药品注册管理办法-英文版

1、DRUG REGISTRATION REGULATION (SFDA Order 28) (Translation by RDPAC, for Member use only)Drug Registration Regulation was approved on June 18, 2007 by SFDA executive meeting and is hereby published, which become effective from October 1, 2007. SFDA CommissionerShao MinliJuly 10, 2007DRUG REGISTRATION

2、 REGULATION Chapter 1: General PrinciplesArticle 1: This Regulation is promulgated according to the Drug Administration Law of The Peoples Republic of China (Drug Administration Law), Administrative Licensing Law of The Peoples Republic of China (Administrative Licensing Law), and the Implementing R

3、egulation of the Drug Administration Law of The Peoples Republic of China (Implementing Regulation) to ensure the safety, efficacy and quality control of drugs and standardize drug registration.Article 2: This Regulation shall apply to all drug research and clinical studies, application for clinical

4、 study, drug production and / or importation, as well as the drug approval review, registration inspection and drug administration in The Peoples Republic of China (PRC).Article 3: Drug registration means the legal process by which a decision is made by SFDA, upon application of registration applica

5、nt, to either approve or not approve the conducting of a drug clinical trial, production or importation of a drug to be marketed, based on a systematic evaluation of the safety, efficacy and quality control of the drug. Article 4: The State shall encourage research and development of new drugs and e

6、xercise the approval via a special process of innovative new drugs, those for difficult to treat and life threatening diseases.Article 5: The State Food and Drug Administration (SFDA) is the competent national authority for drug registration, responsible for the review and approval of clinical studi

7、es, production and importation of drugs. Article 6: Drug registration should follow the principles of openness equality, fairness, and for the convenience of the publics. During drug registration, SFDA shall apply the systems of joint responsibility of the presiding reviewer, public disclosure and r

8、escuing of the related staff, responsibility investigation for any wrongdoing, in order to administer the steps from acceptance, inspection, review, approval, through delivery, and subject to monitoring by the publics. Article 7: During drug registration, should the drug administrative authority con

9、sider any permitting issues of significant interest to the publics, the issues should be announced to the publics and public hearing should be held. Should the administrative permitting be related to any significant interest between applicant and other parties, before any decision is made, drug admi

10、nistration authorities should notify applicant and other parties of their entitlement to requesting hearings, statement and defending.Article 8: Drug administration authorities shall provide applicant with accessible information regarding drug registration acceptance, inspection, test, evaluation, a

11、pproval progress and conclusion and so on. Drug administration authorities should publicly disclose the following information at the official website and / or office location. 1. Drug registration application items, procedure, fee standards and basis, timeline, table of content of all required dossi

12、er, as well as reference application documents.2. name list and the related information of the staff at each steps from acceptance, inspection, test, review, through approval. 3. general information of drug registration such as formulary of the approved drugs.Article 9: The drug administration autho

13、rity, units and staffs involved shall assume the responsibility of protecting the technical secrets and data provided by applicants during the process of drug registration. Chapter 2: Basic RequirementsArticle 10: A drug registration applicant (applicant) means an institution that makes drug applica

14、tion and assumes corresponding liability for drug registration. A local applicant shall be a legally registered institution in China and be competent to independently assume legal liability. A foreign applicant shall be a legally established pharmaceutical company outside of China. In making applica

15、tion for an imported drug registration, the foreign applicant shall use its office in China, or authorize an agent in China to handle the application.The person(s) handling the drug registration application shall have technical expertise, and be familiar with drug administration laws, regulations an

16、d technical requirements.Article 11: Drug registration application includes application for new drug, generic drug applications, application for imported drug, supplemental application, as well as re-registration application. A local applicant shall make application according to new drug or generic

17、drug applications; a foreign applicant shall make application according to imported drug.Article 12: A new drug application means a registration application for a drug that has not been marketed in China. Applications made for a change in dosage form, or route of administration, additional new indic

