Drug Registration Procedures (Trial Implementation)

Original Language Title: 药品注册管理办法(试行)

Read the untranslated law here: https://www.global-regulation.com/law/china/161448/.html

Subscribe to a Global-Regulation Premium Membership Today!

Key Benefits:

Get a Day Pass for only USD$19.99.
(Released October 30, 2002 the State Drug Administration, 35th) contents chapter I General provisions chapter II chapter III of the application for registration of a drug preclinical drug research the fourth chapter of drug clinical research section I section II prior to the implementation of the basic requirements section III clinical study management at the request of the fifth chapter of new drug application, examination and approval section I section II basic requirements for clinical research of new approvals     Third section drug production of approval fourth section drug monitoring period of management sixth chapter has has national standards drug of declared and approval seventh chapter imports drug of declared and approval eighth chapter non-prescription drug of declared and approval Nineth chapter drug added application of declared and approval tenth chapter drug of again registered 11th chapter drug of technology transfer 12th chapter imports drug points packaging of declared and approval 13th chapter drug registered test of management 14th chapter management section of the standard basic requirements for registration of pharmaceuticals positive drug trial standards in section II, section III of drug standard substance management chapter 15th registration time limits stipulated the 16th chapter review Chapter 17th penalty 18th Chapter by-laws chapter I General provisions article to ensure safe, effective and quality control, standardize drug registration, in accordance with the People's Republic of China Law on drug management (     Hereinafter referred to as the drug management law), the People's Republic of China pharmaceutical administration law implementing regulations (hereinafter referred to as the pharmaceutical administration law implementing regulations), these measures are formulated.     Article People's Republic of China engaged in drug development and clinical research, apply for clinical research, drug production or importation of drugs, as well as associated registration examination, supervision and management, application of this approach.     Third drug registration, is in accordance with legal procedures to be marketed drug safety, effectiveness, quality control and carry out a systematic evaluation, and whether or not to consent to clinical drug research, production or import of medicines and drug approval process of decision, including the applications for drug approval document and its annex containing the content to be approved.     Fourth the State encourages research and development of new drugs, and to create new drugs and treatment of severe diseases for swift approval of new drugs.     Article fifth competent national drug registration and administration of the State food and drug administration, which is responsible for drug approval in clinical research, pharmaceutical production and imports.     The province, autonomous region, or municipality directly under the Administration authorized by the State Drug Administration, integrity of the drug registration documents, normative and check its authenticity. 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 in the territory should be the institution legally registered in China, 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 be familiar with the 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 a national drug application and import drug applications and supplemental applications.     According to new drug application, the applicant in the territory have been standard drugs to apply, apply for overseas applicants in accordance with imported drugs. Article eighth new drug applications, means no applications for registration of the drug went on sale in China.     Changed dosage form, changing the route of administration of drugs already on the market, in accordance with the new management.     Has a national drug application, refers to the production of the State food and Drug Administration has issued official standards of drug registration.     Application of imported drugs, is the overseas production of applications for registration of pharmaceutical sales in the Chinese market. Supplementary application, refers to new drug applications, has a national drug application or import drug applications approval, change, add to, or cancel the original matter or content of the application for registration.     Technology transfer, packaging of imported drugs, new drugs drugs tentative standards full member, supplements apply.     Nineth application of drug registration, the applicant shall, to the local drug administration of provinces, autonomous regions and municipalities directly under the proposed and to submit relevant data and drug samples which applied for registration of imported medicine, the applicant shall submit to the State food and drug administration.     Tenth article two a above units common as drug applicants of, should to which drug production enterprise location province, and autonomous regions, and municipalities drug supervision authority proposed application; application units are for drug production enterprise of, should to application preparations of drug production enterprise location province, and autonomous regions, and municipalities drug supervision authority proposed application; application units are not drug production enterprise of, should to samples trial site location province, and autonomous regions, and municipalities drug supervision authority proposed application.     11th applicant shall apply for registration of drug prescriptions, or use technology, provides Chinese patent and ownership status description and submit patent does not constitute an infringement of the guarantee to others, commitment may be responsible for the consequences of infringement.     Article 12th drug patent disputes arising after the approval of the application for registration, the parties should negotiate on their own, or in accordance with the provisions of the relevant laws, regulations, judicial or administrative authorities for patent settlement. 13th has obtained a Chinese patent medicines, other applicants in the 2 years before patent expiration can be applied for registration.     State Drug Administration be reviewed according to these measures, in conformity with the provisions and approved for production or imports after expiration of the patent. 14th article according to drug management method implementation Ordinance 35th article of provides, on get production or sales contains new chemical ingredients drug license of producers or sellers submitted of itself made and not disclosure of test data and other data, national drug supervision authority since approved the license of day up 6 years within, on other without has get license of applicants agreed, using its not disclosure data of application not approved.     But the other except for themselves access to data submitted by the applicant.     Other applicants at the time of application for drug registration, shall undertake all test data are self made and guarantee its authenticity. 15th delegate that accepts foreign pharmaceutical manufacturers in China for processing drugs, sold but not in use, processed by drug manufacturer located in the territory of province, autonomous region, or municipality directly under the administration of applications.     Comply with provisions of the provinces, autonomous regions and municipalities directly under the food and Drug Administration approval, and report to the State food and Drug Administration for record, but no approval number. 16th chapter preclinical drug research carried out for the application of drug registration drug preclinical studies, including drug synthesis, extraction method, physical and chemical properties and purity, formulation choice, formulation, manufacturing process, inspection methods, quality, stability, pharmacokinetics, pharmacology, toxicology, animal.     Original medicinal preparation also includes the origin, processing and preparation; biological products also include bacteria and viruses, cell lines, the biological starting materials such as quality standards, preservation conditions, genetic stability, and immunology research.     Article 17th 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 18th 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. 19th separate applications for pharmaceutical preparations used chemical raw materials and implement approval number management of Chinese herbal medicine and Chinese herbal medicine, must have an approval number, to the imported drugs registration certificate or the certificate of pharmaceutical product registration, the API must be obtained through legal means.     API 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. 20th 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. Article 21st drug registration documents in the 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 already registered foreign legal and notarized documents, after the approval by the State food and drug administration, can be used as application information submitted for registration of pharmaceuticals.     State Drug Administration the review of the need for on-site visits.     22nd State Drug Administration and the provincial, autonomous region, municipality directly under the food and drug administration required for the verification of research, may require the applicant or bear the test of the drug agency, in accordance with its reporting project, repeat test methods and data, and the costs of site investigation process; or Commission drug testing to repeat experiments or other drugs by research institutions. Article 23rd drug pre-clinical studies should refer to relevant technical guidelines issued by the State Drug Administration.     Applicants use other assessment methods and techniques tested, shall be submitted to prove that scientific information.     The fourth chapter clinical research of drugs ~23. section I basic requirements of article 24th drug clinical research including clinical trials and bioequivalence testing.     Clinical research must be approved by the State food and Drug Administration for approval, you must code for implementation of the quality management of drug clinical trials.    Section 25th for registration of new drugs, bioequivalence clinical trial or trials should be carried out. Applications for drug registration of an existing national standard, generally do not need to conduct clinical research.     Clinical research is needed, chemicals, bio-equivalence trials only; requires proprietary Chinese medicines using processes and standards to control the quality of drugs and biologics, clinical trials shall be conducted.     In the supplementary application, has marketed drugs with new indications or significant changes in production technology, clinical research is needed. Article 26th clinical trial is divided into stage ⅰ, ⅱ, ⅲ, ⅳ.     Application for new drug registration phase ⅰ, ⅱ, ⅲ clinical trials should be carried out, in some cases only for stage ⅱ and ⅲ, or phase III clinical trials. 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 provide a sufficient basis for registration applications approved.     Testing should generally be randomized blinded controlled trials with adequate sample size. Phase ⅳ clinical trial: study on the application of the drugs listed by the applicant after the independent stage.     Its purpose is to examine in the widespread use of the drug under the conditions of efficacy and adverse reactions; used in evaluation in the ordinary or special groups of relationship between benefits and risks; improvement the dose. 27th drug clinical research should be based on the number of test cases the purpose of clinical research, in conformity with the relevant statistical requirements clinical study and these rules, the minimum number required.     Special diseases, rare diseases and other conditions, and asked to reduce the number of cases of clinical research or clinical trials, must be approved by the State food and Drug Administration for review and approval. 28th in 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, may apply to the State food and Drug Administration for clinical research.     ~23. before the implementation of section II of article 29th clinical drug research at the request of approval, the applicant shall have the qualifications of clinical drug trials institutions, chose to take drug clinical trial Agency, agreed in charge of clinical research units, the main researcher and clinical research unit.     Article 30th applicants shall be selected and clinical study of responsibility and participate in clinical research unit signed contracts, provide a subject informed consent sample and clinical trial investigator's brochure, with reference to the relevant technical guidelines improve clinical research programme, and drew attention to the programme of institutional ethics Committee for clinical research clinical trials scientific review and ethical issues involved.     31st the applicant shall offer selected clinical research clinical research drug and controlled drugs (except phase IV clinical trials), and attach a sample inspection report bear the cost of clinical research needs. 32nd clinical studies with drugs, in accordance with good manufacturing practice conditions for workshop preparation.     Preparation process should strictly enforce the requirements of the good manufacturing practices.     State Drug Administration or authorize the provinces, autonomous regions and municipalities directly under the food and drug administration, the review of the need for on-site visits. 33rd applicant may according to the State food and Drug Administration approval of the drug standard clinical research drug on their own, or Commission of pharmaceutical and biological products or established by the State food and drug administration and drug control inspection, inspected the rear can be used in clinical research.     State Drug Administration to specify the drug testing drugs for use in clinical research and inspection.     Vaccine products, blood products, State drug administration requirements of other biological products and overseas production of clinical studies with drugs, drug testing must be designated by the State food and Drug Administration inspection, after passing can be used in clinical research.     The applicant bears full responsibility for the quality of the clinical research on drugs. Article 34th in clinical drug studies prior to the implementation of the applicant, should the identified clinical research programme and clinical research principal researcher responsible for unit names, lists of those participating in the research unit and the research and Ethics Committee approval, consent forms sample submitted to the State food and Drug Administration for record, and submitting clinical research units of provinces, autonomous regions and municipalities directly under the food and drug administration.     ~23. section III clinical management article 35th of the study drug in the clinical research process, the applicant shall specify who has some expertise in monitoring the implementation of the quality management standard of clinical drug trial.     Article 36th applicants found that clinical researchers in violation of the relevant provisions or in accordance with clinical research programme implementation, should urge their correction in serious cases, may require the suspension of clinical research, or termination of the clinical studies and reports to the national drug authority and the relevant provinces, autonomous regions and municipalities directly under the food and drug administration.     37th after the applicant has completed each phase of clinical trial shall be made to the State Drug Administration and the relevant province, autonomous region, municipality directly under the food and drug administration and the clinical study reports and statistical analysis.     Clinical research for more than 1 year, the applicant shall, from the date of approval each year to the State Drug Administration and the relevant province, autonomous region, municipality directly under the food and drug administration and the clinical study progress report. Article 38th clinical drug studies was approved shall, within 2 years after implementation.     Overdue implementation of the original document itself repealed; clinical research remains to be done, shall apply.     39th participating in clinical research units and personnel should be familiar with the drugs for use in clinical trials, function, efficacy and safety; understand the responsibilities and obligations of clinical researchers obtained informed consent signed by the subject voluntarily; record timely, accurate, and truly do clinical research.     40th units and personnel to participate in clinical research, drug clinical trial quality management to the applicant under the code or require changes to experimental data and conclusions, should be to the local provinces, autonomous regions, municipalities directly under the food and drug administration and the State food and Drug Administration report.     41st article clinical research unit and clinical researchers, have an obligation to take the necessary measures to ensure the safety of subjects.     Clinical researchers should pay close attention to clinical study on incidence of adverse drug events, subjects taking appropriate measures in a timely manner, and for the record.     Of serious adverse events in clinical studies, researchers should be reported within 24 hours of the relevant province, autonomous region, municipality directly under the food and drug administration and the State Drug Administration and the applicant, and shall promptly report to the Ethics Committee.     42nd approved clinical research, State Drug Administration and the provincial, autonomous region, municipality directly under the food and drug administration shall conduct regular site visits or data or inspection.     43rd article clinical research during occurred following case one of of, national drug supervision authority can requirements applicants modified clinical research programme, and suspended or terminated clinical research: (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 research progress report of; (five) has approved of clinical research 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; (VIII) clinical study in deception; (I) in violation of the code for quality management of drug clinical trials. 44th state food and Drug Administration to revise clinical programmes, the decision to order the suspension or termination of the clinical studies, clinical research unit or the applicant shall perform.     Object, you can comment in the 10th and state the reason in writing.     Article 45th in clinical studies a broader, unexpected adverse reactions or serious adverse events, or there is evidence that clinical studies using drugs when there are serious quality problems, the State Drug Administration or province, autonomous region, or municipality directly under the administration of emergency control measures can be taken, order the suspension or termination of the clinical studies, the applicant must immediately stop clinical studies with clinical research units. Article 46th clinical research clinical research on drug use by responsible. Researchers must ensure that all drugs are used only for the subjects of clinical research, its dosage and usage should be consistent with the study programme. Study on combinations of drugs should not be referred to any participants in the non-clinical studies.     Clinical study of drugs may not be sold.     47th article outside applicants in China for international more Center drug clinical research of, should according to this approach to national drug supervision authority proposed application, and meet following provides: (a) clinical research with drug should is has in outside registered of drug or has into II period or III period clinical test of drug; national 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 research application; (Ii) national drug supervision authority in approved for international more Center drug clinical research of while, can according to need, requirements applicants in China first for ⅰ period clinical test; (three) in China for international more Center drug clinical research 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 drug supervision authority; (four) clinical research end Hou,    The applicant shall complete the clinical studies submitted to the State food and drug administration; (E) International multicenter clinical study data, used for drug registration in China, must be consistent with the drug management law, the drug administration law implementing regulations and provisions relating to clinical studies in these measures, all applicants must submit a multi-center clinical research study. Fifth chapter application, examination and approval of new drugs ~23.48th section basic requirements apply to new drug registration information submitted should be complete, standard, data must be true and reliable 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.     49th article national drug supervision authority on following drug application can implemented fast approval: (a) not in domestic listed sales of from plant, and animal, and mineral, medicinal material made of preparations and from medicine, and natural drug in the extraction of effective ingredients and preparations; (ii) not in both at home and abroad allowed listed of chemical raw materials drug and preparations, and biological products; (three) anti-AIDS virus and the for diagnosis, and prevention AIDS of drug, treatment malignant tumors, and rare disease, of drug;     (D) drugs to treat, there is no effective treatment for the disease. 50th of provinces, autonomous regions, municipalities directly under the food and Drug Administration has received the approaches listed in the 49th after the application for registration of new drugs, whether or not the application should be eligible for fast-track review and comment.     In accepting, the State food and Drug Administration to determine whether the new drug application for swift approval. 51st multiple unit jointly developed new drugs can be one of these units to apply 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 49th (a), (b) provision of drugs, new drug application approval by only one unit in each species, varieties of different specifications do not score produced by the different units. During the 52nd in the approval of new medicines, new technical requirements due to changes in the same varieties in overseas listing, and upheld the technical requirements unchanged.     ~23. section II clinical study approvals of new 53rd applicant upon completion of the preclinical studies, fill in the application form for registration, to the local provinces, autonomous regions, municipalities directly under the food and drug administration and drug samples to submit relevant information. 54th provincial, autonomous region, or municipality directly under the administration of declarations should be reviewed, organization development and conditions of site visits, taking samples for inspection, and drug testing to determine the registration test notification.     Completion of this work will review comments, the inspection reports and information submitted to the State food and drug administration, and notify the applicant accordingly.     55th received notification of registration test of drug control on the extraction of the samples tested, reviews on the declared drug standards, and within the time limits specified in the inspection report and review opinions submitted to the State food and drug administration, with a copy to inform their test of provinces, autonomous regions, municipalities directly under the food and drug administration and the applicant.     56th State drug administration of provinces, autonomous regions, municipalities directly under the food and drug administration review submitted applications for clinical research of new materials, to meet the requirements of, admissibility and issued a notice of acceptance and, if necessary, may require the applicant to provide drug samples.     57th State drug administration new drug application, the Organization of pharmaceutical, medical and other technical staff, to conduct technical reviews of new drugs, in the form of the drug clinical study documents and decide whether to approve its clinical research. Article 58th drug control considered undeclared drug standards control quality, the applicant may withdraw the new drug applications.     Is not withdrawn, the State food and Drug Administration approved its drug standards are beyond the control of quality, be returned.     59th test does not match the sample declaration of drug standards, after verification of the State drug administration new drug application for refund.     Section 60th new drug application, the applicant again discussed, in line with the eligibility criteria, you can resubmit the request, and in accordance with the original application procedures. 61st State Drug Administration during the review of applications for drug registration, in addition to innovative pharmaceutical ingredients or new discoveries relating to drug safety to no additional new technical information. New technical information must be added, the applicant shall withdraw his application for registration, in accordance with the original program again to declare.     ~23. section III production of new drug approval 62nd complete clinical drug studies, applicants to the local drug administration of provinces, autonomous regions and municipalities directly under the submitted clinical studies 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.     63rd a province, autonomous region, or municipality directly under the administration of declarations should be reviewed; conditions for the Organization of production and on-site visits; extraction of 3 consecutive batch samples, drug testing to determine the registration examination notice will be reviewed within a specified time frame views, reports, and information submitted to the State food and drug administration, and notify the applicant accordingly.     Section 64th for 3 batches of samples required of new drugs, should 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.     65th received notification of registration test of drug control on the extraction of the samples tested, and within the time limits specified in the inspection reports submitted to the State food and drug administration, with a copy to inform their test of provinces, autonomous regions, municipalities directly under the food and drug administration and the applicant.     66th State drug administration of provinces, autonomous regions, municipalities directly under the food and drug administration review of the information submitted, to meet the requirements of, admissibility and issued a notice of acceptance. 67th information reported by State food and Drug Administration to conduct a comprehensive review, in the form of the drug registration documents, and decide whether to ratify it.     In conformity with the provisions and new drug certificate issued; the drug manufacturing license and the conditions of drug production and drug approval numbers.     68th State food and Drug Administration approval of new drug applications at the same time, release the drug registration standards and specifications. Drug description according to the applicant the information declared by the State Drug Administration approval.     Drug manufacturers should be responsible for medicines correctness and accuracy, and should track post-marketing drug safety and effectiveness and, if necessary, shall promptly amend the drug application.     Medicines must be printed in accordance with the provisions of the State Drug Administration. 69th to application of new drugs in the production of 3 samples, in a pharmaceutical production permit and the certificate of good manufacturing practice certification workshop, established by the State food and Drug Administration for drug testing by qualified and obtained an approval number, during the period of the drug went on sale.     ~23. the fourth section management article 70th national monitoring of new drugs and drug administration according to the requirements of the protection of public health, 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, State Drug Administration not to approve other production and imports. 71st new monitoring period calculated from the date of approval of the new drug production, not more than 5 years.     For different drugs, according to safety research information, both inside and outside of their existing situation, determine different monitoring periods. 72nd after a period of drug detection, the State Drug Administration is no longer accepting applicants with other varieties of new drug applications.     The provinces, autonomous regions, municipalities directly under the food and Drug Administration has received applications should be returned to the applicant.     73rd monitored period of new drugs, drug manufacturers should always study, production, quality, stability, efficacy and adverse reactions, and so on, every year to the local provinces, autonomous regions and municipalities directly under the food and Drug Administration report.     Related to drug production, distribution, use or testing, Inspection Unit finding new drugs have serious quality problems, serious or unexpected adverse reactions must be reported to the provincial, autonomous region, or municipality directly under the administration.     74th of provinces, autonomous regions, municipalities directly under the food and Drug Administration for new drugs have serious quality problems, serious or unexpected adverse reactions, shall immediately conduct investigations and reports the State food and drug administration.     75th manufacturer is not required to perform monitoring responsibilities of new drugs, drug administration of provinces, autonomous regions and municipalities shall be ordered to correct it.     76th set monitoring period of 2 years from the date of approval of new drugs did not produce, State food and Drug Administration can approve other drug manufacturers in the production of the new drug application, and continued monitoring.     