that may affect the protection of clinical trial subjects; Recognition and management of identified and potential risks; updates on clinical research/development program status and findings
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All safety issues identified during the reporting period should be discussed in the DSUR; however, the DSUR should not be used as the initial reporting route for new important safety information, nor should it be used as the route for the detection of new safety issues
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The specific DSUR scope is shown in the following table: ?"E2F: Example of Safety Update Report During Research and Development" ICH-E2F, the DSUR example is the 4th annual report of the variety ZB3579, which summarizes Zoboryn Pharmaceuticals from January 1, 2009 to Safety data received on December 31, 2009
.
PS: ZB3579 is an α-6-acetylhydrogentransferase inhibitor, developed for the treatment of gastroesophageal reflux disease (GERD), oral tablet 10-20mg, once daily; a total of 3800 patients and healthy volunteers were recruited of patients entered the ZB3579 clinical development program, in which approximately 2,900 subjects received ZB3579; A retrospective analysis of data from a recently completed Phase II dose-ranging trial identified adverse reactions that may be related to ZB3579; A recently completed study in dogs A 12-month in vivo study suggested mild dose-related hepatic inflammatory changes; 3 cases of pancreatitis were reported in the clinical development program; hepatotoxicity, pancreatitis, and severe skin reactions were identified as significant potential risks, requiring To be closely monitored during the Phase III clinical program; the potential risk associated with ZB3579 can be justified by the likely expected benefit in GERD patients, given the risk minimization measures that have been taken for patients participating in the Phase III clinical trial
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04 Summary The above is the flat content of the ICH-E series/E1~E18/E2/E2F.
.
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When the sponsor gets an IND, the most likely thing to advance is the clinical trial, which is accompanied by the annual DSUR
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The content of the report not only reflects the progress of the project, but also reflects the rational design and control of the project by the sponsor, which is difficult to learn and use through some literature or a report.
Insights into the project
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Fortunately, with the increase in the number of new drug application projects each year, more practitioners are naturally required to participate in it; then, the overall level of new drug development practitioners in China will naturally increase steadily; on the contrary, it will also better promote future new drugs.
item
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References: 1.
E2F: Development Safety update Report.
CDE official website 2.
Example DSUR – Phase III Investigational Drug.
CDE official website 3.
《Quality Management Practice for Pharmacovigilance》.
NMPA 2021