Drug Registration Authorities, State Drug Administration
August 6, 2002
Chapter 1: General Principles
Article 1: This Regulation is promulgated according to the Drug Administration Law of The People¡¯s Republic of China (hereinafter Drug Administration Law) and the Implementing Regulation of the Drug Administration Law of The People¡¯s Republic of China (hereinafter Implementing Regulation) to ensure the safety, efficacy and quality control of drugs and standardize drug registration.
Article 2: All parties and individuals engaged in drug research, application for clinical trial, application for production and importation including those responsible administrations of related drug testing, supervision, registration administration in The People¡¯s Republic of China (PRC) shall observe by this Regulation.
Article 3: The State Drug Administration (SDA) is the competent national authority for drug registration, and review and approval of clinical research, production and importation of drugs.
Article 4: The state shall encourage and support research and development of innovative drugs and exercise fast track approval for innovative drugs and those which treat difficult and serious diseases.
Article 5: All research institutions and individuals applying for drug registration shall possess all rights to engage in civil activities.
The application for registration of import drugs shall be handled by offices of foreign manufacturers or their registered agents in the PRC.
A drug registration applicant £¨hereinafter: applicant£©or its agent shall be a lawful institution registered with the administrative authorities for commerce and industry in PRC. An institution which acts as an agent for drug registration shall be staffed with professional personnel and authorized by the drug registration applicant.
Personnel engaged in drug registration application shall be familiar with laws and regulations of drug registration administration and relevant technical requirements.
Chapter 2: Application for Drug Registration and its Acceptance
Article 6: Applications for drug registration are classified into new drug application, abbreviated application and supplementary application.
A new drug application refers to the application for registration of a drug that has not been marketed in PRC. A drug that has been marketed in PRC with a change in dosage form, administration route or new combination formulation shall be administrated as a new drug.
Abbreviated application refers to the application for registration of a drug for which the state has already set standards. Raw materials of TCM, TCM preparations and TCM extractions are also administered through abbreviated application.
Supplementary application refers to application for registration of a change, additional, cancellation and withdrawal of items or contents in the original application after acceptance or approval of the new drug application or abbreviated application by SDA.
Article 7: The registration application of a new drug shall be made in two steps: application for clinical research; and, application for production (importation).
A drug for which an abbreviated application is made normally can directly be made for production. If a clinical study is necessary, the application shall be made in two steps, for clinical study and for production (importation).
In a special situation, after approval by SDA, the applicant may directly apply for production (importation) of drugs used in the treatment of diseases that seriously harm human health.
Article 8: For a new drug application, the applicant shall apply and submit necessary materials and sample products to the drug administration authorities of the people¡¯s government of¡¡each¡¡province,¡¡autonomous¡¡region,¡¡or¡¡municipality directly under the Central Government (hereinafter ¡°provincial drug administration authorities¡±) designated by SDA.
The provincial drug administration authorities shall review the submitted materials for completeness. The authorities shall register (accept) an application which complies with requirements, inspect research and production sites, examine the conditions, data, authenticity and standardization of materials for pilot manufacture, take samples and notify the institutes for control of pharmaceutical products to test the samples. After completion of the above-mentioned items, these authorities shall submit the review recommendations, inspection report and materials and sample products provided by the applicant to SDA, notifying the applicant of the review recommendations.
The samples of biological products, import drugs and new drugs not having obtained marketing approval in any country shall be tested by the National Institute for the Control of Pharmaceutical and Biological Products (NICPBP) or a SDA-designated drug control institute. The samples of other new drugs and drugs administered as new drugs shall be tested by the provincial drug control institutes.
SDA shall accept submitted materials which after its review meet requirements.
Article 9: The provincial drug administration authorities shall complete review of submitted materials within 25 days after acceptance of the new drug application.
SDA shall complete review and determine whether to accept the application within 5 days of receipt of the materials and sample products provided by the provincial drug administration authorities.
Article 10: Generally, the provincial drug administration authorities shall complete review within 10 days after acceptance of the application for registration of the following new drugs:
1) new drug not approved for marketing in any country;
2) new drug for treatment of AIDS, tumor and rare diseases, etc;
3) new drug for treating diseases for which there is no effective treatment;
4) new vaccine.
SDA shall complete review and determine whether to accept the application within 3 days of receipt of the materials and sample products provided by the provincial drug administration authorities.
Article 11: For a drug for which an abbreviated application is made, the applicant shall apply and submit materials and sample products to the provincial drug administration authorities.
Within 30 days of acceptance of the application, the provincial drug administration authorities shall examine the conditions, data, authenticity and standardization of materials for pilot manufacture, conduct on-site sampling, and notify the institutes for control of pharmaceutical products to test the samples. After completion of the above-mentioned items, these authorities shall submit the review recommendations, inspection report and materials and sample products provided by the applicant to SDA, notifying the applicant of the review recommendations.
If clinical study is necessary, after the sample products passed test requirements, the study shall be conducted after review and approval by the provincial drug administration authorities. After completion of the clinical study, the provincial drug administration authorities shall submit the review recommendations, inspection report and materials provided by the applicant to SDA, notifying the applicant of the review recommendations.
SDA shall complete review and determine whether to accept the application within 3 days of receipt of the materials and sample products provided by the provincial drug administration authorities.
Article 12: For a supplementary application, the applicant proceed according to the original application procedures. The provincial drug administration authorities shall complete review within the time limit of the original application, and after making recommendations, report to SDA for review and approval.
If clinical study is necessary for a supplementary application, the study shall be reviewed and approved by the provincial drug administration authorities.
Article 13: For application for registration of an import drug and a corresponding supplementary application, the drug registration applicant or its agent shall apply and submit materials and sample products to SDA or, the provincial drug administration authorities authorized by SDA and provide relevant supporting documents. SDA shall be responsible to examine the conditions, materials, authenticity and standardization and completeness.
For a drug for which application is made according to Article 8 and Article 11, Paragraph 1, SDA shall determine whether to accept the application within 30 days; for drug whose application is made according to Article 10, SDA shall determine whether to accept the application within 15 days.
Article 14: The application for registration of a new drug developed by two or more institutions shall be submitted to the provincial drug administration authorities in the jurisdiction where the preparation manufacturer is located. If all the applicants are manufacturers, the application shall be submitted to the provincial drug administration authorities in the jurisdiction where the preparation manufacturer is located.
Article 15: The applicant for abbreviated application of registration shall be a lawful drug manufacturer with Drug Manufacturing License and GMP Certificate. A drug for which application is made shall be within the scope applied for registration of production described in the Drug Manufacturing License and GMP certificate.
Chapter 3: Pre-clinical Laboratory Study of Drugs
Article 16: The scope of clinical laboratory study of a drug for registration includes synthetic process, extraction methods, purity, screening of formulas, preparation process, physical-chemical properties, dosage form selection, testing methods, quality standard, stability, pharmacology and toxicology and animal pharmacokinetic study, etc. TCM preparations should include source of raw materials, processing, etc. As for biological products, it also includes names of bacterial colony or initial material and specification for preparation and testing, etc.
