Provisions for Drug Registration
(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.
国庆节画一等奖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 ot
her 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 按摩spa
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
用糖纸做手工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 dru
g 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 accordan
ce with the approved manufacturing processes and quality specifications.
Chapter III
萨塞克斯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.
西厢记长亭送别
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 phar
macokinetic 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