(SFDA Order No. 28)


Provisions for Drug Registration

Chapter I
General Provisions

Article 1 The Provisions are formulated for the purposes of ensuring the safety, efficacy and quality of drugs and regulating drug registration in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as the Drug Administration Law), Administrative Permission Law of the People's Republic of China (hereinafter referred to as Administrative Permission Law) and the Regulations for Implementation of the Drug Administration Law of the People's Republic of China (hereinafter referred to as the Regulations for Implementation of the Drug Administration Law).

Article 2 The Provisions apply to the applications for drug clinical trial, drug production or import, and conducting drug approval, relevant testing for drug registration, or regulation thereof, within the territory of the People's Republic of China.

Article 3 Drug registration refers to the process of review and approval on which the State Food and Drug Administration, in accordance with the official procedures, evaluates the safety, efficacy and quality of the drugs applied for marketing, and decides whether or not to approve such an application.

Article 4 The State encourages the research and development of new drugs and adopts the special review and approval with respect to innovative drugs, new drugs for serious and life-threatening diseases and to address unmet medical needs and drugs.

Article 5 The State Food and Drug Administration is in charge of drug registration nationwide, and responsible for reviewing and approving the clinical trial, production and importation of drugs.

Article 6 The drug registration shall follow the principles of openness, fairness and justice.

The State Food and Drug Administration adopts the system of collective responsibility of the chief reviewers, the system of publicizing and challenging relevant persons, and the system of responsibility tracing, with social supervision in such procedures as acceptance, inspection, review and approval and sending.

Article 7 In the process of drug registration, the drug regulatory department shall make known to the general public, and hold hearings on, the matters which it deems of vital importance and involving public interests for the granting of permission.

Prior to making the decision of administrative licensing that has a direct bearing on the vital interest between the applicant and the other party, the drug regulatory department shall inform the applicant and the interested party of their rights of requesting for hearings, making statements and argues.

Article 8 The drug regulatory department shall provide the applicant with access to information on the status of the acceptance, examination, inspection, review and approval of drug registration application and the final resolution.

The drug regulatory department shall publicize the following information on its official websites or at the official premises for accepting applications:

(1) the items, procedures, fees and their basis, and timelines of the drug registration, index of all the data needed to be submitted and model text of the application form;
(2) the name list and other relevant information on the persons involved in the acceptance, examination, inspection, review and approval of drug registration; and
(3) general information about categories of approved drugs, etc.

Article 9 The drug regulatory department, relevant institutions and persons involved in the drug registration have an obligation to keep the technical secrets and trial data submitted by the applicant confidential.

Chapter II
Application for Drug Registration

Article 10 An applicant for drug registration (hereinafter referred to as applicant) refers to the institution that submits a drug registration application and assumes corresponding legal liability.

A domestic applicant shall be an institution legally registered within the territory of People's Republic of China that independently assumes civil liability and an overseas applicant shall be a legal overseas drug manufacturer. Where an overseas applicant applies for import drug registration, it shall be done by its branch or entrusted agency within the territory of People's Republic of China.

The persons who handle the application for drug registration shall have professional knowledge and be familiar with the laws and regulations on, and the technical requirements for, drug registration.

Article 11 Drug registration applications include applications for new drugs, generic drugs, import drugs and their supplementary applications as well as re-registration applications.

Applications of domestic applicants shall be handled according to the procedures and requirements for new drugs or generic drugs, whereas applications of overseas applicants shall be handled according to those for import drugs.

Article 12 Application for new drugs refers to application for registration of drugs that have not been marketed within the territory of People's Republic of China.

Application for changing dosage form or route of administration, or claiming a new indication for marketed drugs, shall be submitted as the process of new drug application.

Application for generic drugs refers to registration application for producing the drugs having existing national drug standard which is approved to be marketed by the State Food and Drug Administration, whereas the application for biological products shall be submitted as the process of new drug application.

Application for import drugs refers to registration application for drugs manufactured abroad to be marketed within the territory of the People's Republic of China.

Supplementary application refers to application for variation, addition, or cancellation of the items or contents approved in the original application for new drug, generic drug or import drug.

Re-registration application refers to application for continued production or importation of a drug after the expiration of the valid term of the drug approval document.

