Provisions for Post-approval Changes of Drugs (Interim)

Chapter II Circumstances of Change

Section 1 Change Management of MAHs

Article 7 For the application for changing drug MAH, items such as the manufacturing site, formulation, manufacturing process and specifications of the drug shall be consistent with those of the original drug; if not, the new MAH shall conduct sufficient study, evaluation and necessary verification, and implement or report after approval and filing as required after the MAH change is approved.

Article 8 For the application for changing the MAH of drugs produced within the territory of China, the transferee shall submit a supplementary application to the Center for Drug Evaluation, NMPA (hereinafter referred to as the "CDE") after obtaining the Drug Manufacturing Certificate with the corresponding production scope. Among them, for the application for changing the MAH of narcotics and psychotropics, the transferee shall also meet the requirements for the quantity and layout of designated manufacturers of narcotics and psychotropics determined by the NMPA.

CDE shall make decision on whether to approve the change within the specified time limit. Where it approves the change, it shall issue a Notice of Drug Supplementary Application, keep the drug approval number and the validity period of the certificate unchanged, and copy to the provincial drug regulatory department where the transferor, transferee and manufacturer are located.

The new MAH shall have a production quality management system meeting the requirements of Good Manufacturing Practice for Drugs, assume the obligations of lifecycle management of drugs, complete the continuous study of the drug, ensure that the drug manufacturing meets the current technical requirements after approval, and focus on describing the transferred drugs in the initial annual report.

The transferred drug may be placed on the market after passing the GMP compliance inspection if it meets the requirements for product release.

The provincial drug regulatory department where the transferee is located shall focus on strengthening the supervision and inspection on the transferred drugs, and include them in the routine supervision plan in a timely manner.

Article 9 For the change between overseas MAHs, the new MAH shall submit a supplementary application to CDE.

CDE shall make decision on whether to approve the change within the specified time limit. Where the change is approved, CDE shall issue a Notice of Drug Supplementary Application and keep the drug approval number and the validity period of the certificate unchanged.

Article 10 Where a drug manufactured overseas and marketed in China is to be transferred to manufacturing within the territory of China, the domestic applicant shall submit an application in accordance with the requirements and procedures for drug marketing registration application. The original registration application dossier of the drug manufactured overseas may be submitted for relevant CMC, non-clinical and clinical data (if applicable), and those meeting the requirements may be applied for becoming reference preparations. Specific requirements for application dossiers shall be separately formulated by CDE.

Article 11 For changing the names of MAH, manufacturer, manufacturing site and so on, after the change of corresponding items in the Drug Manufacturing Certificate is completed, the change shall be filed to the local provincial drug regulatory department to change the corresponding management information of drug approval documents.

The change of the above information for drugs manufactured overseas shall be filed to the CDE.

Section 2 Change Management of Drug Manufacturing Site

Article 12 The drug manufacturing site includes the manufacturing site owned by the MAH or the corresponding manufacturing site of the contract manufacturer. The change of drug manufacturing site refers to the change or addition of manufacturing address, or the new construction, reconstruction and expansion of manufacturing site with the same production address. The manufacturing site information shall be specified in the Drug Manufacturing Certificate and drug approval document of the MAH.

Article 13 For the change of drug manufacturing site, the formulation, production process and quality standard of the drug shall be consistent with those of the original drug, and the MAH shall ensure that the product consistent with the quality and efficacy of the original drug can be continuously and stably produced.

In case of any change to the formulation, manufacturing process and specification of a drug, the MAH shall conduct sufficient study, evaluation and necessary verification, and implement or report the change after being approved and notified as regulated.

Article 14 Where the MAH or drug manufacturer within the territory of China makes internal change on the manufacturing sites, or the MAH within the territory of China makes change on their manufacturers (including change of contract manufacturers, addition of contract manufacturers, change of self-production by MAH to contract manufacturer, and change of contract manufacturing to self-manufacturing), MAH (drug manufacturers) shall conduct study, evaluation and necessary verification in accordance with the requirements in the Provisions for the Supervision and Administration of Drug Manufacture and relevant technical guidelines for changes, and file an application for changing the Drug Manufacturing Certificate with the local provincial drug regulatory department and submit relevant dossiers.

Provincial drug regulatory departments shall carry out on-site inspection and technical review in accordance with the requirements in the Provisions for the Supervision and Administration of Drug Manufacture, the Provisions for Drug Registration and relevant technical guidelines for changes, and change the relevant information of their Drug Manufacturing Certificate if the requirements are met. After completing the change of Drug Manufacturing Certificate, the provincial drug regulatory department shall update the change information of the manufacturing site or manufacturer as indicated in the drug registration approval document of the MAH and its annexes in the change system for drug registration filing by virtue of the changed Drug Manufacturing Certificate. Where there is a need to submit a supplementary application to the CDE for the change of biological products, the MAH shall submit a supplementary application in accordance with the Provisions.

Article 15 Where the overseas MAH changes the drug manufacturing site and the new manufacturing site is still overseas, it shall conduct study, evaluation and necessary verification in accordance with relevant technical guidelines and submit supplementary application or filing to CDE.

Article 16 For the change of drug manufacturing site of biological products, MAH shall conduct study and verification in accordance with the requirements in relevant normative documents and technical guidelines for the change after the change of Drug Manufacturing Certificate is approved. For a major change, it shall be implemented after submission to CDE for approval.

Section 3 Change of Other Drug Registration Management Items

Article 17 For the change in the production process including the production equipment, the source and type of raw materials, excipients and packaging materials, technical parameters and quality standards, MAHs shall fully evaluate the risk degree of the change that may affect the drug safety, efficacy and quality, define the change management category, conduct sufficient study, evaluation and necessary verification in accordance with relevant technical guidelines and Good Manufacturing Practice for Drugs, and implement or report the change after approval or filing.

Article 18 The change management of package inserts and labels shall be carried out in accordance with relevant regulations and technical requirements.

Article 19 Where there is a change to the active drug ingredients that have passed the review and approval, the active drug ingredients registrant shall define the change management category in accordance with the relevant provisions for drug registration, the Good Manufacturing Practice for Drugs, the technical guidelines and the Provisions, and implement or report it after approval or filing. The active drug ingredients registrant shall update the change information on the registration platform in a timely manner.

Before the implementation of the change, the active drug ingredients registrant shall notify the relevant drug product MAH of the relevant information in a timely manner. After receiving the above notice, the drug product MAH shall, in a timely manner, evaluate or study the corresponding changes on the risks affecting the quality of pharmaceutical preparations, and submit supplementary application, file or report in accordance with relevant regulations.

For the change of the active drug ingredients failing to pass the review and approval and not yet included in the review procedure, the active drug ingredients registrant may update relevant dossiers at any time through the registration platform on the website of CDE.