Registration Classification and Application Dossiers of Chemical Drugs for NMPA

 Requirements for Registration Classification and Application Dossiers of Chemical Drugs 

I. Registration classification of chemical drugs

The registration classification of chemical drugs covers innovative drugs, modified new drugs, generic drugs and chemical drugs marketed overseas but not in China, which fall into the following 5 categories:

Class 1: Innovative drugs that have not been marketed in China or overseas. They refer to drugs that contain new compounds with clear structures and pharmacological effects, and have clinical values. 

Class 2: Modified new drugs that have not been marketed in China or overseas. They refer to drugs that have their structure, dosage form, formulation and process, route of administration and indications optimized on the basis of known active ingredients and have significant clinical advantages.

2.1 Drugs that contain an optical isomer of known active ingredients obtained by resolution or synthesis, or esterification of known active ingredients, or salification of known active ingredients (including salt containing hydrogen bonds or coordination bonds), or change in acid group, basic group, or metallic element of known active ingredients of salt, or formation of other non-covalent bond derivatives (e.g., complex, chelate or clathrate), and have significant clinical advantages.

2.2 Drugs that contain known active ingredients with new dosage form (including new drug delivery system), new formulation process or new route of administration, and have significant clinical advantages.

2.3 New compound preparations that contain known active ingredients and have significant clinical advantages.

2.4 Drugs for new indications that contain known active ingredients.

Class 3: Drugs manufactured by domestic applicants by imitating the original drugs that have been marketed overseas but not yet in China. Such drugs shall have the quality and efficacy consistent with the reference listed drug.

Class 4: Drugs manufactured by domestic applicants by imitating the original drugs that have been marketed in China. Such drugs shall have the quality and efficacy consistent with the reference formulations. 

Class 5: Drugs that have been marketed overseas and are under application for being marketed in China. 

5.1 Original drugs and modified drugs that have been marketed overseas and are under application for being marketed in China. Modified drugs shall have obvious clinical advantages.

5.2 Generic drugs that have been marketed overseas and are under application for being marketed in China. 

Original drugs refer to drugs that have been firstly approved to be marketed in China and overseas and have complete and sufficient safety and effectiveness data as the basis for being marketed. 

Reference listed drugs refer to the reference drugs used in the R&D of generic drugs that have been evaluated and confirmed by NMPA. The selection and promulgation of reference listed drugs shall be performed according to the relevant regulations of NMPA.

II. Relevant registration management requirements

(1) Class 1 chemical drugs are innovative drugs that contain new compounds with clear structures and pharmacological effects and have clinical values. Class 2.1 drugs in modified new drugs are not included. New compound preparations containing new compounds with clear structures and pharmacological effects shall be applied in accordance with Class 1 chemical drugs.

(2) Class 2 chemical drugs, being modified new drugs, are optimized on the basis of known active ingredients, and shall have obvious clinical advantages over those before modification. Known active ingredients refer to the active ingredients of drugs that have been marketed in China or overseas. If such drugs meet the requirements of multiple conditions at the same time, such conditions shall be described at application.

(3) Class 3 chemical drugs are drugs manufactured by domestic applicants by imitating the original drugs that have been marketed overseas but not yet in China. They have identical active ingredients, dosage forms, specifications, indications, routes of administration, usage and dosage with those of the reference formulations, and have proven consistency of quality and efficacy with those of the reference formulations. 

With sufficient research data to prove the rationality, the specifications, usage and dosage may be inconsistent with those of the reference formulations.

(4) Class 4 chemical drugs are drugs manufactured by domestic applicants by imitating the original drugs that have been marketed in China. They have identical active ingredients, dosage forms, specifications, indications, routes of administration, usage and dosage with those of the reference formulations, and have proven consistency of quality and efficacy with those of the reference formulations.

(5) Class 5 chemical drugs are drugs that have been marketed overseas and are under application for being marketed in China. Drugs manufactured in China and overseas are included. Among them, Class 5.1 chemical drugs are original drugs and modified drugs, and the latter are optimized on the basis of known active ingredients, and shall have obvious clinical advantages over those before modification. Class 5.2 chemical drugs are generic drugs, whose quality and efficacy shall be proven to be consistent with those of the reference formulations, and whose technical requirements are the same as those of Class 3 and Class 4 chemical drugs. Generic drugs developed simultaneously at home and abroad but produced overseas shall be applied in accordance with Class 5.2 chemical drugs. If clinical trials for such drugs are applied, the supporting documents for approval of marketing and sales can be exempted. 

(6) The application for registration of additional indications approved abroad but not yet in China shall be handled in accordance with the application channels for drug clinical trial and marketing authorization. 

(7) During the review and approval of the drug marketing application, the drug registration classification and technical requirements shall not be changed because the preparation with the same active ingredients is approved to be marketed at home and abroad. Drug registration classification shall be determined when marketing authorization is applied.

III. Requirements for application dossiers

(1) While applying for drug clinical trials, drug marketing registration and chemical APIs, the applicants shall carry out the study in accordance with the requirements of relevant technical guidances promulgated by NMPA, collate and submit the application dossiers as per the format number and item order of the current version of M4: Common Technical Document for the Registration Application of Pharmaceuticals for Human Use (hereinafter referred to as CTD). If some items are not applicable, they can be missing, but "not applicable" shall be indicated and the reasons shall be specified. (Non-applicable items can be left default but "not applicable" shall be indicated and reasons shall be specified.)

(2) While applying for drug marketing registration upon completion of the clinical trial, the applicant shall submit the electronic clinical trial database on the basis of CTD. For specific requirements such as database format and related documents, please refer to the relevant guidances for clinical trial data submission.

(3) According to the needs of drug evaluation and the status of revision of the ICH technical guidance, the Center for Drug Evaluation of NMPA will update the CTD on a timely manner on its website.