Article 13 The applicant shall provide sufficient and reliable research data to prove the safety, efficacy and quality of the drug, and be liable for the authenticity of all the dossiers submitted.

Article 14 The cited literature of the dossier of drug registration shall indicate the title of works or the name, volume number, issue and page of the journal. Where the cited references are not published, an author's permission shall be provided. For foreign literatures, Chinese translation shall be provided as required.

Article 15 The State Food and Drug Administration shall obey the development plan and policies on the pharmaceutical industry constituted by the State, and may conduct assessment to the market value of drugs.

Article 16 In the process of drug registration, the drug regulatory department shall conduct on-site inspection and causal inspection to the non-clinical studies and clinical trials, as well as production site inspection for the pre-marketing approval to confirm the authenticity, precision and integrity of the dossier submitted.

Article 17 Where two or more institutions jointly apply for drugs, the application shall be submitted to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government, in which the drug manufacturer is located; where the applicants are all drug manufacturers, the application shall be submitted to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government, in which the manufacturer of pharmaceutical preparations is located; where none of the applicants is a drug manufacturer, the application shall be submitted to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government, in which the site for pilot production of drug samples is located.

Article 18 An applicant shall provide the information on patent and its ownership of the applicant or other parties in China, in respect of the drug applied for registration, its formula, manufacturing processes and/or uses, etc. Where another party owns the patent in China, the applicant shall provide a statement of non-infringement. The drug regulatory department shall publish the information or the statement submitted by the applicant on its official website.

Where a patent dispute occurs in the process of drug registration, it shall be settled in accordance with relevant laws and regulations on patent.

Article 19 For a drug patented in China, applicants other than the patentee may submit the application for registration two years prior to the expiry date of the patent. The State Food and Drug Administration shall review the drug application in accordance with the Provisions, and after the expiry date of the patent, check and issue the drug approval number, Import Drug License or a Pharmaceutical Product License if the application conforms with the provisions.

Article 20 In accordance with the provisions in Article 35 of the Regulations for Implementation of the Drug Administration Law, where a manufacturer or distributor submits undisclosed drug experimental and other data which are independently acquired in order to obtain approval for production or marketing of the drug in question which contains any new chemical entity, the State Food and Drug Administration shall, within six years from the approval date of the drug, reject any application made by any other applicants by using the undisclosed data of the drug in question without permission of the original applicant who has obtained the drug approval, unless the data submitted are independently acquired by the applicants other than the original one.

Article 21 Pre-clinical drug study for drug registration application includes drug synthetic processes, extraction methods, physical and chemical properties, purity, selection of dosage form, screening of formula, preparing processes, testing methods, quality specifications, stability, pharmacology, toxicology and animal pharmacokinetics, etc. For traditional Chinese medicine preparations, in addition to the above-mentioned items, pre-clinical drug study also includes the study in the source of the crude drugs, and of their pre-treatment and processing, etc. For biological products, it also includes study on the source, quality specifications, storage conditions, biological characteristics and genetic stability of the starting materials such as bacterial and viral seeds/strains, cell lines, bio-tissues, and immunological study, etc.

Article 22 A pre-clinical drug study shall be in conformity with relevant requirements, among which the Good Laboratory Practice for Non-Clinical Laboratory Studies shall be implemented in the study of safety evaluation.

Article 23 The drug research institution shall have relevant staff, premises, equipment, instruments and management system, which are appropriate to the research project, and ensure the authenticity of all experimental data. Experimental animals, reagents and raw materials used in the study shall conform with the provisions of the State.

Article 24 An applicant who entrusts other institutions with a drug research, individual experiment, testing, or pilot production, etc. shall conclude a contract with the trustee, and state it clearly in the registration application. The applicant shall be responsible for the authenticity of the research data in the application dossier.

Article 25 Where the application is only for registration of pharmaceutical preparations, any drug substance used for the study shall have a drug approval number, an Import Drug License or a Pharmaceutical Product License, and be acquired through legitimated means. Where a drug substance used for the study has no drug approval number, Import Drug License or Pharmaceutical Product License, the use of drug substance in study shall be approved by the State Food and Drug Administration.

Article 26 The research data in application dossier for drug registration provided by an overseas drug research institution shall be attached with the items and pages of the information, and with notarized documents proving that the said drug research institution is legally registered overseas. The State Food and Drug Administration may send staff to conduct on-site inspection in needs of drug review.