77th new drug detection periods, State food and Drug Administration has approved another applicant for drug clinical study, the application can continue with the drug registration and approval procedures to handle; comply with provisions of the State food and Drug Administration approved for production or import, and domestic drug manufacturers to produce the new drug be monitored.     78th when new drugs enter the monitoring period, the State Drug Administration has accepted but has not yet been approved by other varieties of drug clinical research applications, should be returned to the applicant; the monitoring of new drugs expires, applicants may submit applications for registration of a standard drug. 79th First approval of an application for registration of imported medicine, clinical research has approved a domestic applicant, the application can follow the drug registration and approval process to proceed; compliance, State food and Drug Administration approved 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 research applications should be returned to the applicant applicants may submit applications for registration of a standard drug. The sixth chapter has a national drug report and 80th in production has already a standard drug, applicant should possess the drug manufacturing license, certification of good manufacturing practices certificate of drug manufacturers.     The medicines and the drug manufacturing license applied for and the good manufacturing practices set out in the certificate of the production scope.     81st article new opened drug production enterprise, and drug production enterprise new drug production workshop or added production formulations, not made drug production quality management specification certification certificate of, must in drug management method implementation Ordinance sixth article provides of time within made drug production quality management specification certification certificate; late not made of, its drug approved paper, itself abolition, and by national drug supervision authority be cancellation.     82nd applicants in accordance with the relevant technical requirements to complete development work, fill in the application form for registration, to the local provinces, autonomous regions, municipalities directly under the food and Drug Administration to submit relevant data and drug samples.     83rd article province, and autonomous regions, and municipalities drug supervision authority on declared information for form review, meet requirements of be accepted, to accepted notification single; organization on production situation and conditions for site study, extraction continuous 3 a production batch of samples, notification determine of drug test by for samples test; in provides of time within will review views and the declared information submitted national drug supervision authority, and notification applicants.     84th received the registration test laboratories notified by the extraction of the samples tested, and within the specified time frame will test report books, State Drug Administration, with a copy to inform their test provinces, autonomous regions and municipalities directly under the food and drug administration and the applicant.     85th information reported by State food and Drug Administration to conduct a comprehensive review, the need for clinical research, clinical research documents will be issued.     The applicant after the completion of clinical studies, clinical studies shall be submitted to the State food and drug administration. 86th State Drug Administration in the form of the drug registration documents, and decide whether to approve the production.     Compliance, drug approval number.     87th State Drug Administration and the provincial, autonomous region, municipality directly under the food and Drug Administration does not receive according to tentative standards of existing national standards of drug registration applications.     88th article needs further evaluation of drug efficacy and safety of existing national standards of drug registration, can be suspended and the State Drug Administration approval.     89th applications for drug approval, the production of 3 samples, in a pharmaceutical production permit and the certificate of good manufacturing practice certification workshop, established by the State food and Drug Administration for drug testing by qualified and obtained an approval number, during the period of the drug went on sale.     The seventh chapter of imported drugs, and approving applications for the 90th article import drugs, 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 by the State food and Drug Administration confirmed the drug safe and effective clinical needs and 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.     91st applying for registration of imported medicine, applicants should fill in the application form for registration, submit the relevant materials and samples, provide relevant supporting documents, to apply to the State food and drug administration.     92nd State food and Drug Administration to review the information, and meets the requirements of admissibility and issued a notice of acceptance and notification of pharmaceutical and biological products of the samples submitted by the applicant by the registration test of national drug organization.     State drug administration according to needs, to inspect the conditions for development and production, and samples.     93rd of pharmaceutical and biological products after completing the import registration test of national drug, should review drug standards, inspection report and review opinions submitted to the State food and drug administration.     94th State drug administration organizations to submit information to conduct a comprehensive review in drug clinical research clinical research documents in the form of a decision on whether to approve it.     95th clinical research upon approval, the applicant shall, according to the fourth chapter and the requirements for these measures.     Clinical study after the applicant shall comply with the requirements to submit clinical data, samples and other information on changes and additions, and detail the basis and reasons for providing relevant documents. 96th State drug administration organization submitted information on clinical studies for a full review, 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, pharmaceutical product registration certificate will be issued. Section 97th 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 yet obtained approval of the State Drug Administration, you should submit the relevant production processes, quality index and test method of research data.     98th State food and Drug Administration approval of imported drugs at the same time, publish approved standards of imported drugs registration and instructions.     Eighth chapter application, examination and approval of non-prescription drugs 99th articles 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.     100th article application registered of drug belongs to following case of, can while application for non-prescription drug: (a) has has national drug standard of non-prescription drug of production or imports; (ii) by national drug supervision authority determine of non-prescription drug change formulations, but not change indications, and to drug dose and to drug way of drug; (three) using national drug supervision authority determine of non-prescription drug activity ingredients composition new of compound preparations.     101th line with applications for registration of non-prescription drugs-related regulations of the State, State food and Drug Administration approved for production or import at the same time, the drugs identified as non-prescription drugs.     Not as a non-prescription drug medicines seeking registration, after extensive clinical application, before their applications can be converted to non-prescription drugs.     102th production or import of national drug standards is a non-prescription drug, according to the sixth chapter of this approach, the seventh chapter of the regulations.     103th over-the-counter change forms, but without changing the route of administration, and its formulation meets the requirements of non-prescription drugs, generally without the need for clinical trials, oral solid preparation bioequivalence tests should be carried out.     104th uses determined by the State Drug Administration nonprescription drugs active ingredients to form a new compound, should clarify its prescription basis, clinical trials shall be conducted as necessary. 105th specification language of non-prescription drugs should be scientific, understandable, easy for consumers to judge for themselves, choosing and using the drug, and must be approved by the State food and drug administration.     Packages of nonprescription drugs must be prescribed by the State proprietary non-prescription drugs identification.     106th by the State food and Drug Administration approved the over-the-counter drugs, found unsuitable to continue as in the use of non-prescription drugs, State Drug Administration can be converted to prescription drugs.     Nineth drugs supplement report and approval of 107th drug approval document and its accompanying pharmaceutical standards, pharmaceutical items contained in the manuals, labels, as well as changes to the production process influencing the quality of medicines, the applicant shall submit a supplementary application.     108th supplementary application by the applicant, should be the holder of a drug approval documents or registration applicants. 109th applicant should fill out the drug of the supplementary application form to the local provinces, autonomous regions, municipalities directly under the food and Drug Administration to submit relevant information and instructions. Relates to drug changes of ownership, should provide valid identification documents.     Provinces, autonomous regions, municipalities directly under the food and Drug Administration to review the information, meet the requirements of admissibility and issued a notice of acceptance. The supplementary application of the 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 information, meet the requirements of admissibility and issued a notice of acceptance.     110th increased drug indications or indications, modify applications for drug registration standards, changing accessories, such as supplementary of the province, autonomous region, or municipality directly under the administration of the audit opinion, submitted to the State food and Drug Administration approval, and notify the applicant accordingly.     Changing the packaging specifications, change of corporate name, according to the State food and Drug Administration's requirements for brochures and other supplementary application by provinces, autonomous regions and municipalities directly under the food and Drug Administration approval and submitted to the State food and Drug Administration for record, and notify the applicant accordingly.     111th are received by the State Drug Administration filing no objection within the 20th, provinces, autonomous regions, municipalities directly under the food and Drug Administration can notify the applicant to perform the supplementary application. 112th of imported drugs to add to the application, by the State food and Drug Administration for approval.     Is filing for approval of supplementary application of imported drugs, within 30th of the State Drug Administration accepted without objection, the applicant can perform the supplementary application. 113th Certificate request approval of new drugs, and altering the drug production address supplement, provinces, autonomous regions, municipalities directly under the food and Drug Administration should be organized on the trial scene investigation, taking samples for inspection, notified drug testing to determine the samples tested.     Modify the supplementary application of drug registration standards, standard drug inspection Office shall if necessary review. 114th State Drug Administration on drug review supplement, in the form of supplementary application documents in the drug, deciding whether to agree to.     Need new drug approval documents, the original approval documents be written off; need additional drug approval documents, the original approval certificate shall remain valid.     115th 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 116th re-registration of pharmaceuticals, refers to the drug-approval certificate file is valid after the expiration of production and importing the drug approval process is implemented. 117th drug approval issued by the State food and drug administration, 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.     118th applications for re-registration of pharmaceuticals made by drug manufacturers, drug approval to provincial, autonomous region, municipality directly under the food and Drug Administration proposed, fill in the application form for the re-registration of pharmaceuticals in accordance with regulations, and provide relevant information.     Import drug re-registration application is filed by the applicant to the State food and drug administration.     119th of provinces, autonomous regions, municipalities directly under the food and Drug Administration commissioned by the State food and drug administration, in 50 days to complete the review of applications for re-registration of pharmaceuticals, and submitted to the State food and Drug Administration for record.     120th State Drug Administration in 50 days after receiving the filing does not give notice of no longer registered, by provinces, autonomous regions and municipalities directly under the food and Drug Administration be registered again. 121th State Drug Administration import drug re-registration of the application, shall be completed within 100 days for review.     Eligible be registered again. 122th article has following case one of of drug, not again registered: (a) not in provides time within proposed again registered application of; (ii) not completed national 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 drug supervision authority again evaluation belongs to eliminated varieties of; (six) according to drug management method of provides belongs to revoked drug approved proved file of; (seven     ) Does not have the production conditions of the drug administration law; (VIII) does not carry out the monitoring responsibilities, and (IX) other do not comply with the relevant requirements.     123th article does not meet the requirements of re-registration of pharmaceuticals, issued by the State food and drug administration no longer registering notifications and cancellation of its drug approval number, the imported drugs registration certificate or the certificate of pharmaceutical product registration.     11th chapter technology transfer 124th new drug technology transfer refers to the holder of the certificate of new drugs, new drug production technology to drug manufacturers, and manufactured by the drug manufacturers to apply for the new behavior. 125th new drug technology transfer should be new drug certificate holders.     