Article 17: Non-clinical drug safety evaluation shall be conducted in accordance with Good Laboratory Practice for Pre-Clinical Laboratory Studies (GLP). Various pharmacodynamic and pharmaceutical studies shall be conducted according to relevant regulations.
Article 18: Institutions engaged in drug research and development shall have the necessary personnel, facility, equipment, instruments, conditions and management system for the research project. The animals, reagents and raw materials used for experiments shall comply with relevant national regulations and requirements; the authenticity of all data and materials shall be ensured.
Article 19: The raw materials for research and development of preparations shall be those with an approval number provided by a drug manufacturer. If import drug substances are necessary, they shall be provided by a foreign drug manufacturer with Import Drug Certificate or Pharmaceutical Product Certificate for the drug substances.
Article 20: If a drug registration applicant authorizes a drug research institution, drug manufacturer or other research institution to conduct a study of drugs or a single experiment, inspection or pilot production and manufacture, the applicant shall sign a contract with the contract receiver and maintain responsibility for the authenticity of study data and materials.
Article 21: The pilot production and manufacture of drugs for clinical study shall be conducted by a manufacturer with the GMP certificate and in accordance with the requirements of GMP.
Sample drugs for clinical study manufactured abroad, shall meet the above requirements, supporting documents including GMP Certificate. SDA may send people to do on-site inspection if necessary.
Article 22: If the drug registration applicant uses the non-clinical laboratory study documents by a foreign drug research institution as supporting materials for a drug registration application, an explanation of the and pages of the submitted materials by the foreign drug research institution and governmental document proving its lawful foreign registration shall be attached. After authentication by SDA the documents can be used as the application materials. SDA may send people to do an on-site inspection, if necessary.
Article 23: SDA and the provincial drug administration authorities may audit and inspect drug studies, requiring the applicant or designed drug research institute to repeat experiments according to items, methods and data listed in the application materials and conduct on-site inspection, or designate other drug control institutes or drug research institutions to repeat the experiments.
An applicant who refuses to repeat the experiments according to relevant requirements shall be warned, ordered to correct the situation within or have its application cancelled.
Article 24: The non-clinical laboratory study of drugs shall be conducted in accordance with relevant technical guidelines issued by SDA.
The drug registration applicant may conduct experiments according to scientific and advanced evaluation means and techniques. However, if the methods and techniques have not been widely used and scientifically proven, the applicant shall discuss the scientific and feasibility aspects in advance with SDA in advance.
Article 25: The research of narcotics, psychotropic, medical-use toxic drugs and radioactive drugs shall be conducted after approval in accordance with relevant national regulations.
Chapter 4: Clinical Study of Drugs
Section 1: Basic Requirements
Article 26: Clinical study of drugs includes clinical trials and bioequivalence trials and shall be conducted according with of Good Clinical Practice (GCP).
An applicant for new drug registration shall conduct clinical trials or bioequivalence trials.
An abbreviated application of drug registration for solid oral dosage generally only needs to conduct bioequivalence trials. Generally, injections, liquid oral dosage and preparations for external use may be exampled from bioequivalence trials unless otherwise required by SDA.
For a supplementary application, bioequivalence trials are generally needed for drugs already marketed for a change in formulation or significant changes in preparation process, or equipment, etc. If clinical trials are needed due to special conditions, the applicant shall conduct them according to requirements of SDA.
Article 27: Clinical trials of new drugs are divided into Phase I, Phase II, Phase III and Phase IV. Clinical trials of Phase I, Phase II and Phase III are needed for a new drug application.
Phase I Clinical Trial: Initial study on clinical pharmacology and human safety. The objective is to observe the tolerability and pharmacokinetics of a new drug in human body, to provide the basis for drug usage protocol.
Phase II Clinical Trial: Randomized blind controlled clinical trial. The purpose is to make preliminary evaluation on the efficacy and safety of a new drug and recommend the dosage for medication.
Phase III Clinical Trial: Extended controlled and non-controlled multi-center clinical trials to further evaluate the efficacy and safety of a new drug.
Phase IV Clinical Trial: New drug post-marketing study. The objective is to investigate the efficacy and adverse drug reactions of new drug under the conditions of wide use.
Article 28: The number of cases in the clinical study of a drug should meet statistical requirements. A reduction or exemption for the number of cases in the clinical study for drugs used in treatment of rare and special diseases or, under other special circumstances, must be approved after review by SDA.
Article 29: If a small-size human study must be conducted because of the lack of available animal experimental model during the selection stage of bacterial and toxicity strains for a vaccine; or if a drug or preparation cannot be evaluated by in vitro study or animal trial, application may be made to SDA for special clinical studies provided that safety is ensured.
Article 30: Clinical study of new drugs may not be conducted without approval of SDA. The clinical study of drugs on which an abbreviated application is made may not be conducted without approval by the provincial drug administration authorities.
Section 2: Requirements before Implementation
Article 31: Before approval for a clinical study, the drug registration applicant may, from legally qualified institutions for clinical trials, select, negotiate and determine the responsible institution, principal investigator and participating institutions for the clinical study.
Article 32: The drug registration applicant shall sign a letter of intent with the responsible institution it selected for clinical study, and then negotiate the clinical trial protocol with reference to technical guiding principles and draft Informed Consent Form and Investigator¡¯s Brochure. The applicant shall have Ethics Committee of the responsible institution review the scientificness of clinical trial protocol and involved ethical issues.
Article 33: The ethics committee of the selected responsible institution for clinical study shall comply with GCP and issue its recommendations in written form after review and discussion of the scientificness of the clinical trial protocol, qualifications of the investigators, facilities for clinical trial and contents and methods for obtaining agreement to Informed Consent Form. The written recommendations shall be submitted by applicant to SDA before completion of the review of the clinical trial application.
Article 34: After approval of the clinical study, the applicant should sign a contract with the responsible and participating institutions for clinical study and provide the investigative drug and comparator drugs at no cost (expect for Phase IV clinical trials). The applicant should cover the expenses of the clinical study and work with the selected institutions to study and optimize the protocol and familiarize those involved with the clinical study with technical materials such as the Investigator¡¯s Brochure, etc.
Article 35: Before implementation of the clinical study, the applicant shall file for the record with SDA regarding the responsible institution, principle investigator and participating institutions for the clinical study, agreement by the ethics committee, protocol for the clinical study and sample of the Informed Consent Form, etc. and notify in writing the provincial drug administration authorities where the institutions participating in the clinical study are located.
Section 3: Administration of Clinical Study
Article 36: After approval of the clinical study application, the drug registration applicant shall designate personnel with certain professional knowledge, in accordance with relevant requirements of the GCP, to monitor the clinical study to ensure its implementation is based on the protocol, examine the accuracy and completeness of study data, inspect appropriate use of experimental facilities, continuously monitor the study, analyze the safety and efficacy of the investigative drugs and duly provide relevant information to the clinical trial institutions and investigators.