Article 27 The drug regulatory department may request the applicant or the drug research institution responsible for testing to repeat the test based on the items, methods and data specified in the application documents, and may also authorize a drug testing institute or another drug research institution to repeat the test or conduct methodological verification.

Article 28 The drug study shall be conducted according to the relevant technical guidelines issued by the State Food and Drug Administration. Where an applicant conducts the study by adopting other evaluation methods and techniques, supporting data proving the scientific feasibility of such methods and techniques shall be provided.

Article 29 An applicant who obtains the drug approval number shall manufacture according to the manufacturing processes approved by the State Food and Drug Administration.

The drug regulatory department shall supervise and inspect the applicant's manufacture in accordance with the approved manufacturing processes and quality specifications.

Chapter III
Drug Clinical Trials

Article 30 Any drug clinical trial, including bioequivalence study, shall be approved by the State Food and Drug Administration, and shall be in compliance with the Good Clinical Practice.

Drug regulatory department shall supervise and inspect the approved clinical trials.

Article 31 Clinical trials shall be conducted for new drug registration applications. As for generic drug registration applications and supplementary applications, clinical trials shall be conducted in accordance with the requirements in the Annex of the Provisions.

A clinical trial consists of phases I, II, III and IV.

Phase I Clinical Trial: initial clinical pharmacology and safety evaluation studies in humans. These studies are designed to observe tolerability of humans to and pharmacokinetics of a new drug, in order to provide basis for establishing the administration regimen.

Phase II Clinical Trial: preliminary evaluation of therapeutic effectiveness of a drug. The purposes are to preliminarily evaluate the therapeutic effectiveness and safety of the drug for particular indication(s) in patients, and provide evidence for design of Phase III clinical trial and settlement of administrative dose regimen. According to specific trial objectives, this phase of trial may be designed in various forms, including the randomized blind controlled clinical trial.

Phase III Clinical Trial: confirmation of therapeutic effectiveness of a drug. The purposes are to further verify drug therapeutic effectiveness and safety on eligible patients with target indication(s), to evaluate overall benefit-risk relationships of the drug, and to ultimately provide sufficient evidence for the review of drug registration application. The study, in general, shall be a randomized blind controlled trial with an adequate sample size.

Phase IV Clinical Trial: a new drug post-marketing study. The purposes are to assess therapeutic effectiveness and adverse reactions when a drug is widely used, to evaluate overall benefit-risk relationships of the drug when used among general population or specific groups, and to adjust the administration dose, etc.

Bioequivalence study refers to a human study, which applies bioavailability study methods with pharmacokinetic parameters as indicators to compare active ingredient absorption rate and extent of the preparations in the same or different dosage forms of a drug in terms of statistical differences under the same experimental condition.

Article 32 The sample size of a drug clinical trial shall conform to the objectives of the clinical trial and fulfill statistical requirements, and shall be no smaller than the minimum number of subjects required by the Annex of the Provisions. Where there are circumstances, regarding rare or special diseases, etc., which request clinical sample size reduction or clinical trial exemption, a request shall be made with the clinical trial application, and reviewed and approved by the State Food and Drug Administration.

Article 33 As for vaccines prepared during bacterial or viral strain screening or other special drugs, if confirmed without any suitable animal model and laboratory measurement in terms of curative effectiveness, clinical trials may be applied for to the State Food and Drug Administration, subject to ensuring the safety of trial subjects.

Article 34 When a drug clinical trial is approved, the applicant shall select institutions for the clinical trial from those certified for conducting drug clinical trials.

Article 35 Drugs used for clinical trials shall be manufactured in facilities in compliance with the Good Manufacturing Practice for Pharmaceutical Products (GMP). The manufacturing process shall strictly meet the requirements of the GMP.

The applicant shall be responsible for the quality of the drugs used for clinical trials.

Article 36 The applicant may conduct the testing for clinical trial drugs by itself, or entrust a drug testing institute specified in the Provisions to conduct such testing, according to its proposed specifications. Vaccines, blood products and other biological products specified by the State Food and Drug Administration shall be tested by drug testing institutes designated by the State Food and Drug Administration.

A drug can be used for a clinical trial only after tested as qualified.

