Tuesday, 24 September 2024 / Published in News, NMPA Registration in China, Pharmaceuticals & DMF

Clinical Trial Requirements Q&A Draft For Comments

China’s Center for Drug Evaluation (CDE) has issued a notice soliciting public opinions on a document titled “Questions and Answers on Clinical Trial Requirements for Drugs Listed Outside China and Not Listed in China (Draft for Comment).” This Q&A focuses on the research, development, and approval of drugs to meet the urgent clinical needs of Chinese patients.

Key Points from the Draft:

The draft addresses common questions concerning the clinical technical requirements for drugs that are listed overseas but not yet listed in China. The questions focus on innovator and generic drugs.

Question 1: How to understand the specific requirements for the exemption from clinical trials mentioned in the notice (No.29, 2020) for innovator drugs listed overseas but not in China ?

Answer:

Definition of “Innovator Drug”: The term “innovator drug” in this context refers to a drug that has completed clinical trials overseas, showing that the benefits for Chinese patients outweigh the risks, without any significant racial influence compared to foreign populations.
If the innovator Drug is Not Listed in China: If the innovator drug is not listed in China but a generic version with the same active ingredient is already available, and sufficient data shows that the benefits outweigh the risks for Chinese patients, this data can be used to support the approval of the innovator drug. This is valid as long as there is no significant racial influence. If racial differences do exist, the application will require further analysis on a case-by-case basis.
Overseas Clinical Data for New Dosage Forms/Combinations: The overseas clinical trial data of new dosage forms, new routes of administration, or new combinations of the drug can be used to fully evaluate its safety and efficacy for Chinese patients.

Question 2: What are the key considerations for adding new indications approved overseas to a domestically marketed drug ?

Answer:

When adding a new indication that has been approved overseas for a drug already marketed in China, the following considerations are critical:

Existing Clinical Data: Data from both domestic and overseas clinical trials should show that the benefits for Chinese patients outweigh the risks, with no significant racial differences.
Foreign Clinical Trial Data: The overseas clinical trial data for the new indication must fully evaluate the drug’s safety and efficacy.
Similarity of Indications: The new indication should share similarities in terms of pathogenesis, pathological changes, therapeutic targets, and drug effects with the already approved indication.
Consistency in Medical Practice: The new indication should align with both domestic and international clinical practices. Any differences in dosage, combination therapies, or disease pathology must be carefully considered, and if necessary, bridging studies should be conducted to account for regional differences.
Supporting Studies: If the cause of the disease, therapeutic practice, or antibiotic resistance differs between regions, additional studies (e.g., in vitro bacteriostatic tests on Chinese clinical isolates) may be required to support the new indication.
Safety Window: The drug should have a wide safety window for the new indication to be considered.

Question 3: Under what circumstances can generic drugs be considered for modified or exempted clinical trials (V(II)1)?

Answer:

Generic drugs may be eligible for modified or exempted clinical trials under the following conditions:

Urgent Clinical Need: Generic drugs for serious, life-threatening diseases or rare conditions, for which there are no effective alternatives in China, may use publicly available clinical data from the innovator drug as supporting evidence. Approval can be considered if the drug is assessed to be safe and effective for Chinese patients, with no significant racial differences.
Pediatric Drugs: For generic drugs already marketed in China, if the innovator drug has been approved for pediatric use overseas, publicly disclosed clinical data from the innovator drug may be used to support the expansion of indications to include pediatric populations in China, provided there are no significant racial factors affecting efficacy or safety.
New Dosage Forms or Combinations: For generic drugs with new dosage forms, new routes of administration, or new combinations that have been approved overseas but not yet in China, publicly available data from the innovator drug can be used to support the registration of the generic drug in China. This is applicable if the same active ingredient has already been marketed in China and there is evidence showing that the benefits for Chinese patients outweigh the risks, with no significant racial influence.

If you would like more details, please contact Cisema.

Key Takeaways for Pharmaceutical Companies:

For pharmaceutical manufacturers with products registered in China, this draft document represents an important step toward clarifying the clinical trial requirements for bringing overseas-marketed drugs to the Chinese market. The ability to leverage existing foreign clinical trial data to meet domestic requirements could expedite the approval process and address urgent patient needs in China.

However, the draft also highlights the complexity involved in evaluating the safety and efficacy of drugs for the Chinese population. Manufacturers should be aware that even when using foreign clinical trial data, thorough documentation and justification will be required to ensure that the data are applicable to Chinese patients.

Recommendations:

Engage with the Public Consultation Process: Pharmaceutical companies are encouraged to review the draft document in detail and provide feedback to the CDE. This is an opportunity to contribute to the regulatory framework that will impact the development and approval of drugs in China.
Prepare Comprehensive Clinical Data: Companies looking to introduce overseas-marketed drugs to China should ensure that they have comprehensive clinical trial data, including an analysis of potential racial factors and the applicability of foreign clinical practices to the Chinese market.
Consider Regulatory Pathways: Manufacturers should explore the possibility of using existing overseas clinical trial data to support new indications, dosage forms, or routes of administration for drugs already listed in China. By doing so, they may be able to reduce the need for additional clinical trials within China.

How to submit comments

If you have any suggestions, comments or improvements, please send the feedback table and relevant materials to yanggy@cde.org.cn or xuxw@cde.org.cn by September 26, 2024.