Article 37: If an applicant discovers clinical trial institution is in violation of relevant regulations in not implementing the clinical study protocol, the applicant shall urge them to rectify the situation. For serious violations, the applicant may and suspend or stop the clinical study and shall submit a written report to SDA and the relevant provincial drug administration authorities.
Article 38: If the duration of clinical study exceeds 1 year, the applicant shall submit annual clinical study progress report to SDA and relevant provincial drug administration authorities.
Article 39: The participating clinical study institutions shall be know of and familiarize themselves with the properties, therapeutic activities, efficacy and safety of the investigational drugs and clearly know their responsibility and duties, and they shall sign Informed Consent Form together with the subjects before implementing the clinical study. They shall keep accurate, true and timely records during the clinical study.
Article 40£º If a drug registration applicant violates GCP by asking that source data and conclusions be changed during the process monitoring and inspection, etc., the participating clinical study institutions shall report the circumstances to the provincial drug administration authorities and SDA.
Article 41: During clinical study, the research sites shall strictly observe serious adverse events and take necessary measures to protect the subjects from risk. If a serious adverse event occurs, the institution shall immediately take all appropriate treatments to protect the subjects from risk, and report the events to the provincial drug administration authorities and SDA within 24 hours.
Article 42: The participating institutions for the clinical study shall take necessary measures to ensure the safety of the subjects and make written record. If a serious adverse event occurs, the investigator shall immediately take therapeutic measures for the subject and report to drug administration authorities, sponsor and Ethics Committee and sign its name and date.
Article 43: The provincial drug administration authorities and SDA are responsible for inspection and monitoring of the clinical study. As for the approved clinical study, SDA and provincial drug administration authorities shall conduct routine or, based on a particular reason, an on-site verification or data check.
Article 44: During the clinical study, if one of following circumstances, SDA may order suspension or cessation of the clinical study or request the applicant to amend clinical study protocol:
1) the clinical study progress report is not timely or not based on facts, submitted;
2) the safety of the subjects cannot be effectively ensured;
3) the clinical study has exceeded its completion date by more than 2 years and these are still no evaluable results;
4) quality problems of the investigational drugs;
5) fraud in the clinical study;
6) serious adverse event is not timely reported;
7) a evidence exists showing the test drug is not effective;
8) other circumstances violating GCP.
9) the Ethics Committee has failed its duty; or
10)appearance of death or large number of cases of other serious adverse reactions during clinical study or such circumstances have been reported abroad.
Article 45: After decision or notification regarding amending the clinical study protocol and suspension or cessation of the clinical study by SDA, the applicant or the institutions for the clinical study shall amend, or within 10 days issue an explanation or, request to hold meeting for technical discussion. If no request for a meeting is made or explanation issued, the decision shall be implemented.
Article 46: If during the clinical study group or unexpected adverse reaction or serious adverse events occur or, there is evidence to prove that the investigational drugs have significant quality problems, SDA or the provincial drug administration authorities may adopt mandatory administrative measures to suspend or cease the clinical study and the applicant and institutions for clinical study shall immediately stop the study.
Article 47: After approval by SDA, the clinical study of new drugs shall be started within 2 years. Otherwise, re-application must be made.
Article 48: An investigator is responsible for use of the investigational drugs and shall ensure that the investigational drugs are only used by subjects of the study and their dosage and usage are according to the clinical study protocol. The investigator shall not give the drug to any person not participating in the clinical study and the investigational drugs shall not be marketed.
Chapter 5: Application and Approval of New Drugs
Section 1: Basic Requirements
Article 49: The materials submitted for application for registration of a new drug shall be complete and standard and data be authentic and reliable. Experimental data and materials not disclosed by other people shall not be used. In citing literature and materials, the name of the work(s), name of the journal(s) as well as volume, issue and page number etc. shall be provided. For unpublished literature and materials, an authorization letter from the owner must be provided. Chinese versions of the foreign language materials shall be annexed in accordance with relevant regulations.
Article 50: The government shall protect against unfair commercial use by any other person the undisclosed clinical data and other data that are generated as well as submitted by a manufacturer or a marketer in obtaining the approval of manufacturing or marketing a drug containing new chemical ingredients.
Within 6 years from the date of obtaining the approval of manufacturing or marketing a drug containing new chemical ingredients, any other application for manufacturing or marketing a drug containing new chemical ingredients by using the above mentioned data without the express consent of the original applicant shall not be approved by the drug administration authorities, unless the submitted data were generated by the subsequent applicant itself.
The drug administration authorities shall not disclose the data mentioned in above except the following situations:
(1) the need of public interest;
(2) measures have been taken to ensure such data is protected against unfair commercial use.
Article 51: The sample products and samples which have seen drawn, shall be those owned and pilot-produced by the applicant, gift or purchased sample products shall not be provided. Active components extracted from products manufactured by other institutions shall not be used as the sample products.
Article 52: An applicant for clinical study or production (importation) of a new drug shall submit documents showing patent status and ownership for the drug or its formulation, process, etc. and letter of guarantee stating that the new drug not infringe on the patent rights of others.
Article 53: If during the drug registration process SDA meets issues concerning intellectual property protection, for instance an infringement dispute before drug registration approval, after providing documents evidencing a lawsuit before judicial or patent institutions, SDA may suspend the marketing approval review process. If the intellectual property dispute occurs after the drug registration approval, the two parties shall resolve through negotiation or legal proceedings such as filing a lawsuit
Article 54: If parties jointly develop a new drug, the drug registration application shall be made jointly. However, after approval, each kind (during substance or preparation) shall only be manufactured by one party. Different strengths of the same kind shall be regarded as one kind and shall not be manufactured by different parties.
Article 55: If after receipt of an application for new drug registration, while the drug is still in the review or clinical study approval process, another applicant receives registration (import or production), the registration for new drug will not change [still a new drug registration], and generally its technical requirements will not have corresponding changes. Any changes shall be approval by SDA.
Article 56: SDA shall review the new drug registration. If supplementary experiment, clarification or explanation is needed, SDA shall issue normally one notification regarding needed supplementary materials.
The applicant shall submit supplementary materials; clarification or explanation within 4 months. If the supplementary materials, clarification or explanation are not submitted within the time limit, the application shall be considered withdraw.
For a withdraw application, if the applicant is able to supplement materials including experiments, and these materials comply with relevant regulations of SDA, then 6 months after withdraw, the application may be re-submitted.
Article 57: If an applicant objects to the notice of supplementary materials needed by SDA or the supplementary materials cannot be implemented due to technical reasons, the applicant may directly submit a report for amendment or exemption to SDA, explaining the reasons and providing technical materials and a scientific basis. SDA shall, after reviewing, make a determination.
Article 58: In applying for an import drug license, after completion of the clinical study in China of a new drug developed abroad, a marketing license should have been obtained from drug administration authorities of the country or region of manufacture.
