(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 production batches shall also be collected for testing, and a notice of specifications verification shall be issued to the drug testing institute.
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 59 Drug testing institutes shall verify the submitted drug specifications and give the verification opinions to the Center for Drug Evaluation of the State Food and Drug Administration within the specified timeline, and at the same time copy to the drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government that notify them to conduct the verification, and the applicants.
Article 60 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.
Where the regulations are conformed to as reviewed, the Center for Drug Evaluation of the State Food and Drug Administration shall notice the applicant to apply for production site inspection and inform the Center for Drug Certification of the State Food and Drug Administration. Where the regulations are not conformed to as reviewed, the Center for Drug Evaluation of the State Food and Drug Administration shall report the review opinions and relevant documents to the State Food and Drug Administration; the State Food and Drug Administration shall make a disapproval decision to the application based on the technical review opinions, and issue a Disapproval Notice with reasons.
Article 61 The applicant shall apply for on-site inspection to the Center for Drug Certification of the State Food and Drug Administration within six months from the date it receives the notice of production site inspection.
Article 62 The Center for Drug Certification of the State Food and Drug Administration shall, within 30 days from the date it receives the application for production site inspection, organize on-site inspection of large-scale samples production, verify the applicability of the manufacturing processes and at the same time take samples of one batch of products (samples of three batches of products for biological products), and provide production site inspection report to the Center for Drug Evaluation of the State Food and Drug Administration within ten days after the site inspection.
Article 63 Samples shall be produced at a plant with the GMP Certificate. As for a new manufacturer, a new workshop established or the production of a dosage form added at an existing manufacturer, the sample production shall meet the GMP requirements.
Article 64 Drug testing institutes shall conduct sample testing according to the verified specifications, and within the specified timeline, provide testing reports to the Center for Drug Evaluation of the State Food and Drug Administration, and copy to the relevant drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government and the applicants.
Article 65 The Center for Drug Evaluation of the State Food and Drug Administration shall make a general opinion based on the technical review opinions, production site inspection reports and sample testing results, and report the general opinion together with relevant documents to the State Food and Drug Administration. The State Food and Drug Administration shall make a review and approval decision based on the general opinion. Where the regulations are conformed to, a New Drug Certificate shall be issued; if the applicant already has a Drug Manufacturing Certificate and possesses the production conditions, a drug approval number shall be issued at the same time; where the regulations are not conformed to, a Disapproval Notice shall be issued with reasons.
A New Drug Certificate shall not be issued to the approved registration applications for changing dosage forms without changing route of administration or claiming for new indications, with exceptions for special dosage forms such as targeting delivery, sustained release and controlled release preparations, etc.
Section 3
New Drug Observation Period
Article 66 In order to protect the public health, the State Food and Drug Administration may set an observation period for any new drug approved for production. The observation period of a new drug shall be no longer than five years from the date the drug is approved for production.
During the observation period of a new drug, the State Food and Drug Administration shall not approve other manufacturers to produce, change dosage form of or import the drug.
Article 67 A drug manufacturer shall investigate the manufacturing processes, quality, stability, therapeutic effect and adverse reactions, etc. of a new drug in the observation period, and report annually to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government, where it is located. Where a drug manufacturer fails to perform its duties in the observation period, the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government shall order it to make rectifications.
Article 68 Where institutions for drug manufacturing, distribution, use, testing or supervision find any critical quality problem, serious or unexpected adverse reaction of a new drug, they shall report to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government in time. Once receiving the report, the drug regulatory department of a province, autonomous region, or municipality directly under the Central Government shall organize prompt investigation, and report to the State Food and Drug Administration.
Article 69 Where a drug manufacturer does not conduct production of the new drug, for which an observation period is set, within two years from the date of the approval, the State Food and Drug Administration may approve the application of another drug manufacturer to produce the new drug and reset the observation period of the drug.
Article 70 Starting from the date a new drug enters the observation period, any other application for the clinical trial of the same drug already approved by the State Food and Drug Administration may proceed along drug registration application, review and approval procedures; where regulations are conformed to, the State Food and Drug Administration shall approve the production or importation of the same drug. The observations of the drugs produced by the domestic manufacturers should be conducted together with the drug already in the observation period.
Article 71 Starting from the date a new drug enters the observation period, other registration applications for the same drug shall no longer be accepted. The other applicants’ applications for the same drug already accepted but not yet approved for clinical trials shall be returned; upon the expiration of the observation period of the drug, the registration of a generic or import drug may be applied for.
Article 72 Where an application for an import drug registration is approved first, the domestic application already approved for clinical trial of the drug may proceed along drug registration application, review and approval procedures; where regulations are conformed to, the State Food and Drug Administration shall approve the production of the drug; or, the applicant may withdraw the application, and submit a generic drug application. The other applications for the same drugs already accepted but not yet approved for clinical trials shall be returned; the registration of a generic drug may be applied for.
