China Requires ANDAs Without Reference Drugs to Demonstrate Clinical Value

by Grace Wang Oct 17, 2023

On Oct. 13, 2023, China National Medical Products Administration (NMPA) announced regulations on generic drug registration / abbreviated new drug application (ANDA) have no reference listed drugs (RLDs). On the same day, the Center for Drug Evaluation (CDE) implemented the supportive regulations on technical dossiers and communication applications regarding such ANDAs.

As per the announcement, ANDA without RLD means that the applicant plans to copy a drug that is not in the RLD Catalog. For such a generic candidate, NMPA requires the applicant to fulfill the following requirements:

  • Conducting chemistry, manufacturing, and controls (CMC) studies to prove the proposed generic drug’s equivalence to marketed drugs with the same active pharmaceutical ingredient (API);

  • Assessing and demonstrating the proposed drug’s clinical value; and

  • Submitting a communication application for having a type-III meeting with CDE.

1. CMC Study for Proving Equivalence

The ANDA applicant is required to conduct studies on manufacturing process, quality, and stability. With the studies, the applicant should prove that the proposed generic drug’s quality is no lower than those of the drugs which meet the following conditions:

  • Having the same API with the proposed generic drug;

  • Supported by sufficient quality studies;

  • Having solid foundation for marketing authorization;

  • Accounting for a fairly large market share in the therapeutic area of the proposed generic drug.

The ANDA dossier should contain the following information:

1) Information of multiple drugs which have the same API of the generic drug;

     - Generic name (Chinese and English);

     - Dosage form;

     - Brand name;

     - Strength;

     - Marketing authorization holders (MAHs)’ names and addresses;

     - Manufacturers’ names and addresses;

     - The countries and corresponding dates of the marketing authorizations;

     - Evidence demonstrating the legal acquisition of the product, such as purchase invoices or donation certificates, etc.

     - Medication package insert (in the original language) and its Chinese translation;

     - Photo of the product.

2) Comprehensive information of the quality studies of the multiple drugs mentioned in 1) above.

* A summary of 1) and 2) should be included in Module 2 regional information.

* Comprehensive and detailed information of 1) and 2) should be placed in Module 3 regional information.

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2. Clinical Value Assessment

The ANDA applicant should assess the expected clinical value of the generic drug. It will be deemed to possess the value only when it meets all three conditions:

1) The proposed indication is clearly defined, with a well-defined dosage regimen. The drug aligns effectively with the requirements and practices of clinical diagnosis and treatment in China.

2) The proposed drug is a mainstream, widely-used therapy without alternative treatment available. Its clinical benefits outweigh risks. For example,

     - The drug exhibits notable advantages in terms of therapeutic efficacy; or

     - The drug demonstrates distinct clinical value in specific group of populations (e.g., children, the elderly, etc.).

3) The proposed drug has substantial data supporting its entry into clinical trials.

Based on the assessment, the applicant should include the following information in the Module 2 of the application dossier.

  • Epidemiological characteristics;

  • Disease prognosis;

  • Current clinical treatment and progress;

  • Particularly, the position and function of the proposed drug in the current clinical practice;

  • Sufficient evidence for demonstrating expected clinical value of the proposed drug.

3. Clinical Trial

The clinical trial application should include

  • Clinical trial plan;

  • Statistics analysis plan;

  • Other materials supporting the proposed clinical trial.

The applicant should conduct randomized trials based on the indication and the common effective therapies. 

If a safe and proven effective drug has been approved the specific therapeutic area, the applicant should use the approved drug in the comparison study. In cases there are no such approved drugs, placebos should be used for the study. 

The clinical trial will only be approved when CDE determines that the proposed drug holds the anticipated clinical value and the design of the clinical trial plan is scientific and reasonable.

Some drugs such as Glucose Injection, Sodium Chloride Injection, Vitamin B2, Vitamin B6, Calcium Carbonate and Vitamin D3 are exempted from clinical trials.

4. Communication Application

The generic drug applicants should submit a type-III meeting application to communicate with CDE, in accordance with the Provisions for Communication About Drug R&D and Technical Review. Additionally, for the generics exempted from clinical trials, the applicants should also have the meeting with CDE to undergo product-by-product analysis.  

Ask BaiPharm if you’d like to know more about generic drug registration / ANDA in China.

Grace Wang
ChemLinked Regulatory Analyst & Editor
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