Drug approval number has been achieved, when applying for a new drug technology transfer, it shall submit a cancellation application for drug approval number. 126th new drug technology transfer should be a one-time transfer to a manufacturer. For special reasons the drug manufacturers cannot produce, a new drug certificate holder can take the original assignee to abandon production of the contracts and other supporting documents of the drug, new drug technology transfer again.     State Drug Administration shall write off the original licensee of the varieties of drug approval number.     Accept new drug technology transfer the technology enterprises shall not be transferred again. 127th accepts new drug technology transfer drug manufacturers must obtain the drug manufacturing license and certification of good manufacturing practices.     Transfer of new drugs should be the transferee of the pharmaceuticals production license and the good manufacturing practices set out in the certificate of the production scope.     128th new drug certificate holders to transfer drug production technologies, the transfer contract should be linked to the transferee, and the transfer of technology and information to the transferee, guide the transferee produced 3 consecutive samples of acceptable quality.     129th multiple unit jointly developed new drugs, new drug technology transfer, new drug certificate should be jointly sponsored by the undersigned, and sign the assignment contract.     130th new drug technology transfer should be held by a new drug certificate jointly with the transferee the transferee is located province, autonomous region, or municipality directly under the administration of applications, filling out the drug supplemental application form, and submit the relevant materials and attached to the contract of assignment.     131th a province, autonomous region, or municipality directly under the FDA acceptance of new drug application for technology transfer, the transferee should be development of field samples, production equipment, production and inspection records for inspection and sampling, as well as inform the testing Institute for drug control.     Article 132th drug testing drug testing tasks, shall, within the prescribed time limit on completion of the survey, a survey report, submitted to inform their province, autonomous region, or municipality directly under the administration of the test.     133th of provinces, autonomous regions, municipalities directly under the food and Drug Administration received the inspection report and related information for review and comment, and submitted to the State food and drug administration, and will inform the applicant review. 134th State food and Drug Administration to new supplementary application for transfer of technology to conduct a comprehensive review.     Need for clinical research, clinical research documents will be issued.     The applicant shall complete the clinical studies, clinical research data submitted to the State food and drug administration. 135th State Drug Administration in the form of supplementary application documents in the drug, deciding whether to approve the production.     Compliance, drug approval number; for drug approval number of the transfer has been made, and cancellation.     136th monitored period of drug, new drug technology transfer should not be conducted.     12th chapter import drug packaging Declaration and approval article 137th imported pharmaceutical packaging, refers to the drug has completed final preparations outside process, within the packing to small packaging, or completed within the packaging of pharmaceutical packaging and placed brochures, stickers, and so on.     138th article application for 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, term General not over 5 years.     139th overseas pharmaceutical manufacturers should be signed with the pharmaceutical production enterprises in the territory imported drug repackaging contract, fill out the drug of the supplementary application form.     140th accept packaging manufacturer, must be in possession of the drug production licenses, and obtain certification of good manufacturing practices; packaging of medicines and the consignee of the pharmaceuticals production license and the good manufacturing practices set out in the certificate of the production scope. Section 141th for pharmaceutical packaging, which shall be entrusted with the direction where province, autonomous region, or municipality directly under the administration of applications submitted by applicant to fill out the drug supplemental application form, and submit the relevant materials and samples as well as contract and so on.     The provinces, autonomous regions, municipalities directly under the supervision authority shall, within the prescribed time limit to complete the examination and submitted to the State food and drug administration. 142th State Drug Administration on the review of the information submitted, in the form of supplementary application documents in the drug, deciding whether to agree to the packaging.     Meet the required approval, drug approval number.     Section 143th for pharmaceutical packaging, the drugs should be in the imported drug registration certificate or pharmaceutical product registration certificate before the expiry of 1 year earlier.     144th repackaging of medicines imported drug registration criteria should be performed.     145th packaging pharmaceutical packaging, labels and must comply with the relevant provisions of the State food and drug administration, while Mark's drug-packaging the approval number and import drugs or pharmaceutical product registration card, registration number. 146th overseas packaging preparation of import inspection in accordance with the relevant provisions of the State food and drug administration. Packaging imported product testing and inspection after the implementation of the same standard.     Repackaging the first 3 batches of products shall be designated by the national drug administration and testing by qualified before the sale.     147th medicines overseas pharmaceutical manufacturers should be responsible for packaging pharmaceutical quality, quality problems, the State Drug Administration can undo 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.     148th delegate that accepts foreign pharmaceutical manufacturers, providing preparation for pharmaceutical packaging and packaging materials in the territory, but does not use sold in, wrapped by drug manufacturer located in the territory of province, autonomous region, or municipality directly under the administration of applications, approval for packaging, and to the State food and Drug Administration for the record, but no approval number. The 13th chapter of the registration test of national drug administration article 149th 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 of targets can be set, scientific, control the quality of drugs and other laboratory tests and audits. 150th registration test of national drug by provinces, autonomous regions and municipalities directly under the drug control commitments.     Register inspection of imported drugs of pharmaceutical and biological products examination organization.     Tests of 151th following drug registration from pharmaceutical and biological products or designated by the State food and drug administration and drug control commitments: (a) this article 49th (I), (ii) drugs, (ii) biological products, (iii) other drugs as prescribed by the State Drug Administration.     152th in accordance with the provisions of article 49th drugs drug inspection Office shall give priority to testing and drug standards review.     153th engaged in the registration test of national drug Institute for drug control, should be in accordance with 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. 154th applicant drug testing 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.     The sample size should be 3 times the quantity of times, should also include appropriate verification record of batch manufacture of biological products.     155th 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 indicators, to ensure the quality of medicines can be controlled.     156th standard for review of new drugs, drug testing except for sample surveys, should also be based on studies of the drug data, drug standards and national requirements for similar products at home and abroad, of the drugs and drug standards, inspection items and methods, 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 applicants submit the complaint together with the State Drug Administration, with a copy to the applicant and give notice of registration test of national drug of provinces, autonomous regions, municipalities directly under the food and drug administration.     157th new drug standards, the applicant may not authorize drug testing advice the drug standard research work carried out by; the drug inspection offices shall not accept such a Commission.     14th chapter management of drug registration standards ~23. section 158th State drug standard basic requirements, 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 approval of the State Drug Administration to the applicant certain pharmaceutical standards, produce the drug manufacturer must implement the standard.     159th drug registration standards project and its set of test methods, shall comply with the national drug supervision Administration issued technical guidelines and the relevant requirements of the principles and the rules for drafting national drug standards. 160th applicant should be quality of raw material and production process is stable and the premise, selecting representative samples of standard research. ~23. section II drug trial standard regularization 161th new drugs after they have been approved for production, its pharmaceutical standards for pilot standard trial period for 2 years.     After a drug is approved, needs further investigation, production and product quality stability, drug standards may also be approved for experimental standards.     162th production pilot standard medicines, pharmaceutical producing enterprises shall, before the expiration of the trial period of 3 months to the local provincial, autonomous region, or municipality directly under the Administration 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.     163th of provinces, autonomous regions, municipalities directly under the food and Drug Administration should be completed in the 10th after receiving the drug trial standard regularization applications reviewed review comments and relevant information submitted to the State food and drug administration.     164th State drug administration organization the State Pharmacopoeia Commission of 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.     Standards review is required, related drug trial conducted drug testing standards for review and inspection.     165th 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.     166th among applicants to declare the same variety of tentative standards full member, shall not be less than the approved drug standards and related substances should be combined with their own characteristics making the necessary checks.     167th after the applicant receives notification of the standard review and inspection, requires additional testing or improving information, should be completed within 50 days of the experiment, or the complement and perfection of information and shall submit the location of provinces, autonomous regions and municipalities directly under the food and drug administration.     168th State food and Drug Administration to review the information submitted to the national pharmacopoeia Committee, with the approval of the State drug standard promulgated in the form of a positive drug trial standards. 169th standard pilot different varieties of the same deadline, before expiration of start positive.     Standard trial period has not expired, from national pharmacopoeia Committee notifies the applicant in advance to the provincial, autonomous region, or municipality directly under the administration process a regular application.     170th tentative standards expire is not in accordance with the provisions of article submitted regularization applications or the pilot standard does not meet the requirements of positive by the State Drug Administration revoke the pilot standards and drug approval number according to the tentative standards production. During the processing of pilot standard regularization applications, pharmaceutical producing enterprises shall, according to tentative standards of production.     ~23. section III management of drug standard substance 171th pharmaceutical standards, 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.     172th of pharmaceutical and biological products are responsible for calibration and management of national drug standards.     Of pharmaceutical and biological products can also be organized by the relevant province, autonomous region, or municipality directly under the inspection or research institution or pharmaceutical manufacturing enterprises by the calibration.     173th 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.     174th article of pharmaceutical and biological products which 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.     15th chapter the registration time limit article 175th 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.     176th of provinces, autonomous regions, municipalities directly under the food and Drug Administration received after submission of the application the applicant, should be started in the 5th and 30th to complete site visits, samples, notifications and drug control for sample inspection, will review and report, together with the applicant submitted information to be submitted to the State food and drug administration, and will inform the applicant review.     177th drug testing after receiving the test notification and sample, should be finished in 30th inspection and issue an inspection report.     Special drug and vaccine products can be completed in 60 days.     178th must sample test and drug standards review, drug testing should be completed within 60 days.     Special drug and vaccine products can be completed in 90 days.     179th State Drug Administration in the receiving province, autonomous region, or municipality directly under the administration of submitted information should be completed in the 5th accepts the application for review and decide whether to accept it.     180th applications for registration of imported drugs, State food and Drug Administration should be completed in the 30th accepting review and notify of pharmaceutical and biological products testing organization.     181th of pharmaceutical and biological products received information and samples should be in the 5th test arrangements relating to drug control.     Article 182th imported drug testing drug testing information received after, samples and related reference materials, testing should be completed within 60 days and submit the inspection report of pharmaceutical and biological products.     