Chapter V
Application and Approval of Generic Drugs
Article 73 The applicant applying for registration of a generic drug shall be a drug manufacturer. The applied drug shall be within the production scope specified in the Drug Manufacturing Certificate.
Article 74 The generic drug shall have the identical active ingredients, route of administration, dosage form, strength and therapeutic effects with the registered drug. Where a drug has been produced by more than one manufacturer, the selection of registered drugs for comparative study shall be in accordance with relevant technical guidelines.
Article 75 To apply for the registration of a generic drug, the applicant shall fill the Application Form for Drug Registration, submit relevant dossiers and apply for production site inspection to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where the applicant is located.
Article 76 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.
As for a drug for which the protection of traditional Chinese medicine preparations has been applied, from the date the application for the protection is accepted through the date an administrative decision is made, the acceptance of the application of its generic drug shall be suspended.
Article 77 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 as well as raw data, and production site inspections according to the manufacturing processes and quality specifications provided by the applicant, and take samples of three consecutive batches of products, and send to the drug testing institutes for testing within five days starting from the date they accept an application.
The production of samples shall be in conformity with the requirements in Article 63 in the Provisions.
Article 78 Drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government shall review the submitted dossiers within the specified timeline and give review opinions. Where the regulations are conformed to, they shall provide for the Center for Drug Evaluation of the State Food and Drug Administration with the review opinions, the check report, the production site inspection report and the application dossiers, and inform the applicant. Where the regulations are not conformed to, they shall issue a Disapproval Notice with reasons, and notify the drug testing institute to terminate the testing for registration.
Article 79 Drug testing institutes shall conduct sample testing, provide testing reports to the Center for Drug Evaluation of the State Food and Drug Administration within the specified timeline, and copy to the drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government that notify them to conduct the verification, and the applicants.
Article 80 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.
Article 81 The Center for Drug Evaluation of the State Food and Drug Administration shall make a general opinion based on the technical review opinions, production site inspection reports and sample testing results, and report the general opinion together with relevant documents to the State Food and Drug Administration. The State Food and Drug Administration shall make a review and approval decision based on the general opinion. Where the regulations are conformed to, it shall issue a drug approval number or a Drug Clinical Trial Approval; where the regulations are not conformed to, it shall issue a Disapproval Notice with reasons.
Article 82 After completing drug clinical trials, applicants shall submit clinical trial data to the Center for Drug Evaluation of the State Food and Drug Administration. The State Food and Drug Administration shall issue a drug approval number or a Disapproval Notice based on the technical review opinions.
Article 83 As for a marketed drug with confirmed safety problems, the State Food and Drug Administration may decide to suspend the acceptance or review and approval of the application of its generic drugs.
Chapter VI
Application and Approval of Import Drugs
Section 1
Registration of Import Drugs
Article 84 A drug being applied for importation shall have already obtained the drug marketing authorization in the producing country or region where the overseas pharmaceutical manufacturer is located; those not yet obtained marketing authorization in the producing country or region, however confirmed with safety, efficacy and clinical needs by the State Food and Drug Administration may be approved for importation.
The production of a drug applied for importation shall comply with the GMP requirements of both the producing country or region where the drug manufacturer is located and China.
Article 85 To apply for import drug registration, the applicant shall fill the Application Form for Drug Registration, submit relevant dossiers and samples, provide relevant approval documents, and submit the application to the State Food and Drug Administration.
Article 86 The State Food and Drug Administration shall conduct the preliminary review of the application dossiers, and issue an acceptance notice of drug registration application and notify the National Institute for the Control of Pharmaceutical and Biological Products to conduct testing for registration of samples from three batches if requirements are met; or issue a non-acceptance notice of drug registration application with reasons if requirements are not met.
The State Food and Drug Administration may organize to conduct on-site inspection of development and production conditions, and take samples.
Article 87 The National Institute for the Control of Pharmaceutical and Biological Products shall organize to conduct the testing for drug registration within five days from the date it receives the dossiers and samples.
Article 88 The drug testing institutes undertaking the import drug testing shall complete the testing for registration and submit the certificate of analysis for drug registration to the National Institute for the Control of Pharmaceutical and Biological Products within 60 days from the date they receive the documents, samples and relevant reference standards.
Sample testing and verification of specifications for controlled drugs or vaccines shall be completed within 90 days.
Article 89 The National Institute for the Control of Pharmaceutical and Biological Products shall organize experts to conduct technical review within 20 days from the date it receives the certificate of analysis for drug registration and the verified import specifications, and if necessary, conduct further verification according to the review opinions.
Article 90 After completing the testing for import drug registration, the National Institute for the Control of Pharmaceutical and Biological Products shall give the verified specifications, certificate of analysis and opinions thereof to the Center for Drug Evaluation of the State Food and Drug Administration, and copy the applicants.
Article 91 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.
