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Drug Registration Regulation

Original Language Title: 药品注册管理办法

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(February 28, 2005 order of the State food and drug administration released 17th come into force May 1, 2005) contents chapter I General provisions chapter II chapter III of the application for registration of a drug preclinical drug research fourth fifth chapter clinical drug trial new drug application, examination and approval of the sixth chapter of the national drugs declared with the approval of the seventh chapter of imported drugs, and non-prescription drug approval eighth chapter registration Nineth drugs supplementary application and approval the tenth chapter drug re-registration of the 12th chapter of the 11th chapter of the registration test of national drug management Management chapter 13th drug drug registration standards in their timelines and 15th General Chapter 14th review legal liability the 16th chapter by-laws Annex: Chinese herbal medicine, natural medicine registration category and information requirements of annex II: classification and information requirements of annex III chemicals registered:     Real products registered classification and the declared information requirements annex four: drug added application registered matters and the declared information requirements annex five: drug again registered declared information project first chapter General first article for guarantee drug of security, and effective and quality can control, specification drug registered behavior, according to People's Republic of China drug management method (following referred to drug management method), and People's Republic of China drug management method implementation Ordinance (following referred to drug management method implementation Ordinance), developed this approach.     Article People's Republic of China engaged in clinical drug trials, drug production or import, for inspection, supervision and administration of drug registration, application of this approach.     Drug registration in article, refers to the State food and drug administration, according to the drug registration applicant's application in accordance with legal procedures, to be marketed drug safety, effectiveness, quality control and carry out a systematic evaluation and decide whether they agree that the approval process for the application.     Fourth the State encourages research and development of new drugs, and to create new drugs, treating difficult and severe diseases drugs and emergency medicines required for swift approval.     Fifth the State food and drug administration in charge of national drug registration process is responsible for approval for clinical drug trials, pharmaceutical production and imports.     Provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall declare their drug development situations and conditions to verify integrity of drug registration documents, normative and check its authenticity, and organizations on the preparation of the samples tested.     Article sixth drug registration applicant (hereinafter the applicant), refers to the drug registration applications submitted, and bear the corresponding legal responsibility, and the application for approval of drug approval documents of the institutions. Applicants must be legally registered in China in the territory and able to bear civil liabilities independently of institutions, foreign applicants shall be lawful outside of pharmaceutical manufacturers.     Overseas applicants apply for registration of imported medicine, should be determined by its China offices within China or its authorized agency.     Dealing with applications for drug registration, should be the appropriate professional and technical personnel, and should be familiar with the drug registration laws and regulations and the technical requirements for registration of pharmaceuticals. Chapter II the application for registration of a seventh drug registration application includes new drug applications, has been the national standard of import drug applications and supplemental drug applications, applications.     Applications for drug registration in the territory in accordance with the new drug applications and the standard new drug application procedures and requirements, foreign applicants in accordance with imported drug application procedures and requirements for registration of pharmaceuticals. Article eighth new drug applications, means no applications for registration of the drug went on sale in China.     Drugs already on the market to change form, changing the route of administration, new indications, according to the new drug application management.     Drug applications of an existing national standard, refers to the production of the State food and Drug Administration has issued official standards of drug registration.     Import drug applications, refers to the overseas production of application for registration of the drug went on sale in China.     Supplementary application, refers to new drug applications, there are national standards of drug application or import drug applications approval, change, add to, or cancel the original items or contents of the application for registration.     Nineth application of drug registration, the applicant shall provide the location of provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and administrative departments, and submit relevant data and drug samples; import drug applications for registration shall be made directly to the State food and drug administration.     Applicants should be responsible for authenticity of all reporting information. Tenth article two a above units common as drug applicants of, should to which drug production enterprise location province, and autonomous regions, and municipalities (food) drug supervision management sector proposed application; applicants are for drug production enterprise of, should to application production preparations of drug production enterprise location province, and autonomous regions, and municipalities (food) drug supervision management sector proposed application; application per capita not drug production enterprise of, should to samples trial site location province, and autonomous regions, and     Municipality (food), apply to the pharmaceutical supervisory and administrative departments.     11th should apply for registration of the applicant's drug or prescription, processes, uses and so on, provided the applicant or others in the description of the China patent and ownership of State; others patents in China, the applicant shall submit a statement does not constitute an infringement of a patent to others.     Article 12th drug patent disputes arising after the approval of the application for registration, the parties may resolve on their own, or in accordance with the provisions of relevant laws and regulations, resolved by administrative authorities for patent Affairs or the people's Court. Patentee pursuant to administrative authorities for patent Affairs the final decision or the people's Court found infringement verdict, to apply for cancellation of the infringer's State food and Drug Administration approval.     According to the State food and Drug Administration drug approval documents of the cancellation of the infringer. 13th has access to Chinese patent drugs to others, applications can be processed before the expiry of the patent applied for registration within 2 years.     The State food and Drug Administration be reviewed according to these measures, in conformity with the provisions, after the expiration of the patent, issued an approval number, the imported drugs registration certificate or the certificate of pharmaceutical product registration. Article 14th access to production or marketing with new chemical drugs licensed producers or sellers submit themselves and made undisclosed test data and other data, the State food and Drug Administration approval within 6 years from the date of the license, without the consent of applicants licensed, use of its undisclosed data shall not be approved.     But except for themselves access to data submitted by the applicant. Chapter 15th preclinical drug research for preclinical drug research in the application of drug registration, include drug synthesis, extraction method, physical and chemical properties and purity, choice of dosage form, formulation, manufacturing process, inspection methods, quality, stability, pharmacological, toxicological, pharmacokinetic studies of animals, etc.     Traditional Chinese medicine preparation also includes the original source, processing and preparation of research biological products also include bacteria and viruses, cell lines, tissues and other starting materials sources, quality standards, preservation, biological characteristics, genetic stability and immunological research.     16th preclinical research should implement the relevant provisions on the administration of drugs, which must implement the drug safety evaluation research non-clinical research and the quality control practices.     Article 17th engaged in pharmaceutical research and development institutions must be compatible with the experimental research project personnel, space, equipment, instruments and management systems; using experimental animals, reagents and materials should comply with the relevant national provisions and requirements, and should guarantee the authenticity of all data and information. 18th individual applications for registration of pharmaceutical preparations, using raw materials must have the approval number, the imported drugs registration certificate or registration certificate of pharmaceutical products, the raw material must be obtained through legal means.     APIs for use in research does not have an approval number, the imported drugs registration certificate or registration certificate of pharmaceutical products must be approved by the State food and drug administration. 19th applicant entrust other institutions for drug research individual testing, testing, sample or prototype, production, contracts shall, together with the principal.     Applicants should be declarations of the drug responsible for the authenticity of the data. 20th in drug registration documents have drug test information drug research institutions abroad, must be accompanied by a foreign drug information provided by the research institutions issued by the project, page numbers, information notes and evidence that the institution has legally registered outside the notarized documents, and approved by the State food and Drug Administration approval, may be made of drug registration information.     According to the State food and drug administration review require on-site verification organizations.     21st article national food drug supervision authority and province, and autonomous regions, and municipalities (food) drug supervision management sector according to need on research situation for verification Shi, can requirements applicants or bear test of drug research institutions according to its declared information of project, and method and data for repeat test, and organization on test process for site verification; also can delegate drug test by or other drug research institutions for repeat test. 22nd drug pre-clinical studies should refer to the State food and Drug Administration issued the relevant technical guidelines.     Applicants are evaluated by other testing methods and techniques, supporting scientific information shall be submitted.     Fourth chapter of drug clinical trials section I basic requirements article 23rd drug in clinical trials (including bio-equivalence trials) and must be approved by the State food and drug administration; the need to implement the code for quality management of drug clinical trials.     24th to apply for registration of new drugs, clinical trials shall be conducted. Clinical trials are divided into stage ⅰ, ⅱ, ⅲ, ⅳ. New drugs before approval, phase ⅰ, ⅱ, ⅲ clinical trials should be carried out.    After approval, some cases may only be phase II and phase III clinical trials or phase III clinical trials only. Phase ⅰ clinical trial: a preliminary evaluation of clinical pharmacology and human safety testing.     Observation of human tolerance and pharmacokinetics of the drug and provide basis for the dosage regimen. Phase ⅱ clinical trial: preliminary evaluation of the therapeutic effect of stage. Aimed at evaluation of drugs to target patients with indication for treatment and security, also includes the phase III clinical trial study design and the dosage scheme to provide evidence.     This phase of the study design can be tailored to specific research purposes, using a variety of forms, including randomized blinded controlled clinical trial. Phase ⅲ clinical trial: the effect of confirmation stage. Its goal is to further validate drug target indication for treatment of patients with effect and safety evaluation of benefits and risks, and ultimately reviewed provide sufficient basis for registration applications.     Testing should generally be randomized blinded controlled trials with adequate sample size. Phase ⅳ clinical trial: drugs listed by the applicant after the application phase.     Its purpose is to examine in the widespread use of the drug under the conditions of efficacy and adverse reactions, evaluation used in the ordinary or special groups of interests and improving the relationship between dose and risk, and so on. 25th to apply for registration of an existing national standard, generally do not require clinical trials; requires clinical trials, bioequivalence testing chemicals; need processes and standards to control drug quality medicines, clinical trials shall be conducted.     In the supplementary application, drug already on the market, production, significant changes or add new functions of traditional Chinese medicine, clinical trials shall be conducted.     Bio-equivalence trials, refers to methods of bioavailability studies, pharmacokinetic parameters for indicators, preparation of same or different forms of the same drug, under the same experimental conditions, the active ingredient absorption and faster there is no statistically significant difference in human trials. Article 26th number of drug clinical trial subjects shall comply with the clinical trial purposes and related statistical requirements, and shall not be less than the minimum clinical trials number of cases provided in this way.     Special diseases, rare diseases and other conditions, and asked to reduce the number of cases of clinical trials or clinical trials must be approved by the State food and drug administration review.     27th bacteria virus seed selection stage of preparation of vaccines or other special drugs, no suitable animal models and laboratory is unable to evaluate its efficacy, on the premise of ensuring the security of the participants, you can apply to the State food and Drug Administration clinical trials.     Prior to the implementation of section II of the 28th drug clinical trial approval, the applicant shall have the qualifications of clinical drug trials institutions, chose to take drug clinical trial Agency, agreed that clinical trials unit responsible, the main research and clinical trials unit.     Article 29th applicants should be responsible with the selected clinical trials unit and participation in the clinical trial contracts signed, investigator's brochure provided, with reference to the relevant technical guidelines with the researchers to design and improve the clinical trial protocol.     Clinical trial of clinical trial protocols should be brought to the Ethics Committee for review.     30th the applicant should be provided free of charge to selected clinical trials unit in clinical trials with drugs and controlled drugs (except phase IV clinical trials), and attach a sample inspection report; clinical trials needed for expenses shall be borne by the applicant. 31st drugs for use in clinical trials should be in conformity with good manufacturing practices workshop preparation.     Preparation process should strictly enforce the requirements of the good manufacturing practices.     States or provinces, autonomous regions and municipalities directly under the food and Drug Administration (food) the pharmaceutical supervisory and administrative departments may review the need for on-site verification. Articles 32nd to the applicant in accordance with national standards for food and Drug Administration approval of drug test used in clinical trials on their own drugs, can also be commissioned by the article 147th and 148th laboratories determined by inspection.     Drugs for use in clinical trials inspected the rear can be used for clinical trials.     Drug testing can be specified by the State food and Drug Administration to test the drugs for use in clinical trials.     Vaccine products, blood products, the State food and drug administration regulations of other biological products and overseas production of clinical trial drugs, must be specified by the State food and Drug Administration's drug testing by qualified before the clinical trials.     The applicant is responsible for the quality of the drugs for use in clinical trials.     33rd article applicants in drug clinical test implementation Qian, should will has determine of clinical test programme and clinical test is responsible for units of main researchers name, and participate in research units and research who list, and Ethics Committee audit agreed book, and informed agreed book sample, submitted national food drug supervision authority record, and CC clinical test units location and accepted the application of province, and autonomous regions, and municipalities (food) drug supervision management sector.     Article 34th section III clinical trials management clinical drug trials in the process, the applicant shall appoint inspectors, in accordance with the quality control supervision of drug clinical trials testing process.     35th applicant researchers found in breach of the regulations or is not in accordance with the programme of clinical trials to perform, should urge their correction in serious cases, suspension of clinical trials, or termination of the clinical trials, and will report to the State food and drug administration and the relevant provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments. 36th after the applicant has completed each phase of clinical trial, shall be filed with the State food and drug administration and the relevant provinces, autonomous regions and municipalities (food) drug supervision and management departments to submit clinical trial reports and statistical analysis.     After the completion of phase IV clinical trials, and shall submit a report to the State food and drug administration.     Clinical trials for more than 1 year, applicant shall from the date of approval each year to the State food and drug administration and the relevant provinces, autonomous regions and municipalities (food) drug supervision and management departments to submit clinical trial progress report. 37th clinical drug trials are approved shall, within 3 years after implementation.     Overdue implementation of the original document itself repealed; clinical trials is needed, should apply.     Article 38th clinical trials units and personnel should be familiar with the drugs for use in clinical trials of nature, action, efficacy, and safety of understand the responsibilities and obligations of researchers; by the subjects or voluntary signed the informed consent of their legal representatives, true, accurate, complete, timely, and lawful to do clinical trial records.     39th units and researchers participating in the clinical trials, drug clinical trial quality management to the applicant under the code or require changes to experimental data and conclusions shall be made to the location of provinces, autonomous regions, or municipalities directly under the (food) and national drug regulatory food and Drug Administration report.     40th article of clinical trials units and researchers have an obligation to take the necessary measures to ensure the safety of subjects.     Researchers should pay close attention to the clinical trials with incidence of adverse drug events, subjects taking appropriate measures in a timely manner, and for the record.     Serious adverse events occurred during the clinical trial, researchers should be reported within 24 hours of the relevant province, autonomous region, municipality directly under the (food) the pharmaceutical supervisory and administrative departments and the State food and drug administration and the applicant, and shall promptly report to the Ethics Committee.     41st on the clinical trials that have been approved, the State food and drug administration and the provincial, autonomous region, or municipality directly under the (food) the pharmaceutical supervisory and administrative departments shall conduct supervision and inspection.     42nd article clinical test during occurred following case one of of, national food drug supervision authority can ordered applicants modified clinical test programme, and suspended or terminated clinical test: (a) Ethics Committee not perform duties of; (ii) cannot effective guarantee by try who security of; (three) not according to provides time report serious bad event of; (four) not timely, and truthfully submitted clinical test progress report of; (five) has approved of clinical test over original scheduled research end time 2 years still not made can evaluation results of;     (Vi) there is evidence that drugs for use in clinical trials is not valid, (VII) used in clinical trials of drug quality problems; (h) fraud in clinical trials, and (IX) a violation of the code for quality management of drug clinical trials in other circumstances.     43rd State food and Drug Administration ordered to modify the clinical trials program, suspension, or termination of clinical trials, clinical trials unit or the applicant shall comply with.     44th article appears in a wide range of clinical trials, unexpected adverse reaction or serious adverse event or if there is evidence that drugs for use in clinical trials when there are serious quality problems, the State food and drug administration or the provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and administrative departments to take emergency control measures, to order the suspension or termination of the clinical trial, applicant, and clinical trials clinical trials must be stopped immediately. Article 45th is responsible for clinical trials with drug use by researchers. Researchers must ensure that all clinical trials of drugs for use in clinical trials is intended only for the subjects, its dosage and usage shall comply with the clinical trial protocol. Researchers shall not be diverted to any non-experimental drug clinical trial participants.     Drugs for use in clinical trials may not be sold.     46th article outside applicants in China for international more Center drug clinical test of, should according to this approach to national food drug supervision authority proposed application, and by following requirements handle: (a) clinical test with drug should is has in outside registered of drug or has into II period or III period clinical test of drug; national food drug supervision authority not accepted outside applicants proposed of yet in outside registered of prevention with vaccine class drug of international more Center drug clinical test application;    (B) the State food and Drug Administration approved an international multicenter clinical drug trials at the same time, if needed, ask the applicant to phase I clinical trials in China; (Three) in China for international more Center drug clinical test Shi, in any national found and the drug about of serious bad reaction and non-expected bad reaction, applicants should according to about provides timely report national food drug supervision authority; (four) clinical test end Hou, applicants should will full of clinical test report submitted national food drug supervision authority; (five) International more Center drug clinical test made of data for in China for drug registered application of,     Provisions relating to clinical trials must conform to these measures, the applicant must also submit all international multi-center clinical trial research information. Fifth chapter of new drug application and approval section 47th basic requirements apply to new drug registration information submitted should be complete, standard, true and reliable data; reference documents should indicate the name, journal name, volume, issue, page, etc; unpublished documents should provide proof of information used by the permission of the owner.     Chinese translation should be provided in accordance with the requirements of foreign language materials.     48th article national food drug supervision authority on following application can implemented fast approval: (a) not in domestic listed sales of from plant, and animal, and mineral, material in the extraction of effective ingredients and preparations, new found of herbs and preparations; (ii) not in both at home and abroad allowed listed of chemical raw materials drug and preparations, and biological products; (three) for treatment AIDS, and malignant tumors, and rare disease, of drug; (four) treatment is no effective treatment means of disease of drug; (five) burst event emergency by required of drug. 49th of provinces, autonomous regions and municipalities (food) drug regulatory Department accepting drugs listed in this article 48th after the application for registration, whether or not the application should be eligible for fast-track review and comment.     State food and Drug Administration received from provinces, autonomous regions and municipalities (food) information and views submitted by the drug regulatory agency to determine whether the application for swift approval. 50th multiple unit jointly developed drugs, by one of the units shall be applied for registration, shall not be applied for other units; need to jointly apply for registration, new drugs should be jointly signed by the applicant.     These measures are in addition to 48th (a), (b) provision of drugs, new drug applications approved by only one unit in each species, varieties of different specifications do not score produced by the different units. The same new technologies must not be declared or de facto double claims for different applicants, the State food and drug administration and the provincial, autonomous region, or municipality directly under the (food) Drug Administration can review the need to organize for the verification of relevant information.     Verify true, inadmissible has been accepted, be returned.     During the 51st in the approval of new drugs, new drug registration, classification and technical requirements for the same active ingredient preparations abroad allowed to change listed.     During the period of new drug approval, registration, classification and technical requirements for domestic pharmaceutical production enterprise reporting preparation in our listing of the same active ingredient vary.     Section II clinical trial approval 52nd of the applicant upon completion of the preclinical studies, fill in the application form for the registration of pharmaceuticals to the local provinces, autonomous regions and municipalities directly under the (food) to submit information on the drug regulatory agency and drug samples.     53rd of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall review the declarations, meet the requirements of admissibility, issued notice of drug registration applications; inadmissible does not meet the requirements, issued notice of drug registration application as inadmissible, and explain the reasons. Provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall, from the date of filing within the 5th organization on drug development and conditions of on-site verification; from 1 to 3 production batches of samples for inspection and registered a notice to drug testing.     Provinces, autonomous regions and municipalities (food) shall, within the time limit set by the drug regulatory agency review, verification reports and information submitted to the State food and drug administration, and notify the applicant accordingly.     