Drug regulatory departments may conduct sampling and testing on drugs used for clinical trials.

Article 37 Prior to conducting a clinical trial, the applicant shall report to the State Food and Drug Administration for record while copying to the drug regulatory department of the seat of the clinical trial institution and that of the province, autonomous region or municipality directly under the Central Government to receive the application a confirmed clinical trial protocol, the name of the principal investigator at the institution in charge of the clinical trial, a list of participating institutions and names of investigators wherefrom, an ethic committee approval letter, and a template of the informed consent form, etc.

Article 38 Where the applicant finds a clinical trial institution violating relevant regulations or failing to implement the clinical trial protocol, it shall urge the institution to make corrections; if the circumstances are serious, the applicant may demand suspension or termination of the clinical trial, and shall report the matter to the State Food and Drug Administration and the drug regulatory departments of the relevant provinces, autonomous regions or municipalities directly under the Central Government.

Article 39 After completion of a clinical trial, the applicant shall submit a clinical trial final report, a statistical analysis report and its database to the State Food and Drug Administration.

Article 40 A clinical trial shall be conducted within three years after approval. If overdue, the original approval documents shall be invalid. If the clinical trial is still needed, the application shall be reapplied for.

Article 41 If any serious adverse event occurs during the clinical trial, the investigators shall report to the drug regulatory departments of the relevant provinces, autonomous regions or municipalities directly under the Central Government and the State Food and Drug Administration and notify the applicant within 24 hours, and report to the ethic committee in time.

Article 42 In any of the following circumstances during a clinical trial, the State Food and Drug Administration may order the applicant to modify the protocol, suspend or terminate the clinical trial,:

(1) the ethic committee fails to perform its duty;
(2) safety of the subjects cannot be adequately ensured;
(3) a serious adverse event is not reported within the specified timeline;
(4) there is evidence to prove that the drug used for the clinical trial is not effective;
(5) a quality problem of the drug used for the clinical trial occurs;
(6) there is a fraud in the clinical trial; or
(7) there is any other case violating the Good Clinical Practice.

Article 43 Where there is any large-scale of and unexpected adverse reaction or serious adverse event, or there is evidence to prove any serious quality problem of the drug used for a clinical trial, the State Food and Drug Administration or the drug regulatory department of the province, autonomous region or municipality directly under the Central Government may take emergency control measures and order to suspend or terminate the clinical trial. The applicant and clinical trial institution must stop the clinical trial immediately.

Article 44 An overseas applicant intending to conduct an international multi-center clinical trial in China shall submit an application to the State Food and Drug Administration in accordance with the Provisions, and fulfill the following requirements:

(1) the drugs used for clinical trials shall be already approved or in phase II or III clinical trial overseas. The State Food and Drug Administration does not accept any overseas applicant’s international multi-center clinical trial application for any preventive vaccine not being registered overseas yet;
(2) while approving to conduct an international multi-center clinical trial, the State Food and Drug Administration may require the applicant to conduct phase I clinical trial first in China;
(3) when conducting an international multi-center clinical trial in China, if there are any observed serious adverse reaction and unexpected adverse reaction associated with the drug in any country, the applicant shall, in accordance with relevant regulations, report to the State Food and Drug Administration in time;
(4) the applicant shall submit a complete clinical trial report to the State Food and Drug Administration after the completion of a clinical trial; and
(5) the data obtained from an international multi-center clinical trial for drug registration application in China shall be in conformity with the requirements on clinical trial in the Provisions. All the study materials of the international multi-center clinical trial shall be submitted.

Chapter IV
Application and Approval of New Drugs

Article 45 The State Food and Drug Administration may implement special review and approval in cases of the following applications:

(1) active ingredients extracted from plants, animals and minerals, etc. and their preparations not yet marketed in China, and newly discovered Chinese crude drugs and their preparations;
(2) chemical drug substances and their preparations and biological products not yet approved for marketing in China or abroad;
(3) new drugs for the treatment of diseases such as AIDS, malignant tumors and rare diseases, etc. with significant clinical advantage; and
(4) new drugs for the treatment of diseases, for which effective therapeutic methods are not available.

For drugs specified in the previous clause, applicants may apply for special review and approval in the process of drug registration. The Center for Drug Evaluation of the State Food and Drug Administration shall organize expert meetings to discuss and determine whether or not to conduct special review and approval for the drugs.