183th of pharmaceutical and biological products received have been reviewed by the standards of imported drugs should organize experts to conduct technical reviews in the 20th and, if necessary, can review individual projects based on review comments.    184th State drug administration period for the technical review of the drugs in the application for registration, in accordance with the following provisions: (a) clinical studies: 120 days; in line with the provisions of article 49th varieties: 100 days to complete. (B) the new drug production: 120 days; in line with the provisions of article 49th varieties: 100 days to complete.     (C) has a national drug application: 80 days to complete.     Time limits for the technical review of an application for registration of imported medicine, and in accordance with this section.     185th State Drug Administration in conducts a technical review of the applications for drug registration, requires the applicant to provide supplementary information, should be a one-time notice in supplementary information.     The applicant shall, within 4 months of disposable follow the notification requirements to complete additional information; not additional information within the prescribed time limit, be returned. 186th disagrees with the applicant of the additional information, notification, and may, within the prescribed time limit for comments.     Still have objections, written comments may be made directly 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.     187th was returned to the application, applicants to the test or complement and complete the information, and in accordance with the provisions of this approach for the monitoring period, can be in the back of the 6 months after the original procedures apply.     188th State Drug Administration after the receipt of additional information, which should not exceed the technical review process completed within the original time limit one-third time meet the 49th of these measures does not exceed one-fourth of the original time limit.     189th State Drug Administration shall upon completion of technical reviews completed within 40 days after the approval in line with the provisions of article 49th varieties, should be completed in the 20th for approval.     Shall be supplemented by the State food and Drug Administration approval of the drug application, shall be completed within 40 days of the State Drug Administration approval which the need for technical review, technical review process shall be completed within 60 days.     190th national pharmacopoeia Committee should become a full member within 60 days to complete drug trial standards validation. Take medicines to positive drug testing standards for review and inspection tasks, review and testing standards shall be completed within 60 days, issued to the national pharmacopoeia Committee review and inspection report. Special drug and vaccine products is generally not more than 90 days.     Several drug manufacturers in the production of the same species to tentative standards of positive reviews and testing, should be completed within 80 days. 191th drug registration time is generally carried out in accordance with these measures.     In special circumstances, approved by the State food and drug administration, may be appropriately extended.     192th 16th chapter review the applicant is not granted to the National Drug Administration disagrees with the decision, you can receive notification of the approved 10th days apply to the State food and Drug Administration for review and review reasons stated.     Review is limited to the contents of the original application items and original reporting. Article 193th after receiving the application for reconsideration, the State Drug Administration re-examination decision shall be made within 50 days.     Decision to withdraw the original rejection, issue appropriate drug approval documents upheld the decision, the State Drug Administration no longer accepts applications for review again.     194th review needs for technical examination, State Drug Administration shall organize relevant professional and technical personnel in accordance with the original time limit for an application. 17th chapter penalty 195th applicant in the reporting of clinical studies, submit false drug registration documents and samples, State food and Drug Administration not to grant the prescribed drug clinical study, giving warning to applicants; approved clinical study, revoke approval of the drug in clinical research documents, and a fine of between 10,000 yuan and 30,000 yuan.     In serious cases, will not be accepted within three years of the applicant's applications for clinical trials of the drug.     State Drug Administration to submit false information and samples of the applicants to establish record of bad behavior, and to the public.     196th application of drug production or importation, applicants submit false drug registration documents and samples, the State Drug Administration not to grant the application, giving warning to applicants had been approved for production or import, withdrawal of drug approval documents does not handle applications within five years and a fine of between 10,000 yuan and 30,000 yuan.     State Drug Administration to submit false information and samples of the applicants to establish record of bad behavior, and to the public.     197th pharmaceutical producing enterprises revoked the production license of medicines, drug approval number held by the enterprise itself repealed, State food and Drug Administration to be cancelled.     198th in the drug registration was not in accordance with the provisions in the non-clinical research and the quality control standard or the quality management standard of clinical drug trial, as provided for in article 79th of the drug administration law will be punished.     199th drug testing take drug tests required for drug approval, issues a false inspection report, in accordance with the provisions of the drug administration law 87th penalty.     Article No. 200 in accordance with the provisions of this article 22nd required repeat drug trial, the applicant refused, State food and Drug Administration for its warning and ordered corrective action and cancel the Declaration eligibility of varieties that are not correct.     18th Chapter by-laws No. 201 in these measures work in terms of daily average for working days, excluding holidays.     Article No. 202 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 Drug Administration.     Article No. 203 of biology, microbiology, Immunology and nucleic acids in vitro diagnostic reagents for registration management regulations, according to the State food and Drug Administration issued registration management method for vitro diagnostic reagents.     Article No. 204: direct contact with drugs packaging materials and containers, materials management, shall be separately formulated by the State Drug Administration.     Article No. 205 of the packaging, labelling and manuals as well as drug product regulations formulated by the State food and Drug Administration separately.     Article No. 206 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 conform to the relevant regulations of the State.     Article No. 207 applications for drug registration, shall pay the registration fee. Section No. 208 these measures shall take effect on December 1, 2002.       On April 22, 1999, issued by the State drug administration new drug approval, the new bio-product approval, the new drug protection and technology transfer requirements, and the generic drug approval and drug import regulation repealed simultaneously.     Annex 1: traditional Chinese medicine, natural medicine registration classifications and reporting requirements, registration, classification and description (a) the registration category 1. from which is not listed on the domestic sales of medicine, natural medicine extracting active ingredients and preparations.     2. is not listed in the domestic sales, derived from plants, animals, minerals and other medicinal preparations made of material.     3. alternatives to traditional Chinese medicine.     4. is not listed on the domestic sales of Chinese herbal preparation made from new parts.     5. from which is not listed on the domestic sales of medicines made of the effective part extracted, natural medicine preparation.     6. is not listed on the domestic sales of traditional Chinese medicine, natural medicine compound preparation made from.     7. is not listed on the domestic sales of the medicine, made of natural medicine injections.     8. changes in domestic sales of drugs already on the market route of administration of the preparation.     9. change the marketed dosage formulations.     10. preparation of changes in domestic sales of drugs already on the market process.     11. the existing national standard of proprietary Chinese medicine and natural medicine preparations. (B) Note 1. "     Is not listed on the domestic sales of Chinese herbal medicine extract active ingredients, natural medicines and their preparations "refers to the national drug standards is not collected from medicine, natural medicine has been without the chemical modification of single ingredients and preparations.     2. "is not listed in the domestic sales come from plants, animals, minerals and other medicinal preparations made from material" means not by the national drug standards or local drug codes of provinces, autonomous regions and municipalities (hereinafter "legal standard") containing the preparation made from Chinese herbal medicines and natural drugs.     3. "substitute for traditional Chinese medicine" is used to replace some features of traditional Chinese medicine pharmaceutical substances, including: (1) has been the legal standard and listed Chinese medicine and (2) were not legal standards containing medicinal substances.     4. "is not listed on the domestic sales of Chinese herbal preparation made from new parts" is a legal standard of Chinese herbal medicine to the original plant and animal preparations made from new parts.     5. "is not listed on the domestic sales of Chinese herbal medicine extract, natural medicine made of the effective part of preparations" is derived from traditional Chinese medicine, natural medicine, one or several types of preparations made from ingredients.     6. "is not listed on the domestic sales of compound preparation made from Chinese medicine, natural medicine" includes: (1) traditional Chinese medicine compound preparation, (2) modern compound preparation of traditional Chinese medicine, (3) natural medicine compound preparation.     7. "is not listed on the domestic sales of traditional Chinese medicine, natural medicine injections made of", including injection, powder for injection, infusion mutual changes and other dosage forms into injections.     8. "the changes in domestic sales of drugs already on the market and administration route of preparation" include: (1) preparation of change between different routes of administration, (2) topically to systemic drug delivery formulation.     9. "change the marketed dosage form of preparation" refers to the route of Administration is not constant changing form of preparation.     10. "the changes in domestic sales of drugs already on the market process of preparation" include: (1) preparation of process there is a qualitative change, (2) process no qualitative change in the preparation.     Process quality change refers to changes in the production process of extraction solvent, purification or other preparation conditions, so that large changes in the composition of the extracts.     11. "the existing national standard of proprietary Chinese medicines or natural medicine preparations" means China has approved the sale of Chinese herbal medicine or natural applications for registration of pharmaceutical preparations.     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. drug samples, preparation of notes and the latest references.     6. packaging and labelling design artwork.     (B) the 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. the characteristics, organizational characteristics, physical and chemical research (methods, data, pictures and conclusions) and literature.     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 provides information about drug standard substance.     16. samples and 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.     (C) the Pharmacology and toxicology 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; dependence of test data and literature.     24. allergic (local, systemic and photo toxicity), hemolysis and partial (blood vessels, skin, Mucosa, muscles, etc) irritation, 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.     (D) clinical study information 29. Summary of clinical study data.     30. clinical research projects and research programmes.     31. Handbook of clinical researchers.     32. the informed consent form template, approved by the Ethics Committee.     33. clinical studies.     Third, the declared data item description 1. information item 1 name of the drug including: Chinese, Pinyin and English names and named basis. 2. item 2 supporting documents include: (1) proof of legal registration of the applicant, the drug manufacturing licenses, certification of good manufacturing practices certificate.     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, patent situation and ownership state situation description, and on others of has has patent not constitute infringement of guarantee; (3) anesthesia drug, and spirit drug, and medical with toxicity drug development project reply file copies; (4) application drug production Shi should provides drug clinical research documents copies;     (5) packing material direct contacted with drugs (or container) of drug packing materials and vessel registration certificate or the copy of the certificate of registration of imported packaging materials and containers. 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; (2) 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,     Instruments should be entrusted, notarial documents copies of business license and Chinese agencies, and (3) shall provide appropriate drug safety test data specification for non-clinical research and the quality control documents for clinical specimens should be provided with appropriate good manufacturing practice certificates.     3. item 3 is made objective by: 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 the theory of the traditional Chinese medicine, ancient literature, research or production, the usage summary, and the variety innovation, feasibility analysis, including comparison of similar varieties and existing national standards (specific requirements be developed).     4. 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. 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. 6. item 16 sample inspection report refers to the Declaration of the self test of the sample reports.     Clinical study submitted to the information provided at least 1 sample self-test report completes the clinical study submitted to the information provided for 3 consecutive samples of the self test report.     7. 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. 8. because of the diversity and complexity of new drugs, in return, should be combined with a variety of features necessary for the appropriate research.     