54th received notification of registered drug inspection Office shall take samples for testing, to declare the drug review standards and within the time limits specified in the registration test of national drug report and review of the comments submitted to the State food and drug administration, with a copy to inform its inspection of the provinces, autonomous regions and municipalities directly under the (food) drug regulatory agency and the applicant. 55th after the State food and Drug Administration received information, pharmacology, medicine and other disciplines should be organized and technical personnel, to conduct technical reviews of new drugs and, if necessary, may require the applicant to provide supplementary information, provide drug samples.     Considered eligible, drug clinical trial documents will be issued; do not meet the requirements, approval notice will be issued, and explain the reasons. 56th after the applicant reviewed the comments received, for drug control considered undeclared drug standards control quality, can ask to withdraw the new drug applications.     Applicant fails to make the withdrawal, the State food and Drug Administration approved drug standards does not control the quality, should be returned.     57th samples were tested and found not to comply with the Declaration of drug standards, the State food and drug administration new drug application for refund after verification. 58th at the State food and Drug Administration on drug registration applications for the period under review, in addition to innovative pharmaceutical ingredients or new discoveries relating to drug safety, and requests additional information, the applicant shall not be replenished new technical information.     New technical information considered necessary by the applicant, should withdraw his application for registration, the information added after the new declaration.     Article 59th of withdrawn or rejected drug application, the applicant again discussed, in line with the options provided there is no variety and entered a period of monitoring of new drugs, the applicant may declare again, and in accordance with the original application procedures.     Section III production of new drug approval article 60th after clinical trials have been completed the applicant should fill out the application form for the registration of pharmaceuticals to the local provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and administrative departments to submit clinical trial data and other information on changes and additions, and detail the rationale and the justification for, and to the preparation of pharmaceutical and biological products submitted by standards of raw materials.     61st of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications; think does not meet the requirements of inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons. 62nd of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall, from the date of filing within the 5th organization of production and conditions of on-site verification; extraction of 3 consecutive batch samples, and registered a notice to drug testing.     Provinces, autonomous regions and municipalities (food) shall, within the time limit set by the drug regulatory agency review, verification reports and information submitted to the State food and drug administration, and notify the applicant accordingly.     63rd new drug application 3 consecutive batch of samples required shall be made of the good manufacturing practices certification workshop; new drug manufacturer, pharmaceutical production enterprises of new pharmaceutical production plant or released production forms, sample manufacturing process must comply with the requirements of the good manufacturing practices.     64th received notification of registered drug inspection Office shall take samples for testing, and within the time limits specified in the registration test of national drug report submitted to the State food and drug administration, with a copy to inform its inspection of the provinces, autonomous regions and municipalities directly under the (food) drug regulatory agency and the applicant. 65th after the State food and Drug Administration received information, should conduct a comprehensive review and, if necessary, may require the applicant to provide supplementary information. Considered eligible, drug registration documents will be issued and a new drug certificate applicant already holds the drug production licenses and production conditions of the drug can also issue to drug approval.     Considered to be in conformity with the provisions and to inform about the approval, and explain the reasons. Article 66th description proposed by the applicant, the State food and drug administration, according to the Declaration of approval of the drug, and drug when approved drug application instructions and registration standards for the drug to be released.     Applicants are responsible for medicines correctness and accuracy.     Pharmaceutical producing enterprises shall track post-marketing drug safety and effectiveness information, and when necessary modify drug applications in a timely manner.     Medicines must be approved by the State food and drug administration and the prescribed format.     67th to application of new drugs in the production of 3 consecutive batch of samples in a pharmaceutical production permit and the certificate of good manufacturing practice certification workshop, in pursuance of this article 147th and 148th laboratories determined by examination and obtained an approval number, can be listed in the validity of the drug sales.     Drug monitoring management article 68th fourth section under the protection of public health, the State food and drug administration requirements, can be produced with the approval of new drugs to establish a monitoring period, to continue monitoring the safety of the new drug.     New drugs during the monitoring period, the State food and Drug Administration not to approve other production and imports.     69th monitoring period for new drugs based on existing safety data and research inside and outside conditions determine, calculated from the date of approval of new drugs, should not be longer than 5 years.    70th pharmaceutical producing enterprises shall regularly review new drugs in the monitored period of production, quality, consistency, efficacy and adverse reactions, and annually to the seat of the provincial, autonomous region, municipality directly under the (food) reports the drug regulatory agency. Related to drug production, distribution, use, inspection or supervision unit found drugs there are serious quality problems, serious or unexpected adverse reactions, must to the provinces, autonomous regions and municipalities directly under the (food) reports the drug regulatory agency.     71st of provinces, autonomous regions and municipalities (food) drug supervision and management departments of serious quality problems, serious or unexpected adverse reaction of drug discovery, shall immediately conduct investigations and report to the State food and drug administration.     72nd manufacturer is not required to perform new responsibilities of the monitoring period, provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall be ordered to correct.     73rd pharmaceutical producing enterprises to set up monitoring of new drugs from a licensed production is not within 2 years from the date of production, the State food and Drug Administration can approve requests for production of the new drugs from pharmaceutical manufacturers and continues to monitor the drug.     74th new drugs entering the date of monitoring period, the State food and Drug Administration has approved for clinical drug trials by other applicants, can follow the drug registration and approval process continues to handle the applications considered in conformity with the provisions and State food and Drug Administration can approve the production or importation of new drugs, and drug manufacturing companies in the production of the new drugs be monitored. 75th new drugs entering the date of monitoring period, no longer accept other applicants with the application for variety registration.     Have been accepted but not yet approved for clinical drug trials of other applicants with the application, shall be returned to the applicant; monitoring of new drugs expires, applicants can apply for standard drugs have been imported or new drug application. 76th after an application for registration of imported medicine first approved, approved clinical trials on a domestic applicant, may follow the drug registration and approval process continues to deal with his application considered in conformity with the provisions, the State food and Drug Administration can approve its production; the applicant may withdraw the application and re-submit applications for registration of a standard drug.     Has been accepted but not yet ratified the other varieties of drug clinical trial applications should be returned to the applicant applicants may submit applications for registration of a standard drug.     Fifth new drug technology transfer section 77th new drug technology transfer refers to the holder of the certificate of new drugs, new production technologies to pharmaceutical manufacturers, and manufactured by the drug manufacturers to apply for the new behavior. 78th new drug technology transfer should be new drug certificate holders.     Transfer of drug approval numbers have been made, when applying for a new drug technology transfer shall also cancel its application for drug approval number. When the 79th new drug technology transfer should be one-time transfer to a manufacturer. The drug manufacturer for special reasons cannot be produced, a new drug certificate holders can hold the licensee to give up production of the drug contracts or supporting documents, and new drug technology transfer again.     The transferee in respect of the new drug has been granted approval, the State shall, in accordance with the provisions of the food and Drug Administration to remove his drug approval number.     Accept new drug technology transfer company shall not transfer the technology again. 80th drug manufacturers to accept new drug technology transfer must be in possession of the drug manufacturing license and certification of good manufacturing practices.     New drug technology transfer involving the new drugs should be the transferee of the pharmaceuticals production license and certification of good manufacturing practices set out in the production range and scope of certification. New drug manufacturers, drug manufacturers create a new pharmaceutical production plant or released production forms, with the stated after the corresponding production range of the pharmaceutical production license may submit a new drug application for technology transfer. In obtaining an approval number, must be the pharmaceutical administration law implementing regulations article sixth achieved within the time frame set forth the scope of the corresponding certificate of good manufacturing practices certification.     Before achieved certification, approval, the drug may not be marketed.     81st new drug certificate holders to transfer drug production technologies, the transfer contract should be linked to the transferee, to technology and information transfer to the transferee, and guide the transferee produced 3 consecutive batch of samples of acceptable quality.     82nd units when the joint development of new drugs, new drug technology transfer shall be proposed jointly by the drug unit of the joint signature on the certificate and signing the contract of assignment.     83rd new drug certificate holders to the transferee and the transferee shall jointly where provinces, autonomous regions and municipalities (food) new drug application for transfer of technology to the pharmaceutical supervisory and Administrative Department, fill out the drug supplemental application form, and submit the relevant materials and attached to the contract of assignment.     84th of provinces, autonomous regions and municipalities (food) after the pharmaceutical supervisory and Administrative Department accepts new drug application for transfer of technology, the transferee should be development of field samples, production equipment, production and inspection records for verification and sampling, as well as inform the testing Institute for drug control.     85th received notification of registered drug inspection, shall, within the prescribed time limit on completion of the survey, provide the registration test of national drug report, submitted to notify its inspection of the provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments.     86th of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall receive the registration test of national drug report and review relevant information and review comments, and submitted to the State food and drug administration, and will inform the applicant review.     87th State food and drug administration new drug technology transfer should be supplementary application to conduct a comprehensive review of, and the need for clinical trials, drug clinical trial documents will be issued.     After the applicant completed clinical trials, should be submitted to the State food and Drug Administration clinical trials information.     88th countries considered in conformity with the provisions of the food and drug administration new drug technology transfer supplement to supplement in the drug approval and drug approval numbers, and cancellation of transfer has made drug approval number; do not meet the requirements, approval notice will be issued, and explain the reasons. After 89th new drugs entered a period of monitoring, no longer accepts an application for the transfer of new technologies.     Monitoring of new drugs expires, applicants can apply for registration in accordance with the requirements of existing national standards and drug. The sixth chapter has a national drug report and 90th in production has already a standard drug, should be holding the drug production licenses and the good manufacturing practice certification of drug manufacturers.     Applicants apply for the production of medicines and the drug manufacturing license and certification of good manufacturing practices set out in the production range and scope of certification.     91st new start-up pharmaceutical manufacturers, pharmaceutical producing new pharmaceutical production plant or released production forms, with the stated after the corresponding production range of the pharmaceutical production license, can apply for registration.     92nd in accordance with the relevant technical requirements of the applicant upon completion of the development work should fill out the application form for the registration of pharmaceuticals to the local provinces, autonomous regions and municipalities directly under the (food) drug supervision and management departments to submit relevant data and drug samples.     93rd of provinces, autonomous regions and municipalities (food) drug supervision and management departments to review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications; think does not meet the requirements of inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons. Provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall, from the date of filing within the 5th organization of production and conditions of on-site verification; extraction of 3 consecutive batch samples, and registered a notice to drug testing.     Provinces, autonomous regions and municipalities (food) shall, within the time limit set by the drug regulatory agency to review the information, review comments, and review, verification reports and information submitted to the State food and drug administration, and notify the applicant.     94th received notification of registration test of drug control on the extraction of the samples tested, and within the time limits specified in the registration test of national drug report to the State food and drug administration, with a copy to inform its inspection of the provinces, autonomous regions and municipalities directly under the (food) drug regulatory agency and the applicant. 95th State food and Drug Administration should review and audit the information and, if necessary, may require the applicant to provide supplementary information.     Considered the need for clinical trials, drug clinical trial documents will be issued.     After the applicant completed clinical trials, should be submitted to the State food and Drug Administration clinical trials information.     96th State food and Drug Administration to consider compliance of applications for drug registration documents will be issued and drug approval numbers; not in conformity with the provisions and to inform about the approval, and explain the reasons.     New drug manufacturers, drug manufacturers create a new pharmaceutical production plant or released production forms, not set forth the scope of the corresponding certificate of good manufacturing practices certification, its production of the drug may not be marketed.     97th of provinces, autonomous regions and municipalities (food) inadmissible pursuant to trial the drug regulatory agency standards on national drug registration applications.     98th on the need for further evaluation of drug efficacy and safety of existing national standards of drug registration, the State food and Drug Administration may decide to suspend accepting or approving.     99th applications for drug approval, the production of 3 consecutive batch of samples in a pharmaceutical production permit and the certificate of good manufacturing practice certification workshop, in pursuance of this article 147th and 148th laboratories determined by examination and obtained an approval number, can be listed in the validity of the drug sales. Seventh chapter, section I of the Declaration and approval of imported drugs registration of imported medicine 100th Application for import of medicines, you must obtain a foreign pharmaceutical manufacturers of the country or region in which marketing authorizations; is not listed in the production countries or regions to obtain permission, but by the State food and Drug Administration approval of the drug is safe and effective and clinical needs may be granted for imports.     Application for import of medicines should comply with the country or region where drug production and quality management standard and the requirements of the good manufacturing practices in China.     101th applying for registration of imported medicine, should fill out the application form for registration, submit the relevant materials and samples, provide relevant supporting documents, to apply to the State food and drug administration.     102th State food and Drug Administration to review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications and notify of pharmaceutical and biological products organized by the registration of 3 production batches of samples tested; that does not meet the requirements of the inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons.     According to the State food and Drug Administration needs to organize on-site verification of conditions for development and production, and samples.     103th Chinese drug and biological products after completing the import registration test of national drug, should review the standards, drug registration inspection report and review opinions submitted to the State food and drug administration. 104th State food and Drug Administration to declare the data for a comprehensive review and, if necessary, may require the applicant to provide supplementary information.     Considered the need for clinical trials, drug clinical trial documents will be issued; do not meet the requirements, approval notice will be issued, and explain the reasons.     105th clinical trial approval, the applicant shall, in accordance with the way the fourth chapter and the relevant requirements for testing.     After the end of the clinical trial, the applicant should fill in the application form for the registration of pharmaceuticals, in accordance with the provisions submitted to the clinical trials data, samples and other information on changes and additions, and detail the basis and reasons for providing relevant documents. 106th State food and drug administration organizations to submit information to conduct a comprehensive review of clinical trials and, if necessary, may require the applicant to provide supplementary information. Considered in conformity with the provisions and imported drugs registration certificate will be issued; China's Hong Kong, Macao and Taiwan pharmaceutical manufacturers in the area of application for the registration of medicines, refer to the imported drug registration procedures, that meets the requirements, issue a certificate of pharmaceutical product registration.     That does not meet the requirements, approval notice will be issued, and explain the reasons. Section 107th for importing pharmaceutical preparations, must provide the packaging material and vessels direct contacted with drugs from an approved source of documents, and the preparation of raw materials and auxiliary materials is used to produce documentary proof of lawful origin.     Drug substances and excipients have not been approved by the State food and drug administration, shall be submitted to the relevant production processes, quality and test method research.     108th State food and Drug Administration approval of imported drugs at the same time, publish approved standards of imported drugs registration and instructions.     Section II registration of imported medicine packaging 109th imported medicines packaging refers to drugs to complete the final production process overseas, by the large pack sizes to small pack sizes in the territory, or completed within the packaging of pharmaceutical packaging, placing brochures, stickers, and so on. 110th article application imports drug points packaging, should meet following requirements: (a) application for points packaging of drug has made has imports drug registered card or medicine products registered card; (ii) the drug should is China territory yet production of varieties, or is has production but cannot meet clinical need of varieties; (three) same pharmaceutical manufacturers of same varieties should by a drug production enterprise points packaging, points packaging of term shall not over imports drug registered card or medicine products registered card Validity (iv) apart from the tablets, capsules, and repackaging other dosage forms should have been completed by the outside package; (e) accept the packaging of pharmaceutical producing enterprises shall hold the drug manufacturing license.     Imported nude application in domestic packaging of tablets, capsules, drug manufacturers should also accept packaging consistent with packaged dosage form certificate of good manufacturing practices; (vi) application repackaging of imported drugs, the drugs should be in the imported drug registration certificate or pharmaceutical product registration certificate before the expiry of 1 years previous.     111th overseas pharmaceutical manufacturers should be signed with the pharmaceutical companies in contract packaging of imported drugs, and fill out the drug of the supplementary application form. 112th for import drug-packaging, should accept the packaging manufacturer to the local provinces, autonomous regions and municipalities (food), apply to the pharmaceutical supervisory and administrative departments, submitted by applicant to fill out the drug supplemental application form, and submit the relevant materials and samples.     Provinces, autonomous regions and municipalities (food) drug supervision and management departments to review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications; think does not meet the requirements of inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons.     Provinces, autonomous regions and municipalities (food) after the pharmaceutical supervisory and Administrative Department the audit opinion, information and comments submitted to the State food and Drug Administration approval, and notify the applicant. 113th State food and Drug Administration for review of the information submitted, that in conformity with the provisions and approved drug supplementary application documents will be issued and an approval number.     Considered to be in conformity with the provisions and to inform about the approval, and explain the reasons.     114th imported packaged medicines imported drug registration criteria should be performed.     115th article of imported packaged medicines instruction manuals and packaging labels must be consistent with the instruction manuals and packaging labels of imported drugs, and should at the same time marking packaging of drug approval number name and packaging manufacturer. 116th outside packaging preparation of import inspection in accordance with the relevant provisions of the State food and drug administration.     Inward inspection and packaging of products after testing the implementation of the same standard. 117th medicines overseas pharmaceutical manufacturers are responsible for packaging pharmaceutical quality.     After repackaging of drug quality problems, the State food and Drug Administration may revoke the repackaging of drug approval number and, if necessary, in accordance with the provisions of article of the drug administration law of the 42nd, withdrawal of the drug imported drugs registration certificate or the certificate of pharmaceutical product registration.     Registered 118th eighth chapter of non-prescription drugs non-prescription medicine, is published by the State food and drug administration, do not have to resort to medical practitioners and Assistant medical practitioners of prescriptions, the consumer can judge for themselves, purchase and use of drugs.     119th article application registered of drug belongs to following case of, can while proposed according to non-prescription drug management of application: (a) has has national drug standard of non-prescription drug of production or imports; (ii) by national food drug supervision authority determine of non-prescription drug change formulations, but not change indications or function attending, and to drug dose and to drug way of drug; (three) using national food drug supervision authority determine of non-prescription drug activity ingredients composition of new of compound preparations. 120th article on meet this approach 119th article (a) case of drug, applicants should in drug registered application table of "additional application matters" in the mark non-prescription drug items, national food drug supervision authority approved drug registered of while, will the drug determine for non-prescription drug; not in drug registered application table in the mark non-prescription drug items of, applicants should in national food drug supervision authority approved drug registered Hou,     According to the classification of prescription and non-prescription drug management and OTC registrations the registration of the relevant provisions.     121th article on meet this approach 119th article (ii) or (three) case of drug, applicants can in drug registered application table of "additional application matters" in the mark non-prescription drug items, national food drug supervision authority think meet non-prescription drug about provides of, can in approved drug registered Shi, will the drug determine for non-prescription drug; think not meet non-prescription drug about provides of, according to prescription drug approval and management.     122th meets 119th provided medicines these measures, the applicant is not in the application form for the registration of "additional application" annotation of non-prescription drugs, according to the State food and Drug Administration approval and manage prescription drug. 123th belongs to to the article 119th (a) or (b) chemicals, generally do not require clinical testing, but oral solid preparation bioequivalence tests should be carried out.     Proprietary Chinese medicine clinical trials should be in accordance with the relevant requirements of this approach.     