Article 59: SDA shall begin review for registration of a new drug after accepting the application. After completion of the testing, the drug control institute responsible for drug testing shall timely submit the inspection report in accordance with procedural requirements.
If provincial drug administer authorities do not submit the drug testing report and inspection recommendations to SDA together with application materials and samples provided by the applicant, it may provide them separately to SDA within the required time limit.
Section 2: Application and Approval of Clinical Study for New Drugs
Article 60: To apply for clinical trials or bioequivalence trials, etc. of a new drug after completion of the pre-clinical study, the applicant shall complete the Application Form for Clinical Study of New Drugs, submit relevant materials and sample products and coordinate with the drug administration personnel to conduct on-site inspection, material verification and pilot production sampling.
Article 61: The drug control institute responsible for testing a drug used in clinical study shall timely start testing the drug after receipt of the sample products according to quality standard formulated by the applicant, issue a testing report, and submit its recommendations on whether the sample products conform with the quality standard provided by the applicant, the feasibility of the test methods, whether the quality standards can control the quality and recommendations for content modifications, etc. to the provincial drug administration authorities designated to conduct the testing and send a copy of the recommendations to the applicant.
Article 62: After receipt of the testing report and inspection recommendations provided by the drug control institute, the applicant shall carefully study them, and within 10 days complete supplementation and perfection of relevant materials and report to the corresponding drug control institute.
If the drug control institute concludes that the drug quality cannot be controlled by the quality standards, the applicant shall decide whether to withdraw its application for registration of a new drug. For an application that has not been withdrawn, SDA may return the application if SDA proves through a technical review that the quality cannot be controlled by the quality standards and new quality standards are needed.
SDA shall return an application for registration of a new drug if drug testing shows that the drug does not meet the quality standards provided by the applicant.
If new quality standards are needed after return of the application, the applicant shall not on a compensation basis authorize the original drug control institute to conduct studies on drug quality standard and methods, the said institute shall not accept an authorization.
Article 63: Before review by SDA of the application for clinical study for new drug, the applicant shall submit the written review recommendations for clinical study of the drug by the ethics committee of the responsible institution.
Article 64: SDA shall determine on whether to approve the clinical study by issuing Approval of Clinical Study of New Drugs for an application which meets the requirements.
Section 3: Application and Approval of New Drug Production
Article 65: Only after finishing clinical trials or bioequivalence trials may an application be made for a new drug certificate, new drug production or importation.
Only an applicant which meets production qualifications or conditions shall be issued a new drug certificate and drug approval number. An applicant which does not meet product qualifications or conditions, which has not been confirmed as a drug production enterprise, may only apply for a new drug certificate.
Article 66: To apply for a new drug certificate and new drug production, the applicant shall complete the Application Form for New Drug Certificate and New Drug Production and submit relevant materials and sample products.
Article 67: The provincial drug administration authorities shall inspect the production locality, materials and data and take 3 batches of sample products.
Only after passing inspection by NICPBP and obtaining a drug approval number may the drug begin marketing within a certain period (time).
Article 68: SDA shall conduct a complete evaluation for an application for new drug production and approve an application meeting requirements by issuing an Approval for New Drug Production and issuing a New Drug Certificate and drug approval number.
SDA shall issue a new drug certificate for a drug approved for production except for those with simple change in dosage forms. An Import Drug License shall be issued for an approved new drug which is manufactured (imported) by foreign drug manufacturers. Pharmaceutical Product Certificate shall be issued for an approved new drug produced by manufacturers in Hong Kong, Macao and Taiwan regions of China.
Article 69: In approving a drug for production, SDA shall issue the insert sheet and quality standards of the drug. The insert sheet is approved by SDA according to materials submitted by the applicant and shall be printed according to relevant SDA regulations. The manufacturer shall be responsible for correctness and accuracy of the insert sheet, voluntarily monitor use of the drug after launch and apply for modification of the insert sheet, if necessary.
Article 70: After approval, the quality standards of the new drug are temporary standards for 2 years. The quality standards of other approved drugs whose manufacturing processes and quality stability needs to be further examined, may also be issued temporary standards.
Section 4: Monitoring Period of New Drugs
Article 71: In order to protect public health, SDA shall implement a monitoring period not to exceed 5 years to further monitor newly marketed drugs.
Article 72: SDA shall establish monitoring periods for different kinds of new drugs according to the following principles:
1) 5 years (generally) for the first marketing of a drug in China which has not yet been marketed abroad;
2) 3-5 years (generally) for the first manufacture and then marketing of a drug in China which has been marketed abroad;
3) 3-4 years (generally) for a drug with the new drug certificate for the manufacture and then marketing of a drug in China, except (1) and (2) above;
4) 1-3 years (generally) for a drug administered as a new drug for manufacture and then marketing in China.
Article 73: The monitoring period of a drug shall begin from the date on the production approval documents. If several manufacturers produce the same drug, the monitoring period shall start from the first date, and unexpired portions shall not be used as extensions.
Article 74: During the monitoring period, SDA shall not accept the application for production or importation of the same drug by other applicants.
Article 75: For a drug for which the monitoring period has been set, if SDA had already accepted an application for the same drug from another applicant, SDA shall continue the review and approval process in accordance with provisions in this Regulation. After approval for production, the drug may only be marketed after the expiration of the monitoring period.
Section 5: Approval Process Time Limitations
Article 76: SDA shall exercise fast tract review for clinical study application of a new drug as defined in Article 10 of this Regulation and within 50 days after accepting the application determine whether to approve the clinical study or issue a notice for supplementary materials.
For other new drugs, SDA shall determine whether to approve the clinical study or issue a notice for supplementary materials within 90 days after accepting the application for clinical study.
Article 77: SDA shall, within 60 days after accepting the application, determine whether to approve production of the following new drugs.
In addition to meeting the requirements o Article 10 of this Regulation, the new drug should meet the following requirements:
1) Its efficacy is significantly superior to those of already marketed drugs; (¡°or¡±, or ¡°and¡±)
2) Its safety is significantly superior to those of marketed drugs.
For new drugs other than those described above, SDA shall, within 120 days after accepting the application, determine whether to approve the application for production
Article 78: SDA shall complete with review of supplementary materials, within 30 days of submission by the applicant.
Article 79: If because of difficult technical questions or other special reasons, SDA cannot conclude to approve or issue a notice for supplementary materials within the time limitation, SDA shall extend its time for making the approval decision and provide written notice to the applicant.
Chapter 6: Application and Approval of Drugs Admitted with
National Standards
Article 80: For an abbreviated drug registration application, the applicant shall complete pilot production in according to relevant technical requirements, complete the Form for Abbreviated Application of Drugs and submit relevant technical materials to the provincial drug administration authorities (where the production facility is located).
The provincial drug administration authorities shall inspect trial production facility, equipment, sample production and the in-house inspection records, take samples of the sample production and notify the drug control institute to conduct an inspection.