If you apply for remission of test should be fully justified. Four, and declared information project table and the description (a) medicine, and natural drug declared information project table note: "+": refers to must submitted of information; "±": refers to can with literature reviewed instead of test research of information; "-": refers to can from reported of information; "*": according to description of requirements submitted of information, as *7, refers to see description of 7th article; "23#": has dependence tendencies of drug, needed submitted drug dependence test information; "26#": for childbearing age crowd and may on reproductive system produced Health effect of drug (as pill, and sex hormone, and treatment sex function obstacles drug, and promoting sperm generated drug and to mutation test positive or has cell HIV role of drug), need submitted reproductive toxicity research information; "27#": and known carcinogenic material about, and metabolism product and known carcinogenic material similar of drug, in long-term toxicity test in the found has cell HIV role or on some organ, and organization cell has exception significantly promote role of drug, to     Test positive for drugs, are required to submit the carcinogenicity test information "▲": a legal standard of traditional Chinese medicine, natural medicine (except "#" marked exceptions) can not provide, you must provide information; "①": traditional Chinese compound; "II": modern traditional Chinese medicine compound; "third": natural medicine compound preparation.     (B) Note 1. classification 1~10 of registration for new drugs, registered category 11 varieties of existing national standards of medicine.     2. applications for registration of new drugs, in accordance with the declarations required information items of the list 1~31 (the exception of items 5, 6); after clinical study submitted to the 5, 6, and 15~17, 31~33 project information as well as information on other changes and additions, and detail the basis and reason.     3. application of national drug standards and drug registration, in accordance with the requirements of the information items submitted relevant information. 4. substitute when no statutory standard of Chinese herbal medicines containing, in addition to the registration category 2nd request reporting information, and shall, together with the comparison test of the efficacy of alternative medicine, toxicology, and related clinical equivalence study preparation; substitute for traditional Chinese medicine has been the legal standard and listed should be adopted by the relevant clinical equivalence study preparation. Alternatives to Chinese herbal medicines are 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.     If substitutes for a single component, shall provide the animal pharmacokinetic data and documents.     5. is not listed on the domestic sales of traditional Chinese medicine, natural medicine extracting active ingredients and formulations, its content should be of a single component to the total extract of 90% above, and must provide the dissolution test. 6. is not listed on the domestic sales of traditional Chinese medicine, natural medicine made of the effective part extracted agents, effective parts of their content should be the total extract of 50%. Effective parts of 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 (including and content determination about of control products of related information); (2) 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 added).     Applications made from similar ingredients effective preparations, which from the marketed drug extract active ingredients, natural medicine, and function the same, should be carried out with the active ingredient comparison of pharmacodynamics and others to demonstrate its advantages and characteristics. 7. traditional Chinese compound prescription traditional Chinese medicine must have a legal standard, and the preparation of the main treatment certificate did not include in the national standard of proprietary Chinese medicines, can avoid doing efficacy, toxicology, clinical studies have only done 100 clinical trials.    However, if any of the following circumstances toxicological testing needs to be done: ① contain indication of toxicity in the statutory standard (very toxic or toxic) and the toxicological evidence of toxicity of the medicinal II contains 18 anti-19, fear of incompatibility. 8. modern medicine compound preparations, prescription in the using of medicinal material should has statutory standard, if prescription in the contains cannot set standard of medicinal material, should reference registered classification in the 2nd items of requirements provides clinical Qian of corresponding declared information; if prescription in the contains natural drug, and effective ingredients or chemical drug, is should on above medicinal material in pharmacological, and HIV acting aspects of mutual role (increased effect, and reduction HIV or complementary role) for corresponding of research.     9. 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 registered before the 2nd request for clinical classification of the corresponding declarations.     10. imports of traditional Chinese medicine, natural medicine preparations registered in the classification request for information.     11. topical preparations is still to be submitted to the local drug toxicity test data and literature. 12. the main ingredients of traditional Chinese medicine, natural medicine injections should be clear.     Chinese herbal medicine, natural medicine injections in view of safety and quality control of complex considerations, for its technical requirements separately. 13. the changed dosage form shall state the advantages and characteristics of new preparations. Indications in principle should be the same as in the original formulation of new preparations.     Some indications of effect is not obvious or pass the efficacy or clinical trials, shall provide appropriate information.     Change in dosage form or a change in the production process, if the production process there is a qualitative change, declarations should be made available to the new preparation and preparation in preparation, dosage forms, quality standards, stability, pharmacodynamics, clinical comparison of experiments and toxicological data.     Change in dosage form or a change in the production process, if no qualitative changes in production, may reduce the pharmacological, toxicological, and clinical information submitted.     Changing process of preparation, the variety was limited to the approval number of the production enterprise reporting, process no qualitative changes, in accordance with the supplement to apply.     14. the national standards have been the registration of proprietary Chinese medicines and natural drugs preparation, quality standards should be improved, according to tentative standards of management, specific measures separately.     15. the new drug application for clinical trials of drugs should be. (1) clinical trials should meet the statistical requirements and the minimum number of cases number of cases required; (2) the minimum number of clinical trials (trial group): phase I 20~30, II for a period of 100, for 300 cases of ⅲ stage, phase IV in 2000.     Biological using degrees test for 19~25 cases; (3) pill 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; III period clinical test should completed at least 1000 cases 12 a menstrual cycle of open test; IV period clinical test should full consider the class drug of variable factors, completed enough sample volume of research work. 16. have been listed overseas licensed medicines, human pharmacokinetic studies should be carried out, and at least 100 of randomized clinical trials.     Multiple indications, cases of each of the major indications of not less than 60.     17. the functions of Chinese herbal substitutes alternative studies should be selected from the national drug standards can fully reflect the alternative medicine effect comparative study on the characteristics of Chinese medicine as a controlled drug, each effect or verify indications would require more than two kinds of traditional Chinese medicine preparation, each agent to validate the clinical cases shall not be less than 100.     18. changes to the route of administration, changed formulation or process any qualitative change in preparation. (1) 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; (2) bioequivalence testing of medicines, clinical trials (3) slow and controlled release formulations, pharmacokinetics and clinical trial shall be conducted.     Pre-clinical studies should include slow-release and controlled-release preparations compared with conventional preparation in the areas of medicine and biology research, as a reminder that this type of release agent specific features.       19. application of an existing national standard injections and other national standards have been prescribed by the State drug administration of Chinese medicine, natural pharmaceutical registration, clinical trials shall be conducted, the number of cases of not less than 100.     Annex 2: 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.     2. change to the route and has not been listed at home and abroad sales agents.     3. is listed on the overseas sales but not yet listed in the domestic sales of the drug: (1) is listed on the foreign sales of the drug substance and drug product, (2) have been listed in overseas sales of compound preparation; (3) changing the route of administration and is listed on the overseas sales agents.     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. drug samples, preparation of notes and the latest 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. draft standards and drafting instructions, and provide standards or reference standard.     12. sample inspection report.     13. the sources of materials and quality standards.     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 pharmacological studies of experimental data and literature.     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) irritation, and other major local, special safety tests related to systemic drug delivery research and documentation.     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. animal pharmacokinetic data and documents.     (D) clinical studies 28. Summary of clinical study data at home and abroad.     29. clinical research programmes and research programmes.     30. the Handbook of clinical researchers.     31. the informed consent form template, approved by the Ethics Committee.     32. clinical studies. 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) proof of legal registration of the applicant, the drug manufacturing licenses, certification of good manufacturing practices certificate.     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, patent situation and ownership state description, and on others of patent not constitute infringement of guarantee; (3) anesthesia drug, and spirit drug, and medical with toxicity drug, and radioactive drug development project reply file copies; (4) application drug production Shi should provides drug clinical research documents copies;     (5) direct contact with pharmaceutical packaging materials and containers for pharmaceutical packaging materials and vessel registration certificate or import packing materials and vessel registration certificate copy.     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 samples, preparation of notes and the latest references: included relevant provisions drafted by drug samples, instructions various elements of the drafting instructions, the latest literature or manufacturers original invention to the latest edition of the official manual of the original and translated into Chinese.     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. item 8 raw production data: including processes and chemical reactions, the starting material and organic solvents and reaction conditions (temperature, pressure, time, catalyst) and steps, refined and main physical and chemical constants, and indicate the material mass and yield and in the process may have impurities or inclusions or other intermediate products.    8. item 10 of quality research data and documentation: includes physical and chemical properties, purity, dissolution, content and methodology validation, etc. 9. item 11 drug standards and preparation of notes on the Bill, 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.     Clinical study submitted to the information provided at least 1 sample self-test report completes the clinical study submitted to the information 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 28 domestic and international clinical research related to the review of information: refers to the study on the clinical literature, abstracts and recent review of tracking reports. 14. the information item 30 clinical research Manual: refers to the existing clinical drug research information and abstracts of non-clinical studies in order to provide information to researchers and other personnel involved in the test, helping them understand the characteristics of experimental drugs and clinical research program.     Investigator's brochure should be concise and objective.     Four, and declared information project table and the description (a) declared information project table note: 1, and "+": refers to must submitted of information; 2, and "±": refers to can with literature reviewed instead of test information 3, and "-": refers to can from reported of information; 4, and "*": according to description of requirements submitted information, as *8, refers to see description of 8th article.     5, "": in accordance with this annex "five, clinical study requirements" in the 4th section.     (B) Note 1. classification 1~5 of registration for new drug registration category 6 varieties to have national standards of medicine.     2. applications for registration of new drugs, submitted in accordance with the requirements of the information items 1~30 information items (information item 6); after clinical study reviewed information submitted information include rearranging 1~6, items 12 and 14, and clinical research information 28~32 information as well as other changes and additions, and in order of declaration information items. 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 studies required, upon completion of the clinical studies submitted to the information item 12 28~32 and information items, as well as information on other changes and additions, and in order of declaration information items. 4. applications for registration of an existing national standard drugs, raw materials quality research data should be included and marketed the APIs used to compare with test data, such as related Crystal, isomers and production process into standard impurities other than those stipulated in the quality control data. Which cannot be measured by physical and chemical means the structure and purity of drugs, raw materials and production processes and marketing drugs already on the market should be the same.     Study on the quality of information, and should be compared with the marketed drug tests, oral solid dosage forms should be provided the dissolution of the comparative study on information, releases and other projects. 