药品注册管理办法-英文版

药品注册管理办法-英文版 DRUG REGISTRATION REGULATION (SFDA Order 28) (Translation by RDPAC, for Member use only) Drug Registration Regulation was approved on June 18, 2007 by SFDA executive meeting and is hereby published, which become effective from October 1, 2007. SFDA Commissioner Shao Minli July 10, 2007 DRUG REGISTRATION REGULATION Chapter 1: General Principles Article 1: This Regulation is promulgated according to the Drug Administration Law of The People’s Republic of China (Drug Administration Law), Administrative Licensing Law of The People’s Republic of China (Administrative Licensing Law), and the Implementing Regulation of the Drug Administration Law of The People’s Republic of China (Implementing Regulation) to ensure the safety, efficacy and quality control of drugs and standardize drug registration. Article 2: This Regulation shall apply to all drug research and clinical studies, application for clinical study, drug production and / or importation, as well as the drug approval review, registration inspection and drug administration in The People’s Republic of China (PRC). Article 3: Drug registration means the legal process by which a decision is made by SFDA, upon application of registration applicant, to either approve or not approve the conducting of a drug clinical trial, production or importation of a drug to be marketed, based on a systematic evaluation of the safety, efficacy and quality control of the drug. Article 4: The State shall encourage research and development of new drugs and exercise the approval via a special process of innovative new drugs, those for difficult to treat and life threatening diseases. Article 5: The State Food and Drug Administration (SFDA) is the - 1 - competent national authority for drug registration, responsible for the review and approval of clinical studies, production and importation of drugs. Article 6: Drug registration should follow the principles of openness equality, fairness, and for the convenience of the publics. During drug registration, SFDA shall apply the systems of joint responsibility of the presiding reviewer, public disclosure and rescuing of the related staff, responsibility investigation for any wrongdoing, in order to administer the steps from acceptance, inspection, review, approval, through delivery, and subject to monitoring by the publics. Article 7: During drug registration, should the drug administrative authority consider any permitting issues of significant interest to the publics, the issues should be announced to the publics and public hearing should be held. Should the administrative permitting be related to any significant interest between applicant and other parties, before any decision is made, drug administration authorities should notify applicant and other parties of their entitlement to requesting hearings, statement and defending. Article 8: Drug administration authorities shall provide applicant with accessible information regarding drug registration acceptance, inspection, test, evaluation, approval progress and conclusion and so on. Drug administration authorities should publicly disclose the following information at the official website and / or office location. 1. Drug registration application items, procedure, fee standards and basis, timeline, table of content of all required dossier, as well as reference application documents. 2. name list and the related information of the staff at each steps from acceptance, inspection, test, review, through approval. 3. general information of drug registration such as formulary of the approved drugs. Article 9: The drug administration authority, units and staffs involved shall assume the responsibility of protecting the technical secrets and data provided by applicants during the process of drug registration. Chapter 2: Basic Requirements Article 10: A drug registration applicant (applicant) means an institution that makes drug application and assumes corresponding liability for drug - 2 - registration. A local applicant shall be a legally registered institution in China and be competent to independently assume legal liability. A foreign applicant shall be a legally established pharmaceutical company outside of China. In making application for an imported drug registration, the foreign applicant shall use its office in China, or authorize an agent in China to handle the application. The person(s) handling the drug registration application shall have technical expertise, and be familiar with drug administration laws, regulations and technical requirements. Article 11: Drug registration application includes application for new drug, generic drug applications, application for imported drug, supplemental application, as well as re-registration application. A local applicant shall make application according to new drug or generic drug applications; a foreign applicant shall make application according to imported drug. Article 12: A new drug application means a registration application for a drug that has not been marketed in China. Applications made for a change in dosage form, or route of administration, additional new indication of drugs shall be made according to new drug registration procedure. Generic drug application means application for registration of a drug for which SFDA has already issued formal standards, however, application of biological products shall be follow new drug application. Application for imported drug means application for a drug produced outside China to be marketed in China. Supplemental application means an application for the change, addition, or cancellation of any item or contents in the existing registration approval of a new drug, generic drug applications, or imported drug. A re-registration application means the application to continue the drug production or importation after the expiry of the certified drug approval documents. Article 13: Applicants should provide sufficient and reliable research data to evidence the safety, effectiveness and quality control of the drugs, and assume liability of the truthfulness of the entire dossier. Article 14: In citing literature and materials, the name of the work(s) and journal(s) as well as volume, issue and page number shall be provided in the - 3 - application dossier submitted for drug registration. For unpublished literature and materials, an authorization letter from the owner must be provided. For any foreign language materials a Chinese translation should be provided in accordance with relevant requirements. Article 15: SFDA shall implement the National pharmaceutical industry development plan and policy, and may organize an assessment of the benefit of introduction of drugs to the market. Article 16: During drug registration, drug administration authorities should conduct on site inspection and inspection chosen from decision of the pre-clinical study and clinical trials, as well as conduct on site inspection of production site prior to any marketing approval, in order to confirm the truthfulness, accuracy and completeness of the application dossier. Article 17: If two or more institutions jointly apply for drug registration, the application shall be made to the PDA where the drug manufacturer is located. If all the applicants are manufacturers, the application shall be made to the PDA where the drug manufacturer of the preparation is located. If none of the applicants is a drug manufacturer, the application shall be made to the PDA where the drug sample is pilot manufactured. Article 18: Regarding the drug or its formula, production process, indication etc., the applicant shall submit documents explaining the China patent status and ownership rights. If other party holds patent in China, the applicant shall submit a letter stating that the drug will not infringe on the patent rights of others. Upon acceptance of the application, drug administration authorities should publicly disclose the statement submitted by applicant. If an infringement dispute occurs during registration application, the parties shall resolve the matter according to relevant laws for patent administration. Article 19: For a drug that has obtained patent protection in China, another applicant may apply for registration within two years prior to the patent expiration. SFDA shall review the application according to this Regulation and, after expiration of the patent, issue a drug approval number, Imported Drug License or Drug Product License, for an application that meets requirements. Article 20: According to Article 35 of Implementation Regulation, for a period of 6 years from the date of the original applicant's approval, SFDA shall not approve a subsequent application that used, without the express consent of the original applicant, the undisclosed R&D data and other data generated by the original applicant for submission of application of - 4 - manufacturing or marketing of a drug containing new chemical ingredients, unless the submitted data is generated by the subsequent applicant itself. Article 21: The scope of pre-clinical laboratory study (pre-clinical study) of a drug for registration includes synthetic process, extraction methods, physical-chemical properties and purity, dosage form selection, screening of formulas, preparation process, inspection methods, quality specification, stability, pharmacology, toxicology and pharmacokinetic study. For