Article 81: The drug control institute responsible for drug testing shall complete testing, issue testing report, including recommendations on quality standard, testing methods, etc. of the drug tested to the provincial drug administration authorities within 30 days of receipt of the sample products. For special drugs and vaccines, these procedures may be completed within 40 days.
The provincial drug administration authorities shall finish verification within 5 days of receipt of the materials provided by the drug control institute, make recommendations and report to SDA for review, also notifying the applicant of its recommendations.
Article 82: For a biological product for which an abbreviated application is made, after samples are taken and sealed by the provincial drug administration authorities, the applicant may submit the sample products to NICPBP or a SDA-designated drug control institute for testing.
Article 83: For a drug that had obtained patent protection or administrative protection in China, without authorization for the patent owner or one with exclusive license, other applicants may only for registration only within 2 years prior to the expiration of patent protection period or administrative protection period.
SDA shall issue an approval number for a drug meeting relevant requirements. However, the drug may not leave the production facility and be marketed before expiration of the patent protection period or administrative protection period.
Article 84: SDA shall determine whether to approve production or issue a notice for of supplementary materials within 100 days of receipt of materials and sample products submitted by provincial drug administration authorities.
Article 85: SDA shall determine whether to approve production after completing verification of the submitted materials and shall issue a Drug Approval Number to an application meeting relevant requirements.
Chapter 7: Application and Approval for OTC Drugs
Article 86: An OTC drug refers to a drug that can be selected, purchased and used by consumers without a prescription of a practicing physician or a practicing assistant physician.
Article 87: OTC drugs subject to this Regulation include new preparations and new combination formulations developed from active components of the OTC drugs determined by SDA or, OTC drugs not yet marketed in China but marketed abroad, and OTC drugs with national (China¡¯s) drug standards. For an OTC drug that has not been marketed in China, a new drug application shall be filed, for an OTC drug which already has national standards, an abbreviated application shall be filed.
Article 88: Generally, a preparation developed from new chemical ingredients verified to comply with relevant regulations, shall be approved as prescription drugs. Only after wide clinical use may an application be made to change to OTC status. A separate regulation will be issued.
Article 89: Generally, a clinical study is not needed for a new preparation developed from active components of OTC drugs determined by SDA meeting relevant requirements. However, bioequivalence trials may be needed for solid oral dosage forms.
Article 90: For new combination formulations developed from active components of OTC drugs determined by SDA, the basis for their formulation shall be explained and clinical trials may be needed, if necessary.
Article 91: Upon application for importation or production of an OTC drug marketed abroad, documents proving and showing the basis for its OTC status shall be provided.
Article 92: In addition to meeting general requirements for packaging, label and insert sheet of drugs, the label and insert sheet of OTC drugs shall be scientific and easy-to-understand and with a choice of words which enables the consumer to easily select and use himself. The label and insert sheet shall be approval by SDA. The package of OTC drugs shall be printed with the special symbol for OTC designated by SDA.
Article 93: If an OTC drug approved by SDA for marketing has serious ADR during clinical use or, its safety and reasonable use cannot be ensured without prescription by physicians, SDA can change the drug to prescription status.
Chapter 8: Supplementary Application for Drug Registration
Article 94: The original applicant should submit a supplementary application in the following situations:
1) Changes related to drug production: production of a new drug after issuance of the new drug certificate, change of place of production by the original manufacturer, adjustment of drug manufacturers within the group [group company toll manufacturer], toll manufacturing, repackaging, addition or change of samples of drug, change in volume of final dosage form, change in production process, addition or change of coloring, preservatives, taste-rectifying agents and additives, and change of production site of import drug substance.
2) Changes in quality standard: modification of quality standard, change of expiration date, and alteration of immediate packaging materials, or container, etc.
3) Changes related to drug use: addition or reduction of indications, functions, change in usage, dosage, populations and modification of insert sheet, package and label, etc.
4) Others: Changes such as drug name, brand name, manufacturer name, company name, company¡¯s address, drug packaging presentation, etc. described in the documents for drug production approval, Import Drug Certificate or Pharmaceutical Product Certificate.
Article 95: A supplementary application shall not include changes of: components ingredients, composition, dosage form and route of administration of a drug.
For a supplementary application of a drug submitted during verification by SDA of its registration application, generally except for new discovery of the drugs innovation or involving safety, new technical materials shall not be added.
Article 96: For a supplementary application, the applicant shall complete the Form for Supplementary Application, describing items, contents and reasons, and submit the approved documents and their attachments, and documents of relevant competent authorities and relevant technical materials. It should provide a detailed analysis showing the differences in relevant documents and materials before and after the changes. If a possible ownership change of the drug is involved, documents/certificates currently effective shall be provided. For an import drug, the document approving the change issued by the drug administration-authorities of the manufacturing should also be provided.
Article 97: A supplementary application for a change in the applicant, after registration approval of a drug, shall be submitted by the new applicant to the provincial drug administration authorities, providing all the agreements. If needed, the option of the provincial drug administration authorities where the original production enterprise is located shall be solicited.
Article 98: For a supplementary application which meets requirements, SDA should issue the amended of approval document and may describe the amendments on the original approval document. If a new approval document is required, the original document should be withdrawn or annulled. If a new approval document needs to be issued, in addition, the original document continues to be effective.
The term of validity for approval documents for a supplementary application of a drug shall expire on the expiration date of the original approval documents. Reapplication must be made upon expiration.
Article 99: A supplementary application shall be submitted to the provincial drug administration authorities at the location of the manufacturer for the following items:
1) change of manufacturer¡¯s name for a drug produced in PRC (without change of production address);
2) change of production address by the original manufacturer (without change of the manufacturer¡¯s name);
3) addition or perfection in the insert sheet involving safety.
4) reducing shelf life of a drug;
5) extending the shelf life of a drug according to new data of the drug¡¯s stability after approval by the drug administration authorities;
6) modification of insert sheet and package labeling according to national drug standards or SDA¡¯s recommendations for modification.
7) changes in form of the package and format of the labeling;
8) supplementary application for changes to content of label, etc. within the scope of safety and efficacy described in the original insert sheet.
The provincial drug administration authorities shall duly file these approved changes for the record with SDA.
Article 100: A supplementary application for an import drug regulated by Article ? in this Regulation shall be filed for the record with SDA.
Article 101: If a supplementary application for a drug is submitted during verification of the original registration application, SDA shall verify the two applications together and approve a supplementary application which meets relevant requirements. The time limit for verification of the original registration application may be extended depending on the effect of the supplementary application.
Chapter 9: New Drugs Technology Transfer
Article 102: New drug technology transfer refers to the process whereby the owner of new drug certificate transfers its new drug processing technology to a pharmaceutical production enterprise. The transfer of new drug technology shall generally only have a New Drug Certificate without a drug approval number.
Generally, the new drug technology may only be transferred once and the transferee enterprise may not retransfer the technology.