5. apply separately for drug preparation, you must provide proof of the legitimate source of the API, including raw material production of the enterprise's business license, drug production licenses and the good manufacturing practice certification, sales invoices, copies of inspection reports, information on pharmaceutical standards. Use of imported raw materials, it shall provide the imported drugs registration certificate or registration of pharmaceutical products, the port drug inspection offices inspection report, copy of drug standards.     API 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.     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, should be according to the indications and new features (such as birth control pills, sex hormones, drugs for treatment of sexual dysfunction and promote spermatogenesis drug test positive or cytotoxic, mutagenic effects of new drugs) shall submit the corresponding reproductive toxicity study material.     8. the following drugs should be submitted to the carcinogenicity test information: (1) new drug or its metabolites of structure and structure similar to known carcinogens; (2) found in long term toxicity test cytotoxicity or some abnormal promoted the growth of organs, tissues and cells, (3) test results positive 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, 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) research or related 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 and medication crowd, factors integrated consider, provides single isomers of 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", such 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", such as long-term toxicity tests show its toxicity does not increase, target organ toxicity was not changed, the information items from the 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.     If necessary, should be provided with the original way of comparative pharmacokinetics of tests or relevant toxicological information (such as local toxicity test or repeated dose toxicity test).     17. a registered in category 3 "change to the route have been listed overseas sales agents", which should pay attention to the preparation of the excipients on drug absorption or local toxic effects of and, if necessary, provide its pharmacokinetic trials or toxicological studies. 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. the immediate-release and sustained-release and controlled-release preparations should be provided compared with conventional preparation of single or multiple dosing pharmacokinetic studies of animal information.     Five clinical studies requiring 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. 3. is registered classification 5 of drug, clinical research 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) speed release, and sustained release, and control release preparations should for single times and times to drug of human drug generation dynamics of compared research and 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, generally avoid clinical studies.     4. register for oral solid dosage forms of the category 6, bioequivalence trials should be, generally 18 to 24; bio-equivalence trials difficult, compared to dissolution, releasing only tests.     Injection of such other non-oral solid dosage forms, materials and production processes consistent with the drug already on the market, from clinical research.     5. the reference drug in clinical trials should be listed in the domestic sales of the drug.   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. 2. item 5, drug samples, preparation of notes and the latest references, there is need to provide production country or region drug authority approved the original instructions, 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 regions for sale of all clinical and research 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.     Application is not allowed to market drugs at home and abroad, this documentation can be completed clinical studies in China, together with the clinical studies 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 for or use of drugs prescribed description and their ownership status, process patents, and patents do not constitute an infringement of the guarantee to others. 2. Description of: (1) production country or region drug authority issued by the pharmaceutical market and the drug manufacturers comply with good manufacturing practice certificate shall comply with the who recommended common format. Other format of 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) not in production national or area allowed listed sales of, can provides in other national or area allowed listed sales of proved file, And shall be recognized by the State food and drug administration.     But the drug production enterprise meet drug production quality management specification of proved file by production national or area drug management institutions issued; (4) raw materials drug can provides 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, also can provides the raw materials drug main control system file DMF (Drug Master File) of information and file. (C) the requirements of clinical research in China 1. applications for drugs that are not allowed to go on sale at home and abroad, clinical studies shall be carried out in accordance with the register of category 1.     The requested drug, should be in foreign countries to enter phase II or phase III clinical trials of the drug.     2. application in foreign market but not yet marketed medicines in China, shall, in accordance with the provisions of category 3 clinical studies.     3. the application is the national drug standard of drug substance or drug product, if the information item 28 meet the requirements, can follow the registration category 6 requirements for clinical research does not meet the requirements, shall, in accordance with the provisions of category 3 clinical studies.     4. apply separately for imports, there is no national drug standard APIs, you should use its agents to conduct clinical research.     Seven, radioactive drug application information and requirements (a) the declaration information item 1. application for radioactive drugs shall, in accordance with radionuclide, raw material medicine, pill boxes and preparation organized information, and follow the chemicals will category and the declaration information items required, which data item 22, 26.     2. applications for radiopharmaceuticals for diagnosis, from data items 23, 24, 25.     3. application for radionuclides, raw materials and pill boxes, data items from 18.     (Ii) declared information project description 1. information project 8 by following requirements submitted: (1) radioactive drug in the of radioactive radionuclide, should provides the radionuclide of 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, target material and other by with chemical reagents of specifications standard and the analysis test data, both at home and abroad about literature information; (2) radioactive drug in the raw materials drug as for chemical synthesis, should provides synthesis route of selected, synthesis process of detailed chemical reactions type, reaction conditions and detailed operation steps, indicate feeding volume, and received have rate and the may produced or inclusion of impurities, the step intermediate quality control method, eventually products refined (purification) of method, raw materials of quality standard, both at home and abroad about literature information; (3) radioactive drug in the of drug box, should provides drug box of selected and preparation process, and route, and reaction conditions, and     Step test basis, each component API is to provide quality medical specifications and standards, (4) non-Kit radioactive drugs shall provide synthesis, reaction conditions, procedures, purification or purification methods, raw material quality standards and analysis of test data and related documentation. 2. information project 9 by following requirements submitted: (1) radioactive drug in the of radioactive radionuclide if China Pharmacopoeia yet containing, should provides the radionuclide of decay outline figure, confirmed with nuclear nature of test data (or maps) and and both at home and abroad recognized of the radionuclide of nuclear nature for compared of test information and the literature information; (2) radioactive drug in the of raw materials drug as for chemical synthesis, should provides confirmed its chemical structure of test data, including elements analysis, and infrared absorption, and purple outside absorption, and NMR spectrum, and Mass spectrometry data. All maps should be original or a copy of photos (clearly appropriate) and Atlas peak parse tables and detailed analysis of the text.     The maps should indicate using instrument of model, and test conditions, and for try products of batch, and samples concentration, and by with solvent, and within standard real, and for integrated analytical; (3) radioactive drug in the of drug box, should provides drug box of detailed component and dosage, and description the component in drug box in the of role; (4) non-drug box class radioactive drug, should provides confirmed its chemical structure of test data, as does have difficult, should description reason, and for reasonable inferred may of chemical structure or reference literature according to. 3. information project 10 by following requirements submitted: (1) radioactive drug in the of radioactive radionuclide (except China Pharmacopoeia containing outside), should provides radioactive nuclear purity and the main nuclear impurities of content, and radioactive live degrees, and chemical purity, and solution pH value, of test method, test data and the provides limits of according to; (2) radioactive drug in the of raw materials drug, should according to samples of characteristics and specific situation, determine physico-chemical constants research project (as melting point, and than spin degrees, and stick degrees, and absorption coefficient,). Purity check content (as chloride, and heavy metal, and reaction intermediate, and Deputy product or residues solvent,) and content determination method filter process and method determine of according to,, and provides detailed test method and determination data; (3) radioactive drug in the of drug box, should provides characters, and identification, and solution of clarified degrees and color, and acid (alkali) degrees, analysis test method, and principle and the data, which raw materials drug, and restore agent or oxidant, or other main additives content determination method of selected and the test research data. Pill box-free bacteria, bacterial endotoxin test methods and limits for research data, (4) non-Kit radioactive drugs, should be provided with physical and chemical properties, properties, identification method and principle of radioactive nuclear purity, pH value, (including major impurities), radiochemical purity, radioactivity, chemical purity.     If the injection, bacterial endotoxins test should be provided with sterile, method, data, set limits based on such information.     4. information project 14 by following requirements submitted: (1) radioactive radionuclide solution can characters, and pH value, and radiation chemical purity, and radioactive nuclear purity, for study index; (2) raw materials drug can characters, and melting point, and degradation product, and content, for study index; (3) drug box can characters, and radiation chemical purity, and restore agent or oxidant content (particles degrees), for study index; (4) drug preparations can characters, and pH value, and radiation chemical purity, for study index. 5. information project 17 by following requirements submitted: (1) diagnosis with radioactive drug, should provides rabbit, and dog or Primate of target organ and the body plane explicit like or simulation clinical function determination test of research method, and test conditions and results explained, information, test observation the time of explicit like or function determination results of image photos or its copies; (2) treatment with radioactive drug, should provides treatment main indications of animal model, to big, and in the, and small three a dose group and set positive drug control group,     Observed responses in laboratory animal test data, and providing this product or similar drugs at home and abroad of researches on pharmacodynamics of detailed documentation.     Radionuclide, raw materials and pill boxes as the raw materials do not submit this information. 6. information project 19 by following requirements submitted: except registered classification 1 and 3 radioactive drug of raw materials drug, should for small rat acute toxicity outside, radioactive radionuclide, and drug box and the preparations can for exception toxicity test, method and the judge standard should meet China Pharmacopoeia Appendix "exception toxicity check method", for try products of to pharmacy volume can according to clinical dosage (radioactive live degrees and volume) of must multiples calculation.     If BPC limited production of synthesis and refinement, clinical dosage and minimal acute toxicity tests may be used. 7. information items 20 submitted according to the following requirements: (1) a registered category 1 radioactive drugs, chronic toxicity in rats and dogs should be provided information and medical internal radiation dose (MIRD) of information or documents;     (2) a registered category 1 radioactive drug for the 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 clinical research clinical research of radiation medicine, according to the chemical requirements of the corresponding category.     Annex 3: Biologicals registration classifications 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. dope or raw materials production process of research information.     10. the formulation and technology of information, sources of materials and quality standards, and related documents.     11. product 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 clinical samples for research applications.     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 study information 29. Summary of clinical study data at home and abroad.     30. clinical research programmes and research programmes.     31. Handbook of clinical researchers 32. informed consent form template, approved by the Ethics Committee.     33. clinical study (v) other 34. preclinical work brief summary.     35. clinical study on improving the technology, perfect quality standards 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. three consecutive trial manufacturing and testing records.     Third, the information note 1. clinical research applications submitted to the data items 1~31; completion of the clinical studies submitted information 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 legal registration proved file, and drug production license, 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 guarantee; (3) application new biological products production Shi should provides drug clinical research documents copies; (4) directly contact products of packaging material and container of     Drug packing materials and vessel registration certificate or the copy of the certificate of registration of imported packaging materials and containers.     