Innovative drugs: obtain implied clinical license, please pay attention to ICH-E series

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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https://

Figure 1.

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

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.

(Note: E13 has not yet been announced by the CDE-ICH Work Office)

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Figure 2.

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.

Figure 2.

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➣ "E2F: Security Update Report During R&D"

The Development Safety Update Report during R&D, or DSUR for short, aims to provide a unified standard for the regular reporting of drugs in the research and development stage (including drugs that have been marketed but are still under further research) in the ICH region; the United States and the European Union The regulatory agency believes 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

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)

Check whether the information obtained by the sponsor during the reporting period is consistent with the original safety information of the investigational drug;

Describe new safety issues that may affect the protection of clinical trial subjects;

Summarize current awareness and treatment 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 range is shown in the following table:

Table 3.
1 DSUR scope and related content requirements

➣ "E2F: Example of Security Update Report During R&D"

ICH-E2F, DSUR example for species ZB3579 tranche 4 annual report summarizing the safety data received by Zoboryn Pharmaceuticals from January 1, 2009 to December 31, 2009
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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 into the ZB3579 clinical development program, of which about 2900 subjects took ZB3579;

A retrospective analysis of data from a recently completed Phase II dose-ranging trial to identify adverse reactions that may be related to ZB3579;

A recently completed 12-month study in dogs suggested mild dose-related hepatic inflammatory changes;

Three cases of pancreatitis were reported in the clinical development program;

Hepatotoxicity, pancreatitis, and severe skin reactions are identified as important potential risks that require close monitoring 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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Table 3.
2 Catalogue of safety update reports during research and development - appendix content

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Summary

The above is the plane content of the ICH-E series/E1~E18/E2/E2F.
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When the sponsor gets an IND, the clinical trial is usually the most hoped to advance, 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.
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refer to:

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