Article 103: The pharmaceutical production enterprise accepting the new drug technology transfer shall have obtained a Drug Manufacturing License, GMP Certificate and the transferred drug shall be consistent with the production conditions and scope of GMP Certificate of the manufacturer.
Article 104: In transferring the new drug technology, the Drug Certificate owner shall sign technology transfer contract with the transferee and transfer all technology and materials to the party without reservation. The transferee shall independently trial manufacture 3 continuous batches of qualified products.
Article 105: An application for technology transfer of a new drug jointly developed by several parties shall be submitted by all the parties with the new drug certificate. All parties shall sign the technology transfer contract.
Article 106: An Application for Technical Transfer of a New Drug shall be jointly submitted by the owner of the New Drug Certificate and the transferee to the provincial drug administration authorities where the transferee is located. They should complete the Application Form for Technical Transfer of a New Drug and submit relevant materials and attach the technology transfer contract.
Article 107: After acceptance of an Application for Technology Transfer of a New Drug, the drug administration authorities shall inspect on trial production facility, equipment, production of sample products and testing records, conduct sampling and notify the drug control institute to test the drug.
Article 108: The drug control institute responsible for drug testing shall complete testing and issue testing report to the provincial drug administration authorities within 30 days of receipt of the sample products. For special drugs and vaccines, these procedures may be completed within 40 days.
Article 109: The provincial drug administration authorities shall finish verification within 5 days of receipt of the materials provided by the drug control institute, make recommendations and report to SDA for review, also notifying the applicant of its recommendations.
Article 110: After completion of verification of the materials, SDA shall determine whether to approve production by issuing the Paper for Drug Manufacturing License and issue approval number for a drug fulfilling relevant requirements.
Article 111: If without special reason a drug production enterprise does not commence production and marketing of a drug within 2 years after accepting the new drug technology transfer and obtaining a drug approval number, SDA shall cancel the approval number.
Chapter 10: Approval of Toll Manufacturing and Repackaging
Section 1: Basic Requirements
Article 112: A pharmaceutical production enterprise in China with a drug approval number which wants to authorize another pharmaceutical production enterprise to toll manufacture and repackage shall apply to SDA for approval.
A foreign pharmaceutical manufacture which has obtained an Import Drug Certificate or Pharmaceutical Product Certificate which wants to authorize a local pharmaceutical production enterprise to repackage its drug must provide its China patent certificate.
Article 113: A toll manufacturing contract receiver shall hold a Drug Manufacturing License and GMP Certificate. The drug to be toll manufactured shall suit the production licence conditions and be within the scope of the GMP Certificate. The repacking contract receiver shall hold a Drug Manufacturing License and GMP Certificate.
Article 114: The contract giver shall instruct and supervise the contract acceptor in producing drugs according to GMP, be responsible for the quality of the toll manufactured or repackaged drugs. The toll manufactured drugs may only be sold and bear all legal liability.
Article 115: An application for toll manufacturing or repackaging of a drug shall be treated as a supplementary application.
Article 116: A drug produced under the temporary standards or during the monitoring period is not eligible for toll manufacturing. Vaccines, blood products and other drugs as specified by SDA are not eligible for toll manufacturing.
Article 117: An application for toll manufacturing or repackaging of a drug shall be submitted at least one year before expiration of the drug approval documents.
Section 2: Application and Approval of Toll Manufacturing of Drugs
Article 118: In making application to toll manufacture a drug, the two parties shall first sign the toll manufacturing contract which clearly states the responsibilities and obligations of both parties, technical requirements, term of toll manufacturer, volume of production, implementation standards, sources and standards for drug substances and supplements, volume of production, as well as supply of packaging materials and containers, etc. The contract shall comply with Chinese laws, regulations and relevant drug administration requirements and be notarized.
Article 119: The two parties shall jointly make application to the provincial drug administration authorities where the party with approval number is located and provide relevant materials. If the contract giver and receiver are in different province, the contract acceptor shall obtain permission by the provincial drug administration authorities where it is located. These authorities shall issue a verification based on daily production and GMP implementation by the contract acceptor.
Article 120: After acceptance of the application, the provincial drug administration authorities shall inspect production facility, examine equipment, test devices and trial-production conditions, take samples and notify provincial drug control institute to test the samples. If the contract giver and receiver are in different province, the provincial administration authority where the contract acceptor is located shall responsible to inspect production facility.
Article 121: After verification, the provincial drug administration authorities shall submit the application materials, test report, inspection report and verification recommendations to SDA. After verification, SDA shall determine whether to approve the toll manufacturing in the form of Supplementary Application Approval Document.
Article 122: The drug to be toll manufactured shall be manufactured according with the approved production process, formulation and strength and, meet all approved quality standards. The package size, label and insert sheet shall be consistent with those of the original drug. The names of the two parties, place of production locality and approval number issued to the contract giver shall also be indicated.
Article 123: After acceptance of the application for toll manufacture, the provincial drug administration authorities shall finish verification within 40 days. SDA shall complete the review and approval within 20 days of receipt of the materials submitted by the provincial drug administration authorities.
Section 3: Application and Approval for Repackaging of Drugs
Article 124: ¡°Repackaging of drugs¡± means taking the manufactured drug which has been put into its finished preparation, and by large packs into small packs or taking immediate packs and placing into finished packages with insert sheets and affixing labels, etc.
After approval by SDA, the following drugs may also be administered according to repackaging requirements:
1) drugs for external use and preparations for oral administration without immediate packs;
2) finished intermediate preparations to be filled into capsules.
Article 125: The quality standard for repackaging drugs shall be in meet the standards approval by SDA for import drug registration or drug production.
Article 126: The package, label and insert sheet of a repackaged drug shall be in consistent with those approved by SDA for import drug registration or drug production. The name of the manufacturer responsible for repackaging and import drug registration number or approval number issued to the contract giver shall also be marked.
Article 127: An application for repackaging of a drug shall be submitted by the contract acceptor to the provincial drug administration authorities where it is located, providing the contract signed by both parties, technical materials and sample products, etc. The provincial drug administration authorities shall complete verification within 10 days and report to SDA. SDA shall finish verification within 30 days and approve an application which meets relevant requirements.
Chapter 11: Administration of Testing for Drug Registration
Section 1: Basic Requirement
Article 128: Testing must be conducted for drug registration. Testing includes testing of sample products of the drug for which registration application is made and inspection of the drug¡¯s quality standards.
Testing of sample products refers to test of sample products according to quality standards provided by the applicant.
Inspection of drug quality standards refers to laboratory tests on the feasibility and scientificness of testing methods described in the quality standards to determine and whether the drug quality can be controlled by the quality standards etc.
Article 129: The drug control institute engaged in drug testing for registration shall, according to the Good Laboratory Practice of Drug Control Institutes and national measures certificate and laboratory certificate, have the corresponding number of personal and equipment to meet the needs of the quality assurance system and technical requirements
Article 130: Generally the amount of sample products supplied for drug registration shall be three times the amount needed for testing.
