Provisions for Drug Registration

Section III Bundling Review and Approval

Article 41 When evaluating a drug registration application, the CDE shall conduct bundling review of the chemical active drug ingredients, excipients and primary packaging materials and containers used for the drug products.

Manufacturers of chemical active drug ingredients, excipients and primary packaging materials and containers shall register product information and research data on the registry platform for chemical active drug ingredients, excipients and primary packaging materials and containers in accordance with requirements of the bundling review and approval system. The CDE shall disclose general information including registry number, product name, enterprise name, and manufacturing address etc. to the public for selection by drug product registration applicants.

Article 42 When submitting a drug registration application, the drug product applicant may directly select chemical active drug ingredients, excipients and primary packaging materials and containers that have been registered; where chemical active drug ingredients, excipients and primary packaging materials and containers that have not been registered are selected, relevant study data shall be submitted together with the drug registration application.

Article 43 When evaluating a drug registration application, the CDE conducts bundling review of the chemical active drug ingredients, excipients and primary packaging materials and containers of the drug product. Where supplementary dossiers are needed, the drug product applicant or the enterprise that registers chemical active drug ingredients, excipients and primary packaging materials and containers shall be required to provide supplementary dossiers in compliance with relevant procedures. When necessary, extended inspection on enterprises of chemical active drug ingredients, excipients and primary packaging materials and containers may be proposed based on risks.

For the generic chemical active drug ingredients already used in marketed drug products within the territory of the People’s Republic of China, separated review and approval may be applied.

Article 44 Where chemical active drug ingredients, excipients and primary packaging materials and containers have passed a bundling review or a separated review and approval, the CDE shall update the registry status flag on the registry platform and disclose relevant information to the public. For the chemical active drug ingredients, a chemical active drug ingredients approval notice shall be issued together with the approved manufacturing process, specifications and labels. The chemical active drug ingredients approval notice shall bear the registry number. In case of disapproval, a chemical active drug ingredients disapproval notice shall be issued.

Where chemical active drug ingredients, excipients and primary packaging materials and containers have failed a bundling review and approval, their registry status shall remain unchanged, and application of the corresponding drug product shall be disapproved.

Section IV Drug Registration Inspection

Article 45 Drug registration inspection refers to the inspection of drug R&D and manufacturing site in order to verify the authenticity and consistency of the application dossiers and the conditions for commercial manufacturing of the drug to be marketed, and to check the compliance and data integrity of drug R&D; when necessary, inspection may be extended to the manufacturers, suppliers or other contracted organizations for chemical active drug ingredients, excipient and primary packaging materials and containers involved in the drug application dossiers.

The principles, procedures, timelines and requirements for initiating drug registration inspection shall be formulated and issued by the CDE; the principles, procedures, timelines and requirements for implementing drug registration inspection shall be formulated and issued by the CFDI.

Article 46 The CDE shall decide whether or not to initiate drug registration inspection of the R&D site based on risks, taking into consideration the innovativeness of the drug, the previous inspection results of drug research institution and other factors.

Where the CDE decides to initiate drug registration inspection of the R&D site, the CDE shall notify CFDI to organize inspection during the review period, and inform the applicant at the same time. The CFDI shall complete on-site inspection within the specified timelines and feedback relevant documents including inspection reports and conclusions to the CDE for comprehensive review.

Article 47 The CDE shall decide whether or not to initiate drug registration inspection of the manufacturing site based on risks, taking into consideration the product type under registration application, the process, facilities, previous inspection results and other factors.

Drug registration inspection of the manufacturing site and pre-marketing GMP inspection shall be carried out for innovative drugs, modified new drugs and biological products, etc.

For generic drugs or other products, drug registration inspection of the manufacturing site and/or  pre-marketing GMP inspection shall be carried out based on risks, taking into consideration the circumstances such as whether Drug Manufacturing Certificate covering the corresponding manufacturing scope has been obtained and product of the same dosage form has been marketed,.

Article 48 After the drug registration application is accepted, the CDE shall conduct preliminary review within 40 days. Where it is necessary to conduct drug registration inspection of the manufacturing site, the CDE shall notify the CFDI to organize inspection, provide relevant materials for inspection, and inform the applicant and the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government where the applicant or the manufacturer is located. In principle, the CFDI shall complete the inspection at least 40 days before the review timeline, and feedback relevant documents including the inspection report and result to the CDE.

Where pre-marketing GMP inspection is necessary, the CFDI shall coordinate the relevant drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government to implement the inspection concurrently with the drug registration inspection of the manufacturing site. The administrative requirements for pre-marketing GMP inspection shall be stipulated by the Provisions for Drug Manufacturing Supervision and Administration.