Article 92 The Center for Drug Evaluation of the State Food and Drug Administration shall make a general opinion based on the technical review opinions and sample testing results, and report the general opinion together with relevant documents to the State Food and Drug Administration. The State Food and Drug Administration shall make a review and approval decision based on the general opinion. Where the regulations are conformed to, a Clinical Trial Approval shall be issued; where the regulations are not conformed to, a Disapproval Notice shall be issued with reasons.
Article 93 After a clinical trial application is approved, the applicant shall conduct the trial in accordance with the requirements in Chapter III of the Provisions and the other relevant requirements.
After a clinical trial is completed, the applicant shall fill the Application Form for Drug Registration, submit the clinical trial data, other altered and supplementary data in accordance with regulations, give in detail the basis and reasons, and provide relevant approved documents.
Article 94 The Center for Drug Evaluation of the State Food and Drug Administration shall organize pharmaceutical, medical and other technical personnel to conduct comprehensive review of the submitted clinical trial data within the specified timeline, and may request, with reasons, applicants to provide supplementary materials when necessary.
The State Food and Drug Administration shall make a review and approval decision based on the general opinion. An Import Drug License shall be issued if regulations are conformed to. For a drug applied for registration by a drug manufacturer in Hong Kong, Macao or Taiwan of China, its application shall be handled in reference to the application procedures for import drug registration. If requirements are met, a Pharmaceutical Product License shall be issued; if requirements are not met, a Disapproval Notice shall be issued with reasons.
Article 95 To apply for importation of pharmaceutical preparations, approved documents for the lawful sources of the immediate packaging materials and containers and those of the drug substances and the excipients used for the pharmaceutical preparations shall be provided. Where drug substances and excipients are not yet approved by the State Food and Drug Administration, relevant data of manufacturing processes, specifications and testing methods, etc. shall be submitted.
Section 2
Registration of Import Drug Repackaging
Article 96 The import drug repackaging refers to dividing a large pack into small ones in China or adding outer-package to a drug with inner-package, placing insert sheets and attaching labels, etc., after the production process of the finished pharmaceutical preparations for the drug are completed overseas .
Article 97 To apply for import drug repackaging, the following requirements shall be met:
(1) the Import Drug License or Pharmaceutical Product License of the drug is already obtained;
(2) the drug shall be one that is not produced within the territory of China, or is produced in China but unable to meet clinical needs;
(3) one drug produced by a drug manufacturer shall be repackaged by only one drug manufacturer. The term allowed for repackaging shall not exceed the expiry date of the Import Drug License or Pharmaceutical Product License;
(4) the inner–packaging of a drug in any dosage form for repackaging, except tablets and capsules, shall be completed overseas;
(5) a drug manufacturer that conducts repackaging shall hold the Drug Manufacturing Certificate. To apply for repackaging of import unpackaged tablets and capsules, the manufacturer shall also hold the GMP certificate covering the dosage forms for repackaging; and
(6) An application for drug repackaging shall be made one year prior to the expiration of the Import Drug License or the Pharmaceutical Product License.
Article 98 An overseas drug manufacturer shall sign a contract for import drug repackaging with a domestic drug manufacturer, and fill in the Drug Supplementary Application Form.
Article 99 To apply for the repackaging of an import drug, the drug manufacturer entrusted with repackaging of the drug shall submit an application to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where it is located. The trustee shall submit the Supplementary Drug Application Form filled in by the truster, the relevant data and samples as well as the contract of entrustment, etc. The drug regulatory department shall conduct the preliminary review of the submitted documents. Where requirements are met, it shall issue a notice of acceptance; where requirements are not met, it shall issue a notice of non-acceptance with reasons.
The drug regulatory department shall make review opinions, then submit the application documents and review opinions to the State Food and Drug Administration and inform the applicant at the same time.
Article 100 The State Food and Drug Administration shall review the submitted documents. Where the regulations are conformed to, it shall issue an Approval for Supplementary Drug Application and a drug approval number; where the regulations are not conformed to, it shall issue a Disapproval Notice with reasons.
Article 101 The repackaged import drugs shall comply with the registration specifications for import drugs.
Article 102 The insert sheets and labels of a repackaged import drug shall be in conformity with those of the import drug, and shall be indicated with the approval number of the repackaging drug and the name of drug manufacturer.
Article 103 The testing for import of overseas pharmaceutical preparation in large package shall be conducted according to the State Food and Drug Administration regulations. The same specifications shall be used for the testing of both repackaged and import products.
Article 104 The overseas drug manufacturer providing the drug shall be responsible for the quality of the repackaged drug. If there is any quality problem, the State Food and Drug Administration may withdraw the approval number of the repackaged drug, revoke the Import Drug License or the Pharmaceutical Product License when necessary according to the requirements of Article 42 of the Drug Administration Law.
Chapter VII
Application of Non-Prescription Drugs
Article 105 Where the applied generic drug is regulated as a non-prescription drug, the applicant shall indicate the item of non-prescription drug in the “additional application items†of the Application Form for Drug Registration.
