Chapter V Post-marketing Changes and Registration Renewal of Drugs

Section I Post-marketing Studies and Changes of Drugs

Article 76 MAHs shall proactively carry out post-marketing studies to further verify the safety, efficacy and quality of drugs and enhance ongoing management of marketed drugs.

Where the Drug Approval License and its attachments require the MAH to carry out relevant post-marketing studies, the MAH shall complete the studies within the specified timeline and submit a supplementary application, filing or report as required.

After a drug is marketed after approval, the MAH shall continue to carry out studies on drug safety and efficacy, promptly file for record or submit supplementary applications for revision of the package inserts based on the relevant data, and keep updating and improving the package inserts and labels. Drug regulatory departments may, as per their duties, require the MAH to revise the package inserts and labels based on the results of adverse drug reaction monitoring and post-marketing evaluation.

Article 77 For post-marketing changes to drugs, classified management shall be implemented depending on their risks to and impact on the safety, efficacy and quality of the drugs. Post-marketing changes are classified into changes subject to approval, filing and reporting.

MAHs shall, in accordance with relevant regulations, fully assess and verify the impact of changes on the safety, efficacy and quality of drugs and carry out related studies in reference to relevant technical guidelines.

Technical guidelines for studies on post-marketing changes to drugs shall be formulated and published by the CDE.

Article 78 MAHs shall report the following changes in the form of supplementary applications for approval prior to implementation:

(1) Major changes in the drug manufacturing process;

(2) Changes in drug package inserts pertinent to efficacy information and to other information on increasing safety risks;

(3) Changes involving a MAH's transfer of the drug marketing authorization;

(4) Other changes subject to approval as specified by the NMPA.

Article 79 MAHs shall report the following changes to the drug regulatory departments of the provinces, autonomous region or municipalities directly under the Central Government where they are located for filing prior to implementation:

(1) Moderate changes in the drug manufacturing process;

(2) Changes to the content of drug packaging labels;

(3) Sub-packaging of drugs;

(4) Other changes subject to filing as specified by the NMPA.

Where a drug manufactured overseas undergoes the aforementioned changes, they shall be reported to the CDE for filing prior to implementation.

The procedures and requirements for filing of sub-packaging of drugs shall be formulated and issued by the CDE.

Article 80 For MAHs shall report the following changes in annual reports:

(1) Minor changes in the drug manufacturing process;

(2) Other changes subject to reporting as specified by the NMPA.

Article 81 For where inspection and testing are needed with post-marketing supplementary applications, they shall be performed as per the procedures for drug registration inspection and testing in these Provisions.

Section II Drug Registration Renewal

Article 82 MAHs shall apply for registration renewal at least 6 months prior to expiration of the Drug Approval License. The application for registration renewal of a drug manufactured within the territory of the People's Republic of China shall be submitted by the MAH to the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government where it is located; the application for registration renewal of a drug manufactured overseas shall be submitted by the MAH to the CDE.

Article 83 After a drug registration renewal application is accepted, the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government or the CDE shall review the MAH’s activities on post-marketing evaluation and adverse reaction monitoring, relevant work carried out as required in the drug approval documents and by the drug regulatory departments as well as changes to information listed on the drug approval documents. Where requirements are met, registration shall be renewed and a Drug Registration Renewal Approval Notice shall be issued. Where requirements are not met, registration shall not be renewed, and a request for cancellation of the Drug Approval License shall be reported to the NMPA.

Article 84 The registration shall not be renewed in any of the following circumstances:

(1) No application for registration renewal has been submitted prior to expiration of the term of validity;

(2) The MAH has failed to fulfill the responsibility for consistent investigation of the quality, efficacy and adverse reactions of the drug during the term of validity of the Drug Approval License;

(3) Studies required in the drug approval document and by the drug regulatory departments have not been completed within the specified timeline while no rationale reasons are provided;

(4) Post-marketing evaluation indicates the drug has uncertain efficacy, serious adverse reaction, or harmful to human health due to other reasons;

(5) Other circumstances where registration renewal shall be disapproved as per laws and administrative regulations.

Where renewal is disapproved, the Drug Approval License shall be revoked upon expiration of the term of validity.

Chapter VI Acceptance and Withdrawal of Application, Decision of Review and Dispute Resolution

Article 85 Upon receiving a drug registration application, the drug regulatory departments shall conduct preliminary review and make a decision of acceptance or rejection according to the following circumstances respectively:

(1) Where no administrative permission is needed for an application item in accordance with the law, a decision of rejection shall be made in time and the reasons shall be stated;

(2) Where an application item is not subject to the jurisdiction of the relevant authorities in accordance with the law, a decision of rejection shall be made in time and the applicant shall be informed to apply to the relevant authorities;

(3) Where there is an error that can be corrected on-site in the dossier, on-site correction shall be allowed; where the dossier is complete and in compliance with the defined format- after the correction, the application shall be accepted.