124th belongs to to the article 119th (c) medicines, should clarify its prescription basis, clinical trials shall be conducted as necessary.     125th applications for registration of non-prescription drugs, pharmaceutical directions and labels shall conform to the relevant provisions of the non-prescription drugs, other information submitted shall conform to the relevant provisions of the prescription drug.     126th as a non-prescription drug import drug applications, applicable notification and approval procedures for imported drugs, their technical specifications and technical requirements for production of non-prescription drugs in the same. 127th as when applying for the registration of imported drugs to non-prescription drugs, according to the State food and Drug Administration import drug registration and relevant regulations and approval of non-prescription drug management.     Re-registration of imported drugs as over-the-counter applications, applicants do not need to the provinces, autonomous regions and municipalities directly under the (food) non-prescription drugs the pharmaceutical supervisory and administrative departments approving registrations.     128th by the State food and Drug Administration approved the over-the-counter drugs, found in use is not fit to continue as a non-prescription drug management, State food and Drug Administration can be converted to prescription drugs. Nineth part Drug supplementary application, examination and approval article 129th drug approval document and its accompanying pharmaceutical standards, drugs matters, contained in directions and labels, as well as the change may affect the quality of the production process and other matters, it shall submit a supplementary application of drugs. 130th applicant should fill out the drug of the supplementary application form to the local provinces, autonomous regions and municipalities directly under the (food) submitted to the drug regulatory agency for information and instructions.     Provinces, autonomous regions and municipalities (food) drug supervision and management departments to review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications; think does not meet the requirements of inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons. Article 131th supplementary application of imported drugs, the applicant shall submit to the State food and Drug Administration for information and instructions, submit production country or region drug authority approved changes to files.     State food and Drug Administration to review the declarations, considered to meet the requirements of, to be admissible, issued notice of drug registration applications; think does not meet the requirements of inadmissible, issue notice shall not accept an application for registration of pharmaceuticals, and explain the reasons.     132th article change enterprise name, and by provides change drug packaging label, and according to national food drug supervision authority of requirements modified manual, of added application, by province, and autonomous regions, and municipalities (food) drug supervision management sector accepted and approval, think meet provides of, to drug added application documents, and submitted national food drug supervision authority record; think not meet provides of, to approval views notification pieces, and description reason.     133th modifying drug registration standards, change materials, additional functions, such as the supplementary application of traditional Chinese medicine, by provinces, autonomous regions and municipalities directly under the (food) after accepting drug regulatory authorities and the audit opinion, submitted to the State food and Drug Administration approval, and notify the applicant. 134th of imported drugs to add to the application by the State food and Drug Administration approval. According to the national drug standard or modified at the request of the State food and drug administration manual, supplement manual safety, required changing drug labels or the drug looks, change the registered agent of the supplementary application, filed by the State food and drug administration.     State food and drug administration in the 20th after no objections, the applicant can perform the appropriate supplemental application.     135th to change drug production sites, holding its supplementary new drug certificate applications for drug approval applications for provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall organize the manufacture on-site inspections, taking samples for inspection, and inform drug testing for sample inspection.     Modify the supplementary application of the standards for registration of pharmaceuticals, drug testing standard of review should be carried out when necessary. 136th State food and Drug Administration on drug review supplement, if necessary, may require the applicant to provide supplementary information.     Considered in conformity with the provisions and issue supplementary application documents in the drug; do not meet the requirements, approval notice will be issued, and explain the reasons.     Needs to renewal of drug approval documents, the original approval documents be written off by the State food and Drug Administration needs additional drug approval documents, and the original approval certificate shall remain valid.     137th drug supplemental applications approval documents the validity of same and the original approval documents, and expiration should be re-registration of the application.     The tenth chapter drug re-registration of the 138th re-registration of pharmaceuticals, refers to the drug-approval certificate file is valid after the expiration of production, imports of the drug approval process of implementation. 139th medicines issued by the State food and Drug Administration approval, the imported drugs registration certificate or pharmaceutical product registration certificate is valid for 5 years.     Has expired, the need to continue production or imports, the applicant shall apply for registration before the expiry of 6 months.     140th applications for re-registration of medicines by its drug manufacturers to obtain approval of provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and Administrative Department, fill in the application form for the re-registration of pharmaceuticals in accordance with regulations, and provide relevant information.     Import drug re-registration applications submitted by applicants to the State food and drug administration.     141th in provinces, autonomous regions and municipalities (food) drug supervision and management departments to review the declarations, considered to meet the requirements of, to be admissible, re-registration of medicines issued by filing notice that does not meet the requirements, and inadmissible applications for re-registration of medicines issued a rejection notice and justification.     142th in provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall, within 3 months audit advice on applications for re-registration of pharmaceuticals, and submitted to the State food and drug administration review.     State food and drug administration, 3 months after the receipt of an audit opinion issued no longer registers a notification by provinces, autonomous regions and municipalities directly under the (food) re-registration of pharmaceuticals supervision and management departments. 143th State food and drug administration after accepting an application for re-registration of imported drugs shall be completed within 6 months of the review.     Considered eligible be registered again. 144th article has following case one of of drug, not again registered: (a) not in provides time within proposed again registered application of; (ii) not reached national food drug supervision authority approved listed Shi proposed of about requirements of; (three) not according to requirements completed IV period clinical test of; (four) not according to provides for drug bad reaction monitoring of; (five) by national food drug supervision authority again evaluation belongs to eliminated varieties of; (six) according to drug management method of provides should revoked drug approved proved file of     And (VII) not with the provisions of the drug administration law of production conditions; (VIII) does not carry out the monitoring responsibilities, and (IX) other circumstances that do not comply with the relevant requirements.     145th article does not meet the requirements of re-registration of pharmaceuticals, issued by the State food and Drug Administration notice that are not re-registered, and justified, inter alia due to legal cause revocation of drug approval documents outside, on expiry, cancellation of its drug approval number, the imported drug registration certificate or the certificate of pharmaceutical product registration. The 11th chapter of the registration test of national drug administration article 146th drug registration applications for registration must be tested.     Registration test of national drug, including sample test on the applicant for registration of the drugs and drug standards review.     Sample inspection, refers to the drug testing in accordance with Declaration of drug standards for testing of samples.     Drug standards review refers to the drug testing on the declared drug standard method for the determination of the feasibility and scientific nature, set items and the capability to control the quality of drugs and laboratory tests and audits. 147th registration test of national drug by pharmaceutical and biological products, or borne by the provinces, autonomous regions and municipalities directly under the drug testing.     Register inspection of imported drugs of pharmaceutical and biological products examination organization.     148th following registration of drug testing by the pharmaceutical and biological products or designated by the State food and drug administration and drug control implications: (a) article 48th of this approach (a), (b) prescribed drugs, (ii) biological products and radiopharmaceuticals; (c) other drugs as prescribed by the State food and drug administration.     149th in accordance with the provisions of article 48th drugs, drug test samples shall give priority to testing and drug standards review.     150th in the registration test of national drug Institute for drug control, should follow the drug testing laboratory quality management norms and national metrological certification requirements, with fitting in with the registration test of national drug task personnel and equipment, conforms to the registration test of national drug quality assurance systems and technical requirements. 151th applicants should be required to provide registration test of national drug-related information, submit samples or with the extracted samples for inspection, and providing reference material for inspection.     As reported or extract the sample size should be 3 times of the amount of times Biologics manufacturing verification of registration should also provide related batch records.     152th in production of an existing national standard medicines, where drug testing after receiving the samples shall be tested in accordance with the national drug standards, and because technology changes that have resulted in a comprehensive analysis of the changes of quality indexes and, if necessary, shall require the applicant to develop appropriate quality specifications and test methods to ensure drug quality control.     153th drug test standard criteria for new drug review, except for sample surveys, should also be based on research data, drug standards and national requirements for similar products at home and abroad, about drugs and drug standards, test items, such as review comments. Drug testing issue before review and, if necessary, shall inform the applicant. Applicant has objections, should appeal in the 10th report of the Institute for drug control.     Drug test if you do not agree with the applicant's complaint, should be reviewed and the applicant to submit the complaint together with the State food and drug administration, with a copy to inform its inspection of the provinces, autonomous regions and municipalities directly under the (food) drug regulatory agency and the applicant.     154th requested the applicant to develop pharmaceutical standards, the applicant shall not entrust my original review of drug testing the drug standard research work carried out by; the drug inspection offices shall not accept such a delegate.    The 12th chapter management section of the standard basic requirements for registration of pharmaceuticals 155th national drug standards, refers to the country in order to ensure the quality of drugs developed quality indicators, test, and production of technical requirements, including the State food and Drug Administration issued by the People's Republic of China Pharmacopoeia, the registration criteria and other drug standards. Drug registration standards, refers to the State food and Drug Administration approval to the applicant certain pharmaceutical standards, produce the drug manufacturer must implement the standard.     156th drug registration standards project and its set of test methods, shall conform to the national food and drug supervision Administration issued technical guidelines and the relevant requirements of the principles and the rules for drafting national drug standards.     157th applicant should be quality of raw material and production process is stable and the premise, selecting representative samples of standard research. Section II drugs after the trial standard to become a full member of the 158th new drugs approved production, pharmaceutical standards for pilot standard trial period for 2 years.     Other medicines approved production needs further investigation, production and product quality stability, drug standards may also be approved for experimental standards.     159th production pilot standard medicines, pharmaceutical producing enterprises shall, before the expiration of the trial period of 3 months to the local provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and administrative departments to submit a regularization application, fill out the drug supplemental application form, and submit the drug quality assessment in the standard trial period information and revisions to the tentative standards.     Amended drug registration standards supplemented after the application is approved, the original standard is within the trial period, the applicant shall, in the original standards apply in full member 3 months prior to the expiration of the trial period.     160th of provinces, autonomous regions and municipalities (for food) the pharmaceutical supervisory and administrative departments shall, in accepting an application for drug trial standard regularization in the 10th after completion of the review, will review the comments and relevant information submitted to the State food and drug administration.     161th national pharmacopoeia Committee of the Organization of the State food and drug administration a comprehensive review of drug trial standards. National Pharmacopoeia Committee shall, in accordance with the drug standard during the pilot implementation of related products, domestic and international standards and the relevant national requirements, comments on the pharmaceutical standards need to be reviewed.     Considered necessary by standards of review, should organize the relevant standard of drug testing drug trial conducted by review and testing.     162th multiple drug manufacturers in the production of the same kind of tentative standards of positive tests and reviewed by Chinese drugs and biological products or designated by the State food and drug administration and drug control.     163th different applicants to declare the same kind of tentative standards full member, shall not be less than the approved drug standards, and should be combined with their own characteristics making the necessary checks.     164th after receipt of the standards review and inspection of the applicant requires additional testing or improving information, should be completed within 50 days of the experiment, or the complement and perfection of information, and submit the location of provinces, autonomous regions and municipalities directly under the (food) the pharmaceutical supervisory and administrative departments. 165th State food and Drug Administration to review the information submitted to the national pharmacopoeia Committee, considered in conformity with the provisions and to the enactment of national drug standards, approved drug trial standard to positive.     Considered to be in conformity with the provisions and to inform about the approval, and justified, and revocation of the pilot standard and according to the tentative standards in the production of drug approval number. 166th standard pilot different varieties of the same deadline, become a full member by the expiring start.     Standard trial period has not expired, be advanced to the national pharmacopoeia Committee notifies the applicant of provinces, autonomous regions and municipalities directly under the (food) pharmaceutical supervisory and Administrative Department for regular applications.     167th tentative standards of failing to submit a regularization application expiration by the State food and Drug Administration revoke the pilot standard and according to the tentative standards in the production of drug approval number.     During the processing of pilot standard regularization applications, pharmaceutical producing enterprises shall, according to tentative standards of production.     Section III management of drug standard substance 168th drug standard substance refers to standard physical and chemical testing and biological methods for drug testing, has determined characteristic values used to calibrate the device, evaluation method or test medicines assignment of substances, including standards, control, control medicines, reference product.     169th of pharmaceutical and biological products is responsible for calibrating the State drug standard substance.     Of pharmaceutical and biological products can be organized by the relevant provinces, autonomous regions and municipalities directly under the drug testing, drug research institution or pharmaceutical production enterprise calibration the national drug standard substance.     170th applicants when applying for a new drug production shall be made to the preparation of pharmaceutical and biological products offered by the drug standard substance of raw materials, and to submit the relevant reference material of research data.     171th of pharmaceutical and biological products are responsible for the calibration of reference materials from raw material selection, preparation method, calibration, calibration results, accuracy, traceability, stability and technology of packaging and package information for a comprehensive audit, and will serve as the national drug standard substance of conclusions.     The 13th chapter of drug registration time limit article 172th General provisions and the State food and drug administration of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall, in its Executive website and places public drug registration drug registration required conditions, procedures, deadlines, need to submit a list of all materials and application model.     173th country and provinces, autonomous regions and municipalities directly under the food and Drug Administration (food) drug regulatory agency to accept or not to accept an application for registration, it shall issue a special seal and date stamp registration accepted in written form. 174th drug registration time limit means relating to the drug registration review, testing, as well as additional information such as the maximum amount of time allowed by.     Of completed work in drug registration within the time limit, shall be carried over to the next process in time.     175th State and provinces, autonomous regions and municipalities directly under the food and Drug Administration (food) are received by the pharmaceutical supervisory and administrative department applicants upon submission of the application, for application materials are incomplete or do not meet the review requirements, shall inform the applicant within the 5th need correction the entire contents, inform overdue, from the date of receipt of the application materials is accepted.     Complete declarations, in accordance with the form request for review, or submit all supplementary information requested by the applicant, shall be admissible within the 5th.     176th of provinces, autonomous regions and municipalities (food) the pharmaceutical supervisory and administrative departments shall begin within the 5th after the filing organization work, and finished in 30th spot verification, samples, notifications registered drug inspection inspection, review and verification report submit together with the applicant's declarations, the State food and drug administration, and will inform the applicant review.     177th drug testing after receiving the registration test notification and sample, should be completed on 30th test, provide the registration test of national drug report.     Special registration of medicines and vaccines products testing can be completed in 60 days.     Article 32nd according to these measures, must be specified in the clinical trials of the drug testing of samples for testing, in accordance with the preceding two paragraphs time limit requirement.     178th must sample test and drug standards review, drug testing should be completed within 60 days.     Special drug and vaccine products sample inspection and drug standards review can be completed in 90 days.     179th applications for registration of imported drugs, the State food and Drug Administration should carry out the formal examination, considered to meet the requirements of, is admissible in the 5th; that does not meet the requirements, shall notify the applicant in writing within the 5th, and state the reasons; notification of overdue, from the date of receipt of the application materials is accepted.     China State food and Drug Administration notified organization registered by the drug and biological products inspection, determine the review or approval of matters relating to work, should be completed in the 30th after accepting.     180th of pharmaceutical and biological products received information and samples should be related to drug testing carried out by a registered organization in the 5th test.     Article 181th imported drug testing registration test of national drug information received after, samples and related reference materials, shall, within 60 days to complete the registration examination and submit the registration test of national drug report of pharmaceutical and biological products.     Special drug and vaccine products sample inspection and drug standards review can be completed in 90 days.     182th of pharmaceutical and biological products received by the registration test of national drug report and review of standards of imported drugs should organize experts to conduct technical reviews in the 20th and, if necessary, for further review based on review comments.     183th article national food drug supervision authority on drug registered application in the of technology review time, according to following provides implementation: (a) drug clinical test: 120 days completed; meet this approach 48th article provides of varieties: 100 days completed; (ii) drug production: 120 days completed; meet this approach 48th article provides of varieties: 100 days completed; (three) has has national standards drug of application: 80 days completed;     (D) the technical review of the need for supplementary application: 40 days.     Imported drugs registration period for the technical review of the reference implementation of this article.     184th national drug, food and Drug Administration conducts a technical review of an application for registration, requires the applicant to provide supplementary information, should be a one-time notice in supplementary information. In addition to 48th applications by these measures, the applicant shall, within 4 months of disposable follow the notification requirements to complete additional information.     Not additional information within the prescribed time limit, the State food and Drug Administration for the application for refund. 185th disagrees with the applicant of the additional information, notification, and may, within the prescribed time limit for comments.     Still have objections can be directly written opinions to the State food and drug administration, state the reasons and the provision of technical information and scientific evidence, after review by the State food and Drug Administration to make a decision. 186th Applications withdrawn or rejected, the applicant need to declare, on the trial or after the supplement and complete the information, shall in accordance with the original procedures apply.     Consistent with this approach the relevant provisions there is no variety and entered a period of monitoring of new drugs, the State food and drug administration and the provincial, autonomous region, or municipality directly under the (food) the pharmaceutical supervisory and administrative departments shall be admissible.     187th after receiving additional information, the State food and drug administration, shall not exceed the original time limit one-third time completed the technical review process; 48th of compliance with these measures, technical review time limit may not exceed one-fourth of the original time limit.     188th State food and Drug Administration should be finished 20th after the completion of technical reviews and approval must be approved by the State food and Drug Administration's drug supplement, should be completed in the 20th for approval.     Unable to complete the vetting within 20th, approved by the competent Council, can extend the 10th extension more than a 10th of, must be reported to the State Council for approval.     Shall be completed within 60 days of the 189th State Pharmacopoeia Committee drug trial standard regularization of censorship. Assume positive drug trial standards review and inspection tasks in Institute for drug control, review and testing standards shall be completed within 60 days, and sent to the national pharmacopoeia Committee review and inspection report. Tentative standards of special drug and vaccine products to positive reviews and testing is generally not more than 90 days.     Multiple drug manufacturers produce the same tentative standards full member of review and examination shall be completed within 80 days. 190th national food and drug supervision and administration of provinces, autonomous regions and municipalities (food) drug supervision and management departments to review the applications for drug registration, shall publish the approval process and the results.     The applicant and interested parties to submit written views on matters directly related to the vital interests of State and to defend themselves.     191th country and provinces, autonomous regions and municipalities directly under the food and Drug Administration (food) the pharmaceutical supervisory and administrative departments shall make inadmissible or not to register a written decision, and shall explain the reasons and inform the applicant drew attention to the administrative reconsideration or bring an administrative lawsuit in accordance with law's rights.     192th in the drug registration, the State food and Drug Administration consider major licensing matters involving the public interest shall be announced to the public, and hold a hearing.     Section 193th registration and approval of drugs once a decision, the State food and Drug Administration should be since the date of the decision in the 10th issue, service-related decisions.     194th national food and Drug Administration should be published regularly in their official site has list of approved drugs, is available for public inspection.     195th in special circumstances require extended registration test of national drug and technical review time frames, should be reported to the State food and Drug Administration approval.     