Article 106 Where the applied generic drug is regulated as both a prescription and non-prescription drug, the applicant may submit an application for either a prescription or non-prescription drug according to the respective requirements.
Article 107 For any of the following circumstances, the applicant may indicate the item of non-prescription drug in the “additional application items†of the Application Form for Drug Registration. If relevant requirements for non-prescription drugs apply, the drug shall be reviewed and approved, and regulated as a non-prescription drug; if relevant requirements for non-prescription drugs do not apply, it shall be reviewed and approved, and regulated as a prescription drug:
(1) To alter the dosage form of a non-prescription drug determined by the State Food and Drug Administration without changing the indications or functions, dosage and route of administration; or
(2) To formulate a new fixed dose combination using active ingredients of non-prescription drugs determined by the State Food and Drug Administration.
Article 108 For the registration application of a non-prescription drug, the insert sheet and package label shall comply with the relevant regulations on non-prescription drugs.
Article 109 For the registration application of an import drug categorized as non-prescription drug, the application, review and approval procedures for import drugs shall apply, and the technological requirements shall be the same as those for the domestically produced non-prescription drugs.
Chapter VIII
Submission, Review and Approval of Supplementary Application
Article 110 For the variation of the items specified in the approval document and its attachment for approved new drug development, drug production and import drug, supplementary applications shall be made.
The applicant shall assess the implications of the variation to the safety, efficacy and quality of the drug, and conduct corresponding technical studies in reference to relevant technical guidelines.
Article 111 The applicant shall fill in Supplementary Drug Application Form and submit relevant dossier and explanation to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where the applicant is located. 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, with reasons, of drug registration application if requirements are not met.
Article 112 For the supplementary application of an import drug, the applicant shall submit relevant dossier and explanations to the State Food and Drug Administration, and provide documents approving the variation issued by the drug regulatory department of the producing country or region. The State Food and Drug Administration 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 113 For any supplementary application to amend the drug registration specifications, change excipients for pharmaceutical use in the drug formulation, or modify the manufacturing process that affects the drug quality, etc., the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government shall provide a review opinion, report it to the State Food and Drug Administration for review and approval, and inform the applicant at the same time.
For supplementary application to amend the drug registration specifications, the drug testing institute shall verify the specifications when necessary.
Article 114 For any supplementary application to change the name of a domestic drug manufacturer, the shelf-life of a domestically produced drug, or the production site by a domestic drug manufacturer internally, etc., the drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government shall conduct the acceptance, review and approval. Where the regulations are conformed to, it shall issue an Approval for Supplementary Drug Application, and report to the State Food and Drug Administration for record; where the regulations are not conformed to, it shall issue a Disapproval Notice with reasons.
Article 115 Any supplementary application to alter drug packaging label in accordance with regulations, or amend the insert sheet as required by the State Food and Drug Administration, etc. shall be filed to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government for record.
Article 116 Supplementary applications of import drugs shall be reviewed and approved by the State Food and Drug Administration. Those supplementary applications to change the place of production of the drug substance used for any import drug preparation, change the appearance of an import drug not resulting in specification changes, amend the insert sheet of an import drug according to the national specifications or the requirements of the State Food and Drug Administration, update the safety information in the insert sheet of an import drug, alter drug packaging label in accordance with regulations, or change the registration agent shall be filed to the State Food and Drug Administration for record.
Article 117 For supplementary applications of drug manufacturing technology transfer, altering formula or manufacturing process that may affect product quality, etc., the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government shall organize production site inspection, according to the attachment of the Letter of Approval for Drug Registration or the verified manufacturing process. Drug testing institutes shall conduct testing on samples of three batches of product.
Article 118 While reviewing drug supplementary applications, the State Food and Drug Administration may require, with reasons, the applicants to submit additional documents when necessary. Where the regulations are conformed to, it shall issue an Approval for Supplementary Drug Application and a drug approval number; where the regulations are not conformed to, it shall issue a Disapproval Notice with reasons.
Article 119 After the supplementary application is approved, if a drug approval document is to be renewed, the original one shall be cancelled by the State Food and Drug Administration; if an additional drug approval certificate is to be issued, the original one shall remain valid.
Chapter IX
Drug Re-Registration
Article 120 The valid term of a drug approval number, Import Drug License or Pharmaceutical Product License issued by the State Food and Drug Administration is five years. To continue its drug production or importation, the applicant shall submit a re-registration application six months prior to the expiry date.
Article 121 Within the valid term of a drug approval number, Import Drug License or Pharmaceutical Product License, the applicant shall conduct systematic assessment on the safety, efficacy and quality control of the drug such as relevant research results in the observation period, adverse reaction monitoring, production control and product quality consistency, etc.
Article 122 Where applying for drug re-registration, the holder of a drug approval number shall submit the application to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government, fill in the Application Form for Drug Re-registration, and provide relevant data.
Where applying for an import drug re-registration, the applicant shall submit the application to the State Food and Drug Administration.