Section 2: Testing of Drugs for Clinical Study and Production
Article 131: For a drug for which application is made for clinical study and production, the responsible drug control institute shall conduct testing according to the quality standards provided by the applicant after receiving the sample products, and issue the test report showing whether it meets requirements.
Article 132: The drug control institute shall inspect the drug quality standards, and on the basis of the pre-clinical study data, domestic and foreign quality standards of the same kind of drug, make recommendations for modification of quality standards, test items and methods.
Article 133: Generally, the testing of sample products shall be completed and test report issued within 25 days. For special drugs and vaccine products, generally the report shall be issued within 50 days.
Generally, the inspection of drug quality standard shall be completed and recommendations for modifications be issued within 50 days. For special drugs and vaccine products, generally those shall be issued within 90 days.
Article 134: For a drug for which an abbreviated application is made, the responsible drug control institute shall conduct testing according to national drug standards. A comprehensive analysis should be made of the impurities introduced due to change in processing. If necessary, the institute shall request the applicant to include control of impurities in the quality standards.
Article 135: If an applicant modifies national drug standards and test methods, the drug control institute shall inspect the drug standards of the drug for which application is made.
Section 3: Import Drug Testing
Article 136: Import drug testing shall be conducted according to the requirements in the Notification for Import Drug Testing issued by SDA and the testing shall be organized by NICPBP.
Article 137: After receiving the Notification for Import Drug Testing issued by SDA, the applicant shall timely submit the following materials and samples to the NICPBP:
1) Chinese and English versions of quality standards and testing methods of the drug;
2) three batches of sample products (e.g. marketed abroad, should be formally[not temporarily] marketed) and their test reports. The amount of each batch shall be three times the total needed for testing. For a biological product, the records of production and testing for three batches of the product shall also be provided;
3) standard materials used for testing.
NICPBP shall arrange for a relevant drug control institute to conduct testing within 3 days after receipt of submitted materials and sample products.
Article 138: The responsible drug control institute for import drug testing shall finish testing within 50 days of receipt of the submitted materials, sample products, and relevant standard materials, and submit the test report to NICPBP, including inspected drug quality standards with explanation in triplicate and the test report for 3 batches of samples.
Article 139: NICPBP shall organize experts to perform technical review within 20 days of receipt of the inspection report. If necessary, NICPBP may inspect separate items again according to recommendations of the inspection.
Article 140: Drug standards which have been inspected, verified and approved by SDA shall become the import drug registration standards and be regarded as the legal standards for the import drug.
Section 4: Drug Testing for the Transfer of Temporary Standards to Forma Standards
Article 141: SDA authorizes the State Pharmacopoeia Commission to organize drug control institutes to inspect the temporary standards of drugs, and make recommendations for modification of temporary quality standards, test items and methods on the basis of the usage situation during the period of the temporary standards, quality standards of the relevant products worldwide and relevant national requirements. Both the recommendation and the testing report shall be submitted to the State Pharmacopoeia Commission, at the same time, copied to the applicant to enable the applicant to apply to transfer temporary standards to formal standards.
Article 142: Generally, the drug control institutes responsible for the testing shall finish inspection and testing of the interim specification and provide opinions for modification and reports within 50 days. For special drugs and vaccine products, these shall be done within 90 days.
Chapter 12: Administration of Drug Registration Standards
Section 1: Basic Requirements
Article 143: ¡°National drug standards¡± refers to technical requirements for quality parameters, testing methods and production processes etc. of drugs established by the state to ensure the drug quality.
A drug registration standard refers to the standards approved by SDA for the specific drug of the applicant. The drug registration shall not be lower than national drug standards.
The registration application of an import drug should be use the drug standards approved in the country of original approval.
Article 144: A drug marketed or used for clinical study in China must meet national drug standards or drug registration standards of relevant regulations. Raw materials of TCM and TCM preparations without national drug standards are excepted.
Section 2: Establishment of and Requirements for Specifications for
Drug Registration
Article 145: The establishment of drug registration standards shall meet the requirements of safety, efficacy and quality control.
Article 146: An institution engaged in research and production of a drug shall, on the basis of stability of the raw materials and production process, select representative sample products for study of standards.
Article 147: The items and testing methods for drug registration standards shall observe technical guidance principles issued by SDA and relevant principles and rules for compiling of national drug standards.
Section 3: Temporary Drug Standards and Their Transfer to
Formal Standards
Article 148: An application for production of a drug with temporary standards shall be submitted to the provincial drug administration authorities where the applicant is located according to SDA requirements for supplementary application, including materials of quality verification of the drug during the trial period and recommendations for modification of the standards. After inspection by the provincial drug control institute and review by the provincial drug administration authorities, the application shall be submitted to SDA within 30 days after acceptance.
For the same kind of drug with different validity period for temporary standards, the applicant whose standards first expire should begin the procedure for transfer to formal standards. For these a drug whose validly period of temporary standards do not expire, the State Pharmacopoeia Commission shall notify the applicant in advance to apply to transfer the temporary standards to formal standards with the provincial drug administration authorities.
Article 149: The standards for the same kind of drug submitted by another applicant shall not be lower than already approved standards and may include additional testing items depending on the characteristics of the drug production procession.
Article 150: If an applicant does not apply to transfer to formal standards after expiration of the temporary standards according to relevant regulations or, the temporary standards do not meet the requirements for transfer, SDA shall cancel the temporary standards and corresponding drug approval number for drug production.
During the period of application to transfer of the temporary standards to formal standards, the drug shall continue to meet the requirements of temporary standards.
Article 151: The technical laboratory inspection of a drug produced by two or more manufacturers, to set uniform standards and new drugs and new biological products referred to in this Regulation shall be conducted by NICPBP.
The temporary standards shall be unified according to scientifically advanced and rational principles. The State Pharmacopoeia Commission shall notify NICPBP to conduct laboratory inspection within 20 days.
The NICPBP shall complete the inspection within 80 days.
Article 152: The State Pharmacopoeia Commission shall finish verification to transfer of temporary standards to formal standards within 60 days.
The State Pharmacopoeia Commission shall report drug standards which have passed verification to SDA within 20 days for review, approval and issuance.
For drug standards needing further experiments, the State Pharmacopoeia Commission shall notify the provincial drug administration authorities where the applicant is located about relevant requirements and request such authorities to inform the applicant.
Section 4: Establishment and Administration of Drug
Standard Materials
Article 153: NICPBP shall be responsible for standardization and administration of standard materials (including standards, control and reference), used in national drug standards.
Article 154: In applying for production of a new drug, the applicant shall directly provide NICPBP with the raw materials used to manufacture and standardize the standard materials during the drug testing and relevant research data about the standard materials.
Article 155: NICPBP shall organize the provincial drug control institutes, drug research institutions or drug manufacturers to undertake cooperative standardization of the standard materials.