(4) Where the dossier is incomplete or not in compliance with the defined format the applicant shall be informed on-site or within 5 days in a one-time notification of what to be supplemented or corrected. Where the dossier needs to be returned when the applicant is informed as per regulations, the dossier shall be returned. The applicant shall complete the supplementation and correction of the dossier within 30 days. Where the applicant fails to make the supplementation or correction within the specified timeline without justifiable reasons, the application shall be deemed to have been abandoned, and there’s no need to make a decision of rejection. Where the applicant is not informed of the need for supplementation and correction within the timeline, the application shall be regarded as- accepted on the date the dossier is received.

(5) Where the application item is under the jurisdiction of the relevant authorities and the dossier is complete and in compliance with the defined format or the applicant has submitted all the required supplementary or corrected dossiers, the drug registration application shall be accepted.

After the drug registration application is accepted, where it is necessary to pay fees, the applicant shall pay the fees as required. If the applicant fails to pay the fees within the specified timeline, review and approval of the drug registration shall be terminated.

Article 86 After the drug registration application is accepted, where there are new safety issues, the applicant shall report and provide supplementary materials in a timely manner.

Article 87 After the drug registration application is accepted, where it is necessary for the applicant to provide new technical dossier on the basis of the original submission dossier, the CDE shall, in principle, make a one-time requirement for supplementary dossier. The CDE shall list all the issues and inform the applicant in a written notice to submit supplementary dossier within 80 days. The applicant shall submit all the supplementary dossier together as required in one submission, and the time needed for the supplement of dossier will not be counted into the drug review timeline. The CDE shall restart review upon receiving all the supplementary dossier from the applicant, and the review timeline shall be extended by 1/3 of the original review timeline; where the priority review and approval procedure is applicable, the review timeline shall be extended by 1/4 of the original review timeline.

Where the applicant is only required to interpret and explain the original submission dossier instead of providing new technical dossier, the CDE shall inform the applicant to submit relevant interpretation and explanation as required within 5 days.

Where the CDE considers that there are substantial defects which cannot be addressed by supplement or correction, the applicant shall not be required to supplement the dossier. The application shall be denied based on the existing dossier submitted.

Article 88 For drug clinical trial applications and supplementary applications during ongoing drug clinical trials, additional technical dossier cannot be submitted during the review period; where new studies are needed, the applicant may submit a new application after withdrawing the original.

Article 89 After a drug registration application has been accepted, the applicant may apply for withdrawal. Where the application is granted, the CDE or the drug regulatory departments of the provinces, autonomous regions or municipalities directly under the Central Government shall terminate the registration procedure thereof and inform the drug registration inspection, testing and other technical institutions. Where suspected illegal acts such as concealing the truth and providing false information are found during review, the case shall be managed according to the law and the applicant is not allowed to withdraw the drug registration application.

Article 90 During the drug registration process, where the review conclusion is not passed, the CDE shall inform the applicant of the reasons, and the applicant may raise an objection to the CDE within 15 days. The CDE shall take into account the objection raised by the applicant, make a comprehensive assessment and give feedback to the applicant.

Where the applicant still disagrees about the comprehensive assessment result, the CDE shall, as per regulations, organize an expert advisory committee for discussion within 50 days and make a final review conclusion with the expert discussion results taken into account.

Time needed for the applicant to file the objection and for the expert discussion shall not be counted into the review timeline.

Article 91 During the drug registration process, where the applicant deems that any staff member has violated the regulations or code of conduct in areas such as drug registration acceptance, review, inspection, testing and approval, the applicant may complain and report to the entity where the staff member works or the superior regulatory authority.

Article 92 Drug registration applications that are in compliance with legal requirements shall be approved.

In any of the following circumstances, the drug registration application shall not be approved:

(1) Study data in the drug clinical trial application are inadequate to support the conduct of drug clinical trials or cannot guarantee subjects’ safety;

(2) The submission dossier indicates relatively significant defects in the safety, efficacy, quality and other aspects of the drug under application;

(3) The application dossier cannot demonstrate the safety, efficacy and quality of the drug or it is considered upon evaluation that the drug’s risks outweigh its benefits;

(4) The applicant fails to submit supplementary dossier within the specified timeline;

(5) The applicant refuses to accept drug registration inspection and testing or, without justifiable reasons, fails to accept drug registration inspection and testing within the specified timeline.

(6) During the drug registration process, the application dossier is considered untruthful, and the applicant cannot prove the authenticity thereof;

(7) The results of the registration site inspection or sample testing do not meet the requirements;

(8) Other circumstances in which the application shall not be approved as specified by laws and regulations.

Article 93 After completion of review and approval of the drug registration application, where the applicant disagrees about the administrative approval decision, an administrative reconsideration or administrative litigation may be raised in accordance with the law.