TCM preparations, information such as the source and the processing of raw materials should also be included. For biological products, information such as source, quality standards, storage condition, biological identity, genetic stability and immunology study of strain, cell strain as well as biological tissue should also be included. Article 22: Pre-clinical study of a drug shall be conducted in accordance with relevant regulations, where the drug safety evaluation must be conducted in accordance with Good Laboratory Practice for Pre-Clinical Laboratory Studies (GLP). Article 23: Institutions engaged in drug research and development shall have the necessary personnel, facility, equipment, instruments, conditions and management system needed corresponding to the research project, and shall guarantee the authenticity of all data and materials. The animals, reagents and raw materials used for experiments shall comply with relevant national regulations and requirements. Article 24: If an applicant authorizes another institution to conduct the study of drugs, or any single experiment, inspection or pilot production and manufacture, the applicant shall sign a contract with the authorized party, and make notes in the application dossier. The applicant is responsible for the truthfulness of the drug study data used in the application dossier. . Article 25: When an application is only made for registration of preparation, the raw materials of the investigative drug substance used for this preparation must have a Drug Approval Number, Imported Drug Certificate or Pharmaceutical Product Certificate, and must have been obtained from legal channels. Any investigative drug substance which does not have a Drug Approval Number, Imported drug Certificate or Pharmaceutical Product Certificate must be approved by SFDA. Article 26: If an applicant uses the drug study data from a foreign drug research for a drug registration application, an explanation for the study items, and referencing the page numbers issued by this institution shall be provided, and notarized certificate of the institution's legal overseas registration shall be attached. Only after the documents are authenticated - 5 - by SFDA may they be included in the registration documents. SFDA may send people to conduct on-site inspections, if necessary. Article 27: During the verification of drug studies, drug authorities may request the applicant or the drug research institute that conducted the experiments to repeat an experiment for any items by using the methods and data listed in the application dossier. SFDA may also designate other drug control institutes or drug research institutions to repeat the experiments or to validate the methodology. Article 28: Drug study shall be conducted in accordance with relevant technical guidelines issued by SFDA. If the applicant conducts the experiments according to other methods and techniques, the applicant shall provide information to evidence that the methods and techniques are scientific. Article 29: After obtaining the drug approval number, the applicant should produce the drug according to the process approved by SFDA. Drug administrations shall monitor the production according to the approved production process and standards. Chapter 3: Clinical Trials of Drugs Article 30: Clinical study of drugs, including bioequivalence trials, must be approved by SFDA, and must be conducted in accordance with Good Clinical Practice (GCP). Drug administrations shall monitor the approved clinical studies. Article 31: Clinical trials should be conducted for the registration of a new drug. For registration application of generic drugs and supplemental application, clinical trails should be conducted in accordance with provisions specified in Appendix of this Regulation. Clinical trials are divided into Phase I, Phase II, Phase III and Phase IV. Phase I: Basic clinical pharmacology and human safety evaluation studies. To observe tolerance in human bodies and pharmacokinetics, providing a basis for a drug administration program. Phase II: A preliminary exploration on the therapeutic efficacy. The purpose is to evaluate the safety and efficacy of a new drug on patients within the target indication of the drugs, and providing the basis to devise Phase III Clinical Trial and to determine a drug administration program. Phase II Clinical Trial may be conducted in many ways including - 6 - randomized blind controlled clinical trial in accordance with the purpose of the study. Phase III: The phase to confirm the therapeutic efficacy. The purpose is to further verify the safety and efficacy of a new drug for patients with targeted indication, to evaluate the benefit and risks relationship, and finally to provide sufficient data to support the registration approval of the drug. The trials usually are randomized, blind and controlled clinical trial with a large number of sample subjects. Phase IV: A new drug post-marketing study, conducted by the applicant. The objective is to investigate the efficacy and adverse reactions under the conditions of wide use, and to evaluate the benefit and risk relationship when used by ordinary and special groups of patients and to improve dosage of the drug. Bioequivalence trials means those human trails to determine if there is any statistical difference in absorption and absorption speed of active component between the same or different dosage form of the same drugs under the same test conditions, by using methodology of bioavailability study and with pharmacokinetic parameters. Article 32: The number of human subjects in the clinical study of a drug should be decided in accordance with the objective of the clinical trials and shall meet both the statistical requirements and the minimal cases required by this Regulation for a clinical study. For a drug used for the treatment of rare and special diseases or other special circumstances, any requirements for reduction in the number of human subjects in the clinical study or exemption should be made at the same time of clinical trial application and be approved by SFDA. Article 33: For a vaccine and other special drugs prepared during the strains selection stage, if there is indeed neither suitable animal experimental model nor a way to evaluate the efficacy of the drugs in laboratory study, application of clinical trials may made to SFDA, provided that safety of the subjects can be ensured. Article 34: After approval of a clinical study, the applicant shall select from the institutions qualified for drug clinical trial to conduct the clinical study. Article 35: The investigational drugs shall be produced in a workshop which meets GMP requirements and the production process shall be strictly in accordance with the requirements of GMP. The applicant is responsible for the drug quality of the investigational drugs - 7 - Article 36: The applicant may inspect the investigational drug itself in accordance with the drug's standards for its selected drugs for clinical trial, or authorize a drug control institute designated by this Regulation to conduct the quality test. Vaccine, blood products and other bio-products designated by SFDA must be inspected by a drug control institute designated by SFDA. The drug must not be used for Clinical Trails before it has passed the inspection. Drug administration authorities may conduct a random inspection for the investigational drug. Article 37: Before conducting the clinical study, the applicant shall file with SFDA information such as the clinical study protocol, name of the principle investigator of the leading institution, participating institutions and investigators, approval letter from ethics committee, and the sample of the Informed Consent Form, also providing a copy to the PDA where the institutions are located and PDA where the application was filed. Article 38: If an applicant discovers that an institution conducting clinical study is in violation of relevant regulations, or is not following the clinical study protocol, the applicant shall try to have the situation corrected. For serious violation, the applicant may request to suspend or stop the clinical study and shall submit a written report to SFDA and the relevant PDA. Article 39: Upon the completion of the clinical study, the applicant shall submit a clinical study summary report, statistical analysis report, and database to SFDA. Article 40: A clinical study shall start within 3 years of approval. Otherwise the approval certificate shall automatically become null and void. A re-application shall be submitted to resume the study. Article 41: Should any serious adverse event occur during clinical trails, the institutions should report to PDA, SFDA, as well as the applicant within 24 hours of occurrence, and timely report to the Ethics Committee. Article 42: SFDA may request the applicant to amend the clinical study protocol, suspend or stop the clinical study in any of the following circumstances: 1) the Ethics Committee has failed to perform its duty; or; 2) the safety of the subjects cannot be effectively ensured; 3) serious adverse event was not timely reported; 4) evidence that the investigative drug is not effective; 5) quality problems in the drug used for clinical trials; - 8 - 6) fraud in the clinical study; 7) other circumstances violating GCP. Article 43: During the clinical study, in case a large range or unexpected adverse reaction or serious adverse event occurs, or there is evidence to prove that the investigational drug has significant quality problems, SFDA or PDA may adopt emergency mandatory administrative measures to suspend or stop the clinical study, and the applicant and institutions must immediately stop the study. Article 44: A foreign applicant who wants to conduct an international multi–center clinical study shall apply at SFDA in accordance with the following provisions: 1) The investigational drug used for an international multi–center clinical study shall be one already registered in a foreign country or in phase II or phase III clinical trials. An application for an international multi–center clinical study of new preventive vaccine from a foreign applicant still not registered outside China shall not be accepted by SFDA. 2) In approving an international multi–center clinical study in China, SFDA may request the applicant to firstly conduct the Phase I clinical trials in China. 