Article 123 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall review the application dossiers, and issue a acceptance notice of drug re-registration application if requirements are met, or issue a non-acceptance notice, in which reasons shall be given, of drug re-registration application if requirements are not met.
Article 124 Drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government shall review the application dossiers within six months starting from the date of acceptance, and approve the re-registration application if regulations are conformed to, or report to the State Food and Drug Administration if regulations are not conformed to.
Article 125 The State Food and Drug Administration shall deal with import drug re-registration applications, complete the review within six months, and approve the re-registration application if regulations are conformed to, or issue a non-acceptance notice, in which reasons shall be given, if regulations are not conformed to.
Article 126 In any of the following circumstances, a drug shall not be re-registered:
(1) the application for re-registration is not made prior to the expiry date;
(2) the relevant requirements set by the State Food and Drug Administration when approved for marketing are not met;
(3) the phase IV clinical trial is not completed as required;
(4) the adverse drug reaction monitoring is not conducted in accordance with regulations;
(5) there are uncertain therapeutic efficacy, serious adverse reaction or other factors harmful to human health upon re-evaluation by the State Food and Drug Administration;
(6) the drug approval documents shall be withdrawn in accordance with the provisions of the Drug Administration Law;
(7) the production conditions prescribed in the Drug Administration Law are not met;
(8) the obligation of observation period is not fulfilled in accordance with regulations; or
(9) there are other circumstances not in conformity with relevant regulations.
Article 127 After receiving the opinions from the drug regulatory departments of the provinces, autonomous regions, or municipalities directly under the Central Government, the State Food and Drug Administration shall review the application. Where the regulations on drug re-registration are not conformed to, a notice of rejection for re-registration shall be issued with reasons.
Where a re-registration application has been rejected, except where the drug approval document is withdrawn due to lawfully defined reasons, the drug approval number, Dug Import License or Pharmaceutical Production Certificate shall be withdrawn on the expiry date.
Chapter X
Testing for Drug Registration
Article 128 Testing for drug registration consists of sample testing and verification of specifications.
Sample testing refers to the testing of samples conducted by a drug testing institute according to the specifications submitted by an applicant or checked by the State Food and Drug Administration.
Verification of specifications refers to the laboratory testing and review conducted by a drug testing institute on the feasibility and scientific basis of the testing methods and the controllability of the set items and indicators of drug quality in the submitted specifications.
Article 129 The National Institute for the Control of Pharmaceutical and Biological Products or the drug testing institutes of the provinces, autonomous regions, and municipalities directly under the Central Government shall take charge of the testing for drug registration. The National Institute for the Control of Pharmaceutical and Biological Products shall arrange testing for import drug registration.
Article 130 The testing for registration of the following drugs shall be conducted by the National Institute for the Control of Pharmaceutical and Biological Products or the drug testing institutes designated by the State Food and Drug Administration:
(1) drugs prescribed in subparagraph (1) and (2) of Article 45 of the Provisions;
(2) biological products and radioactive pharmaceuticals; and
(3) other drugs specified by the State Food and Drug Administration.
Article 131 Where a drug is permitted entering a special review and approval procedure, the drug testing institute shall give priority to sample testing and specification verification.
Article 132 A drug testing institute engaged in testing for drug registration shall, in compliance with the requirements set forth by the Good Laboratory Practice of drug testing institute and national metrology accreditation, have qualified personnel and adequate equipment, and comply with the quality assurance system and technical requirements of the testing for drug registration.
Article 133 An applicant shall provide the relevant data, samples and reference standards, or assist in sampling, which are required for the testing for drug registration. The amount of samples shall be three times the amount used for testing and, for biological products, manufacturing record for the relevant batches of products shall also be provided.
Article 134 While verifying the specifications of a new drug, the drug testing institute shall, in addition to sample testing, give verification opinions in respect of the specifications and test items, etc., of the drug referring to the study data, the specifications of the same kind of products at home and abroad and relevant requirements.
Article 135 Where the specifications are required to be reestablished, the applicant shall not entrust the drug testing institute that gave verification opinions to conduct the specification study of the drug; and the drug testing institute shall not accept such entrustment.
Chapter XI
Drug Registration Specifications and Insert Sheet
Section 1
Drug Registration Specifications
Article 136 National drug standards refer to the Pharmacopoeia of the People's Republic of China, drug registration specifications, etc. published by the State Food and Drug Administration, including the technical requirements such as specifications, testing methods and manufacturing processes, etc.
Drug registration specifications refer to the specified specifications of the applied drug approved by the State Food and Drug Administration to the applicant. The specifications shall be implemented by the drug manufacturer producing the drug.
Drug registration specifications shall not be lower than those required by the Chinese Pharmacopoeia.
Article 137 The establishment of items and the testing methods for drug registration specifications shall be in conformity with the basic requirements of the Chinese Pharmacopoeia, the technical guidelines and rules for compiling the national drug standards published by the State Food and Drug Administration.
