On June 21st, the National Medical Products Administration (NMPA), to which the Center for Drug Evaluation (CDE) is affiliated, issued the China Drug Evaluation Report 2020.1
This article collects key information from the report to inform global pharmaceutical companies of the drug approvals in China last year and the approval tendency in the past few years.
The following passage is Part 2 of the article.
5. Problems with Applications and Disapproval Reasons
In 2020, CDE disapproved 367 applications for TCMs, chemical drugs and biological products due to reasons including:
The application data has insufficient evidence for proving drug safety, efficacy and quality controllability;
Failing to submit supplementary materials within limited time.
The main rejection reasons for different types of applications are as follows.
5.1 New Drug Application
5.1.1 IND applications
Without proposing pre-IND meeting
The submitted application is found to have a serious lack of data, and the applicant fails to complete the supplemental research and submit the supplemental data within time limits.
Insufficient evidence for supporting the purpose of drug development, and deficient feasibility of developing the chemical entity into a drug product.
Existing research result suggests that the drug's efficacy is low whereas toxicity is high, so the risk-benefit ratio is unfavourable for clinical use;
The clinical development violates the basic principles of clinical diagnosis, treatment and medication;
The existing CMC and pre-clinical researches fail to meet the requirements for starting a clinical trial.
The submitted data is insufficient to support clinical trials or to ensure volunteers' safety.
The overall clinical trial design is seriously flawed, and the risk control measures are insufficient;
Insufficiency in non-clinical research data for combination therapy drugs;
Insufficient data for an individual vaccine in combination vaccines, or the individual vaccine is inconsistent with immunization procedures.
Existing research data cannot prove the drug's safety and efficacy; the deficiency in quality control and management.
The design of pivotal clinical trials is seriously flawed, so the applicant cannot obtain objective and compelling evidence to prove the drug's safety and efficacy;
There are major defects with CMC research studies so that the applicant fails to prove the drug quality can be well-controlled.
Inconsistent experiment drugs are used in different development phases ;
Clinical trial data found to be inauthentic during the inspection for candidate drugs apply for registration.
5.2 ANDA applications
Unsuitable drug development target.
The RLD has been withdrawn from the market, and there is another drugs on the market that are safer and able to serve clinical needs.
The submitted data cannot prove the consistency between the ANDA and the reference listed drug (RLD).
The re-review finds the sample drug does not meet the standard, or there are major defects in analytical methods;
Human bioequivalence study shows that test product is not bioequivalent to the RLD;
Fail to meet the marketing standards due to unfavourable result of the sample drug's stability test, wrong selection of starting materials for active pharmaceutical ingredients (APIs), etc;
Regulatory violations resulting from illegal sources of the chosen API for the ANDA.
5.3 Supplemental Applications
The supplemental data cannot prove that the change is scientific and reasonable, so there is no convincing reason for the change.
The change will induce major alterations to the drug substance;
The change to the drug package insert does not meet the technical requirements for insert writing.
The existing research data cannot ensure the drug, after the change, will still be safe, effective and controllable in quality;
Biased supporting literature for changes, or insufficient data for proving clinical safety and efficacy.
5.4 Other Applications
Lack of similarity comparison data for the biosimilar product, and defects in the selection of RLDs for efficacy comparison studies;
Insufficient pre-clinical research data for starting clinical trials.
Research data does not meet the standard of international multicenter clinical trials or China's basic technical requirements for natural medicines.