196th of the People's Republic of China on administrative licensing law (hereinafter referred to as the administrative licensing law) circumstances prescribed in the 70th, the State food and drug administration shall handle the cancellation procedures relating to drug approval documents.     197th 14th chapter review the applicant disagrees with the decision of the State food and drug administration, before applying for administrative reconsideration or bring an administrative suit, you can fill in the 10th from the date of receipt of the decision of the drugs of the supplementary application form, submit application for review to the State food and drug administration and the grounds for reexamination.     Review is limited to the contents of the original application items and original reporting. 198th State food and drug administration after receiving the application for reconsideration, shall make a decision within 50 days, and notify the applicant accordingly.     Upheld the decision, the State food and drug administration no longer accepts applications for review again.     199th review needs for technical examination, the State food and drug administration shall organize relevant professional and technical personnel in accordance with the original time limit for an application.     The 15th chapter legal liability Article No. 200 of the administrative licensing law of the circumstances prescribed in the 69th, the State food and drug administration, according to the request of the interested party or ex officio, proof of drug approval can be revoked.     No. 201 article applicants in declared clinical test Shi, submitted false drug registered declared information and samples of, national food drug supervision authority not accepted or on the declared drug of clinical test not approved, on applicants give warning, one years within not accepted the applicants proposed of the drug clinical test application; has approved for clinical test of, revoked approved the drug clinical test of documents, and at 10,000 yuan above 30,000 yuan following fine, three years within not accepted the applicants proposed of the drug clinical test application.     The State food and Drug Administration to submit false information and samples of the applicants to establish record of bad behavior, and to the public.     No. 202 article application drug production or imports Shi, applicants submitted false drug registered declared information and samples of, national food drug supervision authority on the application not accepted or not approved, on applicants give warning, one years within not accepted its application; has approved production or imports of, revoked drug approved proved file, five years within not accepted its application, and at 10,000 yuan above 30,000 yuan following fine.     The State food and Drug Administration to submit false information and samples of the applicants to establish record of bad behavior, and to the public. No. 203 article national food drug supervision authority and province, and autonomous regions, and municipalities (food) drug supervision management sector and staff in drug registered process in the violation this approach provides, has following case one of of, in accordance with administrative license method 72nd article, and 73rd article, and 74th article and 75th article of provides processing: (a) on meet statutory conditions of drug registered application not accepted of; (ii) is not accepted places publicity drug registered declared information project of; (three) in accepted, and approval process in the     , Not to applicants perform statutory told obligations of; (four) applicants submitted of drug declared information not complete, and not meet statutory form, not once told applicants must correction of all content of; (five) not law description not accepted or not approved drug registered application reason of; (six) on not meet this approach provides conditions of application made granted registered decided or beyond statutory terms made granted registered decided of;     (G) subject to this regulation the application shall be rejected for registration decision or this way of making registration decisions within the prescribed; (VIII) unauthorized charges are not in accordance with the statutory criteria or charge; (I) the solicitation or acceptance of other people's property, or seeking other interests.     Article No. 204 manufacturer revoked the production license of medicines, drug approval number held by the enterprise itself repealed, the State food and Drug Administration on drug approval number shall be written off, and to the public.     Article No. 205 in the drug registration was not in accordance with the provisions of the implementation of the non-clinical studies in quality management standard or the quality management standard of clinical drug trial, in accordance with article 79th of the drug administration law are punishable.     Article No. 206 drug inspection and testing required to take drug approval work, issues a false inspection report, in accordance with the provisions of the drug administration law 87th penalty.     Article No. 207, based on the provisions of the article 21st required repeat drug trial, the applicant refused, State food and Drug Administration for its warning and ordered corrective action and the applicant refuses, cancel this Declaration eligibility of the applicants.     16th chapter supplementary articles article No. 208 drug approval number is of the form: 国药准字 h (z, s, j) + 4 year + 4-bit sequence number, where h represents chemical z is for traditional Chinese medicine, s for biological products, j is for imported medicines packaging. The imported drug registration certificate number is of the form: h (z, s) + 4 year + 4-bit sequence number; the pharmaceutical product registration certificate of license number format: h (z, s) C+4-year + 4-bit sequence number, where h represents chemical z is for traditional Chinese medicine, s is for biological products.     For packaging specifications for packaging in the territory of registration certificate number original registration number preceded by the letters b.     New drug certificate number is of the form: sinopharm permit h (z, s) + 4 year + 4-bit sequence number, where h represents chemical z is for traditional Chinese medicine, s is for biological products.     Article No. 209 of narcotic drugs, psychotropic substances, toxic drugs for medical use and radioactive pharmaceuticals registration, except in accordance with the provisions of the measures, but should also comply with the other relevant regulations of the State.     Article No. 210 approval number management of Chinese herbal medicine, Chinese herbal medicine and administration of registration of imported Chinese herbal provisions, shall be separately formulated by the State food and drug administration.     Drug Administration registration regulation of in vitro diagnostic reagents, shall be separately formulated by the State food and drug administration.       No. 211 these measures shall come into force on May 1, 2005, issued by the State Drug Administration on October 30, 2002, the drug registration regulation (draft) (State Drug Administration, 35th) repealed simultaneously.     Annex: Chinese herbal medicine, natural medicine registration classifications and reporting requirements in this annex refers to the traditional Chinese medicine theory of traditional Chinese medicine using medicinal substances and preparations.     Natural medicine in this annex refers to the theory of modern medicine natural medicinal substances and preparations when used as directed.     A classification and description, registration (a) registration category 1. is not listed on the domestic sales of plants, animals, minerals and other substances extracted active substances and their preparations.     2. newly discovered medicinal materials and preparations.     3. new herbal substitutes.     4. herbs new parts and its preparation.     5. is not listed on the domestic sales of plants, animals, minerals and other substances extracted from effective fraction and its preparation.     6. is not listed on the domestic sales of compound preparation of traditional Chinese medicine and natural medicine.     7. changes in domestic sales already on the market of preparations of traditional Chinese medicine, natural medicine and administration route.     8. changes in domestic market of preparations of Chinese medicine, natural medicine.     9. the existing national standard of traditional Chinese medicine, natural medicine.    (B) instructions Classification 1~8 of registration for new drugs, registered category 9 variety of existing national standards of medicine.     1. "is not listed on the domestic sales of plants, animals, minerals and other substances in the extraction and preparation of" refers to the national drug standards is not collected from plants, animals, minerals and other substances extracted natural single ingredients and preparation, its content should be of a single component to the total extract of 90%.     2. "the new discovery and its preparation" refers to is not the national drug standards or local drug codes of provinces, autonomous regions and municipalities (collectively, the "legal standard") containing medicinal herbs and its preparation.     3. "new herbal substitutes" refers to the alternative to the national drug standard prescription of traditional Chinese medicine in preparation of toxic herbs or endangered medicinal substances of the legal standard of the medicine have not been collected.     4. "medicine new parts and its preparation" refers to the original statutory standard medicine, the medicinal part of the plant and its preparations.     5. "is not listed on the domestic sales of plants, animals, minerals and other substances extracted from effective fraction and its preparation" refers to the national drug standards is not collected from plants, animals, minerals and other substances extracted from one or several type components of effective fraction and its preparation, effective parts of their content should be 50% of the extract above.     6. "is not listed on the domestic sales of compound preparation of traditional Chinese medicine, natural medicine" includes: 6.1 compound preparation of traditional Chinese medicine; 6.2 the modern traditional Chinese medicine compound; 6.3 natural medicine compound preparation, 6.4, natural medicine and the chemical composition of compound traditional Chinese medicine preparation.     Compound preparation of traditional Chinese medicine traditional medicine under the guidance of prescriptions, traditional handicrafts made of prescription traditional Chinese medicine must have a legal standard.     Modern traditional Chinese medicine compound should group under the guidance of the theory of traditional medicine, can be made using non-traditional technology.     Natural medicine compound preparation should group under the guidance of modern medicine, its indications with modern medical terminology.     Traditional Chinese medicine, natural medicine and chemical composition of compound preparations including traditional Chinese medicine and chemical drugs, natural medicines and chemicals, as well as traditional Chinese medicine, natural medicine and chemical compound consisting of three persons.     7. "the changes in domestic market of traditional Chinese medicine, natural medicine and administration route preparation" include: change between different routes of Administration Agent and topically to systemic drug delivery agents.     8. "changes in domestic market of preparations of Chinese medicine, natural medicine" refers to the route of Administration is not constant changing form of preparation.     9. "the existing national standard of traditional Chinese medicine, natural medicine" means China has approved the sale of Chinese herbal medicine or natural medicine registration application.     Second, information and description of the project (a) reporting project summary information 1. drug name.     2. the supporting documents.     3. purpose made and ...     4. Summary of main findings and evaluation.     5. drug samples, preparation of notes and the latest references.     6. packaging and labelling design artwork.     Pharmaceutical research 7. pharmaceutical research data.     8. the source and identification evidence.     9. ecological environment of Chinese medicines, growth characteristics, morphologic descriptions, cultivation, or cultivation (foster) technology, processing and preparation methods.     10. medicine and preparation of notes on the draft standards, and providing drug standard substance and relevant information.     11. the provision of plant, mineral specimens, specimens should be included, such as flowers, fruits, seeds.     12. research information and documentation of the production process, material sources and quality standards.     13. confirm the chemical structure or composition of test data and literature.     14. quality research data and documents.     15. drug standards and preparation of notes on the Bill and provide drug standard substance and relevant information.     16. a sample inspection report.     17. drug stability study testing data and documents.     18. the packaging material and vessels direct contacted with drugs of choice and quality standards.     Pharmaco-toxicological studies 19. Summary of the Pharmacology and toxicology studies.     20. the main pharmacodynamic data and documents.     21. General pharmacological studies of experimental data and literature.     22. acute toxicity test data and documents.     23. long-term toxicity testing data and literature.     24. allergic (local, systemic and photo toxicity), hemolysis and partial (blood vessels, skin, Mucosa, muscles, etc) stimulus, dependence and other major local, special safety testing of systemic drug delivery-related data and literature.     25. Mutagenicity test data and literature.     26. reproductive toxicity test data and documents.     27. a carcinogenicity test data and documents.     28. animal pharmacokinetic data and documents.     Clinical trial information 29. Summary of clinical trial information.     30. clinical trial plans and programmes.     31. Handbook of clinical researchers.     32. the informed consent form template, approved by the Ethics Committee.     33. the clinical trial reports.     (B) Note 1. information project description review of information declared (1) information item 1 name of the drug including: ① Chinese name ② Hanyu Pinyin name ③ name basis. (2) information item 2 supporting documents including: ①the legal registration certificate of the applicant, the drug manufacturing license, certification of good manufacturing practices certificate. Application drug production Shi should provides samples preparation workshop of drug production quality management specification certification certificate copies; II application of drug or using of prescription, and process, and uses, in China of patent and ownership state of description, and on others of patent not constitute infringement of statement; ③ anesthesia drug, and spirit drug, and medical with toxicity drug development project reply file copies; II application drug production Shi should provides drug clinical test documents copies; ⑤ directly contact drug of packaging material (or container) of     Drug packing materials and vessel registration certificate or the copy of the certificate of registration of imported packaging materials and containers; ⑥ other supporting documents. As for imports application, also should provides: ① production national or area drug management institutions issued of allows drug listed sales and the the drug production enterprise meet drug production quality management specification of proved file, and notary instruments; export country species competent authorities agreed export of proved; II by outside pharmaceutical manufacturers permanent China representative institutions handle registered Affairs of, should provides foreign enterprise permanent China representative institutions registration card copies; outside pharmaceutical manufacturers delegate China agent institutions agent declared of, should provides delegate instruments, and     Notarial documents copies of business license and Chinese agencies c safety test data shall provide appropriate non-clinical research and the quality control specifications document clinical specimens should be provided with appropriate good manufacturing practices certificate. (3) data item 3 purpose made and based on: Chinese herbal medicine, natural medicine should provide a synthesis of information about ancient and modern literature. Should provide a source of prescription of traditional Chinese medicine, natural medicine preparation and selection based on research or production, the usage summary, and the variety innovation, feasibility analysis, including comparison of similar varieties and existing national standards.     Should also be provided on traditional medicine of traditional Chinese medicine theory and ancient literature data.     (4) information item 4 a summary of research results and evaluation: the applicant's summary of the main findings, and safety, effectiveness, quality control and other aspects of the comprehensive evaluation of the reported species.     (5) data item 5 drug samples, preparation of notes and the latest references: included relevant provisions drafted by drug samples, instructions various elements of the drafting instructions, about security and the validity of the latest literature. Pharmaceutical research data (6) information item 16 sample inspection report: refers to the Declaration of the self test of the sample reports.     Before the clinical trials submitted to the information provided at least 1 sample self-test report, after completing the clinical trials reported data provided for 3 consecutive samples of the self test report. Pharmacology and Toxicology research information (7) information items 24 allergic (local, systemic and photo toxicity), hemolysis and partial (blood vessels, skin, Mucosa, muscles, etc) stimulus, dependence and other major local, special safety testing of systemic drug delivery-related data and literature: Drug Administration routes and preparation safety test data preparation features available.     New drugs of dependence tendency should provide data on drug dependence.     (8) information project 25 to mutation test information and the literature information: If prescription in the contains cannot set standard of herbs, or from cannot set standard herbs of effective parts, and for childbearing age crowd and may on reproductive system produced effect of drug (as pill, and sex hormone, and treatment sex function obstacles drug, and promoting sperm generated drug, and baotai drug or has cell HIV role, of drug), should submitted to mutation test information.     (9) data item 26 reproductive toxicity data and literature: for the people of childbearing age and may have an impact on the reproductive system of new drugs (such as birth control pills, hormone promoting sperm production, treatment of sexual dysfunction drugs, drugs, tocolytic drugs and mutation test positive or cytotoxic drugs) should be provided on a case study of reproductive toxicity data.     (10) data item 27 carcinogenicity test data and literature: new drug found to be cytotoxic in long term toxicity test or abnormal tissue growth promoting effect of positive test results for mutagenicity carcinogenicity test must be provided information and documents.     2. reporting requirements (1) application for clinical trials of new drugs, should submit information project 1~4, 7~31.     (2) upon completion of the clinical trial application drug production, General information should be submitted to the project 1~6, 15~17, 29~33, and other information on changes and additions, and detailed explanations and evidence.     (3) application is the national standard of traditional Chinese medicine, natural medicine (traditional Chinese medicine, natural medicine injections), should be submitted to the project in general information 2, 4~8, 12, 15~18.    (4) import application production provided by national or regional Governments supporting documents and all the technical information should be in the text and the original text which the Chinese quality standards must organize submitted by China's State drug standard prescribed format. (5) due to the diversity and complexity of new drugs, in return, should be combined with a variety of features necessary for the appropriate research.     If the relief pilot, should be fully justified. (6) the main ingredients of traditional Chinese medicine, natural medicine injections should be clear, and oral routes of Administration have a clear advantage, its indications or indications for acute and serious illness.     Chinese herbal medicine, natural medicine injections in view of safety and quality control of complex considerations, for its technical requirements separately.     (7) "registration category 1" is not listed on the domestic sales of plants, animals, minerals extraction and preparation of, as the active ingredient, or its metabolites associated with known carcinogenic substances or similar, expected continuation for more than 6 months or treatment of chronic recurrent disease, when used in regular intervals, you must provide the carcinogenicity data.     (8) for "registered classification 3" of new of Chinese herbal medicines substitutes, except by "registered classification 2" of requirements provides clinical Qian of corresponding declared information outside, also should provides and was alternative herbs for efficacy learn compared of test information, and should provides for human tolerance sex test and through related preparations for clinical equivalent sex research of test information, if substitutes for single ingredients, is should provides drug generation Dynamics test information and the literature information.     New herbal substitute is approved, preparation of applications use the substitutes shall be supplemented to apply, but should be strictly limited to the approved alternative within the scope of. (9) for "registered classification 5" not in domestic listed sales of from plant, and animal, and mineral, in the extraction of effective parts and preparations except by requirements provides declared information outside, is needed provides following information: ① declared information project 12th items in the needed provides effective parts filter of research information or literature information; declared information project 13th items in the needed provides effective parts main chemical ingredients research information and the literature information; II by number class ingredients composition of effective parts, should determination each class ingredients of content,     And the representation of each type of ingredient composition determination and provides lower limit (Cap on toxic ingredients should also be increased).     ③ apply effective parts made up of similar ingredients and preparations, such as it has marketed from plants, animals, minerals and other active ingredients extracted, you should work with that comparison of the pharmacodynamics of effective components and other aspects to demonstrate its advantages and characteristics. (10) "registration category 6" is not listed on the domestic sales of traditional Chinese medicine, natural medicine compound preparation should provide the information requested according to different categories: ① compound preparation of traditional Chinese medicine syndrome of primary treatment did not include in the national standard of proprietary Chinese medicines, not efficacy, toxicology, clinical trials can do 100.     However, if you have one of the following conditions are required to provide toxicological test data: one is marked in the statutory standard toxicity and prove toxic ingredients of modern Toxicology; second, containing 18 an 19, fear of incompatibility.     ② modern traditional Chinese medicine compound prescription pharmaceutical substances should be given a statutory standard that is used in, if medicinal materials of prescriptions containing not normative, reference should also be "registration category 2" requirements pre-clinical information.     ③ natural medicine compound preparation shall provide the multi-component pharmacodynamics and toxicology test information and documentation of the interaction, if contained in the prescription laid down standards of medicinal substances, reference should also be "registration category 2" requirements pre-clinical information. II medicine, and natural drug and chemical drug composition of compound preparations in the of medicinal material required has statutory standard, declared clinical Shi should provides medicine, and natural drug and chemical drug between efficacy, and HIV acting mutual effect (increased effect, and reduction HIV or complementary role) of compared sex research test information and the literature information and the medicine, and natural drug on chemical drug biological using degrees effect of test information; declared production Shi should through clinical test proved its Group Party of need, and provides medicine, and Effect of natural medicines on bioavailability of chemicals test data.     Prescription containing chemicals (single or compound) must be the national drug standards and listed. (11) "registration category 8" changes in domestic market of preparations of Chinese medicine, natural medicine, and shall explain the advantages and characteristics of new preparations.     New indications or indications for preparation should in principle be the same as preparation, which cannot be pharmacodynamic or clinical trials, shall provide appropriate information.     When the dosage is changed, if the production process there is a qualitative change, declarations should be made available to the new preparation and preparation in preparation, dosage form, quality standards, stability, pharmacodynamic and clinical aspects of comparative tests and toxicological data.     When the dosage is changed, if no qualitative changes in production, may reduce the pharmacological, toxicological and clinical claims data (except for sustained-release and controlled-release formulations and injections).     Preclinical study of sustained-release and controlled-release preparation should include slow-release and controlled-release preparations and common in pharmacy, biology, comparative study of the pharmacokinetics and clinical trials information to such agent specific release feature.     (12) "registration category 9" national standard of traditional Chinese medicine, natural medicine, when necessary, to improve quality standards, improving the quality of standards according to tentative standards of management.     (13) of cyclophosphamide on clinical trials clinical trials number of cases should be consistent with statistical requirements and minimum number requirements.     II the minimum number of clinical trials (test group) requirements for phase I for 20~30, for 100 cases of ⅱ stage, for 300 cases of ⅲ stage, phase IV in 2000.     ③ a registered category 1, 2, 4, 5, 6.2, 6.3, 6.4, drugs, phase IV clinical trials should be carried out.     ④ bioavailability tests are generally 18~24.     ⑤ contraceptives in phase I clinical trials should be carried out in accordance with these regulations; phase II clinical trials should be completed at least 100 for 6 randomized controlled trials of menstrual cycle; phase ⅲ clinical trials should be completed at least 1000 12 menstrual cycles open; phase ⅳ clinical trial should take fully into account the variables of such medicines, adequate sample size study is completed.     ⑥ new functions of Chinese herbal substitutes as an alternative should be selected from the national drug standards to fully reflect the alternative medicine effect comparative study on the characteristics of Chinese medicine as a controlled drug, indications of each function or disease would require more than two kinds of traditional Chinese medicine preparation verify each preparation to validate the clinical cases of not less than 100 pairs.     ⑦ application is the national standard of injection and the State food and drug administration regulations of other existing national standards of Chinese medicine, natural pharmaceutical registration, clinical trials shall be conducted, the number of cases of not less than 100. ⑧ importing traditional Chinese medicine, natural medicine preparations registered in the classification request for information. And shall provide in-country human pharmacokinetic studies and clinical trial data, the number of cases of not less than 100.     Primary treatment certificate or indications, cases of each of the major indications of not less than 60.     ⑨ When the dosage form is changed, if the production process there is a qualitative change should be based on the characteristics of drug design of clinical trials for different purposes, General clinical trials number of cases not less than 100.     Three, and declared information project table and the description (a) medicine, and natural drug declared information project table ┌-the-the ┬-the-the ┬-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the ┐ │ funding │ funding │ registered classification and the information project requirements │ │ material │ material ├-the-the ┬-the-the ┬-the-the ┬-the-the ┬-the-the ┬-the-the-the-the-the-the-the-the-the-the-the ┬-the-the ┬-the-the ┬-the-the ┤ │ points │ items │ │    │    │    │    │          6           │    │    │    │ │ 类 │ 目 │ 1  │ 2  │ 3  │ 4  │ 5  ├──┬──┬──┬──┤ 7  │ 8  │ 9  │ │    │    │    │    │    │    │    │6.1 │6.2 │6.3 │6.4 │    │    │    │ ├──┼──┼─ ─┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 1  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 2  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │ 综 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 述 │ 3  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ - │ │ 资 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 料 │ 4  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 5  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 6  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 7  │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 8  │ + │ + │ + │ + │ + │ + │ + │ + │   + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 9  │ - │ + │ ▲ │ - │ ▲ │ - │ ▲ │ ▲ │ ▲ │ - │ - │ - │ │ ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 10 │ - │ + │ ▲ │ + │ ▲ │ - │ ▲ │ ▲ │ ▲ │ - │ - │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 11 │ - │ + │ ▲ │ - │ ▲ │ - │ ▲ │ ▲ │ ▲ │ - │ - │ - │ │ 药 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 学 │ 12 │ + │ + │ ▲ │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │ 资 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 料 │ 13 │ + │ + │ ± │ ± │ ± │ - │ - │ - │ - │ - │ - │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 14 │ + │ + │ ± │ ± │ ± │ ± │ ± │ ± │ ± │ ± │ ± │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 15 │ + │ + │ ▲ │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 16 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 17 │ + │ + │ ▲ │ + │ + │ + │ + │ +  │ + │ + │ + │ + │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 18 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 19 │ + │ + │ *  │ + │ + │ *  │ + │ + │ + │ + │ *  │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 20 │ + │ + │ *  │ + │ + │ *  │ + │ + │ + │ + │ *  │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 21 │ + │ + │ * │ + │ + │ - │ - │ + │ - │ - │ - │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 药 │ 22 │ + │ + │ *  │ + │ + │ *  │ + │ + │ + │ + │ *  │ - │ │ 理 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 毒 │ 23 │ + │ + │ *  │ + │ + │ *  │ + │ + │ + │ + │ *  │ - │ │ 理 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 资 │ 24 │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ │ 料 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼─ ─┤ │    │ 25 │ + │ + │ ▲ │ + │ *  │ - │ *  │ *  │ *  │ *  │ - │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 26 │ + │ + │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ - │ - │ │    ├──┼──┼──┼──┼──┼── ┼──┼──┼──┼──┼──┼──┼──┤ │    │ 27 │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ *  │ - │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 28 │ + │ - │ *  │ - │ - │ - │ - │ - │ - │ - │ - │ - │ ├──┼─ ─┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 29 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ - │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 临 │ 30 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ *  │ *  │  │ 床 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │ 资 │ 31 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ *  │ *  │ │ 料 ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 32 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ * │ *  │ │    ├──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │    │ 33 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ *  │ *  │ └──┴──┴──┴──┴──┴──┴──┴──┴──┴──┴──┴──┴──┴──┘     (二)说明     1.“ + "Means information must be submitted by 2." -"Means the exempt information; 3." ± "Refers to the literature review can be used in place of experimental data. 4. "▲" Statutory standard of traditional Chinese medicine, natural medicine can be provided, otherwise must provide information; 5.       "*" In accordance with the declared data item descriptions, and information requirements.     Annex II: chemical drug registered classification and the declared information requirements a, and registered classification 1. not in both at home and abroad listed sales of drug: (1) through synthesis or half synthesis of method business have of raw materials drug and preparations; (2) natural material in the extraction or through fermentation extraction of new of effective monomer and preparations; (3) with split points or synthesis, method business have of known drug in the of optical isomers and preparations; (4) by has listed sales of more group copies drug preparation for less group copies of drug; (5) new of compound preparations;     (6) the preparations that have been listed in the domestic sales increase at home and abroad are new indications that are not approved.     2. change to the route and has not been listed at home and abroad sales agents.     3. has in abroad listed sales but yet in domestic listed sales of drug: (1) has in abroad listed sales of preparations and raw materials drug, and/or change the preparations of formulations, but not change to drug way of preparations; (2) has in abroad listed sales of compound preparations, and/or change the preparations of formulations, but not change to drug way of preparations; (3) change to drug way and has in abroad listed sales of preparations; (4) domestic listed sales of preparations increased has in abroad approved of new indications.     4. change the marketed drugs acid, salts of bases (or metal), but does not change its pharmacological actions of the drug substance and drug product.     5. change the formulation of domestic sales of drugs already on the market, but without changing the route of administration of the preparation.     6. the national drug standard of drug substance or drug product.     Second, information projects (a) summary information 1. drug name.     2. the supporting documents.     3. purpose made and ...     4. Summary of main findings and evaluation.     5. specifications, preparation of notes and references.     6. packaging and labelling design artwork.     (B) the pharmaceutical research 7. pharmaceutical research data.     8. study on raw materials, production of information and documents; preparation of and study on the technology of information and documentation.     9. confirm the chemical structure or group of test data and the literature.     10. quality research data and documents.     11. drug standards and drafting instructions, and provide standards or reference standard.     12. sample inspection report.     13. the sources of raw materials, auxiliary materials and quality standards, inspection reports.     14. drug stability study testing data and documents.     15. the packaging material and vessels direct contacted with drugs of choice and quality standards.     (C) the Pharmacology and toxicology studies 16. Summary of the Pharmacology and toxicology studies.     17. the main pharmacodynamic data and documents.     18. General pharmacology tests and documentation.     19. acute toxicity test data and documents.     20. long-term toxicity testing data and literature.     21. Henoch (local, systemic and photo toxicity), hemolysis and partial (blood vessels, skin, Mucosa, muscles, etc) special safety test data and literature such as irritation.     22. the variety of ingredients in compound preparations of efficacy, toxicity and pharmacokinetic interaction data and literature.     23. Mutagenicity test data and literature.     24. reproductive toxicity test data and documents.     25. a carcinogenicity test data and documents.     26. the dependence of test data and literature.     27. non-clinical pharmacokinetic data and documents.     (D) clinical trial information 28. Summary of relevant clinical trial information at home and abroad.    29. the clinical trial and research programmes. 30. the Handbook of clinical researchers.     31. the informed consent form template, approved by the Ethics Committee.     32. the clinical trial reports. Third, the declared data item description 1. data item 1 name of the drug: includes the common name, chemical name, English name, Hanyu Pinyin, and indicate the chemical structural formula, molecular weight, molecular formula, and so on.     New name, description should be named according to. 2. item 2 supporting documents: (1) applicant organization legal registration certificate (business license), the drug production licenses and change log page, a certified copy of the certificate of good manufacturing practices. Application drug production Shi should provides samples preparation workshop of drug production quality management specification certification certificate copies; (2) application of drug or using of prescription, and process, and uses, patent situation and ownership state description, and on others of patent not constitute infringement of statement; (3) anesthesia drug, and spirit drug and belongs to drug of radioactive drug needed provides development project reply file copies; (4) application drug production Shi should provides drug clinical test documents Copies and the clinical test medication of quality standard; (5) application preparations of, should provides raw materials drug of legal source proved file, including raw materials drug of approved proved file, and drug standard, and test report, and raw materials drug production enterprise of license, and drug production license, and drug production quality management specification certification certificate, and sales invoice, and supply agreement, of copies; (6) directly contact drug of packaging material and container of drug packaging material and container registered card or imports packaging material and container registered card     A copy of.     3. item 3 is made objective by: including the product research and development at home and abroad, market situation and review of related literature, or the production, usage.     4. item 4 a summary of research results and evaluation: including the applicant's summary of the main results and safety, effectiveness, quality control and other aspects of the report were evaluated.     5. item 5 drug specifications, preparation of notes and references: included relevant provisions drafted by drug manual, instructions various elements of the drafting instructions, the relevant literature.     6. item 7 pharmaceutical research data: refers to the drug pharmacy research (synthesizing technique, choice of dosage form, formulation, structure, quality research and quality standards development, stability studies, etc) and domestic and international literature review of test.     7. information project 8 raw materials drug production process of research information: including process and chemical reactions type, and starting raw materials and organic dissolved media, and reaction conditions (temperature, and pressure, and time, and catalyst,) and operation steps, and refined method, and main physico-chemical constants and the stage of data accumulated results,, and indicate feeding volume and received have rate and process process in the may produced or introduced of impurities or other Middle product.     8. item 10 of quality research data and documentation: includes physical and chemical properties, purity, dissolution, assay and method validation and periodic data accumulation results. 9. item 11 drug standards and drafting instructions, and provide standards or reference standard: quality standard should be consistent with the format of the current edition of the Pharmacopoeia, and uses the terminology and units of measurement. The reagent solution, buffer, titration solution shall be made in the current edition of the pharmacopoeia contains variety and concentration, there are different, and detailed instructions.     Provide standards or reference information should be attached, indicating their origin, physical and chemical constants, methods for determination of purity, and data.     Drug standards control project in the drafting instructions should include standard selected, method of selection, inspection and purity and limited basis. 10. information items 12 sample inspection report: Declaration sample self-test report.     Before the clinical trials submitted to the information provided at least 1 sample self-test report, after completing the clinical trials reported data provided for 3 consecutive samples of the self test report.     11. the information item 14 drug stability study testing information: including direct contact with the drug packaging materials and containers carried out stability tests.     12. information on item 16 Summary of the Pharmacology and toxicology studies: refers to the applied study on Pharmacology and toxicology of drugs (including Pharmacology, mechanism, general pharmacology, toxicology, pharmacokinetics, etc) and domestic and international literature review of test.     13. item 27 non-clinical pharmacokinetic data and documentation: refers to the application of drugs in vitro and in vivo (animal) pharmacokinetic (absorption, metabolism, distribution and excretion) test data and literature.     14. item 28 domestic and international clinical trial information related to the review of information: refers to the clinical trials both at home and abroad about the variety of literature, abstracts and recent review of tracking reports. 15. the information item 29 clinical trials programmes and research programmes: the clinical trial and research programmes to develop the indications, dosage, such as clinical trials and important content is described in more detail, and have submitted data to support.     Clinical trial and research programmes should be scientific, complete, and working to develop tests of potential risks and benefits related to the non-clinical and clinical data were an important summary of the comprehensive analysis. 16. Handbook of clinical study information item 30: refers to applications for drugs already in clinical trials information and abstracts of non-clinical trial management information in order to provide information to researchers and other personnel involved in the test, to help them understand the characteristics and clinical trials of experimental drugs programme.     Investigator's brochure should be concise and objective.                                                          四、申报资料项目表及说明     (一)申报资料项目表 ┌──┬──┬─────────────────────────────┐ │ 资 │ 资 │                                                          │ │ 料 │ 料 │                  注册分类及资料项目要求                  │ │ 分 │ 项 │    │ │ 类 │ 目 ├────┬────┬────┬────┬────┬────┤ │    │    │   1    │   2    │   3    │   4    │   5    │   6    │ ├──┼──┼────┼────┼────┼────┼────┼────┤ │  │ 1  │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 2  │   +   │   +   │   +   │   +   │   +   │   +   │ │ 综 ├──┼────┼────┼────┼────┼────┼────┤ │ 述 │ 3   │   +   │   +   │   +   │   +   │   +   │   +   │ │ 资 ├──┼────┼────┼────┼────┼────┼────┤ │ 料 │ 4  │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 5  │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 6  │   +   │   +   │   +   │   +   │   +   │   +   │ ├──┼──┼────┼────┼────┼────┼────┼────┤ │    │ 7  │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 8  │   +   │   *5   │   +   │   +   │   *5   │   *5   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 9  │   +   │   +    │   +   │   +   │   +   │   +   │ │ 药 ├──┼────┼────┼────┼────┼────┼────┤ │ 学 │ 10 │   +   │   +   │   +   │   +   │   +   │   +   │ │ 研 ├──┼────┼────┼────┼────┼────┼────┤ │ 究 │ 11 │   +   │   +   │   +   │   +   │   +   │   +   │ │ 资 ├──┼────┼────┼────┼────┼────┼────┤ │ 料 │ 12 │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 13 │   +   │   +   │   +   │   +    │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 14 │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 15 │   +   │   +   │   +   │   +   │   + │   +   │ ├──┼──┼────┼────┼────┼────┼────┼────┤ │    │ 16 │   +   │   +   │   +   │   +   │   +   │   +   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 17 │   +   │  *16   │   ±   │ *18   │   -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 18 │   +   │  *16   │   ±   │  *18   │   -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 19 │   +   │  *16   │   ±   │    *18   │   -   │   -   │ │ 药 ├──┼────┼────┼────┼────┼────┼────┤ │ 理 │ 20 │   +   │  *16   │   ±   │  *18   │   -   │   -   │ │ 毒 ├──┼────┼────┼────┼────┼────┼────┤ │ 理 │ 21 │  *19   │  *19   │  *19   │  *19   │  *19   │  *19   │ │ 研 ├──┼────┼────┼────┼────┼────┼────┤ │ 究 │ 22 │  *13   │   -   │   -   │   -   │   -   │   -   │ │ 资 ├──┼────┼────┼────┼────┼────┼────┤ │ 料 │ 23 │   +   │   ±   │   ±   │   ±   │    -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 24 │   +   │   ±   │   ±   │   ±   │   -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 25 │   *8   │   -   │   *8   │   *8   │   -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 26 │   *9   │   -   │   -   │   -   │   -   │   -   │ │    ├──┼────┼────┼────┼────┼────┼────┤ │    │ 27 │   +   │  *20   │  *20   │   +   │  *20   │   -   │ ├──┼──┼────┼────┼────┼────┼────┼────┤ │    │ 28 │   +   │   +   │   +   │   +   │   +   │   +   │ │ 临 ├──┼────┼────┼────┼────┼────┼────┤ │ 床 │ 29 │   +   │   +   │   +   │   +   │   +   │   △    │ │ 试 ├──┼────┼────┼────┼────┼────┼────┤ │ 验 │ 30 │   +   │   +   │   +   │   +   │   +   │   △   │ │ 资 ├──┼────┼────┼────┼────┼────┼────┤ │ 料 │ 31 │   +   │   +   │   +   │   +   │   +   │   △   │ │ ├──┼────┼────┼────┼────┼────┼────┤ │    │ 32 │   +   │   +   │   +   │   +   │   +   │   △   │ └──┴──┴────┴────┴────┴────┴────┴────┘ 注:1.“     + ": You must submit information and/or data.     2. the "±" means documentation can be used in place of experimental data.     3. "-" means information can be required.     4. "*": follow the instructions to submit the request data, such as *8, see description of the 8th clause.     5. "": in accordance with this annex "five, clinical trial requirements" in the 4th section.     6. the documentation for the application the Pharmacology and toxicology of drugs (including Pharmacology, mechanism, general pharmacology, toxicology, pharmacokinetics, etc) to study literature and/or its literature review information. (B) Note 1. classification 1~5 of registration for new drug registration category 6 varieties to have national standards of medicine.     On the monitored period new medicines, such as production process does have significant improvements, upon approval by the State food and drug administration, can be classified according to the original registration of new drugs declared.     2. applications for registration of new drugs, submitted in accordance with the requirements of the information items 1~30 information items (information item 6); clinical trials completed review of submitted information include rearranging information 1~6, data items 12 and 14 28~32, clinical trial information and reorganizing information and additional information associated with the change, and in order of declaration information items.     Registration category 1 species completed clinical trials should be based on studies conducted during the clinical results, refresh to submit information 1~30 all the information of the project.     Simultaneous registration of registered category 3 drug substance and agents belonging to the registration category 6, the raw material medicine registration application shall comply with the reporting requirements. 3. the application for registration has been standard drugs, submitted in accordance with the requirements of the information items information items 1~16 and 28~30.     Clinical trials required, upon completion of the clinical trial submission information project 28~32 and other data changes and additions, and in order of declaration information items. 4. the application for registration has been standard drugs, depending on the species of the process, conduct a comprehensive study on the quality of prescription, according to national standards and comparative study of the quality of products already on the market.     In accordance with national standards and comparative study on the quality of products already on the market, shall be carried out in accordance with the requirements for new drugs quality and, if necessary, of national drug standards project updates and/or amendments. 5. register pharmaceutical preparations alone, you must provide proof of the legitimate source of the API, a-2, respectively in item 2 information (certificate file) information and information project, 13th (the source of raw materials, auxiliary materials and quality standards, inspection report). Applicants who use domestic raw materials, should be provided with the raw materials of drug approval documents, inspection reports, drug standards, the API of the business license, drug manufacturing license, drug manufacturing practices certification, signed with the raw medicine production enterprises of the supply agreement, copy of the sales invoice. Use of imported raw materials, should be provided with the raw medicine production enterprises or domestic legal sales agents to enter into supply agreements, the imported drugs registration certificate or the registration of pharmaceutical products, the port drug inspection offices inspection report, copy of drug standards, and so on.     Drug registration process, developed formulations used imported raw materials without the imported drugs registration certificate or registration certificate of pharmaceutical product must be approved by the State food and drug administration.     6. the same active ingredient made of small pins, powder for injection, infusion between changes of drug registration application, should be examined by the appropriate range of dosage forms production manufacturer Declaration.     7. drugs used for people of childbearing age, according to the indications and actions and submit the corresponding reproductive toxicity studies. 8. for clinical expected continuous medication 6 months above (containing 6 months) or treatment chronic recurrence sex disease and needed often intermittent using of drug, are should provides carcinogenic sex test or literature information; for following situation of drug, needed according to its indications and role features, factors submitted carcinogenic test or literature information: (1) drug or its metabolism product of structure and known carcinogenic material of structure similar of; (2) in long-term toxicity test in the found has cell HIV role or on some organ, and organization cell growth has exception promote role of     And (3) of positive test results for mutagenicity.     9. new drugs acting on the central nervous system, such as analgesic drugs, depressants, stimulants and drugs to have dependencies on the chemical structure of the human body, shall submit the test data on drug dependence.     10. a registered category 1 drug, should be carried out in the repeated dose toxicity study in toxicokinetic studies. 11. a registered in cluster 1 "split or synthesis methods of optical isomers in known drug and its preparation" shall submit the racemates compared with the single-isomer of pharmacodynamics, pharmacokinetics and Toxicology (acute toxicity) reflects the rationality of that legislation, such as studies or relevant documents.     In its elimination spin body security range smaller, and has has related information may tips single isomers of non-expected toxicity (and pharmacological role has nothing to do) obviously increased Shi, also should according to its clinical course and dose, and indications and medication crowd, factors integrated consider, provides and elimination spin body compared of single isomers repeat to drug toxicity (General for 3 months within) or other HIV acting research information (as reproductive toxicity).     12. a registered in cluster 1 "prepared by drug groups marketed as a small group of drugs", as the group does not contain the substances referred to in note 8, data items from 23~25.     13. a registered in cluster 1 "new compound", shall be submitted to the information item 22.     14. a registered in cluster 1 "new compound" shall normally be provided with repeated dose toxicity test data as a single agent, such as a repeated dose toxicity study shows its toxicity does not increase toxicity target organ has not changed, but provide information on item 27.     15. a registered in cluster 1 "new compound", such as the animal pharmacokinetic studies showed no significant change, data items from 23~25. 16. a registered category 2 new drugs, the Institute of Pharmacology and toxicology of route of Administration should be consistent with the clinical approaches to be used.     General should be provided with the original way of comparative pharmacokinetics of test and/or relevant toxicological information (such as repeated dose toxicity test and/or local toxicity test).    17. a registered in category 3 "change to the route have been listed overseas sales agents", should pay attention to in preparation of local toxicity of excipients on drug absorption or effect, if necessary, to provide its pharmacokinetic trials or toxicological information. 18. registration category 4 of the new drug should provide compared with the marketed drug pharmacokinetics, pharmacodynamics, general pharmacology and acute toxicity test data, to reflect the difference before and after the change, should also be provided, if necessary repeat dose toxicity and Pharmacology and toxicology studies.     If marketed drugs acid, salts of bases (or metal) made the drug has been marketed in a foreign country, press register category 3 reporting requirements.     19. local administration in addition to the respective registration category and the project submitted to the appropriate information, shall be submitted to the information item 21, local absorption tests when necessary.     20. There are obvious security concerns (such as the security context of small, marked increase in dose) sustained and controlled release preparations, generally listed should provide sustained and controlled release preparations or release preparation of single-dose pharmacokinetic studies of animal information.     Five clinical trial requirements 1. a register of category 1 and 2 new drugs, clinical trials shall be conducted. (1) clinical test of cases number should meet statistics requirements and minimum cases number requirements; (2) clinical test of minimum cases number (Group) requirements: ⅰ period for 20 to 30 cases, II period for 100 cases, III period for 300 cases, IV period for 2000 cases; (3) pill of ⅰ period clinical test should according to this approach of provides for; II period clinical test should completed at least 100 on 6 a menstrual cycle of random control test     ; Completed a phase III trial of at least 1000 12 menstrual cycle open; phase ⅳ clinical trial should take fully into account the variables of such medicines, adequate sample size study is completed. 2. registration category 3 and 4 new drug pharmacokinetics should be human studies and at least 100 of randomized clinical trials. Multiple indications, cases of each of the major indications of not less than 60.     Birth control pills should be human pharmacokinetic studies and at least 500 cases of 12 open trial of the menstrual cycle.     Is one of the following two cases may be exempted from human pharmacokinetic study: (1) local application and only played local treatment preparations and (2) do not absorb oral preparation. 