Article138 An applicant shall select representative samples for drug registration specifications study.
Section 2
Drug Reference Standards
Article 139 Drug reference standards refer to the materials used in physical, chemical or biological testing specified in specifications and have assigned values of a quantity, and are used for equipment calibration, method validation or value assignment of drugs to be tested, and include reference standards, reference substances, reference crude drugs and reference reagents.
Article 140 The National Institute for the Control of Pharmaceutical and Biological Products shall be responsible for the characterization of national reference standards.
The National Institute for the Control of Pharmaceutical and Biological Products may organize relevant drug testing institute of provinces, autonomous regions, and municipalities directly under the Central Government, drug research institutions or drug manufacturers to undertake collaborative assays of such standards.
Article 141 The National Institute for the Control of Pharmaceutical and Biological Products shall be responsible for the overall technical evaluation of the characterized reference standards in respect of the data of source material selection, preparation methods, testing methods and results, accuracy of value assignment, traceability, stability, filling and packaging conditions, etc. and shall conclude whether or not the candidate materials can be used as national reference standards.
Section 3
Drug Name, Insert Sheet and Label
Article 142 The name, insert sheet and label of any drug for which the registration is applied, shall comply with the provisions of the State Food and Drug Administration.
Article 143 The drug insert sheet and label shall be provided by the applicant. The Center for Drug Evaluation of the State Food and Drug Administration shall review the contents thereof except the manufacturer information, and the State Food and Drug Administration shall review and approve the data when approving the drug production.
The applicant shall be responsible for making the drug insert sheet and label scientific, standard and accurate.
Article 144 The applicant shall monitor the safety and efficacy of a marketed drug, and submit supplementary application to modify the drug insert sheet in time.
Article 145 The applicant shall print the insert sheets and labels according to the format and requirements established by the State Food and Drug Administration, and in conformity with the contents approved.
Chapter XII
Timeline
Article 146 The drug regulatory department shall follow the provisions on the timeline for drug registration set forth in the Drug Administration Law, the Administrative Permission Law and the Regulations for Implementation of the Drug Administration Law. The timeline for drug registration in the Provisions refers to the maximum time for acceptance, review and approval of drug registration. The time for the suspension of the review and approval prescribed in laws and regulations or for the applicant to supplement data is not included.
The time for the testing for drug registration and for the review shall be kept in accordance with the Provisions. Where there is a need for time extension in particular situation, it, with reasons provided, shall be reported to the State Food and Drug Administration for approval, and the applicant shall be informed thereof.
Article 147 Drug regulatory departments shall conduct preliminary review on applications, and proceed according to the following circumstances respectively:
(1) Where no administrative approval is needed for any application item by law, the non-acceptance of the application thereof shall be informed to the applicant in time;
(2) Where an application item is not subject to the jurisdiction of the concerned departments by law, it shall be decided not to accept the application in time and informed to the applicant to apply to the relevant administrative departments;
(3) Where there is an error that can be corrected on-site in the dossier, the on-site correction shall be allowed;
(4) Where the dossier is incomplete or not conformed with the defined format, the applicant shall be informed on-site or within five days at once of what to be supplemented or corrected; if it is not informed to the applicant within the timeline, the application is regarded as accepted on the date the dossier is received; and
(5) Where the application item is subject to the jurisdiction of the concerned departments, and the dossier is complete and conformed with the defined format or the applicant has submitted all the required supplementary or corrected data, the application of drug registration shall be accepted.
Where a drug regulatory department accepts or rejects a drug registration application, it shall issue a written receipt on which there shall be a stamp of registration and date.
Article 148 The drug regulatory department of a province, autonomous region, or municipality directly under the Central Government shall complete the check of drug development conditions and raw data, the review of application dossiers, sampling, the notice to drug testing institutes for conducting testing for drug registration, the submission of review opinions, inspection report and application dossiers to the State Food and Drug Administration, and the notice to the applicant of the review opinions within 30 days starting from the date an application is accepted.
Article 149 The time for the testing for drug registration shall be kept in accordance with the following provisions:
(1) sample testing: 30 days; sample testing and specifications verification : 60 days; and
(2) sample testing of a controlled drug or vaccine: 60 days; sample testing and specifications verification: 90 days.
The sample testing for a drug used for clinical trial conducted by a drug testing institute, as prescribed in Article 36 of the Provisions, shall be completed within the time for sample testing in the previous clause.
Article 150 The time for technical review shall be kept in accordance with the following provisions:
(1) new drug application for clinical trial: 90 days; any drug permitted to enter the special review and approval procedures: 80 days;
(2) new drug application for production: 150 days; any drug permitted to enter the special review and approval procedures: 120 days;
(3) the application for changing the dosage form of a marketed drug or for a generic drug: 160 days; and
(4) the supplementary application subject to technical review: 40 days.
The time for the technical review of an import drug registration application shall be kept in accordance with the previous clause.