Article 156: NICPBP shall be responsible for comprehensive technical verification of the standardized standard materials regarding the selection of raw materials, production methods, standardizing methods, standardization results, accuracy of assay values, tracing of origin of various values, stability and conditions for repackaging and packaging, etc. of reaching a conclusion as to whether they can be used as national standard materials.
Article 157: The approved standard materials of drugs shall be issued a uniform number by NICPBP and filed for the record with SDA.
Chapter 13: Re-registration of Drugs
Article 158: The validity period of the drug approval number, the Import Drug License and Pharmaceutical product Certificate issued by SDA is 5 years. 6 months prior to expiration, application for re-registration shall be made to continue production or importation. The application shall include relevant materials according to the requirement of SDA. If upon expiration, no application for re-registration has been made, or the application does not meet the requirements for these authorities after review, these authorities shall cancel the drug approval number, Import Drug License and Pharmaceutical Product Certificate.
Article 159: To re-register a drug, the applicant shall apply with the original approval authorities, complete the Application Form for Drug Re-registration according to relevant regulations and provide relevant materials.
The application for re-registration of an import drug shall be submitted to the original approval authorities by office established in China by the foreign drug manufacture or, by the authorized agent in China of the foreign manufacturer. The Application Form for Re-registration of Import Drug or the Application Form for Re-registration of Pharmaceutical Products shall be completed and relevant materials provided.
Article 160: The provincial drug administration authorities should finish verification of the application and file for the record with SDA. If SDA does not issue a notice to not re-register the drug within 50 days, the provincial drug administration authorities should handle the re-registration.
Article 161: The application for re-registration shall not be accepted and the original approval documents cancelled by SDA in any of the following situations:
1) a drug approval should be withdrawn according to the Drug Administration Law requirements;
2) a drug for which re-registration application has not been made within the time limit;
3) a drug manufacturer without the all production conditions for drugs required in Article 8 of the Drug Administration Law.
4) a drug which does not meet relevant requirements of SDA upon approval for marketing;
5) a drug for which Phase IV clinical trials have not been completed according to relevant requirements;
6) failure to monitor drug adverse reactions according to relevant requirements or the discovery of serious adverse reaction; or,
7) other situations in which relevant requirements have not been met.
Article 162: If an applicant does not apply for re-registration of a drug within the time limit of the original approval document or the application is proven to not meet relevant requirements of re-registration by SDA, the approval number, Import Drug License or Pharmaceutical Product Certificate shall be canceled.
Chapter 14: Reconsideration of Drug Registration Application
Article 163: Reconsideration of a drug registration application refers to the subsequent review by SDA of a rejected application, according to the original application submitted by the applicant.
Article 164: If the applicant objects to rejection of the application, it may apply for reconsideration by completing the Application Form for Reconsideration of Drug Registration and explain the reasons for reconsideration.
In conducting the reconsideration, the administration authorities shall only inspect the original application materials and samples. If an applicant wants to use research material not in the original submissions, the applicant may use them in filing a new application for drug registration.
Article 165: The applicant should apply for reconsideration within one month after the rejection of the first application by SDA. Otherwise, the application for reconsideration will not be accepted.
Chapter 15: Liability
Article 166: If the applicant, institution for pre-clinical laboratory study, institution for clinical study or an individual is found to provide fraudulent materials in an application, application should be canceled. Within 5 years, another application for drug registration with materials signed by the applicant or individual shall not be accepted. The responsible party shall be fined for RMB 10,000 - 30,000. For a drug approved for clinical study, the clinical study approval documents should be canceled.
Article 167: If the subject or user is injured during clinical study or after marketing of the drug due to the submission fraudulent materials in application for drug registration, the responsible party shall be liable for compensation.
Article 168: If a pre-clinical study does not comply with GLP requirements, the institute will be warned and ordered to rectify within a specified period. For a serious violation, the drug approval documents will be canceled and a fine imposed of RMB 5,000 ¨C 20,000. SDA will not again accept drug registration safety evaluation materials researched by that institute.
Article 169: If a clinical study does not comply with GCP requirement, the institute will be warned and ordered to rectify within a specified period. For a serious violation, the qualifications of clinical research institute will be canceled, and a fine imposed of RMB 5,000 ¨C 20,000.
Article 170: Violations by drug administration authorities and their personal who issue Drug Import Certificate for applications which do not meet requirements, who issue approvals for clinical studies, New Drug Certificates and drug approval documents for applications which do not meet the conditions necessary to conduct clinical studies, or engage in production, shall be handle according to Article 94 of the Drug Administration Law.
Article 171: Violations by drug administration authorities and their personal who lose or disclose confidential materials which results in loss to the applicant shall be handled according to Article 79 of the Implementing Regulation of the Drug Administration Law.
Article 172: The drug control institute established or designated by SDA which issues fraudulent test reports as past of the necessary drug testing during the drug registration process, shall be sanctioned according to Article 87 of the Drug Administration Law.
Article 173: The administrative sanctions regulated in Articles to shall be determined by SDA or the provincial drug administration authorities. The administrative sanctions of cancellation of approval documents and sanctions regarding the qualifications study institutes shall only be determined by SDA.
Chapter 16: Supplementary Provisions
Article 174: All days of the working period in this Regulation are considered working days.
Article 175: The terms in this Regulation are defined as follows:
Drug registration means the review and approval process according to legal procedures and requirements, undertaken by systematic evaluation, testing and inspection for applications for clinical study of drug substances and production (including repackaging) or import regarding safety, efficacy and quality control. It includes the review and approval of application for change in approval documents and contents of the annexes.
Drug registration: means the process of verification, confirmation and registration for drugs that will continue to be produced or imported after the expiration of the approval documents.
Drug standard materials means a substance with specific values, in physical, chemical test and biological methods test for drug quality standards, used to calibrate equipments, evaluate measuring methods or assay the test drugs.
Standards means a specific substance established according international standards, or researched by China with specific values (without international standards), in order to measure a product efficacy unitage or toxicity. Its biological activity is expressed as international unit or unitage.
Control means a standard substance with specific value used for measuring ingredients of a drug or content of one special ingredient in raw materials of TCM and TCM preparation.
Reference means a specific substance established according international standards, or researched by China with specific values (without international standards), used as microbial (or their products) identification, biological diagnostic reagents for diseases diagnosis and assay testing for biological materials, specific anti-serum or some products cannot be evaluated by international unitage.
Article 176: An application for biological, microbial, immunological and nucleic acidic reagents, for in vitro diagnosis reagents, shall be handled according to the Regulation for Administration of Registration of Reagents for In Vitro Diagnosis.
Article 177: The fees for an application for clinical study of new drugs, drug production or importation and transfer of temporary standards to formal standards, including the fees for review and approval, technical inspection and drug testing shall be paid by the applicant according to relevant regulations.
Article 178: SDA is responsible for interpretation of this Regulation.
Article 179: This Regulation is effective from the date of publication