3. is registered classification 5 of drug, clinical test according to following principles for: (1) oral solid preparations should for biological equivalent sex test, General for 18 to 24 cases; (2) to for biological equivalent sex test of oral solid preparations and the other non-oral solid preparations, should for clinical test, clinical test of cases number at least for 100 on; (3) sustained release, and control release preparations should for single times and times to drug of human drug generation dynamics of compared research and necessary of treatment learn related of clinical test,     Clinical trials number of cases at least 100; (4) small needles, made of the same active ingredient powder for injection, infusion between changes of drug registration applications, route of administration, dose and method consistent with the original dosage form drugs, may be exempted from conducting clinical trials.     4. register for oral solid dosage forms of the category 6, bioequivalence trials should be, generally 18 to 24 cases.     Need processes and standards to control the quality of medicines, clinical trials shall be conducted clinical trials number of cases at least 100 pairs. 5. applications made of chemical raw materials and small pins, powder for injection, infusion of new drug registration, preparation is exactly the same as the applicant's, can only carry out clinical trials of one of the agents, other agents, provided that they meet the technical requirements of such applications from clinical trials may be exempted from conducting clinical trials.     Agents belonging to different applicants, you should separate clinical trials. 6. relief applications for clinical trials, should be submitted in conjunction with the application for registration, and lists the grounds for relief of clinical trials and related information. Clinical trials for approval, in addition to the regulations can be reduced for clinical trials in the case, generally not approve relief tests.     There is difficulty in completing a clinical trial, the applicant shall apply, details of clinical trials according to relief and programmes, from clinical statistics, test into groups and others justify. 7. controlled drugs in clinical trials should be listed in the domestic sales of the drug. Have to buy medicines from abroad, be approved by the State food and drug administration and port drug inspection offices inspection before they can be used in clinical trials.     Positive control drug in clinical trials is generally chosen should be carried out in the following order: (1) varieties of the original developer, (2) varieties with clear clinical trial data; (3) the same active ingredient and route of administration, dosage form different varieties (4) mechanism of action is similar, same indications of other varieties. Six, imported chemicals information and requirements (a) reporting project requirements 1. declarations in accordance with chemical declaration information item required.     Application is not allowed to market drugs at home and abroad, submitted in accordance with registered category 1 material; other varieties according to the registration category 3 of the submitted information.     Drugs belonging to the registration category 1, shall be at least has entered phase II clinical trials of drugs in a foreign country. 2. item 5 drug specifications, preparation of notes and references, has yet to provide the original producing country or region drug authority approved specifications, listed in the production countries or regions use manual sample translation into Chinese.     Information item 6 needs to provide the drug producing countries or areas listed using the packaging and labelling samples.     3. information items 28 shall be submitted to the drug-producing countries or region as the applications listed for sale for all clinical trial information. 4. all information submitted shall be in Chinese and the original text, and other types of information can be attached as a reference.     Chinese translation should be consistent with the original content.     5. standard Chinese, must comply with the national drug standard format.     (B) the information requirements and instructions of project 2 proof documents 1. data item 2 supporting documents include the following information: (1) production country or region drug authority issued by the pharmaceutical market and the drug manufacturers comply with good manufacturing practice certificates, notarial instrument and its Chinese translation.     Drugs belonging to the registration category 1, documentation can be completed after clinical trials in China, and report be submitted, but in reporting clinical trials must provide pharmaceutical production country or region drug authority issued by the drug manufacturers comply with good manufacturing practice certificates.     (2) permanent representative offices of foreign pharmaceutical manufacturers to register shall provide the copy of the certificate of registration of resident representative offices of foreign enterprises.     Foreign pharmaceutical manufacturers commissioned in our agency agent, principal instruments, notary and its Chinese translation should be provided, as well as the Chinese copy of the business license of the Agency.     (3) application of drugs or use of formulation and technology franchise and its ownership status description and statement does not constitute an infringement of a patent to others. 2. Description of: (1) the applicant issued by the regulatory authorities of the countries or regions to allow drug sales and the drug manufacturers comply with good manufacturing practice certificate shall comply with the who recommended a unified format. Other format of file, must by where country notary institutions notary and the standing where country China makes consulates certification; (2) in a to completed preparations production by another a to completed packaging of, should provides preparations factory or packaging factory where national or area drug management institutions issued of allows drug listed sales and the the drug production enterprise meet drug production quality management specification of proved file; (3) not in production national or area allowed listed sales of, Can provide certified home country or region drug authority issued by allowing drug sales and the drug manufacturers comply with good manufacturing practice certificates.     Provide certified business headquarters in the host country or region other than the regions or countries issued by the regulatory authorities of allowing drug sales and the drug manufacturers comply with good manufacturing practice certificates, recognized by the State food and drug administration; (4) provide the manufacture of APIs country or region drug authority issued by the drug manufacturers comply with good manufacturing practice certificates and allowed the APIs listed for sale or to allow preparations went on sale and the drug manufacturers comply with good manufacturing practice certificates.     The API can also provide master system file (DMF,Drug Master File) information and documents applicable the European Pharmacopoeia or the API documentation (CEP,Certificate of Suitability to the Mono-graphs of the European Pharmacopeia).     (5) international multi-center clinical trial of the application, you must provide the pharmaceutical production country or region drug authority issued by the drug manufacturers comply with good manufacturing practice certificates.     (6) for the raw materials to produce national or regional food management drug or preparation shall provide the country or region drug authority issued by the manufacturers comply with good manufacturing practices certificate or the certificate issued by the manufacturer in accordance with the ISO9000 quality management system certificate, and the country or region relevant regulatory agencies to allow the sale of documents.     (C) the requirement of clinical trials in China 1. applications for drugs that are not allowed to go on sale at home and abroad, clinical trials shall be carried out in accordance with the register of category 1.     2. application in foreign market but not yet marketed medicines in China, should be in accordance with category 3 of the clinical trial.     3. applications for different formulations from the domestic sales of drugs already on the market, but the route of the same drug, if the information item 28 meet the requirements, according to category 5 of the clinical trial; do not meet the requirements shall be in accordance with category 3 of the clinical trial. 4. preparation of the application is the national drug standard, if the information item 28 meet the requirements, you can follow the clinical trials registration category 6 requirements; does not meet the requirements shall be in accordance with category 3 of the clinical trial.     Application is the national drug standard API without the need for clinical trials.     5. apply separately for imports, there is no national drug standards API, its preparation should be used in clinical trials.    Seven, radioactive drug application information and requirements (a) reporting project requirements 1. Declaration of radioactive drugs: shall be in accordance with radioactive chemicals, pill boxes and preparation, reference chemicals corresponding category and organization of the declared data item requests information.     Information of which 22, 26.     2. Declaration of radiopharmaceuticals for diagnosis: not reported information on 23, 24, 25. 3. declare radioactive chemicals, medicine box: data items from 17, 18.     When reporting kit should also submit the requested information under preparation.     (Ii) declared information project description 1. information project 8 by following requirements submitted: (1) radiation chemicals: should provides by with radionuclide production of selected, and irradiation conditions, and nuclear reaction type, and irradiation Hou target material of chemical processing process (attached chemical reactions type and the process figure), detailed operation steps, may produced of radioactive nuclear impurities, refined (purification) method, by with chemical reagents (especially target material) of specifications standard and the analysis test data, both at home and abroad about literature information. (2) the Kit: the kit should be provided prescription selected basis, the reaction conditions, procedures and preparation process, raw material quality standard of each component in the Kit.     If a group is divided into its own preparation, should provide a detailed synthesis of selected basis and synthetic processes, chemical reactions, reaction conditions, procedures, material weight, yield and possible impurities or inclusions, the intermediate quality control methods, refining the final product (purified) methods, quality standards of raw materials, domestic and foreign literature.     (3) preparation: should provide preparation of prescription selection, fabrication process, reaction conditions, steps, purification or purification methods, quality standards and analysis of raw material test data, literature at home and abroad. 2. the information submitted item 9 according to the following requirements: (1) the radioactive chemicals should provide the structure of test data (maps, data and integrated analysis) as well as domestic and foreign literature.     If they contain national standards not yet containing radionuclides, radionuclide decay scheme should also be provided, confirm its nuclear test data (or mapping) and recognized at home and abroad that the nuclear nature of nuclear test to compare information and literature. (2) Kit: Kit components in detail and its content should be provided, and explains the role of each component in the Kit.     Components of the BBR, should provide the structure of test data (maps, data and integrated analysis) as well as domestic and foreign literature. (3) preparation: test data should provide conclusive evidence of its structure.     If there is difficulty, should be justified, and reasonable to infer the possible existence of a structure or based on references. 3. item 10 submitted according to the following requirements: (1) the radioactive chemicals should be determined according to the characteristics and circumstances of the sample research projects of physical and chemical constants, purity content, method and the method to determine the basis for the determination. Such as: purity of radioactive and nuclear impurities content, radioactivity, chemical purity etc.     And provide detailed measurement method and measurement data.     (2) port: should provide property, identification and solution of clarity, pH value of analysis and testing methods, principles and data, experimental study on the selection of the method for determination of main components and data, sterility, bacterial endotoxin test methods and limits for research information. (3) preparation: physical and chemical properties, properties, should be provided to identify radioactive nuclear purity, pH value, and the principle (including major impurities), radiochemical purity, radioactivity, chemical purity testing method and test data and other information.     If the injection should also provide sterile, bacterial endotoxin test methods and data, bacterial endotoxins limit based on such information.     4. submit information item 17, the following requirements: (1) diagnostic radiopharmaceuticals: laboratory animals should be provided the target organ and whole body imaging or simulate the clinical study of functional testing methods, test conditions and results interpretation data, timelines for experimental observation of image or copy of photo image or its function test results.     (2) therapeutic radiopharmaceutical: treatment should be provided indications of the animal model of experimental data, and providing this product or similar drugs at home and abroad of researches on pharmacodynamics of detailed documentation. 5. information submitted item 19 according to the following requirements: registration category 1 and 3 main types of radioactive drugs raw material should be acute toxicity in mice, pill boxes and acute toxicity test preparation can be carried out.     If the synthesis of main raw materials refining limited production, clinical dosage and minimal acute toxicity tests may be used.     6. submit information item 20 the following requested: (1) register of category 1 therapeutic radiopharmaceuticals shall provide information on chronic toxicity in rats and dogs, the medical internal radiation dose (MIRD) of information and literature.     (2) registration category 1 of radiopharmaceuticals for diagnosis, treatment, drugs should be provided after the complete decay of radionuclides in internal radiation absorbed dose, human target and non-target organ dose estimates or foreign literature with the same or similar drugs. (C) the requirements of radioactive drugs in clinical trials clinical trials, generally in accordance with the chemical requirements of the corresponding category.     Special cases, clinical trials number of cases in the case of meet the statistical requirements can be adjusted appropriately.     (D) defining the requirements referred to in the radioactive chemicals, pill boxes and preparation is defined as follows: the chemicals: means the person directly for preparation of radioactive pharmaceutical preparations containing radioactive material.     Kit: means used with radioactive chemicals, rapid preparation of radiopharmaceuticals before using a set of tags ligand, reductants, oxidants, separating agent components in General.       Preparation: means the radionuclides and radioactive drugs made from other raw materials are processed.     Annex III: registration of biological products classification and reporting requirements part I therapeutic biological products, registration category 1. is not listed on the domestic and foreign sales of biological products.     2. monoclonal antibody.     3. gene therapy, somatic cell therapy and its products.     4. allergen products.     5. the extraction of human and animal tissue or body fluids, or through fermentation of biologically active preparation of multi-component products.     6. the sale of biological products to form a new compound products already on the market.     7. went on sale in foreign countries but not yet listed in the domestic sale of biological products.     8. preparation of micro-ecological products contain unapproved strains.     9. the structure of sales of products already on the market is not exactly the same and are not market products at home and abroad (including amino acid mutation, loss, arising because of different expression systems, eliminate or change the post-translational modification, chemical modification of the product, etc).     10. preparation of different products with a marketed product (such as the use of different expression systems, cells, etc).     11. the first products produced by recombinant DNA technology (such as recombinant techniques as an alternative synthesis, biological tissue or fermentation techniques, etc).     12. has not been listed for sale by a non-injecting route to injection drug delivery, or by the local administration to systemic drug delivery products.     13. change of marketed products form without changing the route of administration of biological products.     14. changing the route of administration of biological products (does not include the above 12).     15. the national drug standard of biological products.     Second, information projects (a) summary information 1. drug name.     2. the supporting documents.     3. purpose made and ...     4. Summary and evaluation of results.     5. drug samples, preparation of notes and references.     6. packaging and labelling design artwork.     (B) the pharmaceutical research 7. pharmaceutical research data.     8. production with raw materials research information: (1) production with animal, and biological organization or cell, and raw materials plasma of source, and collection and the quality control, research information; (2) production with cell of source, and building (or filter) process and the identification, research information; (3) seed library of established, and verification, and save and the passage stability information; (4) production with other raw materials of source and the quality standard.     9. liquid or ingredients, production data, theoretical and experimental basis for determining and verifying information.     10. the formulation and technology of information, sources of materials and quality standards, and related documents.     11. quality research data and related documentation, including preparation and calibration of reference or reference, as well as information on the sales of similar products already on the market at home and abroad.     12. the manufacturing and testing records of samples for clinical trial application.     13. the draft manufacturing and testing procedures, preparation of notes and test method validation data.     14. preliminary stability studies.     15. direct contact with product selection and quality standards of the packaging materials and containers.     (C) the Pharmacology and toxicology studies 16. Summary of the Pharmacology and toxicology studies.     17. the main pharmacodynamic data and documents.     18. General pharmacological studies of experimental data and literature.     19. acute toxicity test data and documents.     20. long-term toxicity testing data and literature.     21. the animal pharmacokinetic data and documents.     22. Mutagenicity test data and literature.     23. reproductive toxicity test data and documents.     24. a carcinogenicity test data and documents.     25. the immunotoxic and/or immunogenicity data and documents.     26. hemolysis and partial (blood vessels, skin, Mucosa, muscles, etc) irritation, and other major local, special safety tests related to systemic drug delivery research and documentation.     27. the multiple components in compound preparations efficacy, toxicity and pharmacokinetic interaction data and literature.     28. the dependence of test data and literature.     (D) clinical trial information 29. Summary of relevant clinical trial information at home and abroad.     30. the draft programme of clinical trial planning and research.     31. the draft informed consent.     32. Handbook of clinical researchers and Ethics Committee approval.     33. the clinical trial report (v) other 34. preclinical work brief summary.     35. improvements have also conducted during the clinical trial process, improve the quality standard and pharmaco-toxicological studies summary and test data.     36. the validation verification regulation of the manufacture and modify the content and modify the basis.     37. stability testing data.     38.3 consecutive trial manufacturing and testing records. Three, reporting information on     1. applications for clinical trials submitted to the data item 1~31; after completing the clinical trials submitted to the data items 29~38 and 1~6, 15 applications for new drug certificate submitted to the information items 1~6 and 29~37. 2. item 1 name of the drug, including: common name, English name, Chinese pinyin, molecular weight, and so on.     New name should specify the basis. 3. information project 2 proved sex file including: (1) applicants institutions legal registration proved file (license,), and drug production license and the change records page, and drug production quality management specification certification certificate copies; (2) application of biological products or using of prescription, and process, patent situation and ownership state description, and on others of patent not constitute infringement of statement; (3) application new biological products production Shi should provides drug clinical research documents     Copies of clinical medication quality standards, (4) direct contact with products, packaging materials and containers for the pharmaceutical packaging materials and vessel registration certificate or import packing materials and vessel registration certificate copy.     4. item 3 is made objective and basis, including: research, market the products at home and abroad situation and review of related literature, or the production, usage and the breed innovation, feasibility analysis.     5. the study results summary and evaluation of data item 4, including: research results, safe, effective, quality control and other aspects of the evaluation.     6. item 5, drug samples, preparation of notes and references, including: drafted in accordance with the relevant provisions of the drug samples, instructions various elements of the drafting instructions, literature or the latest version of the specification of the original and the translation.     7. production raw materials related to bovine-derived material, according to the relevant provisions of the food and Drug Administration to provide the corresponding information.     8. human and animal tissue or body fluid extraction products, monoclonal antibodies and eukaryotic expression recombinant products, there is additional viral inactivation process validation information.     9. added during the production process of people of potentially toxic substances, shall provide removal efficiency of production process validation information, limits in specified products and provide evidence. 10. item 11 information quality research materials: production process are determined, according to the trial's findings, determined by statistical analyses.     Includes: analysis of physical and chemical characteristics of the products, structure, identification tests, purity determination, determination, determination and activity information on purification of product impurity analysis of information should also be provided.     11. the extraction or isolation of human tissue or body fluid material dosage dosage should not exceed physiological allowed, and that it was not special and does not use a special solvent in the process of biological products (not including the compound products), to provide relevant information or evidence, from safety research data (data item 19~28).     12. biological products clinical Qian research, should select related of animal species (refers to by try real this class animal body can through expression of receptor or Antigen table bit produced pharmacological activity,) for body, and body outside test; some General of HIV acting research method (as genetic toxicity, and carcinogenic sex, and allergy sex test) if does not apply for by declared of products, should to description, necessary Shi can provides other related of research information.     13. because of the diversity and complexity of biological products, in relation to specific varieties, should be combined with biological characteristics of, refer to the corresponding technical guidelines, from a scientific and rational point of view, to meet the requirements of drug evaluation.     14. in vivo diagnostic use of biological products information by type of therapeutic biological products.                                                          Four, reporting requirements (a) therapeutic biological products information list (data item 1~15,29~38) ┌------┬ ┬-----------------------------------┐││ Chinese │ classification classification and data requirements for registration │ │ information │ │ │ │            │项├─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┤ │            │目│1 │2 │3 │4 │5 │6 │7 │8 │9 │10│11│12│13│14│15│ ├──────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │1 │+│+│  │  │+│+│+│+│ +│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │2 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │3 │+│+│  │  │+│+│+│+│+│+│+│+            │+│+│+│ │  综述资料  ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │4 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │5 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │ ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │6 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ ├──────┼─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │7 │+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ │            ├─  ┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │8 │+│+│  │  │+│-│+│+│+│+│+│-│-│-│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │9 │+│+│  │  │+│-│+│+│+│+│+│-│-│-│+│ │            ├─┼─┼─┤ │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │10│+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │药学研究资料│11│+│+│参│参│+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤照│照├─┼─┼─┼─┼─┼─┼─            ┼─┼─┼─┼─┤ │            │12│+│+│相│相│+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤应│应├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │13│+│+│指│指│+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤导│导├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │   │14│+│+│原│原│+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤则│则├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │15│+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ ├──────┼─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │29│+│+│ │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │30│+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │临床试验资料│31│+│+│  │  │+│+│+│+ │+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │32│+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │33│+│+│  │  │+│+│+│+│+│+│+│            +│+│+│+│ ├──────┼─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │34│+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │35│+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │ ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    其他    │36│+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │37│+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ │            ├─┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │            │38│+│+│  │  │+│+│+│+│+│+│+│-│+│-│+│ └───── -The ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┘ note: 1.+: refers to must submitted of information; 2.