3) During a study conducted in China, the Applicant shall, in accordance with the relevant regulations, report to SFDA any serious adverse events or unexpected adverse events which occur in any countries. 4) Upon the completion of the study, the Applicant shall submit the complete clinical study report to SFDA. 5) Data generated from an international multi–center clinical trial, if used for drug registration in China, shall be in accordance with the relevant provision of this Regulation, and the applicant shall submit the complete research information of the study. Chapter 4: Application and Approval of New Drugs Article 45: SFDA may use special approval process for the following new drug, where detail regulation will be promulgated separately: 1) New drug material and its preparation, active ingredients and its preparation extracted from plant, animal and minerals, which have not been marketed in China and; 2) chemical drug raw material and its preparations, and/or biological product that have not been marketed domestically or outside China; - 9 - 3) new drugs for AIDS, cancer and orphan disease that are superior to the marketed drugs. 4) new drugs which treat diseases for which there is no effective therapy. For those drugs meeting the above provisions of this Regulation, during the drug registration, the applicant may apply for a special approval, SFDA shall organize specialist meeting to decide whether to use special approval for the drug application. Detailed provisions of special approval shall be promulgated separately. Article 46: When a new drug is jointly developed, the application shall be made by one of the parties, and other parties shall not apply in repetition. When a joint application needs to be made, the application shall be signed by all the parties. After approval, all the new drugs, including different strengths of the same drugs shall only be manufactured by one party. Article 47: For those registration applications of change in dosage form of drug but with no change in route of administration, new technology should be used to improve drug quality and safety, and there should be obvious clinical advantage in comparing with original dosage form. Except for targeted delivery preparation, sustained or controlled release preparation, the registration applications of change in dosage form of drug but with no change in route of administration should be made by the company with production condition. Article 48: During review process of new drug, even if the marketing approval of other drug of the same active substance is approved overseas, the registration category and technical requirements of the drug shall remain unchanged in the review process in China. During the review process of new drug, even when the marketing approval of other domestic drug of the same active substance is approved in China, the registration category and technical requirements of the same kind of drug shall remain unchanged in the review process in China. Article 49: Drug applicanion dossier should be submitted in one time, the applicant shall not self submit supplemental technical material to SFDA once any application is accepted, except for new information related to the drug safety or those special approval. If applicant considers the new technical materials must be added, the applicant should withdraw the application. When an applicant re-apply, the application procedures of this regulation should be met and there should not be any same drugs already entering into monitoring period. . - 10 - Section 1: Clinical Trials for New Drugs Article 50: Upon the completion of the pre-clinical study, the applicant shall complete the Application Form for Registration of New Drugs, and submit the authentic dossier to the local PDA. Article 51: PDA shall examine the format of the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with explanation of reasons. Article 52: PDA shall, within 5 days upon acceptance of the application, organize and conduct on-site inspection of the drug research and the original data, conduct preliminary examination of the application dossier. If the drug to be registered is biological product, PAD shall take sample drugs of 3 batches, and notify the drug control institute for inspection. Article 53: PDA should, within the prescribed time limit, submit the examination recommendation, verification report and application dossier to the Center of Drug Evaluation of SFDA, and notify the applicant. Article 54: Drug control institute received the registration inspection notification should inspect the sample according to the drug standards submitted by the applicant, verify the drug standards, and submit the inspection report to Center of Drug Evaluation (CDE) of SFDA within the prescribed time limit, and copy applicant in. Article 55: Upon receipt of the application dossier, CDE of SFDA shall within the prescribed time, organize pharmaceutical, medical and other technical staff to conduct technical examination of the application dossier, and may request, with explanation of reason, the applicant to provide supplemental information and drug sample if necessary. After completing the technical examination, technical examination recommendation will be issued and submitted to SFDA along with the related application information. SFDA shall make approval decision based on the technical examination recommendation. When SFDA consider the requirements are met, Approval for Drug Clinical Study will be issued. When SFDA does not consider the requirements are met, Notification of Approval Opinion will be issued with explanation. Section 2: Production of New Drug - 11 - Article 56: After completion of a clinical study, the applicant shall fill out the Drug Registration Form, and submit production application dossier to the PDA where the applicant is located. At the same time, the applicant shall submit the raw material and research data related to standard substance for the preparation of the standard substance to NICPBP. Article 57: PDA shall examine for form the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with explanation of reasons. Article 58: PDA shall, within 5 days upon acceptance of the application, organize and conduct on-site inspection for the clinical trial and relevant original data, conduct preliminary review and issue examination recommendation. For those drugs other than biological product, PDA should also need to take sample of 3 batches of the drugs, and notify the drug control institute to verify the standards. PDA shall, within the prescribed time limit, submit its recommendations, inspection report and application dossier to CDE, and notify the applicant. Article 59: Drug control institute should verify the drug standards, and then submit the verification recommendation to CDE within the prescribed time limit, at the same time, copy in the PDA that issued the notification to verify, and copy the applicant in. Article 60: Upon receipt of the application dossier, CDE of SFDA shall within the prescribed time, organize pharmaceutical, medical and other technical staff to conduct technical examination of the application dossier, and may request, with explanation of reason, the applicant to provide supplemental information and drug sample if necessary. After the examination, if the related provisions are met, CDE shall notify the applicant to file application for on site inspection of production site, and notify the Centre for Certification Administration (CCA) of SFDA. After the examination, if the related provisions are not met, CDE shall submit the recommendation and application dossier to SFDA. SFDA shall make decision not to approve based on the technical examination recommendation, and Notification of Review Opinion will be issued with explanation. Article 61: Upon receipt of the notification of on site inspection of production site, applicant should file at CCA application for on site inspection of production site within 6 months.. - 12 - Article 62: Upon receipt of the application of on site inspection of production site, CCA shall within 30 days organize on site inspection of the production process of the sample, confirm the feasibility of the verified production process, take sample of 1 batch of product (3 batch for biological product), submit them for inspection to the drug control institute where the drug