What’s new for the clinical technical requirements of the innovative drugs marketed overseas but not in China?
October 14, 2020
By Jianqing Chang, Vice President of Drug Regulatory Policy, Tigermed Co., Ltd.
To accelerate the R&D process and marketing authorization of both innovative drugs and generic drugs marketed overseas but not in China, in accordance with the Drug Registration Regulations became effective in July 2020 and referring to the Technical Guidelines for Acceptance of Overseas Drug Clinical Trial Data released in July 2018, following the draft for public comments released in April 2020, a few days ago, the Center for Drug Evaluation in China issued the Clinical Technical Requirements for Marketing Authorization of Drugs Marketed Overseas but not in China.
The technical requirements apply to 1) innovative chemical drugs and therapeutic biological products marketed overseas but not in China and, 2) local or overseas generic chemical drugs.
The clinical technical requirements for drugs marketed overseas and not in China should be determined by the basic logics of clinical evaluation, and based on the benefits/risk assessment of Chinese patients, after the full evaluation of the clinical needs of Chinese patients, the clinical safety and efficacy, and, the impact of the ethnic factors.
Clinical needs assessment
- The analysis should include the epidemiology, severity and prognosis of the intended indications in China, the existing treatments and their limitations, and the clear comparative advantages of the drug over the existing treatments in China
- For the drugs used for the treatment of critical and rare diseases that lack effective treatment in the clinic, to address the availability of medicines for the public, the encouraging policy is taken for review and approval.
Efficacy and safety evaluation
According to the technical requirements of the National Medical Products Administration, the scientific evaluation is to be carried out to evaluate the drug efficacy and safety.
- Clarify the source of clinical data, mainly including two parts, the clinical trial data used for registration and the post-marketing clinical data. At the same time, close attention shall be paid to the dynamic evaluation of the originators by the foreign regulatory agencies.
- Evaluate the quality of overseas clinical trials GCP must be followed. The site inspection findings by the regulatory agencies of the referring countries might be referred. The site inspection by the Chinese drug regulatory agency may be conducted based on the risk assessment.
- Understand the characteristics of biopharmaceutics and clinical pharmacology. ICH E5 and ICH E17 shall be referred for the evaluation of the racial differences in PK and / or PD might exist among the Chinese patients and oversea trial population.
- According to the current efficacy and safety evaluation standards, it is justified to have the systematic review of overseas clinical trial data and post-marketing data to determine the overall efficacy and safety of the study drug and assess whether the benefits outweigh the risks among the general population.
Ethnic sensitivity analysis shall focus on the safety and efficacy impact that might be caused by the differences of PK and or PD between the Chinese patient population and the overseas population.
On the basis that the clinical data of the originator is sufficient to support the benefits of the drug used in the overall population outweigh the risks, the review decision should be made based on the data analysis of the impact of ethnic factors between the Chinese patients and foreign population.
For the clinical trials requirements of originators marketed overseas, simultaneous early development in China is encouraged to carry out human PK, PD, PK / PD, efficacy and safety research, such as MRCT with the same clinical trial design and conduction conditions. All these systematic trials will help to obtain the direct evidence of the complete evidence chain related to the ethnic factors, to compare and analyze the relationship of dose-exposure-effects, efficacy and safety between Chinese patient population and the global overall patient population so as to weigh comprehensively the clinical benefit / risk assessment of Chinese patients. There might be three major situations.
- Safe and effective without racial sensitivity. If the drug is evaluated safe and effective and has no racial sensitivity, the exemption of clinical trials in China may be considered. For global data that already have PK, and / or PD, efficacy and safety data of Chinese population, if the analysis could confirm that the benefits for Chinese patients outweigh the risks, the registration may be granted directly.
- Safe and effective but lack of racial sensitivity data or with racial sensitivity. After evaluation, If the drug is safe and effective but racial sensitivity data is not available or the existing data suggests racial sensitivity, bridging studies shall be conducted.
- Insufficient safety and efficacy data. If the safety and efficacy data of the drug are insufficient, the necessary exploratory and confirmatory clinical trials should be considered in accordance with the technical requirements of the new drug.
- If there is evidence to prove that the drug is ineffective or with serious safety concern, no recommendation is given to conduct clinical trials in China.
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