Article 151 Where the applicant is required to supplement data in the process of technical review, a Deficiency Notice should be issued at one time. Where the applicant disagrees on the contents of the Deficiency Notice, the opinions of the applicant may be heard vis-Ã -vis. The applicant shall provide supplementary data at one time according to the requirements in the notice within four months; where an application enters the special review and approval procedures, it shall be handled in conformity with the requirements of the relevant procedures.
After receiving the supplementing data, the technical review shall be completed in no more than one third of the original time; for applications entering the special review and approval procedures, the review shall be completed in no more than one fourth of the original time.
Where an application is recalled by the applicant in the process of drug registration, the review and approval procedure is terminated henceforth.
Article 152 The State Food and Drug Administration shall make the review and approval decision within 20 days; where a decision cannot be made within 20 days, another ten days may be extended with the approval of the State Food and Drug Administration head in charge, and the applicant shall be informed of the reason of the time extended.
Article 153 The State Food and Drug Administration shall issue and deliver relevant administrative licensing certificates within ten days from the date the review and approval decision is made.
Chapter XIII
Second Review
Article 154 Where there is any of the following circumstances, the State Food and Drug Administration shall not approve the application:
(1) different applicants submit the same or almost the same research data without justified reasons;
(2) when the application dossier is found false in the process of registration, and the applicant cannot prove the authenticity thereof;
(3) the design and performance of the research project are not able to support to evaluate the safety, efficacy and quality of the drug applied for registration ;
(4) there are critical defects regarding the safety, efficacy and quality in the submitted dossier of the drug applied for registration;
(5) an applicant fails to provide supplementary data within the prescribed timeline;
(6) the source of drug substances does not meet the requirements;
(7) the result of production site inspection or sample testing does not meet the requirements;
(8) other circumstances in which applications shall not be approved according to laws and regulations.
Article 155 The written non-acceptance or unapproval decision made by drug regulatory departments by law shall provide the reasons thereof, and inform the applicant of the right to apply for administrative reconsideration or to bring an administrative suit by law.
Article 156 If holding any dispute on the unapproval decision made by the State Food and Drug Administration, an applicant may, within 60 days after receiving the decision, fill in the Application Form for Drug Registration Second Review, and submit the application to the State Food and Drug Administration and provide reasons.
The content of second review shall not exceed the originally applied items and the original application dossier.
Article 157 The State Food and Drug Administration shall make a second review decision, and notify the applicant the decision within 50 days after receiving an application for second review. Where the original decision is affirmed, the State Food and Drug Administration shall not accept any further application for second review thereof.
Article 158 Where there is any need for technical review in second review, the State Food and Drug Administration shall organize relevant technical personnel to conduct review within the timeline as that for the original application.
Chapter XIV
Legal Liabilities
Article 159 In any of the circumstances prescribed in Article 69 of the Administrative Permission Law, the State Food and Drug Administration may withdraw the relevant drug approval documents upon the request of any interest party or according to its responsibilities and authorities.
Article 160 Any drug regulatory department or its staff members that violate the provisions of this Provisions and constitute any of the circumstances below shall be instructed by its superior administrative department or supervisory departments to make rectification. If the circumstances are serious, administrative sanctions shall be given to the persons directly in charge and the other persons directly responsible in accordance with law:
(1) not accepting a drug registration application that is in conformity with regulatory requirements;
(2) not publicizing at the acceptance place the information that shall be publicized by la]w;
(3) in the process of acceptance, review and approval, not fulfilling the regulatory informing obligation to the applicant or interest party;
(4) not informing the applicant at once of all the contents needed to be supplemented or corrected, where the drug application dossier submitted is incomplete or not conformed with the required format;
(5) not stating the reasons of non-acceptance or unapproval of a drug registration application by law; and
(6) not holding hearings that shall be held by law.
Article 161 If any drug regulatory department and its staff members request for or accept money or valuable articles from others, or pursue other interests in the process of drug registrations, where a crime is committed, criminal liabilities shall be investigated by law; where a crime is not committed, administrative sanctions shall be given by law.
Article 162 Any drug regulatory department that constitutes any of the following circumstances in the process of drug registration shall be instructed by its superior administrative department or supervisory departments to make rectification, and administrative sanctions shall be given to the persons directly in charge and the other persons directly responsible by law; if a crime is committed, criminal liabilities shall be investigated by law:
(1) making a decision to approve any registration application that does not meet the regulatory requirements prescribed in the Provisions or acting beyond regulatory responsibilities and authorities to make such a decision;
(2) making a decision to disapprove a registration application conformed with the regulatory requirements, or failing to make a decision to approve a registration application within the regulatory timeline; and
(3) failing to perform the confidentiality obligation in violating the requirements prescribed in Article Nine of the Provisions.
Article 163 When undertaking testing for drug review and approval, a drug testing institute that issues a false certificate of analysis shall be punished in accordance with the provisions in Article 87 of the Drug Administration Law.