standards was verified, submit the inspection report of production site to CDE within 10 days upon completion of the on site inspection. Article 63: The sample product shall be manufactured in a workshop with the GMP Certificate. For a newly established drug manufacturing enterprise or workshop or for the manufacture of additional drug dosage forms, the process of production of the sample product should comply with requirement of GMP. Article 64: The Drug Control Institute shall test the sample product in accordance with the verified drug standards, and submit the drug test report to CDE within the prescribed time, and send copies to the related PDA and the applicant. Article 65: CDE shall conclude a general examination recommendation based on the technical examination recommendation, inspection report of production site of the sample and sample test report, and then submit to SFDA along with the related data. SFDA shall make approval decision based the general recommendation. If the requirements are met, new drug certificate will be issued, if the applicant is already a holder of Drug Manufacturing License and meet the production requirement, drug approval number will be issued at the same time. If the requirements are not met, Notification of Approval Opinion will be issued with explanation. Except for those special dosage forms such as targeted delivery preparation, sustained and controlled released preparations, after approval, no new drug certificate will be issued for the registration of all other applications of change in dosage form but no change in route of administration, as well as application for additional indication. Section 3: Monitoring Period of New Drugs Article 66: Based on the requirement to ensure public health, SFDA may implement a monitoring period for the approved new drugs so as to continue to monitor the safety of the new drug. The drug-monitoring period shall start from the date of approval for production, and shall not exceed 5 years. - 13 - For the new drugs under the monitoring period, SFDA shall not approve production, dosage change and importation of the drug by other enterprises. Article 67: During the monitoring period of a new drug, drug manufacture enterprise shall regularly inspect the production process, quality, stability, efficacy and adverse reaction, and annually report to local PDA. PDA should order a correction if the enterprise fails to perform the duty required by the monitoring period. Article 68: When a serious quality problem, or serious or unexpected adverse reactions is discovered by relevant institutions during the manufacture, distribution, use or inspection, or administration of the drug, it shall be reported to PDA immediately. PDA shall immediately organize an investigation of the drug with serious quality problems, serious and / or unexpected adverse reactions, and report to SFDA. Article 69: If a new drug under a monitoring period has not begun production within 2 years from the approval date, SFDA may approve the production application for the new drug by another applicant and continue to monitor. Article 70: As a new drug enters monitoring period, for an application whose clinical study has already been approved by SFDA, the application shall continue in the regular review process. SFDA may approve the production or importation if the application meets the requirements, and monitor this new drug together with the previously approved new domestic drug. Article 71: As a new drug enters the monitoring period, application of the same drug by others will not be accepted, and for an application which has been accepted but whose clinical study has not been approved by SFDA, the application shall be returned. Upon the completion of monitoring period, another applicant may apply for generic drug or imported drug. Article 72: For an imported drug that has already received marketing approval, if an application whose clinical study has already been approved, the application may continue in the regular review process. While SFDA may approve the production of the drug if the application meets the requirements, the applicant may withdraw the application and apply for generic drug applications. For an application which has been accepted but whose clinical study has not been approved, the application shall be returned, and applicant may apply for generic drug applications. - 14 - Chapter 5: Application and Approval of Generic Drugs Article 73: Applicant of generic drug applications should a drug manufacturer. The drug for which application is made shall be consistent with the production scope described in Drugs Manufacturing License. Article 74: Generic drugs should have the same active component, route of administration, dosage form, strength and same therapeutic effect with the drug it copies from. When the drugs it copies from are from many companies, a comparison study of the drugs it will copy from should be conducted based on the related technical guidance and principles. Article 75: Applicant of generic drug registration should fill out the Drug Registration Form, and submit production application dossier and application for inspection of production site to the PDA where the applicant is located. Article 76: PDA shall examine the format of the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with explanation of reasons. For those TCM drugs under application for TCM protection, application for generic drug of the same drug will be suspended from the date protection application was accepted to the date an administration decision is made. Article 77: PDA shall, within 5 days upon acceptance of the application, organize and conduct on-site inspection of the drug research and the original data, and conduct on site inspection of the production site according to the production process and quality standards provided by the applicant, take sample drugs of 3 consecutive batches on site, and notify the drug control institute for inspection. Production of the sample drugs should comply with the provisions of Article 67 of this Regulation. Article 78: PDA should within the prescribed time limit conduct examination of the application dossier and issue recommendation. If the requirement are met, the examination recommendation, verification report and inspection conclusion of production site and application dossier will be submitted to CDE, and notify the applicant. It the If the requirements are not met, Notification of Approval Opinion will be issued with explanation, at the same time, notify the drug control institute to stop the registration inspection of the drugs. Article 79: The drug control institute shall test the sample product and submit the drug test report to CDE within the prescribed time, and send - 15 - copies to the PDA that requested the test and the applicant. Article 80: CDE of SFDA shall organize pharmaceutical, medical and other technical staff to examine the verification recommendation and the application dossier, and may request, with explanation of reason, the applicant to provide supplemental information if necessary. Article 81: CDE of SFDA shall conclude a general examination recommendation based on the technical examination recommendation, inspection report of production site of the sample, and sample test report, and then submit to SFDA along with the related data. SFDA shall make approval decision based the general recommendation. If the requirements are met, drug approval number or Clinical Trail Approval will be issued. If the requirements are not met, decision not to approve will be made and Notification of Approval Opinion will be issued with explanation. Article 82: Upon completion of clinical trails, the applicant should submit the clinical trails data to SFDA. SFDA shall, based on the technical examination recommendation, issue with drug approval number or Notification of Approval Opinion. Article 83: For those drugs that confirmed by SFDA to be defective in term of safety, SFDA may decide to suspend acceptance or approval of the application of generic drugs. Chapter 6: Application and Approval for Imported drugs Section 1: Registration of Imported drugs Article 84: The drugs under import application should have obtained marketing approval in its country/region of manufacture. Without such a marketing approval, a drug to be imported may still be approved if SFDA confirms the safety and efficacy of the kind of drug, and if there is a clinical need for the drug. The production of drugs under import application should meet the GMP standard in the foreign country / region as well as the requirements of GMP in China. Article 85: For an imported drug application, the applicant shall complete Application Form for Drug Registration and submit the relevant application dossier and sample product, and provide the relevant certified documents. The application shall be made with SFDA. Article 86: SFDA shall examine for form the application dossier, if the requirements are met, the application shall be accepted, and an acceptance notification shall be issued. SFDA shall notify NICPBP for drug registration - 16 - inspection of 3 batches of drug samples. When SFDA does not consider the requirements are met, Notification of Non- Acceptance will be issued with explanation. SFDA may organize the on-site inspection about the research status and manufacturing status, and take sample. Article 