Specified measures for special review and approval shall be formulated separately.

Article 46 Where a new drug is co-developed by several institutions, the registration can be applied for by one of the institutions, and its duplicate application shall not be made by the others. If a joint application for registration is needed, the institutions shall co-sign as the applicant of the new drug. Each approved new drug, including its different strengths shall be produced by only one institution.

Article 47 For the registration application to change the dosage form without changing administration route of a marketed drug, new techniques shall be employed to improve the drug quality and safety, and the changed dosage form shall have significant clinical advantage compared with the previous dosage form.

Registration applications to change the dosage form without changing the route of administration or to claim any new indication shall be submitted by certified manufacturers, with exceptions for special dosage forms such as targeting delivery, sustained release and controlled release preparations, etc.

Article 48 In the process of the review and approval of a new drug, the registration classification and technical requirements thereof shall not be changed, even though the preparations of the same active ingredients are approved for marketing abroad.

In the process of the review and approval of a new drug, the registration classification and technical requirements thereof shall not be changed, even though the preparations of the same active ingredients applied for by domestic manufacturers are approved for marketing in China.

Article 49 The dossier for drug registration application shall be submitted at one time. No other technical materials should be added by the applicant after a drug registration application is accepted, with the exceptions for applications of special review and approval, new finding regarding drug safety, or supplementary materials as required. Where an applicant deems it integrant for any new technical material to be supplemented, the submitted application shall be withdrawn. Only if no same product is in the new drug observation period, the applicant may re-apply in compliance with the relevant requirements in the Provisions.

Section 1
Clinical Trials for New Drugs

Article 50 After completing the pre-clinical study, the applicant shall fill the Application Form for Drug Registration, and report authentically relevant materials to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where the applicant is located.

Article 51 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall conduct the preliminary review of the application dossiers, and issue a acceptance notice of drug registration application if requirements are met, or issue a non-acceptance notice, in which reasons shall be given, of drug registration application if requirements are not met.

Article 52 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall organize to conduct on-site inspections of the drug research and development conditions and raw data, make preliminary review of the submitted dossiers, and provide review opinions within five days from the date it accepts an application. Where the drug for which the registration is applied is a biological product, samples from three production batches thereof shall also be collected for testing, and a notice for the testing for registration shall be issued to the drug testing institute.

Article 53 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall deliver the review opinions, inspection reports and the application dossiers to the Center for Drug Evaluation of the State Food and Drug Administration within the specified timeline, and notice the applicants.

Article 54 The drug testing institute that receives a notice for the testing for registration shall test the samples according to the drug specifications submitted by the applicant, verify the submitted drug specifications, and submit a certificate of analysis for drug registration to the Center for Drug Evaluation of the State Food and Drug Administration within the specified timeline, and copy to the applicant.

Article 55 After receiving submitted dossiers, the Center for Drug Evaluation of the State Food and Drug Administration shall organize pharmaceutical, medical and other technical personnel to conduct technical review of the submitted dossiers within the specified timeline, and may request, with reasons, applicants to provide supplementary materials when necessary. After completing technical reviews, the Center for Drug Evaluation shall give technical review opinions and report together with relevant documents to the State Food and Drug Administration.

The State Food and Drug Administration shall make review and approval decisions based on the technical review opinions. Where the regulations are conformed to, a Drug Clinical Trial Approval shall be issued; where the regulations are not conformed to, a Disapproval Notice shall be issued with reasons provided.

Section 2
Production of New Drugs

Article 56 After completing drug clinical trials, applicants shall fill the Application Form for Drug Registration, submit production application dossiers to the drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government where the applicant is located, and at the same time provide the raw materials and research information for preparing reference standards to the National Institute for the Control of Pharmaceutical and Biological Products.

Article 57 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall conduct the preliminary review of the application dossiers, and issue an acceptance notice of drug registration application if requirements are met, or issue a non-acceptance notice, in which reasons shall be given, of drug registration application if requirements are not met.

Article 58 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall organize to conduct on-site inspections of the drug research and development conditions and raw data, make preliminary review of the submitted dossiers, and provide review opinions within five days from the date it accepts an application. For the other drugs except biological products, samples of three pr