-: refers to can from reported of information; (ii) treatment with biological products pharmacological HIV acting research information project requirements (information project 16~28) ┌-the-the ┬-the-the ┬-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the-the ┐ │ points │ items │ registered classification and the information project requirements │ │    │    ├─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┬─┤ │ 类 │ 目 │1 │2 │3 │4 │5 │6 │7 │8 │9 │10│11│12│13│14│15│ ├──┼──┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 16 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │    ├──┼─┼─┤  │  ├─┼─┼─┼─  ┼─┼─┼─┼─┼─┼─┼─┤ │    │ 17 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │    ├──┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 18 │+│+│  │  │+│+│+│+│+│+│+│+│+│+│+│ │ 药 ├──┼─┼─┤参│参├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 19 │+│+│  │ │+│+│+│+│+│+│+│+│+│+│±│ │ 理 ├──┼─┼─┤照│照├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 20 │+│±│  │  │+│+│+│+│+│+│+│+│+│+│+│ │ 毒 ├──┼─┼─┤相│相├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 21 │+│±│  │  │±│±│±│-│+│±│+│+│+│+│±│ │ 理 ├──┼─┼─┤应│应├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 22 │+│-│  │  │±│±│±│-│+│±│±│+│-│±│-│ │ 研 ├──┼─┼─┤指│指├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 23 │+│-│  │  │±│±│±│-│+│±│±│+│-│±│-│ │ 究 ├──┼─┼─┤导│导├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 24 │+│-│  │  │±│±│±│-│+│±│±│+│-│±│-│ │ 资 ├──┼─┼─┤原│原├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 25 │+│+│  │  │+│+│+│-│+│+│+│+│-│+│±│ │ 料 ├──┼─┼─┤则│则├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 26 │+│+│  │  │+│+│+│-│+│+│+│+│+│+│±│ │    ├──┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    │ 27 │-│-│  │  │-│+│-│-│-│-│-│-│-│-│-│ │    ├──┼─┼─┤  │  ├─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─     ┤││ 28 │ + │-│││-│-│-│-│ + │-│-│±│-│-│-│ └-the-the ┴-the-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┘ note: 1.+: refers to must submitted of information; 2.-: refers to without provides of information; 3. ±: according to declared varieties of specific situation requirements or not requirements. (C) Note 1 the declarations list. for registration classification articles 7, 10 and 15 from the comparison view, quality research and the preparation of its biological activities (when necessary, including pharmacokinetic characteristics) and marketed products are basically the same. Toxicological experiments on animals should be used only in General, long HIV test is only required to study on the drug for a month, general pharmacology studies can be combined in long term toxicity test, pharmacodynamic studies should be combined with the quality of research activity results to consider. When necessary, depending on the complexity of its molecular structure, pharmacy and marketed products that vary the possibility and extent, indications, such as specific circumstances, provide comparative studies with a marketed product information or other data.     If we can fully confirm their consistency with marketed products, may also apply for remission of the Pharmacology and toxicology studies. 2. for registered classification 2 of products, in design pharmacological HIV acting test Shi, should consider following situation: (1) Dang has Antigen combined information showed that, Primate for most related species Shi, not I joint of single clone antibody of test should consider used this class animal for main efficacy learn and drug generation Dynamics Research; (2) involved HIV acting and drug generation Dynamics test Shi, should select and people has same target Antigen of animal model for test, no right of animal model or no carry related Antigen of animal, And and people organization cross reaction sex test is obviously negative, is can from reported HIV acting research information; (3) on single clone antibody usually not requirements for animal repeat dose to drug of toxicity test and General of genetic toxicity test; (4) on intends to childbearing age crowd repeatedly or long-term using of products, should with appropriate of animal model for reproductive toxicity test; (5) immune toxicity research should study and non-target organization combined of potential toxicity reaction, as and people organization or cell of cross reaction sex or and non-target organization of combined situation,.     If you have the right model, cross reaction tests in addition to in vitro experiments should be carried out in animals, especially with cytolytic immune conjugates and antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies, also should be taken into account more than one animal of dose and repeat dose toxicity animal tests. 3. for registered products of category 8, identified studies using doses should be provided information and research data of the normal flora.     From doing certain projects should provide evidence and explanation. 4. for category 13 product registration should be based on the dosage form changing characteristics and possible related pharmaceutical and clinical aspects considered, selecting the appropriate pilot projects. Apply for certain items, full justification should be provided. Following situation can consider relief: (1) pharmacy meet requirements, and provides clinical medication security according to of situation Xia, can from reported pharmacological HIV acting research information; (2) for not change original formulations of clinical using method and dose of powder injection, and small injection Zhijian of mutual change, can only provides local tolerance sex research information; (3) for speed release, and sustained release, and control release preparations and the fat quality body, other special formulations, should combined biological products itself of nature, and security range, and body metabolism features, and clinical indications, and medication crowd,, Taking into account the effects of such agents on patient safety. From a security perspective, should be made available before the clinical pharmacokinetics of single-dose animal testing research data released to reflect the preparation of special features. Where there are substantial grounds for its security, would also be free from this study.     Instructions may apply in conjunction with the clinical data submitted to the State food and Drug Administration approval.     5. registration category 14 product, if there is sufficient test and/or literature based on confirmed with biological products of metabolism in the body before the change to the route features and security are similar, you can propose relief for some of the other items required for the product.     Five, descriptions of clinical trials 1. applications for new drugs should be tested in clinical trials. 2. clinical trials number of cases should be consistent with statistical requirements and minimum number requirements.     Minimum number of cases including the experimental group and the control group.     3. the minimum number required for clinical trials: phase I: 20-30, second stage: 100 cases of phase ⅲ: 300 cases.     4. classification 1~12 products should be registered according to the requirements for clinical trials of new drugs.     5. classification 13~15 products are generally only required for phase III clinical trials, clinical trial case of not less than 200 cases.     6. innovation for sustained and controlled release preparations should be carried out comparative study of human pharmacokinetics and clinical trials. Six, imported therapeutic biological products information and requirements (a) the declaration information items required to file information required according to the registration documents project.     Application is not listed on the domestic and international sales of products, submitted in accordance with registered category 1 material; others are submitted in accordance with registration category 7 data.     (B) the information requirements and instructions of project 2 proof documents 1. data item 2 supporting documents include the following information: (1) production certificate from the country or region drug authority allows products marketed and the drug manufacturers comply with good manufacturing practice certificates, notarial instrument and its Chinese translation.     Applications for products that are not allowed to go on sale at home and abroad, this documentation can be completed after clinical trials in China, together with the clinical trial report submitted, (2) registering representative offices of overseas pharmaceutical manufacturers in China, should provide the copy of the certificate of registration of resident representative offices of foreign enterprises.    Foreign pharmaceutical manufacturers commissioned in our agency agent, principal instruments, notary and its Chinese translation should be provided, as well as the Chinese copy of the business license of the Agency; (3) application of products or the use of formulation and technology franchise and its ownership, such as status description, as well as the patent does not constitute an infringement of the guarantee to others.     2. Description (1) production national or area drug management institutions issued of allows products listed sales and the the drug production enterprise meet drug production quality management specification of proved file, must by where country notary organ notary and the standing where country China makes consulates certification; (2) in a to completed preparations production by another a to completed packaging of, should provides preparations factory and packaging factory where national or area drug management institutions issued of the drug production enterprise meet drug production quality management specification of proved file; (3) is not listed in the production countries or regions approved sales of the products went on sale in other countries or regions of the documentation provided, and shall be approved by the State food and Drug Administration approval.     But the drug manufacturers comply with good manufacturing practices of the supporting documents required by the production of country or region drug authority issued.     (C) other information item 1. data item 29 shall be submitted with the products in the production country or region to apply for listing all clinical trial information to sales.     2. all information submitted shall be in Chinese and the original text and Chinese translation should be consistent with the original content.     3. bio-standard Chinese, must comply with the national drug standard format.     (D) requests for clinical trials in China 1. application is not listed on the domestic and foreign sales of biological products, should be in accordance with the provisions of category 1 application to register clinical trials.     2. applications which have been marketed in a foreign country, but not yet marketed Biologics in China, according to the registration category 7 of the regulations shall be applied for clinical trials.     3. the application is the national drug standard biological products should be in accordance with the classification 15 of the application to register clinical trials.     Second part of preventive Bioproducts, registration category 1. vaccine that is not listed in the domestic and foreign sales.     2.DNA vaccine.     3. marketed vaccines change new adjuvants, coupling new vaccine change carriers.     4. non-purified or whole-cell (bacteria, virus, etc) to purification of vaccine or component vaccines.     5. adopt without approval of the national virus vaccine (flu vaccine, vaccine of Leptospira).     6. sales in foreign markets but is not listed on the domestic sales of the vaccine.     7. preparation using the vaccine to marketed vaccines or vaccine.     8. and marketed different recombinant vaccines vaccine Antigen spectrum.     9. Replace expression system or other approved approved cell production of vaccines; prepared by using new technology and laboratory research is information on product safety and effectiveness improved vaccines.     10. change the inactivating agent (methods) or virus-free agent (methods) of the vaccine.     11. changing the route of administration of the vaccine.     12. domestic sales of vaccine formulations have been listed, but without changing the route of administration of the vaccine.     13. changing the immunization dose vaccine or immunization program.     14. expanded use of population (increasing age group) of the vaccine.     15. existing vaccines to the national drug standards.     Second, the declaration information item 1. summary information.     (1) new product name; (2) the certificate files; (3) the subject and the basis (4) drug samples, preparation of notes and references; (5) packaging and labelling design artwork.     2. research results summary and evaluation of data.     3. production of bacterial (viral) kinds of research materials. (1) source and characteristics: production with bacteria (HIV) species of source, and can for production of research information or proved file, and history (including separation, and identification and reduction HIV,), characteristics and type don't, and on cell matrix of adaptability, and infection sex drops degrees, and Antigen sex, and immune original sex, and HIV force (or toxicity) and the protection force test, research; (2) seed batch: production with bacteria (HIV) species original seed batch, and main generation seed batch, and work seed batch built library of about information, including various child batch of generation times, and preparation, and save,     On seed library for full verification, verification project including outside source factor detection, and identification test, and characteristics and type don't, and infection sex drops degrees, and Antigen sex, and immune original sex,; main generation seed batch bacteria HIV species also must for gene sequence determination; (3) passage stability: determine qualified generation times of research information, verification project see seed batch of verification project; (4) China drug biological products verification by on production with work seed batch of verification report.     4. study on cell substrate for production information. (1) source and characteristics: production with cell matrix of source, and can for production of research information or proved file, and history (including established cell Department, and identification and passage,), biology characteristics, and nuclear type analysis, and outside source factor check and the to tumor test, research; (2) cell library: production with cell matrix original cell library, and main generation cell library, and work cell library built library of about information, including the cell library of generation times, and preparation, and save, on cell library for full verification, verification project including biology characteristics, and Karyotype analysis and checking of exogenous factors, and (3) generation stability: determine qualified generation, test projects see the cell Bank of test items and increasing cancer experiment and (4) of pharmaceutical and biological products used for the production of working cell bank cell matrix accreditation report (5) sources of culture medium and added ingredients, quality standards, etc.     Bovine-derived materials are involved, according to the relevant provisions of the food and Drug Administration to provide the corresponding information.     5. study on the production technology information. (1) the bulk of vaccine production technology research: theoretical and experimental basis for determining and verifying information. Including optimization production process of main technology parameter, bacteria (or virus) of vaccination volume, and training conditions, and fermentation conditions, and out live or cracking process of conditions, and activity material of extraction and purification, and on human has potential toxicity material of removal, and coupled vaccine in the Antigen and carrier of activation, and coupled and purification process, and joint vaccine in the the activity ingredients of ratio and Antigen compatible sex research information,, provides feeding volume, and the intermediate and end products of harvest volume and quality, related of research information; (2) preparations of prescription and process,     And provide the basis for sources of materials and quality standards.     6. quality research materials: production process are determined, according to the trial's findings, determined by statistical analyses.     (1) joint vaccine, and coupled vaccine and more price vaccine in the the single group copies of quality standard and verification results; (2) verification method of research and validation information; (3) products Antigen sex, and immune original sex and animal test protective of analysis information; (4) production process in the joined on people has potential toxicity of material, should provides production process removal effect of validation information, developed products in the of limited standard and provides according to; (5) animal allergy test research information; (6) and similar products compared research information;     (7) the Antigen components, determination of concentration, molecular weight, purity, specific identification, as well as non-active ingredient content (or residue) testing (8) animal safety evaluation information (9) by DNA recombinant technology to produce vaccines, therapeutic biological products should refer requests.     7. the draft manufacturing and testing procedures, preparation of notes and related documents.     8. the manufacture of clinical trial application sample verification records.     9. preliminary stability tests.     10. production, research and testing laboratory animal certification.     11. clinical trials draft plans, research programmes and informed consent.     12. the pre-clinical work.     13. the relevant summaries of clinical trial information at home and abroad.     14. clinical trials summary report, including informed consent form template, approved by the Ethics Committee.     15. during clinical trials conducted on improving technology, perfect quality standards and other aspects of work and test data.     16. study on stability of determining vaccine storage conditions and expiry date information.     17. the approved manufacturing and modifying the content and modify the basis of the verification procedures.     18. three products in the manufacturing and testing records.     Third, the declared data item description 1. submitted applications for clinical trials data 1~11; completion of the clinical trials submitted information on items 1, 2, and 12~18, application for new drug certificate shall submit the information on items 1 and 2 and 12~17. 2. Summary of information: (1) the new product name: includes the common name, English name, Chinese pinyin, named basis. New developed of name, should description according to; (2) proved sex file including: ① applicants institutions legal registration proved file (license,), and drug production license and the change records page, and drug production quality management specification certification certificate copies; II application of biological products or using of prescription, and process, patent situation and ownership state of description, and on others of patent not constitute infringement of statement; ③ application new biological products production Shi should provides drug clinical research documents Copies and the clinical test medication of quality standard; II directly contact products of packaging material and container of drug packaging material and container registered card or imports packaging material and container registered card copies; (3) State problem purpose and according to: including both at home and abroad about the products research, and listed sales status and the related literature information or production, and vaccination using situation of reviewed; on the varieties of innovation sex, and feasibility, of analysis information; (4) drug manual sample, and drafting description and the reference literature,     Includes: drafted in accordance with the relevant provisions of the drug samples, instructions various elements of the drafting instructions, literature or the latest version of the specification of the original and the translation.     3. with regard to information of items 11, 12 clinical trial scheme and the clinical trial protocol, refer to the corresponding technical guidelines.     4. bacterial vaccines can be data items from 4.     5. item 6 (6), including: (1) comparative study of the vaccine, (2) comparing marketed vaccines and; (3) comparative study of the combined vaccine and the separate vaccines.     6. the purified vaccine should provide information, such as items 6 (7) information.    7. item 6 (8) Note: (1) the toxoid vaccine vaccine or toxoid as carrier shall provide information on toxicity experimental study on reverse; (2) according to vaccine use, vaccine characteristics, immune dose and immune processes, provide information concerning the toxicity studies.     8. in accordance with vaccine administered in vivo diagnostic use of biological products in accordance with the corresponding categories of biological products for prevention information. 四、申报资料项目表 ┌─────┬─────────────────────────────┐ │    资    │             注 册 分 类 及 资 料 项 目 要 求             │ │    料    │                                                          │ │    项    ├─┬─┬─┬─┬─┬─┬─┬─ ┬─┬─┬─┬─┬─┬─┬─┤ │    目    │1 │2 │3 │4 │5 │6 │7 │8 │9 │10│11│12│13│14│15│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    1     │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    2     │ +│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    3     │+│+│-│-│+│+│+│+│±│-│-│-│-│-│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    4     │+│+│-│-│+│+│+│+│± │-│-│-│-│-│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │   5(1)   │+│+│+│+│+│+│+│+│+│+│-│-│-│-│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │   5(2)   │+│+│+│+│+│+│+│+│+│+│+│+│-│-│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    6     │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    7     │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    8     │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    9     │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    10    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    11    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    12    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    13    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    14    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    15    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    16    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│+│ ├─────┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┼─┤ │    17    │+│+│+│+│+│+│+│+│+│+│+│+│+│+│±│ ├-The-the-the-the-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┼-the ┤ │ 18 │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ + │ └-the-the-the-the-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┴-the ┘ note: 1.+ refers to must submitted of information; 2.-refers to can without provides of information; 3. ± According to declared varieties of specific situation requirements or not requirements; five, and     Notes on clinical trials 1. clinical trial subjects (case) number, the statistical requirements and the minimum participant (case) number of minimum number of subjects, including the experimental group and the control group.     2. the minimum participants for clinical trials (case) number: phase I: 20~30, second stage: 300 cases of phase ⅲ: 500 cases.     3. classification of 1~9 vaccine and 14 according to the requirements for clinical trials of new drugs.     4. classification 10 vaccines after they provide proof of their inactivation or detoxification of safety and efficacy research information was changed, from clinical trials.     5. registration category 11 vaccines, clinical trials should be required of new drugs, but by the way to non-injection for injection way can avoid doing phase I clinical trials for the vaccine.     6. registration categories 12 and 15 vaccine phase III clinical trials only.     7. change in classification 13 immunization schedule vaccines, can avoid doing phase I clinical trials.     8. applied to prevention of infant products, shall, in accordance with its phase I clinical test first adults, children, and finally the principles of infant.     9. each phase of the clinical trial should be set upon completion of the schedule for the next phase of clinical trials. Six, imported bio-information and requirements for prevention (a) reporting project requirements information required according to the registration documents project.     Application is not listed on the domestic and foreign sales of vaccines, submitted in accordance with registered category 1 material; other types of vaccines according to the registration category 6 requirements to submit information. (B) information item 1. (2) the certificate requirements and description of the file 1. information item 1.     (2) supporting documents include the following information: (1) producing country or region drug authority issued by allowing vaccines marketed and the drug manufacturers comply with good manufacturing practice certificates, notarial instrument and its Chinese translation.     Application is not listed on the domestic and foreign sales of vaccines, these documents may be completed after clinical trials in China, together with the clinical trial report submitted, (2) registering representative offices of overseas pharmaceutical manufacturers in China, should provide the copy of the certificate of registration of resident representative offices of foreign enterprises.     Foreign pharmaceutical manufacturers commissioned in our agency agent, instrument appointing a notarized instrument, and its Chinese translation should be provided, as well as the Chinese copy of the business license of the Agency, and (3) application of biological products or use of formulation and technology franchise and its ownership, such as status description, as well as the patent does not constitute an infringement of the guarantee to others.     2. Description (1) production national or area drug management institutions issued of allows vaccine listed sales and the the drug production enterprise meet drug production quality management specification of proved file, must by where country notary organ notary and the standing where country China makes consulates certification; (2) in a to completed preparations production by another a to completed packaging of, should provides preparations factory and packaging factory where national or area drug management institutions issued of the drug production enterprise meet drug production quality management specification of proved file; (3) is not listed in the production countries or regions approved sales, went on sale in other countries or regions of the documentation provided, and shall be approved by the State food and Drug Administration approval.     The drug manufacturers comply with good manufacturing practice certificate shall be issued by the producing countries or region drug authority.     (C) other information item 1. item 13 shall be submitted to the information products in the production country or region to apply for listing all clinical trial information to sales.     2. all information submitted should be translated into Chinese and the original text, translation should be consistent with the original content.     3. the Chinese vaccine standards, must comply with the national drug standard format.     (D) requests for clinical trials in China 1. application is not listed on the domestic and international sales of the vaccine, should be in accordance with the provisions of category 1 application to register clinical trials.     2. applications which have been marketed in a foreign country, but not yet marketed vaccines in China should be according to the registration category 6 applications for clinical trials.       3. the application is the national drug standard vaccines, shall follow the classification 15 of the application to register clinical trials.     Annex IV: drug supplement registration and reporting requirements, registration matters (a) the national food and Drug Administration approval of the supplementary application: 1. hold new drug certificate of pharmaceutical production enterprise applies for the drug's approval number.     2. using the drug product.    3. added function of traditional Chinese medicine and chemical drugs, biological products, China has approved indications. 