87: NICPBP should with 5 days upon receipt of the data and sample, organize the registration inspection. Article 88: Within 60 days upon receipt of data, sample and related standard substance, the drug control institute undertaking import drug registration inspection should complete the registration inspection and submit the inspection report to NICPBP. Sample test and drug standard verification for special drugs and vaccine products is allowed to be completed within 90 days. Article 89: NICPBP should, within 20 days upon receipt of verified drug standards and the drug registration inspection report from drug control institute, organize specialist to conduct technical examination, and if necessary, conduct re-verification based on the examination recommendation. Article 90: NICPBP should, upon completion of import drug registration inspection, submit the verified drug standards, drug registration inspection report and verification recommendation to CDE of SFDA, and copy to applicant. Article 91: CDE of SFDA should within limited time organize pharmaceutical, medical and other technical staff to conduct technical examination, and may request, with explanation of reason, the applicant to provide supplemental information if necessary. Article 92: CDE shall conclude a general examination recommendation based on the technical examination recommendation, inspection report of production site of the sample and sample test report, and then submit to SFDA along with the related data. SFDA shall make approval decision based the general recommendation. If the requirements are met, Drug Clinical Trial Approval will be issued. If the requirements are not met, Notification of Approval Opinion will be issued with explanation. Article 93: Upon approval of the clinical study, the applicant shall conduct the clinical study in accordance with the provision under Chapter 3 of this Regulation. Upon the completion of clinical study, the applicant shall, in accordance with relevant requirements, submit to SFDA the clinical study report, relevant changes and supplemental information, with detailed explanation and justifications, and the relevant certified documents. - 17 - Article 94: CDE should organize pharmaceutical, medical and other technical staff to conduct overall examination of the submitted clinical trail data, and may request, with explanation of reason, the applicant to provide supplemental information if necessary. SFDA shall make approval decision based the recommendation from technical examination. If the requirements are met, an Imported Drug Certificate shall be issued to the applicant. Application by companies from Hong Kong, Macao and Taiwan shall proceed by reference to this Regulation, if the requirements are met, a Pharmaceutical Product Certificate shall be issued to the applicant. If the requirements are not met, Notification of Approval Opinion will be issued with explanation. Article 95: For an imported drug preparations application, documents to evidence the legal channels of immediate packaging materials or containers of the drug, documents to evidence the legal channels of drug raw material and excipients must be provided. For raw material and excipients of drug that has not been approved by SFDA, standardized information of relevant production processes, quality specification, and inspection methods should be submitted. Section 2: Approval of Repackaging of Imported drugs Article 96: Repackaging of imported drugs means taking from offshore finished drug preparation in large packaging and putting them into smaller packaging, or taking drugs in smaller packaging and placing them into final (outside) packaging with an insert sheet, labeling, etc. in China. Article 97: The application for repackaging of imported drug shall comply with following requirements: 1) an Imported Drug Certificate or Pharmaceutical Product Certificate has already been obtained for the imported drugs; 2) the drugs are yet to be manufactured in China or, if manufactured, not able to meet the clinical demand; 3) the drugs of one pharmaceutical company shall only be repackaged by one pharmaceutical production enterprise, generally for a period not exceeding the valid period of Imported Drug Certificate or Pharmaceutical Product Certificate. 4) With exception of tablet or capsule, internal packing of repacked drugs in all other dosage form should be finished offshore; 5) the pharmaceutical production enterprise to accept repacking should hold a Drug Manufacturing License. When imported uncoated tablet or capsule are to be repacked, enterprise to accept repacking should also hold a GMP Certificate consistent to the dosage form of the drug to be repacked. - 18 - 6) Any application for repacking of imported drug should be made one year prior to expiration of Imported Drug Certificate or Pharmaceutical Product Certificate. Article 98: The offshore pharmaceutical company shall sign a repackaging contract for imported drugs with an onshore pharmaceutical production enterprise, and complete the Drug Supplemental Application Form. Article 99: An application for repackaging a drug shall be submitted by the onshore pharmaceutical production enterprise to the PDA where the party is located, and the Drug Supplemental Application Form signed by the offshore pharmaceutical company should be submitted with the relevant information and sample products. PDA shall examine for form the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with explanation of reasons. PDA should make recommendation after completion of the review process and submit the application dossier and recommendation to SFDA for approval, and notify the applicant. Article 100: SFDA shall review the submitted application dossier. When SFDA consider the requirements are met, Approval for Drug Supplemental Application and Drug Approval Number will be issued. When SFDA does not consider the requirements are met, Notification of Approval Opinion will be issued with explanation. Article 101: The registration standards for the imported drug shall be applied to the repackaged drug. Article 102: The package, label and insert sheet of a repackaged drug shall be consistent with that of the imported drug to be repacked, and shall include the approval number for drug to be repacked and name of the drug repackaging manufacturer. Article 103: The import inspection of finished drug preparations in large packaging should be conducted in accordance with SFDA regulations. The same drug standards shall apply to both the inspection of the repackaged drug and import inspection. Article 104: The offshore pharmaceutical company shall be responsible for the quality of the repackaged drugs. If a quality problem arise, SFDA may cancel the approval number of the drug repackaging, and if necessary, cancel the Imported Drug Certificate or Pharmaceutical Product Certificate of the drug in accordance with Article 42 of Drug Administration Law. - 19 - Chapter 7: Application of OTC Drugs Article 105: For a generic drug falls into OTC drug, applicant should check the OTC items in the “supplemental application item” of the Drug Registration Form. Article 106: For a generic drug falls into both prescription and OTC drug, applicant may file the application by choosing to follow the requirement of either prescription or OTC drug. Article 107: In the following circumstances, an applicant may check the OTC items in the “supplemental application item” of the Drug Registration Form. If the requirements of OTC drugs are met, the OTC drug regulation and approval shall apply. If the requirements of OTC drug are not met, the prescription drug regulation and approval shall apply: 1) change in dosage form, but without change in indications, dosage, route of administration of an OTC drug as designated by SFDA; 2) new combination preparations developed from active OTC ingredients designated by SFDA. Article 108: For an OTC drug registration application, the insert sheet and label should comply with relevant requirement of OTC drugs. Article 109: If an imported drug falls into OTC drug, regulation and approval procedure of imported drug shall apply where technical requirements for those drugs shall be consistent with requirements for domestic OTC drug. Chapter 8: Supplemental Application and Approval Article 110: A supplemental application should be filed for changes of items in the approval certificate or the content of its attachment of new drug research, drug production and drug importation. The applicant shall assess the impact of the change to the drug safety, efficacy, and quality control, with reference to the applicable technical guidance, and conduct the necessary technical research. Article 111: The applicant should complete the Supplemental Application Form, submit to PDA where the applicant is located with relevant documents and explanations. PDA shall examine for form the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with - 20 - explanation of reasons. Article 112: For a supplemental application related to imported drugs, the applicant shall apply to SFDA with relevant information and document, as well as the approval document of the proposed change from the competent authorities of the foreign country or region where the drug is manufactured. SFDA shall examine for form the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with explanation of