Changes during the China drug registration shall take certain follow-up actions according to the newly implemented “Working procedures for changes during the drug registration application review (Interim)”. The working procedures were announced by the China Center for Drug Evaluation (CDE) on November 11, 2022, and came into effect immediately.
Scope and basic requirements
During the review of the drug registration application,
- If there are any major changes that may affect the drug’s safety, efficacy and quality control, the applicant shall withdraw the original application first before preparing for application resubmission, including carrying out further research for supplementary information. This set of working procedures applies to other changes occurred during the technical review of clinical trial applications, registration applications, supplemental applications, overseas re-registration applications, etc. for drugs.
- The change(s) requested by the applicant or the market authorization holder (MAH) shall not affect the technical review of the originally declared items.
- Applicants are encouraged to notify the CDE as early as possible upon confirmation of change(s) occurred.
When notifying the CDE about a major change, the applicants shall bear in mind that:
- The fee paid for the original application is non-refundable.
- The declaration package submitted for the original application will be destroyed by the CDE and no longer be available for the resubmitted application.
Implemented on July 1, 2020, the “Provisions of Drug Registration” addresses the management of changes for drugs in China in separate phases:
- Changes during clinical trials
- Changes during application review
- Changes after obtaining market approval
According to the working procedures, the differences between the three is summarized in the following table：
|Changes during clinical trials
|Level of impact towards safety
|Changes during application review
|Major or minor changes
|Changes after market approval
|Level of impact towards safety, efficacy and quality control
Changes during clinical trials
- If there is a significant safety issue, a supplemental application for change(s) shall suffice.
- If there is no impact towards safety, submission of a development safety update report (DSUR) during development shall suffice.
Changes during application review
- For major changes that may affect the drug’s safety, efficacy and quality control, the MAH or applicant will need to withdraw the original application, and resubmit the application in the form of an official document, otherwise, a supplemental application shall suffice with the CDE’s confirmation for minor changes.
- For applicant information updates, the MAH or applicant shall notify the CDE as early as possible and submit the updated information together.
Changes after market approval
- The MAH should refer to the separate “Provisions for Change Management of Post-approval Drugs (Interim)” for the implementation details that came into effect on January 12, 2021.
- For major changes, the MAH shall submit a supplemental application to the CDE.
- For medium changes, the MAH shall report to the CDA or provincial medical products administration (MPA) for filing the record.
- For minor changes, the MAH should address the management of changes in the annual report.
A separate work procedures update was also issued on November 16, 2022, by CDE called Administrative Rules on Stopping and Resuming the Time Clock for Drug Review. It makes clear that the relevant time periods for application review is paused when CDE asks applicants to submit supplemental documents. The clock will continue when the required documents are submitted to CDE.