4. change the dose, or application scope.     5. change drug specifications.     6. change in drug prescription has requirements for medicinal use of accessories.     7. change affects the quality of drugs production.     8. revision of drug registration standards.     9. alternative or less toxicity in the national drug standard prescription medicines or endangered medicinal plants.     10. the change of packing material direct contacted with drugs or container.     11. application of drug package.     12. new drug technology transfer.     13. tentative standards into standards.     14. changing imported drug registration certificate of registration items such as drug name, drug name, registered address, medicines, package specifications, such as the validity period.     15. change of origin of imported drugs.     16. change of imported drugs packaging plants abroad.     17. the imported drugs packaging in China.     18. changing the import of production of APIs for use in pharmaceutical preparations.     (B) the supplementary application record of the State food and Drug Administration: 19. change name of domestic pharmaceutical production.     20. domestic drug manufacturers to change drug production sites.     21. According to the national drug standard or modified at the request of the State food and Drug Administration drug instructions.     22. additional security details in the drug.     23. According to the changing drug labels provided.     24. the change of the domestic production of medicines packaging specifications.     25. change the validity of the domestic production of medicines.     26. the API changes in domestic production of pharmaceutical preparations.     27. change drug looks, but does not change the standards of medicine.     28. change the imported drug registration agency. II, and declared information project and description 1. drug approved proved file and annex of copies: including and application matters about of this products various approved file, as drug registered documents, and added application documents, and commodity name approved file, and drug standard issued pieces, and drug standard amendment documents and unified renewal drug approved paper, of file, and drug certificate, and imports drug registered card, and medicine products registered card,.     Annex to the annex including the documents mentioned above, such as pharmaceutical standards, specifications, packaging, label artwork and other attachments. 2. the supporting documents: (1) the applicant is a manufacturer, shall provide the drug production licenses and change log page, business license, certified copy of the certificate of good manufacturing practices.     The applicant is not the manufacturer, its institutions legitimate copies of the registration certificates should be provided.     Permanent Representative offices of foreign pharmaceutical manufacturers to register and shall provide a copy of the certificate of registration of resident representative offices of foreign enterprises. Outside pharmaceutical manufacturers delegate China drug registered agent institutions agent declared of, should provides delegate instruments, and notary instruments and Chinese translations, and China drug registered agent institutions of license copies; (2) for different application matters, should according to "declared information project table" requirements respectively provides about proved file; (3) for imports drug, should submitted its production national or area drug management institutions issued of allows drug change of proved file, and notary instruments and Chinese translations.     Format should be consistent with traditional Chinese medicine, natural medicine, chemicals, bio-information requirements of relevant supporting documents in the project.     3. the revised drug sample containing detailed description thereof.     4. the revised pharmaceutical packaging label artwork, and attach a detailed description thereof.     5. pharmaceutical research information: according to the different requirements of registered matters, respectively provide some or all of Pharmacy research test data and the necessary documents at home and abroad, in the information submitted in accordance with Annex I ~ III declared information projects.     6. the Pharmacology and toxicology studies: according to the different requirements of registered matters, respectively to provide part or all of the Pharmacology and toxicology studies of test data and the necessary documents at home and abroad, in the information submitted in accordance with Annex I ~ III declared information projects. 7. clinical trials information: requirements for clinical trials, shall, in accordance with the corresponding declaration in the annex I ~ III information items required in clinical tests before and after submitting the required project information.     Clinical trials are not required, provides clinical trial related to the document.     8. drug samples. 三、申报资料项目表 ┌──────────────────┬─────────────────────────────┐ │                                    │                       申报资料项目                       │ │                                    ├──┬────────┬──┬                                    ──┬──┬──┬──┬──┤ │            注 册 事 项             │    │       2        │    │    │    │    │    │    │ │                                    │ 1  ├──┬──┬──┤ 3  │ 4  │ 5  │ 6  │ 7  │ 8  │ │                │    │ ① │ ② │ ③ │    │    │    │    │    │    │ ├─┬────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │1.持有新药证书的药品生产企业申请│ + │ + │ - │ - │ - │ + │ *1 │ - │ - │ - │ │  │该药品的批准文号 │    │    │    │    │    │    │    │    │    │    │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │2.使用药品商品名称              │ + │ + │ *2 │ + │ + │ + │ - │ - │ - │ - │ │  ├────────────────┼──┼──┼─ ─┼──┼──┼──┼──┼──┼──┼──┤ │  │3.增加中药的功能主治或者化学药品│ + │ + │ - │ + │ + │ + │ - │ #  │ #  │ - │ │  │、生物制品国内已有批准的适应症  │    │    │    │    │    │    │    │    │    │    │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼── ┼──┼──┤ │  │4.变更服用剂量或者适用人群范围  │ + │ + │ - │ + │ + │ + │ - │ #  │ #  │ - │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │5.变更药品规格                  │ + │ + │ - │ + │ + │ + │ + │ - │ *3 │ + │ │  ├── ──────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │6.变更药品处方中已有药用要求的辅│ + │ + │ - │ + │ *4 │ *4 │ + │ - │ - │ + │ │国│料                              │    │    │    │    │    │    │    │    │    │    │ │家├────── ──────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │食│7.改变影响药品质量的生产工艺    │ + │ + │ - │ + │ *4 │ *4 │ + │ #  │ #  │ + │ │品├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │药│8.修改药品注册标准              │ + │ + │ - │ + │     *4 │ *4 │ *5 │ - │ - │ - │ │品├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │监│9.替代或减去国家药品标准处方中的│ + │ + │ *6 │ + │ + │ + │ #  │ #  │ #  │ + │ │督│毒性药材或处于濒危状态的药材    │    │    │    │    │    │    │    │    │     │    │ │管├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │理│10.变更直接接触药品的包装材料或 │ + │ + │ - │ + │ *4 │ *4 │ *7 │ - │ - │ + │ │局│者容器                          │    │    │    │    │    │    │    │    │    │               │ │审├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │批│11.申请药品组合包装             │ + │ + │ - │ + │ + │ + │ - │ *8 │ *8 │ + │ │的├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │事│12.新药的技术转让 │ *9 │ + │*10 │ - │ + │ + │ *1 │ - │*11 │ + │ │项├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │13.药品试行标准转为正式标准     │*12 │ + │ - │ - │ *4 │ *4 │ #  │ - │ - │ + │ │  ├────────────────┼──┼──┼──┼──┼──┼─ ─┼──┼──┼──┼──┤ │ │ 14. change item imported drug registration registration of │││││││││││││, such as drug name, drug name, registration │ │ │-│ │ + + + + │ *4 │-│-│-│ + │││ address, the drugs period of validity 、包装规格等    │    │    │    │    │    │    │    │    │    │    │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │15.改变进口药品的产地           │ + │ + │ - │ + │ + │ + │ + │ - │ - │ + │ │  ├────────────────┼── ┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │16.改变进口药品的国外包装厂     │ + │ + │*13 │ + │ + │ + │*14 │ - │ - │ + │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │17.进口药品在中国国内分包装     │ + │ + │*15 │ - │ + │ + │*16 │ -    │ - │ + │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │18.改变进口药品制剂所用原料药的 │ + │ + │ - │ + │ - │ - │ + │ - │ - │ + │ │  │产地                            │    │    │    │    │    │    │    │    │ │    │ ┝━┿━━━━━━━━━━━━━━━━┿━━┿━━┿━━┿━━┿━━┿━━┿━━┿━━┿━━┿━━┥ │  │19.改变国内药品生产企业名称     │ + │ + │*17 │ - │ + │ + │ - │ - │ - │ - │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │20.国内药品生产企业内部改变药品 │ + │    + │*18 │ - │ *4 │ *4 │ *1 │ - │ - │ + │ │  │生产场地                        │    │    │    │    │    │    │    │    │    │    │ │国├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │家│21.根据国家药品标准或者国家食品 │    │ │    │    │    │    │    │    │    │    │ │食│药品监督管理局的要求修改药品说明│ + │ + │*19 │ - │ + │ + │ - │ - │ - │ - │ │品│书                              │    │    │    │    │    │    │    │    │    │    │ │药├───────────── ───┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │品│22.补充完善药品说明书的安全性内 │ + │ + │ - │ + │ + │ + │ - │*20 │*21 │ - │ │监│容                              │    │    │    │    │    │    │    │    │    │    │ │督├────────────────┼ ──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │管│23.按规定变更药品包装标签       │ + │ + │*22 │ + │ - │ + │ - │ - │ - │ - │ │理├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │局│24.变更国内生产药品的包装规格   │ + │ + │ - │ - │ + │ + │ *4 │ - │ *3 │ + │ │备├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │案│25.改变国内生产药品的有效期     │ + │ + │ - │ + │ + │ + │*23 │ - │ - │ - │ │的├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │事│26.改变国内生产药品制剂的原料药 │ + │ + │ - │ - │ - │ *4 │*24 │ - │ - │ + │ │项│产地                            │    │    │    │    │    │    │    │    │    │    │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │27.变更药品外观,但不改变药品标 │ + │ + │ - │ + │ + │ *4 │ + │ - │ - │ + │ │  │准的                            │    │    │    │    │    │    │    │    │    │    │ │  ├────────────────┼──┼──┼──┼──┼──┼──┼──┼──┼──┼──┤ │  │28.改变进口药品注册代理机构     │ +     │ + │*25 │ - │ - │ - │ - │ - │ - │ - │ └─┴────────────────┴──┴──┴──┴──┴──┴──┴──┴──┴──┴──┘ 注:*1.仅提供连续3个批号的样品检验报告书。     *2. provider query form.     *3. clinical reports or documentation provided.     *4. If any modification should be provided.     *5. only provide test data of quality research and literature, medicine draft standards and drafting instructions, inspection report of 3 consecutive batches of samples.     *6. with regard to documentation of toxic herbs, endangered medicinal, or relevant departments call for alternative, less files, certificates.     *7. only 3 consecutive batches of sample inspection report, drug stability study testing materials, packaging materials and containers in direct contact with drugs of choice and quality standards. *8. classification of registered in accordance with traditional Chinese medicine and chemical drugs, biological products in foreign markets but not yet listed in the domestic sales of compound preparation of corresponding information available upon request.     Pharmaceutical research section offers only drug stability study data, direct contact with the pharmaceuticals packaging material and container selection and quality standards, inspection report of 3 consecutive batches of samples.     *9. submit new drug certificate.     *10. technology transfer transfer contract signed between the parties concerned, the original production company abandoned production of original documents should be available.     *11. According to the State food and drug administration need to be requested.     *12. at the same time provided by the information of the original new drug application review by synthesis and pharmaceutical research and related reviewed.     *13. provide packaging plant where the national or regional regulatory authorities issued by the drug packaging enterprises in accordance with drug manufacturing practices evidence.     *14. only provide packaging technology, drug stability study of test data, direct contact with the pharmaceuticals packaging material and container selection and quality standards, inspection report of 3 consecutive batches of samples.     *15. import pharmaceutical packaging contracts (including authorization to use trademarks of imported drugs).     *16. provide packaging technology, direct contact with the pharmaceuticals only packaging material and container selection and quality standards.     *17. provide copies of documents about the Administration changed its name, changed its name and renamed the business license, before a pharmaceutical production license, and copy of the certificate of good manufacturing practices certification.     *18. provision of relevant regulatory agencies agree that pharmaceutical companies when evidence of the changed production site.     *19. new national drug standards or requirements for medicines by the State food and drug administration files.     *20. available toxicological test data or literature.     *21. available documentation.     *22. changing drug labels according to stipulations, provisions should be provided on the file content.     *23. only provide drug stability study test information and sample inspection report of 3 consecutive batches.     *24. provide only the approval documents of the API and its legitimate sources, preparation 1 batch inspection report.     *25. provide overseas pharmaceutical manufacturers commissioned new China drug registration agency Agency authorize documents, notarial instrument and its Chinese translation, copy of business license of the new China's drug agency, overseas pharmaceutical manufacturers to lift the original agency registered instruments, the notarial instrument and its Chinese translation.     "#": See "four, description and requirement of registration".     Four, description and requirement of registration 1. register 1, holds a new drug certificate of pharmaceutical production enterprise applies for the drug's approval number, refers to the new unit new drug certificate obtained does not have the new production conditions, and there is no transfer to other drug manufacturers, with appropriate production conditions, applications for production of the drug.     2. register 2, the drug trade names apply only to new chemicals, new biological products.    3. register 3, increasing indications of traditional Chinese medicine and chemical drugs, biological products have been internally the same indications for use, its pharmacological and toxicological studies and clinical trials should be carried out in accordance with the following: (1) indications of adding new features, extend the period or increase the dose of medication is required, it shall provide experimental data of main pharmacodynamics and acute toxicity test in literature, information or documentation, chronic toxicity data or literature, local administration shall provide the relevant test data.     By approved Hou should for clinical test, group cases number not less than 300 cases; (2) increased medicine new of function attending, medication cycle and taking dose are not variable who, should provides main efficacy learn test information and the literature information, and must for at least 100 on random control clinical test; (3) increased has has domestic with varieties using of function attending or indications who, must for at least 60 on random control clinical test, or for to using this indications of with varieties for control of biological equivalent sex test. 4. point 4, change dosage or application scope should be provided in support of the change of security studies or literature, clinical trials shall be conducted as necessary.     Diseases and syndromes in traditional Chinese medicine and natural drugs should be for main, 100 pairs of randomized clinical trials. 5. register 5, change medicines specifications shall comply with the following requirements: (1) the specifications should generally be applied for with the same listing specifications.     If not, shall comply with the principles of scientific, reasonable and necessary.     (2) the specification of the application should be determined according to the drug dosage and reasonable to no less than a single minimum or greater than the amount of single maximum.     (3) if at the same time changing the dosage or application shall be provided in accordance with note 4 requirements for registration information, when necessary to conduct clinical trials. 6. register 7, affect drug quality, production, production process changes should not result in changes of medicinal material base.     Medicinal substances in Chinese medicine is subject to change based on, should provide comparative tests such as pharmacy, Pharmacology and toxicology studies, and should be based on the characteristics of drug, clinical trials for different purposes, the number of cases of not less than 100.     7. register 9, substitute or subtract State drug toxicity in the standard prescription medicines or endangered medicinal herbs, is refers to the applicant's own application for substitute or subtract ingredients, not including provisions for reunification of the country as a substitute or subtract ingredients. (1) applications for use of approved alternative prescription preparations of traditional Chinese medicine herbs herbal substitutes.     Should provide new preparation technology of pharmaceutical research, pharmaceutical standard and stability of information can be reduced for pharmacological, toxicological and clinical trial information. (2) application has been replaced legal standards to include Chinese herbal medicine and alternative medicines on prescription in a secondary position, should provide new preparation technology of pharmaceutical research, pharmaceutical standard and stability of information can be reduced for pharmacological, toxicological and clinical trial information. Alternative medicine as toxic herbs, you should also investigate drug safety information provided, including toxicological test data, and clinical trials. If alternative medicines on prescription in a main position, pharmaceutical research in addition to the above information, the related preparation of clinical equivalence study should also, when necessary, comparison of pharmacodynamics and Toxicology tests are carried out.     Medicine alternative medicine for toxicity, pharmacodynamics and toxicology test should be carried out.     (3) applications for less toxic medicines, should provide a new preparation, drug standards and stability of pharmaceutical studies, pharmacological experiments, and clinical trials. (4) pharmaceutical, pharmacological, toxicological and clinical testing requirements are as follows: Pharmacy: ① production: drug alternatives or reduced drug production should be consistent with the original process. ② drug standard: shall establish specific identification and determination for alternative medicine. Unable to establish the specificity of identification and content determination, research materials should be provided.     ③ stability test: alternative medicines may affect the drug stability, stability testing should be carried out. Pharmacology and Toxicology: medicine replaced, should be carried out with the original drugs for major illnesses main pharmacodynamics and acute toxicity of comparative studies.     After subtracting toxic medicines, should be linked to the original primary comparative study on main pharmacodynamics of the illness.     Clinical trial: should target major diseases, 100 pairs of randomized controlled trials to evaluate the equivalence of the two. 8. point 11, drug combination packaging means two or more have an independent indication of the composition and dosage of medicines packaging.     It does not include the following situations: (1) has the same active ingredient composition of compound listed, (2) lack of mature treatment as the basis of the internationally recognized; (3) the route of Administration is not consistent with the drug, and (4) do not comply with the relevant requirements.     Packaging is not alone to drug approval, a drug combination that it not establish a monitoring period, trade names shall not be used.     Application of drug combination packaging shall meet the following requirements: (1) apply for production enterprises should be made of the good manufacturing practices certification, combined packaging of medicines is the production and drug approval numbers have been made.     (2) brochures, packaging labels shall be formulated according to the results of preclinical studies and clinical trials, rather than the simple addition of the drug, and in conformity with the relevant provisions of the administration of pharmaceutical directions and labels.     (3) packing material direct contacted with drugs should apply to all drugs.     (4) the marking should be consistent with the drug the shortest validity period the validity period.     (5) the storage conditions should be applied to all drugs.     (6) name of "X/Y/Z package", x, y, and z represent the generic names of the drugs. 9. register 13, drug trial standard to formal standards, according to the drug trial standard regularization procedures.     Its declared information project pharmacy research information part should provides following information (national another has provides of except): (1) application positive of drug standard and amendment description (containing and abroad drug standard compared table), should combined itself process features updated necessary of about material, check project; (2) for original drug registered documents in the approval views by work of situation and the description; (3) production total batch and the part products of full check data (General annual statistics many Yu continuous batch 10 batch results);     (4) standard pilot product quality stability and validity of two years.     10. point 19, changes in domestic drug manufacturers name refers to domestic pharmaceutical production approved changes to the pharmaceutical production license after the business name, apply for their registered drug manufacturers name accordingly changed.     11. point 20, domestic pharmaceutical production enterprises to change drug production sites, including in-situ alteration, addition, or new offsite. 12. point 21, is based on harmonization of national drug standards requirements and special requirements of the State food and drug administration, drug instructions modify certain items, such as adverse reactions, contraindications, precautions and other projects.     Unless there are special provisions or requirements, does not include the modified indication or indications, usage, quantity, specification and other projects. 13. point 22, complement security details in the drug, you can only increase the range of adverse reactions, contraindications, precautions, Pharmacology and toxicology, pharmacokinetic project to add new information.     Does not include the indication or indications, dosage and other projects to increase scope of use.     14. point 23, changing drug labels according to stipulations, refers in accordance with the management of drugs-related provisions, the national drug standards or approved drug content, make the changes on the drug's packaging labels. 15. point 24, changes its domestic production of medicines packaging specification should meet the following requirements: (1) pharmaceutical packaging specification should be economical and convenient.     Using a course of drugs, its packaging specification should generally be determined in accordance with the drug treatments.     (2) application of drug injection equipped with disposable syringe or infusion of packaging, packaging of drug injection with its dedicated solvent shall not otherwise named, equipped with syringes, infusion or solvents must be permitted to register, and sterilization of syringes, infusion of validity or validity of the solvent shall not be shorter than the validity of the drug.     16. point 26, API changes in domestic production of pharmaceutical preparations, refers to domestic drug manufacturers to change their production of APIs for use in pharmaceutical preparations production factory, the API must have the approval number or imported drug registration certificate, and provides access to the legitimacy of the API information. 17. registration matters 1, 5~10, 12, 15, 20, 3 batches should be drug registration drug testing.       Registration matters 26, should be carried out for 1 lot number and drug registration test of national drug.     Annex v: Re-registration of medicines information project, domestic production of drugs 1. supporting documentation: (1) drug approval documents and files of the food and drug administration approve the change, (2) copy of the pharmaceuticals production license (3) copy of business license and (4) of the good manufacturing practices of the certified copy of the certificate.     2. production within five years, sales, sampling summary note should be made of the nonconforming product situation.     3. within five years of clinical use and adverse drug reactions summary.     4. has following case one of of, should provides corresponding information or description: (1) drug approved proved file or again registered approved file in the requirements continues to completed work of, should provides work completed Hou of summary report, and attached corresponding information; (2) first application again registered drug need for IV period clinical test of, should provides IV period clinical test summary report; (3) first application again registered drug has drug monitoring period of, should provides monitoring situation report. 5. the provision of drug formulation and production, pharmaceutical standards.     Drug formulation and production, drug standards and previous registration has changed, you should indicate the specific content changes, and provide approval documents. 6. the sources of production of APIs for use in pharmaceutical preparations.     Changing raw material source, approval documents should be provided.     7. minimum sales unit of the existing packaging, labels and sample.    Second, imported drugs 1. supporting documentation: (1) the imported drugs registration certificate or the certificate of pharmaceutical product registration copies and the State food and Drug Administration approval for supplements apply for copies of documents; (2) drug production national or area drug management institutions issued of allows the drug listed sales and the the drug production enterprise meet drug production quality management specification of proved file, and notary instruments and Chinese translations; (3) drug production national or area drug management institutions allows drug for change of proved file, and notary instruments and Chinese translations; (4) by outside pharmaceutical manufacturers permanent China representative institutions handle registered Affairs of, should provides foreign enterprise permanent China representative institutions registration card copies;     (5) foreign pharmaceutical manufacturers commissioned in our agency agent, principal instruments, notary and its Chinese translation should be provided, as well as the Chinese copy of the business license of the Agency.     2. imports in China within five years, and sales reports, for unqualified shall give an explanation.     3. import sales five years clinical uses and summary reports of adverse reactions.     4. re-registration of applications for drugs for the first time, one of the following circumstances, it shall provide appropriate information or clarification: (1) need for phase IV clinical trials summary report of phase ⅳ clinical trial should be provided, (2) drug approval documents or registration required in the approval documents on our work, should provide a summary report, accompanied by appropriate information. 5. the provision of pharmaceutical formulation and production processes, standards and test methods.     Drug formulation and production, drug standards and testing methods and previous registration changes, it should be noted that specific content changes, and provide approval documents. 6. the sources of production of APIs for use in pharmaceutical preparations.     Changing raw material source, approval documents should be provided.     7. minimum sales unit sales in the Chinese market, packaging, labels and sample.  8. country or region drug authority approved the existing description and its Chinese translation of the original.