reasons. Article 113: For a supplemental application of change of the production process affecting drug quality, amendment of drug registration standard, as well as change of excipients of medical purpose in the formula, after PDA issue with examination recommendation, the application shall be submitted to SFDA for approval, and applicant should be notified at the same time. For a supplemental application for amendment of drug registration standards, if necessary, the drug standards should be verified by drug control institute. Article 114 For a supplemental application of internal change of the manufacturing location within the drug manufacturer, name change of domestic drug manufacturer, as well as amendment of valid period of domestic drugs, the application shall be filed and accepted at local PDA. When PDA considers all the requirements are met, Approval of Drug Supplemental Application will be issued and the approval shall be filed for record at SFDA. If the requirements are not met, Notification of Approval Opinion will be issued with explanation. Article 115 For a supplemental application of change of drug label required by regulation, insert sheet amendment required by SFDA, the changes shall be filed at PDA for record. Article 116 Any supplemental application related to an imported drug shall be approved by SFDA. For some of supplemental application of imported drug, such as change of manufacturing location of raw material used for import drug preparation, change in drug appearance with change in drug standards, amendment of insert sheet according to the National Standard or requirement of SFDA, supplementing and perfecting of safety related content of insert sheet, change of design of packing or label of imported drug as requested by regulation, change of registration agent, the application needs to be filed for record at SFDA. Article 117 For a supplemental application for a change due to drug technology transfer, change in formula or process that is assessed to be - 21 - likely to affect the quality of the product, PDA shall, in accordance with attachment to the Drug Registration Approval Letter or the verified production process, organize on-site inspection of the production site, drug control institute should test the 3 batches of sample product taken for inspection. Article 118 SFDA shall examine the supplemental drug application, where SFDA may request, with explanation of reasons, the applicant to provide supplemental information, if necessary. When SFDA consider the requirements are met, Drug Supplementary Application Approval will be issued. When SFDA does not consider the requirements are met, Notification of Approval Opinion will be issued with explanations. Article 119 After the approval of any supplemental application, when the drug approval certificate needs to be renewed, the old drug approval certificate shall be canceled by SFDA. When additional drug approval certificate needs to be issued, the old certificate shall continue to be effective. Chapter 9: Re-registration of Drugs Article 120: The validity period of the Drug Approval Number, the Imported Drug Certificate and Pharmaceutical Product Certificate issued by SFDA is 5 years. 6 months prior to the expiration, application for re-registration shall be made, should there be a need for continuing the production and / or importation. Article 121: While the Drug Approval Number, the Imported Drug Certificate or Pharmaceutical Product Certificate is valid, the applicant should conduct symmetrical assessment as for the drug safety, efficacy, and quality control, such as relevant study result during the monitoring period, monitoring of the adverse reaction, production control and homogeneity of product quality, in order to present as evidence during the re-registration. Article 122: The holder of a drug approval number shall apply for re-registration of the drug with local PDA, by completing the Application Form for Drug Re-registration according to relevant requirements and submitting relevant application material. The application for re-registration of an imported drug shall be submitted to SFDA. Article 123: PDA shall examine the application dossier, and if the requirements are met, the application will be accepted with issuing of acceptance notification of drug registration application. If the requirements are not met, the application will not be accepted with issuing of non-acceptance notification of drug registration application, with - 22 - explanation of reasons. Article 124: PDA shall, within 6 months, examine the re-registration application, if the requirement are met, the re-registration will be approved, if not the re-registration shall be filed at SFDA for record. Article 125: The application for re-registration of the imported drug shall be accepted by SFDA, who shall complete the review of the application within 6 months of receipt, and approve the re-registration that meets the requirements. If not, notification not to approve will be issued with explanation of reasons. Article 126: A re-registration shall not be accepted in any of the following situations: 1) failure in applying for re-registration of the drug within the prescribed time; 2) failure in meeting the relevant approval requirements of SFDA for marketing; 3) failure in completing Phase IV clinical trials according to relevant requirements; 4) failure in monitoring drug adverse reactions according to relevant requirements; 5) the kind of drug considered to be a disputed efficacy, high adverse reaction, or other factors harmful to human health, based on the re-evaluation of SFDA, 6) the kind of drug whose approval should be withdrawn according to the requirements of Drug Administration Law; 7) production condition fails to meet the requirements of Drug Administration Law; 8) failure to fulfill the responsibility during the monitoring period; or, 9) other situations in which relevant requirements have not been met. Article 127: After receipt of the recommendations from PDA, if the drugs to be re-registered fail to meet the requirement by examination, SFDA shall issue the notification of rejection of the drug for re-registration with explanations. For those rejected re-registration, except for those certified drug approval document that have been canceled by lawful enforcement, the drug approval number, Imported Drug Certificate or Pharmaceutical Product Certificate of the drug shall be canceled upon the expiry of the valid period. Chapter 10: Inspection During Drug Registration Article 128: Drug registration inspection includes inspection of sample products and verification of drug quality standards. - 23 - Inspection of sample products means that drug inspection conducted by a drug control institute according to the quality standards submitted by the applicant or approved by SFDA. Verification of drug quality standards means laboratory inspection by a drug control institute to verify the feasibility and scientificness of inspection methods described in the quality standards of the drug and whether or not the assumed parameters can control the drug quality. Article 129: Drug registration inspections shall be conducted by NICPBP or the provincial drug control institute, where inspections for imported drug registration shall be conducted by NICPBP. Article 130: Drug registration inspection shall be conducted by NICPBP or the drug control institute designated by SFDA for the following events: 1) a drug belonging to categories of Article 45.1 and 45.2 of this Regulation; 2) biological product, or radioactive drugs; 3) other drugs designated by SFDA. Article 131: When arranging inspection of sample products and verification of drug quality standards, the drug control institute shall give priority to a drug accepted for special approval. Article 132: A drug control institute engaged in drug inspection for registration shall be staffed and equipped according to requirements of the Good Laboratory Practice of Drug Control Institutes and National Measurement Certification, and complies with the requirements of the quality assurance system and technical requirements of the drug registration inspection. Article 133: The applicant shall provide the drug control institute with information needed for drug registration inspection, submit sample product or co-operate in taking sample products used for inspection, and provide the standard drug substance used for inspection. The amount of sample products supplied shall be three times the amount of the drug needed for inspection. For a biological product, the record of preparation and inspection for the corresponding batches shall also be provided. Article 134: During the verification of drug standards, in addition to inspection of the sample products, the drug control institute shall also issue an verification recommendation regarding the drug standards of the drug, items to be inspected and verification methods, based on the research data of the drug, the drug standards of similar products domestic and in the foreign countries, as well as national requirements. Article 135: In re-making a drug's standards, the applicant shall not authorize the drug control institute that issued the recommendations to conduct the research work. Similarly, such institute shall not accept such authorization. - 24 - Chapter 11: Drug Registration Standards and Insert Sheets Section 1: Drug Registration Standards Article 136: “National Drug Standards” refer to drug registration standards, other drug standards and PRC Pharmacopoeia issued by SFDA, covering technical requirements including quality parameters, inspection methods and production process. “Drug registration standards” means the drug standards approved by SFDA for a specific applicant, which is the basis for drug production and the monitoring and administration of the drugs. Drug registration standards must not decrease from standards of current Pharmacopoeia. Article 137: The determination of items and inspection methods for drug registration standards shall meet basic requirement of the current Pharmacopoeia, the requirements of the technical guidance principles issued by SFDA, and National rules for compiling national drug standards. Article 138: An applicant should select representative sample products for the study of standards. Section 2: Drug Standard Substance Article 139: Drug standard substance, including standards, control products, raw material control products, and reference products, means a substance with specific values, which is to be used in physical, chemical inspection and biological method inspection needed for the drug quality standards, and used to calibrate equipments, to evaluate the measuring methods or to assay the inspection drugs. Article 140: NICPBP shall be responsible for standardization and administration of national drug standard substances. NICPBP may organize the relevant provincial drug control institute, research institutions or pharmaceutical production enterprise for cooperation in standardization and administration. Article 141: NICPBP shall be responsible for the comprehensive technical review of the standard substance regarding the selection of raw materials, production methods, standardization methods, standardization results, accuracy of assay values, tracing of origin of various values, stability, and conditions for repackaging and packaging, in order to reach a conclusion as - 25 - to whether they can be used as national standard substances. Section 3: Drug Name, Insert Sheets and Labels Article 142: Application for drug name, insert sheet and labels should comply with SFDA regulation. Article 143: Drug insert sheet shall be proposed by the applicant, and CDE of SFDA shall examine the content of insert sheet other than those information related to the company itself against the application dossier, and the insert sheets should be approved by SFDA upon approval of production. Applicants shall be responsible for the scientificness, correctness and accuracy of insert sheets and labels. Article 144: The applicant shall monitor the safety and efficacy during the post marketing period, and make timely application for amendment of insert sheets when necessary. Article 145: Applicant shall print the insert sheet and labels according to the content of approved insert sheet, and in accordance with the format and requirements by SFDA. Chapter 12: Prescribed Timeline Article 146: Drug administration authorities should adhere to the requirement of Prescribed Timeline as specified in Drug Administration Law, Administrative Licensing Law, and the Implementing Regulation. The prescribed timeline for drug registration referred in this regulation means the maximum allowed time for the relevant acceptance, examination and approval etc, excluding the time legally required in suspending the approval and the time for applicant to submit supplemental dossier. Timeline for examination and drug regulation inspection should be according to this regulation. Necessary time extension for special cases should be made with explanation of reasons, and obtain approval from SFDA, and the applicant should be notified in writing. Article 147: Upon receipt of any application, drug administration authorities shall examine for form, and act according to the following. 1) Inform immediately the applicant of non-acceptance if there is no need for administrative permits for the application items; 2) conclude immediately a decision of non-acceptance if the application - 26 - items fall outside of lawful jurisdiction of division, and then refer the applicant to the related authorities; 3) allow the applicant to make correction on site, if the defects in the application dossier can be made good on site; 4) when the application dossier is incomplete or fail to meet the lawful requirement for form, the applicant should be notified in one notification on site or within 5 days of the missing data to be supplemented, failure to notify within the timeline should be deemed to have accepted the application dossier on the date of receiving the dossier; 5) when the application items fall into lawful jurisdiction of the division, application dossier is completed and in lawful form, or appliance have supplemented all the missing information, the drug registration application should be accepted. When any drug administration authorities accept or not accept a drug registration application, a paper in writing should be issued with special chop of drug registration and dated. Article 148: Upon acceptance of the application, PDA shall complete within 30 days the inspection for research status and original data, examination of application dossier, taking of sample products, notification of the drug control institute for inspection of sample product, and submission of the recommendation and inspection report together with information submitted by the applicant to SFDA, and at the same time, notify the applicant of the inspection recommendations. Article 149: Timeline for drug registration tests should be in accordance with the following prescribed timeline. 1) Sample tests: 30 days, 60 days if the sample tests and verification of drug standards are conducted at the same time; 2) Sample tests for special drug and vaccine: 60 days, 90 days if the sample tests and verification of drug standards are conducted at the same time; Article 150: Technical review timeline should be in accordance with the following prescribed timeline. 1) 90 days for a new clinical study, 80 days if a drug meets the requirements of special approval; 2) 150 days for production of new drug, 120 days if a drug meets the requirements of special approval; and, 3) 160 days for application registration of generic drugs or application of change in dosage form of a marketed drug. 4) 40 days for supplemental application if a technical review is needed. The above timeline shall be used as reference to the technical examination - 27 - of import drug regulation application. Article 151: During the technical review, SFDA should issue in one notification regarding submission of all needed supplemental materials. The applicant may raise question to the required supplemental materials, and explanation of the applicant should be discussed face to face if necessary. Except for application meeting the requirement of special approval, where special requirement apply, the applicant shall in one time submit all the supplemental materials required by the notification within 4 months. Upon receipt of the supplemental information, the technical review should not exceed one third of original prescribed time, for a drug meets the requirements of special approval, the time should not exceed one quarter of original prescribed time. During the drug registration, if the applicant self withdraws the applicant, the approval process automatically terminates. Article 152: SFDA should conclude the administrative approval decision within 20 days. If it is not possible to conclude a decision within 20 days, a 10 day extension may be granted with approval by the leading department head, where the applicant should be notified with explanation of the reason for the extension. Article 153: SFDA should publish / deliver the relevant administrative licensing certificate within 10 days, once the administrative approval decision is concluded. Chapter 13: Reconsideration Article 154: SFDA shall not approve the application under any the following circumstances: 1) the same or similar data or research information are used in the applications by different applicants without a justified reason; 2) during the registration, the application dossier is found to be untrue, where applicant cannot prove the truthfulness; 3) design and implementing of research items is unable to support the assessment of the quality control, safety, efficacy of the products to be registered; 4) significant deficiency in safety, effectiveness, or quality control of the drug is revealed from the application dossier; 5) Failure to submit the required supplemental information within the prescribed time; 6) Sourcing of raw material fails to comply; - 28 - 7) On site inspection of production site or sample product test fails to comply; 8) Any other situation an approval should not be granted as specified by laws and regulations Article 155: Upon lawful conclusion of non-acceptance or non-approval decision in writing, the reason should be stated, and drug administration authorities shall notify applicant of the entitlement to applying for administrative re-consideration or appeal. Article 156: When an applicant object to the decision of non approval, the applicant may apply for reconsideration with SFDA within 60 days upon receipt of notification of non-approval, by filling out Drug Registration Re-consideration Application Form together with an explanation and its reasons for re-consideration. The scope of re-consideration can only be limited to the original application items and the application dossier. Article 157: SFDA should conclude its re-consideration decision and notify the applicant within 50 days upon receipt of the application for reconsideration. If the original decision is upheld, no further re-consideration will be accepted by SFDA. Article 158: When there is a need for technical review during the reconsideration, SFDA shall organize the technical experts to complete the review within the original prescribed time. Chapter 14: Legal Liability Article 159: If one of the provisions of Article 69 of Administrative Licensing Laws occurs, SFDA should proceed with the cancellation of relevant drug approval document, based on the request of the related party or from its lawful authority. Article 160: If any staff of drug administration authorities is found to violate the provisions of this regulation with one of the following occurrences, their supervising authorities or auditing authorities will request a correction. In any serious violation, disciplinary actions will be imposed to the directly responsible supervisor and other directly responsible people: 1) Did not accept a drug regulation that met the lawful requirement. 