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 substances, in accordance with relevant regulations of the State 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 research on product quality information, including: 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, human tissue or body fluid extraction or isolation of substances in 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 product), free safety information (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, and declared information requirements (a) treatment with biological products declared information project table (information project 1~15,29~38) 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) Note: 1.+: refers to must submitted of information; 2.-: refers to can from reported 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 products of category 2, in the design of Pharmacology and Toxicology tests, you should consider the following: (1) when there are Antigen-binding data show that, when primates the most relevant species, not coupling monoclonal antibody testing should consider the use of such animals are the main pharmacodynamic and pharmacokinetic studies; (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, Reproductive toxicity test should be carried out using appropriate animal models (5) immunotoxicity studies should investigate and non-target tissue the combination of potential toxicity, cross-reaction with human tissues or cells or combination of non-target tissue.     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.     Submit a free application, 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) in pharmacy meet requirements, and clinical to drug way not change, 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, the 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.     Relevant descriptive information can be submitted to the State food and drug administration in obtaining clinical audit.     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.     Note 1 for five, on clinical research. 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.     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.     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 clinical studies in China, together with the clinical studies 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) apply for 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 recognized by the State food and drug administration.     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 countries or regions for sale of all clinical and research information.     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) the requirements of clinical research 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 studies.     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 research.     3. the application is the national drug standard of biological products, shall, in accordance with classification 15 apply for clinical research.     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.     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.     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), 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, production with work bacteria, and     HIV species seed batch of verification report, 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,; (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, in accordance with relevant regulations of the State food and Drug Administration to provide the corresponding information.     5. study on the production technology information.    (1) vaccine dope production process of research: optimization production process of main technology parameter, including 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 combined vaccine in the Antigen and carrier of combined 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) the prescription and process of preparation, and provide the basis for sources of materials and quality standards.     6. product quality data.     (1) products of quality standard and verification results, including joint vaccine, and combined 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) research information compared with similar products (7) Antigen components, determination of concentration, molecular weight, purity, specific identification, as well as non-active ingredient content (or residue) testing (8) animal safety evaluation of the product 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. apply clinical studies for sample manufacturing approval records.     9. preliminary stability tests.     10. production, research and testing laboratory animal certification.     11. clinical research programmes and research programmes.     12. the pre-clinical work.     13. Summary of clinical information at home and abroad.     14. clinical study summary report, including informed consent form template, approved by the Ethics Committee.     15. clinical study on improving the 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. continued 3 batches of products in the manufacturing and testing records.     Third, the declared data item description 1. clinical research applications submitted to the data items 1~11; completion of the clinical studies 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 legal registration proved file, and drug production license, 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 guarantee; ③ application new biological products production Shi should provides drug clinical research documents copies; 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, including: according to about provides drafting of drug manual sample, and manual the content of drafting description,     Related document or the latest version of the specification of the original and the translation.     3. with regard to information of items 11, 12 clinical research and the clinical research programme, 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. components of vaccines, acellular vaccines, 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) is based on the use of population, vaccine characteristics, immune dose and immune processes, provide information concerning the toxicity studies.     Four, declared data item tables Note: 1 + means must submit information; 2-exempt information; 3, ± according to the specific circumstances require or do not require Declaration, v, notes on clinical research 1. clinical trials number of cases should be consistent with statistical requirements and minimum requirements of patients.     2. minimum number requirements for clinical trials: 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. 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 clinical studies in China, together with the clinical studies 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 recognized by the State food and drug administration.     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 countries or regions for sale of all clinical and research information.     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) the requirements of clinical research in China 1. application is not listed on the domestic and foreign sales of vaccines, clinical studies shall be in accordance with the provisions of category 1 application to register.     2. applications which have been marketed in a foreign country, but not yet marketed vaccines in China, according to the registration category 6 requirements shall be applied for clinical research.       3. the application is the national drug standard vaccines, shall, in accordance with classification 15 apply for clinical research.     Annex 4: drug supplement registration and reporting requirements, registration matters (a) the State food and Drug Administration approved 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. Add new indications or indications of drugs.     4. change drug specifications.     5. change in drug prescription has requirements for medicinal use of accessories.     6. changes to the pharmaceutical production process.     7. revision of drug registration standards.     8. change the drugs period of validity.     9. change of packing material direct contacted with drugs or container.     10. the transfer of new technology.     11. tentative standards into standards.     12. change imported drug registration certificate of registration items such as drug name, drug name, registered address, packaging specifications and so on.     13. change of origin of imported drugs.     14. changing the packaging of imported drugs abroad.     15. the imported drugs packaging in China.     16. change the import of production of APIs for use in pharmaceutical preparations.     (B) the State food and Drug Administration filed a supplementary application: 17. change the domestic manufacturer name.     18. domestic pharmaceutical production enterprise change drug production sites.     19. According to the national drug standards or State drug administration requirements for medicines.     20. additional security details in the drug.     21. modify the packaging label design.     22. change of the domestic production of medicines packaging specifications.     23. the API changes in domestic production of pharmaceutical preparations.     24. change the appearance of drugs, but does not change the standards of medicine.     25. change the imported drug registration agency.     Second, the declaration information item 1. copy of the approval certificate and its annexes.    2. the supporting documents: (1) the applicant is a manufacturer, shall be provided to the drug manufacturing license, 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 agent institutions agent declared of, should provides delegate instruments, and notary instruments and Chinese translations, and China 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 data.     6. the Pharmacology and toxicology studies. 7. clinical study: clinical study is required, shall, in accordance with traditional Chinese medicine and natural drugs, chemicals, bio-information requirements in a project, in the clinical study before and after submitting the required project information.     Request clinical study information, but do not require clinical studies, can provide information about clinical research literature.     8. drug samples.     Third, note the declarations list: *1. also submitted new drug certificate.     *2. only 3 consecutive batches of a sample inspection report.     *3. provide proof of trademark queries, accepted or registered.     *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. only provide drug stability study test information and sample inspection report of 3 consecutive batches.     *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. technology transfer transfer contract signed between the parties concerned, shall provide appropriate documentation of the original manufacturers to abandon production.     *9. requirements according to the needs.     *10. at the same time provided by the information of the original new drug application review by synthesis and pharmaceutical research and related reviewed.     *11. provide packaging plant where the national or regional regulatory authorities issued by the drug packaging enterprises in accordance with drug manufacturing practices evidence.     *12. 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.     *13. import pharmaceutical packaging contracts (including authorization to use trademarks of imported drugs).     *14. provide packaging technology, direct contact with the pharmaceuticals only packaging material and container selection and quality standards.     *15. provide relevant regulatory agencies agree with the renaming of files, pharmaceuticals management authority documents, changed its name before and was renamed after the business license, drug production licenses, certificate of good manufacturing practices certification.     *16. provide relevant regulatory agencies agree with the drug manufacturer's production workshop of offsite construction documents.     *17. new national drug standards or State Drug Administration seek to amend the drug file.     *18. available toxicological test data or literature.     *19. available documentation.     *20. provide only the approval documents of the API and its legitimate sources, preparation 1 batch inspection report.     *21. provide overseas pharmaceutical manufacturers commissioned new China Agency Agency authorize instruments, notarial instrument and its Chinese translation, China copy of business license of the Agency, the Agency agreed to give up the proxy file or a valid proof.     "#": See "registration matters, reporting of project descriptions and related requirements" number.     Four, project descriptions and related registration matters, reporting information requirements 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. registered matters 3, increased drug new of indications or function attending, its pharmacological HIV acting research and clinical research should according to following for: (1) increased new of indications or function attending, needed Royale long medication cycle or increased dose who, should provides main efficacy learn test information and the literature information, and general pharmacological research of test information or literature information, and acute toxicity test information or literature information, and long-term toxicity test information or literature information, local medication should provides about test information. Clinical research should for human drug generation dynamics research and random control test, group cases number not less than 300 cases; (2) increased new of indications, abroad has has with varieties allowed using this indications who, should provides main efficacy learn test information or literature information, and must for at least 60 on random control clinical test; (3) increased new of indications or function attending, domestic has has with varieties allowed using this indications who, must for at least 60 on random control clinical test,     Or is permitted to use this indication of the same variety as control of bioequivalence testing.     4. point 4, change specifications of drugs, if you change the dosage or application, shall provide appropriate evidence and, if necessary, to carry out clinical studies.     5.6, changes to the production process, production process changes should not result in changes of medicinal material basis, traditional Chinese medicines, biological products should be provided when necessary pharmacodynamics and acute toxicity test data, as needed, can also be required to complete at least 100 randomized controlled clinical trials. 6. point 11, 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); (2) on original drug registered documents in the approval views of improved 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 two years products stability situation and the validity of determine.     7. point 17, change the domestic manufacturer name, refers to the domestic manufacturer approved after the change of company name, applied for be registered drug manufacturer name changes accordingly. 8. point 23, 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.

Related Laws