Article 164 Any drug regulatory department that charges fees without permission or does not charge fees according to set items and rates shall be instructed by its superior administrative department or supervisory departments to return the illegal charges; and administrative sanctions shall be given to the persons directly in charge and the other persons directly responsible by law.
Article 165 Where the Good Laboratory Practice for Non-Clinical Laboratory Studies or the Good Clinical Practice is not executed in the process of drug registration according to regulations, punishments shall be given in accordance with the provisions in Article 79 of the Drug Administration Law.
Article 166 Where an applicant submits false drug registration dossier and samples when applying for clinical trial, the drug regulatory department shall not accept the application or disapprove the applied clinical trial, give a disciplinary warning to the applicant, and not accept any further application for clinical trial of the drug made by the applicant within one year; where clinical trial of the drug is already approved, the Drug Clinical Trial Approval shall be withdrawn, a fine of no less than 10,000 yuan but no more than 30,000 yuan shall also be imposed, and no further application for clinical trial of the drug made by the applicant shall be accepted within three years.
The State Food and Drug Administration shall keep records of the fraud acts of applicants that submit false dossier and samples, and publicize such records.
Article 167 Where an applicant submits false drug registration dossier and samples when applying for drug production or importation, the State Food and Drug Administration shall not accept or disapprove the application, give a disciplinary warning to the applicant, and not accept any further application made by the applicant within one year; where the production or importation of the drug is already approved, the drug approval documents shall be withdrawn, no further application made by the applicant shall be accepted within five years, and a fine of no less than 10,000 yuan but no more than 30,000 yuan shall also be imposed.
Article 168 According to the provisions in Article 27 of the Provisions, where a drug testing needs to be repeated but the applicant refuses to do so, the State Food and Drug Administration shall give a warning and instruct to make rectification; if the applicant refuses to make rectification, the application thereof shall not be approved.
Article 169 Where there is any of the following circumstances, the State Food and Drug Administration shall withdraw the drug approval number, and announce to the public:
(1) the applicant requests to annul its own drug approval number before the drug approval document expires;
(2) the re-registration is not allowed according to provisions in Article 126 of the Provisions;
(3) the Drug Manufacturing Certificate is revoked or withdrawn by law;
(4) according to provisions in Article 42 of the Drug Administration Law or Article 41 of the Regulations for Implementation of the Drug Administration Law, the drug approval document is withdrawn for any drug with serious adverse reactions or other factors harmful to human health;
(5) a decision is made to give an administrative sanction of revoking the drug approval document by law; and
(6) other circumstances in which the drug approval documents shall be withdrawn or recalled by law.
Chapter XV
Supplementary Provisions
Article 170 The application dossier and requirements of traditional Chinese medicines and natural medicines, pharmaceutical products, biological products, supplementary applications and re-registration application shall be referred to Annex 1, 2, 3, 4, 5 of the Provisions, seriatim. Provisions on observation period are prescribed in Annex 6.
Article 171 The format of drug approval number: Guo Yao Zhun Zi H (or Z/S/J)+ four-digit year number+ four-digit sequence number; H standing for pharmaceutical products, Z for traditional Chinese medicines, S for biological products and J for repackaged import drugs.
The format of Import Drug License number: H (or Z/S)+ four-digit year number+ four-digit sequence number; that of Pharmaceutical Product License number: H (or Z/S) C+ four-digit year number+ four-digit sequence number; H standing for pharmaceutical products, Z for traditional Chinese medicines, S for biological products. For a drug repackaged in China using the license for the large package, the letter B shall be added before the registration number of the original license thereof.
The format of new drug certificate number: Guo Yao Zheng Zi H (or Z/S)＋four-digit year number+ four-digit sequence number; H standing for pharmaceutical products, Z for traditional Chinese medicines, S for biological products.
Article 172 The acceptance of applications, review and approval of supplementary applications and of re-registration applications undertaken by the drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government prescribed by the Provisions are items delegated by the State Food and Drug Administration. The State Food and Drug Administration may also delegate the drug regulatory departments of provinces, autonomous regions, or municipalities directly under the Central Government to conduct other technical review and review and approval of drug registration.
Article 173 The State Food and Drug Administration adopts the coding management for drugs approved for marketing. The provisions for coding management are separately formulated.
Article 174 The registration applications for narcotic drugs, psychotropic substances, toxic medicines and radioactive pharmaceuticals, besides complying with the Provisions, shall also conform with other relevant State regulations.
Article 175 The provisions for registration of Chinese crude drugs, prepared slices of Chinese crude drugs and import Chinese crude drugs regulated via approval numbers shall be separately formulated by the State Food and Drug Administration.
Article 176 The provisions for drug technology transfer and entrusted manufacturing shall be separately formulated.
Article 177 The Provisions shall go into effect as of October 1, 2007. The Provisions for Drug Registration (Order No. 17 of the State Food and Drug Administration) issued by the State Food and Drug Administration on February 28, 2005 shall be repealed at the same time.
+86-400-6578191