2) Did not publicly publish the required information items of drug registration. 3) Failure to fulfill legal obligation to notify applicant or the related party during the process of acceptance, examination, and approval. 4) Failure to notify the applicant in one notification of all the - 29 - supplemental information that must be supplemented, when information submitted by applicant is incomplete or not meeting the statutory form. 5) Failure to explain the reasons not to accept or not to approve. 6) Failure to hold a hearing when the hearing is lawfully required. Article 161: During the drug registration, if any staff of drug administration authorities asked for valuables from other party or sought for other interest, criminal charge will be investigated if the acts constitute a crime. If the acts did not sufficiently constitute a crime, disciplinary actions will be imposed. Article 162: If any staff of drug administration authorities is found to violate the provisions of this regulation with one of the following occurrences, their supervising authorities or auditing authorities will request a correction, and disciplinary actions will be imposed to the directly responsible supervisor and other directly responsible people. Criminal charge will be investigated if the acts constitute a crime: 1) Conclude an approval decision to any registration application not meeting the legal requirement, or conclude an approval decision of a registration application beyond the delegated power of authorities. 2) Conclude a non approval decision to any registration application meeting the legal requirements, or failure to conclude an approval decision within the lawfully prescribed timeline. 3) Failure to fulfill the non disclosure obligation specified in Article 9 of this Regulation. Article 163: If a drug control institute issues a fraudulent inspection report during performance of the duty for drug inspection during the drug registration process, sanctions shall be imposed according to Article 87 of the Drug Administration Law. Article 164: If any drug administration authorities charged unauthorized fees, or beyond the lawful fee category or rate, their supervising authorities or auditing authorities will request to return the illegally overcharged fees, and disciplinary actions will be imposed to the directly responsible supervisor and other directly responsible people. Article 165: In the event that GLP or GCP requirements were not adhered to during the drug registration, sanctions shall be imposed according to Article 79 of the Drug Administration Law. Article 166: If an applicant is found to have provided fraudulent drug registration information and / or sample product of the drugs during the application of clinical study, SFDA shall not accepter the application, or shall not approve the clinical study, and shall warn the applicant. No more new application for clinical trail from the same applicant will be accepted for - 30 - one year. If the application has already been approved, the approval certificate shall be canceled, and a fine of RMB 10,000 - 30,000 shall be imposed. Any clinical trail application by this applicant shall not be accepted for 3 years. A database of fraudulent conduct by applicants shall be maintained, and will be published. Article 167: If an applicant is found to have provided fraudulent drug registration information and / or sample product of the drugs during the application of drug production or importation, SFDA shall not accept or approve the application, and SFDA shall warn the applicant. No more new application for clinical trail from the same applicant will be accepted for one year. If the application of production and / or importation of the drugs have already been approved, the approval certificate shall be canceled, and a fine of RMB 10,000 - 30,000 shall be imposed, an application for the drug by this applicant shall not be accepted for 5 years. Article 168: When provisions of Article 27 calls for an experiment to be repeated, if an applicant refuses to repeat the experiment according to relevant requirements, the applicant shall be warned, and ordered to correct the situation. If the applicant definitively refuses to make corrections, the application shall not be approved. Article 169: Under any of the following events, the drug approval number will be cancelled, and the cancellation will be published: 1) Applicant self propose to cancel the drug approval number before the expiry of the certified approval documents; 2) Re-registration is rejected according to the provision of Article 126 of this Regulation; 3) Drug Manufacture License is revoked or withdraws under legal enforcement; 4) Drug of high adverse reaction or other hazards to human health, where the certified approval documents is withdrawn according to Article 42 of Drug Administration Law, or Article 41 of Implementing Regulation; 5) An administration decision to cancel or withdraw the certified approval documents is lawfully concluded; 6) Other situations leading to lawful cancellation or withdrawal of the certified approval documents. Chapter 15: Miscellaneous Article 170: Application dossier and requirement for TCM and natural drugs, chemical drugs, biological products, supplemental application, and - 31 - re-registration are specified in Annex 1, 2, 3, 4, 5 of this Regulation respectively. Provisions for monitoring period is specified in Annex 6. Article 171: Format of Drug Approval Number should read Guoyaozhunzi H(Z, S, J)+ 4 digit of year + 4 digit of serial number, where H denote chemical drug, Z denote TCM, S denote biological products and J denote imported drug repacking. Format of Imported Drug License should read H (Z, S)+ 4 digit of year + 4 digit of serial number, and format of Pharmaceutical Product License should read H (Z, S)C+ 4 digit of year + 4 digit of serial number, where H denote chemical drug, Z denote TCM, and S denote biological products. For the registration certificate number of repacking of large package from ex-China, B will be added as the prefix of the original certificate number. Format of New Drug Certificate should read Guoyaozheng H (Z, S)+ 4 digit of year + 4 digit of serial number, where H denote chemical drug, Z denote TCM, and S denote biological products. Article 172 Application acceptance, approval of supplemental application, approval of re-registration undertaken by PAD as specified by this Regulation fall into category of delegated authority by SFDA. SFDA may delegate PDA with other technical examination or approval items during the drug registration process. Article 173 SFDA will adopt drug coding management system for marketed drugs. The detailed regulation for drug coding management will be promulgated separately. Article 174: In addition to this Regulation, the application for narcotics, psychotropic, medical-use toxic drugs and radioactive drugs shall also be administered according to other relevant national regulations. Article 175: SFDA shall promulgate separate regulation for the registration of TCM material, TCM herb and import TCM material that regulated with approval number. Article 176: Regulation for technology transfer and toll manufacture shall be promulgated separately. Article 177: This Regulation become effective from October 1, 2007. Drug Registration Regulation promulgated by SFDA (SFDA order no. 17) on February 28, 2005 shall be abolished accordingly. Annex 1: Registration Categories and Application Information Requirements of TCM and Natural Drugs Annex 2: Registration Categories and Application Information Requirements of Chemical Drugs - 32 - Annex 3: Registration Categories and Application Information Items Requirements of Biological Products Annex 4: Registration Items and Application Information Requirements of Supplemental Application of Drug Registration Annex 5: Application Information Items of Drug Re-Registration Annex 6: Timeframe of Monitoring Period for New Drugs (note: no monitoring period for the drugs other than those listed) end - 33 -