The applicant shall be subject to inspection within the specified timeline.

Article 49 During the drug review process, where on-site inspection is needed due to the circumstances such as the authenticity of the application dossiers is in doubt or reports with confirmed evidence are received, the CDE shall initiate for-cause inspection and, when necessary, sampling and testing shall be performed.

Article 50 When applying for drug marketing authorization, both the applicant and the manufacturer should have obtained the corresponding Drug Manufacturing Certificate.

Section V Drug Registration Testing

Article 51 Drug registration testing consists of specification verification and sample testing. Specification verification refers to laboratory assessment of the scientific basis of items included in the drug specifications submitted by the applicant, the feasibility of testing methods and the rationality of quality control criteria. Sample testing refers to laboratory testing conducted on samples according to the drug specifications submitted by the applicant or approved by the CDE.

The principles, procedures, timelines and other requirements for the initiation of drug registration testing shall be formulated and issued by the CDE. The specific work procedures and requirements for drug registration testing proposed before the drug registration application is accepted, as well as the technical requirements and practices for drug registration testing shall be formulated and issued by the NIFDC.

Article 52 Where the testing items and methods are identical with those of the same variety of drugs included in the national drug standards, specification verification is not necessary and only sample testing is required. In other cases, both specification verification and sample testing shall be required.

Article 53 Registration testing of the following drugs shall be conducted by the NIFDC or drug testing institutions designated by the NMPA:

(1) Innovative drugs;

(2) Modified new drugs (excluding TCMs);

(3) Biological products, radiopharmaceuticals and in-vitro diagnostic reagents regulated as drugs;

(4) Other drugs specified by the NMPA.

Registration testing of drugs manufactured overseas shall be conducted by the port drug testing institutions organized by the NIFDC.

Registration testing of other drugs shall be conducted by provincial drug testing institutions where the applicant or the manufacturer is located.

Article 54 Having completed the relevant CMC study supporting drug marketing, the specifications establishment, and commercial-scale manufacturing process validation, the applicant may apply for drug registration testing to the NIFDC or the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government before the drug registration application is accepted; Where the applicant does not propose drug registration testing before the drug registration application is accepted, the drug registration testing shall be initiated by the CDE within 40 days after accepting the drug registration application. In principle, the applicant can only propose drug registration testing once before the drug registration application is accepted, and may not propose drug registration testing to multiple drug testing institutions at the same time.

The drug registration testing dossiers submitted by the applicant shall be consistent with the corresponding contents in the drug registration application dossiers, and the drug testing institution, samples and dossiers cannot be changed during the drug registration testing process.

Article 55 For drugs manufactured within the territory of the People’s Republic of China, where drug registration testing has been proposed before the drug registration application is accepted, the applicant can apply for sampling to the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government, and the drug regulatory department shall organize to conduct the sampling and sealing. The applicant shall send the sampling form, samples, dossiers required for testing and reference standard to the corresponding drug testing institutions.

For drugs manufactured overseas, where drug registration testing has been proposed before the drug registration application is accepted, the applicant shall conduct sampling as required and send the samples, dossiers required for testing and reference standard to the NIFDC.

Article 56 For drugs manufactured within the territory of the People's Republic of China, where drug registration testing is necessary after the drug registration application is accepted, the CDE shall, within 40 days after the acceptance, send the notice for drug registration testing to the drug testing institutions and the applicant. The applicant can apply for sampling to the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government, and the drug regulatory department shall organize sampling and sealing. The applicant shall send the sampling form, samples, dossiers required for testing and reference standard to the corresponding drug testing institutions within the specified timeline.

For drugs manufactured overseas, where drug registration testing is necessary after the drug registration application is accepted, the applicant shall conduct sampling as required and send the samples, dossiers required for testing and reference standard to the NIFDC.

Article 57 The drug testing institutions shall, within 5 days, examine the samples and dossiers submitted by the applicant, decide whether or not to accept them, and notify the CDE of the decision at the same time. Where supplements and corrections are needed, the applicant shall be informed by a one-time notification.

In principle, the CFDI shall complete the inspection at least 40 days before the review timeline, and feedback relevant documents including the inspection report and result to the CDE.

Article 58 During the drug review and inspection process, where it is found that the authenticity of the application dossier is in doubt or reports with confirmed evidence are received, when necessary, sampling and testing shall be performed.

During the review process, the CDE may propose verification for a specific item of the specifications based on risks.