18、ation of drugs shall be made according to new drug registration procedure.Generic drug application means application for registration of a drug for which SFDA has already issued formal standards, however, application of biological products shall be follow new drug application.Application for importe

19、d drug means application for a drug produced outside China to be marketed in China.Supplemental application means an application for the change, addition, or cancellation of any item or contents in the existing registration approval of a new drug, generic drug applications, or imported drug. A re-re

20、gistration application means the application to continue the drug production or importation after the expiry of the certified drug approval documents. Article 13: Applicants should provide sufficient and reliable research data to evidence the safety, effectiveness and quality control of the drugs, a

21、nd assume liability of the truthfulness of the entire dossier. Article 14: In citing literature and materials, the name of the work(s) and journal(s) as well as volume, issue and page number shall be provided in the application dossier submitted for drug registration. For unpublished literature and

22、materials, an authorization letter from the owner must be provided. For any foreign language materials a Chinese translation should be provided in accordance with relevant requirements. Article 15: SFDA shall implement the National pharmaceutical industry development plan and policy, and may organiz

23、e an assessment of the benefit of introduction of drugs to the market. Article 16: During drug registration, drug administration authorities should conduct on site inspection and inspection chosen from decision of the pre-clinical study and clinical trials, as well as conduct on site inspection of p

24、roduction site prior to any marketing approval, in order to confirm the truthfulness, accuracy and completeness of the application dossier. Article 17: If two or more institutions jointly apply for drug registration, the application shall be made to the PDA where the drug manufacturer is located. If

25、 all the applicants are manufacturers, the application shall be made to the PDA where the drug manufacturer of the preparation is located. If none of the applicants is a drug manufacturer, the application shall be made to the PDA where the drug sample is pilot manufactured. Article 18: Regarding the

26、 drug or its formula, production process, indication etc., the applicant shall submit documents explaining the China patent status and ownership rights. If other party holds patent in China, the applicant shall submit a letter stating that the drug will not infringe on the patent rights of others. U

27、pon acceptance of the application, drug administration authorities should publicly disclose the statement submitted by applicant. If an infringement dispute occurs during registration application, the parties shall resolve the matter according to relevant laws for patent administration. Article 19:

28、For a drug that has obtained patent protection in China, another applicant may apply for registration within two years prior to the patent expiration. SFDA shall review the application according to this Regulation and, after expiration of the patent, issue a drug approval number, Imported Drug Licen

29、se or Drug Product License, for an application that meets requirements. Article 20: According to Article 35 of Implementation Regulation, for a period of 6 years from the date of the original applicant's approval, SFDA shall not approve a subsequent application that used, without the express con

30、sent of the original applicant, the undisclosed R&D data and other data generated by the original applicant for submission of application of manufacturing or marketing of a drug containing new chemical ingredients, unless the submitted data is generated by the subsequent applicant itself. Articl

31、e 21: The scope of pre-clinical laboratory study (pre-clinical study) of a drug for registration includes synthetic process, extraction methods, physical-chemical properties and purity, dosage form selection, screening of formulas, preparation process, inspection methods, quality specification, stab

32、ility, pharmacology, toxicology and pharmacokinetic study. For TCM preparations, information such as the source and the processing of raw materials should also be included. For biological products, information such as source, quality standards, storage condition, biological identity, genetic stabili

33、ty and immunology study of strain, cell strain as well as biological tissue should also be included.Article 22: Pre-clinical study of a drug shall be conducted in accordance with relevant regulations, where the drug safety evaluation must be conducted in accordance with Good Laboratory Practice for

34、Pre-Clinical Laboratory Studies (GLP). Article 23: Institutions engaged in drug research and development shall have the necessary personnel, facility, equipment, instruments, conditions and management system needed corresponding to the research project, and shall guarantee the authenticity of all da

35、ta and materials. The animals, reagents and raw materials used for experiments shall comply with relevant national regulations and requirements. Article 24: If an applicant authorizes another institution to conduct the study of drugs, or any single experiment, inspection or pilot production and manu

36、facture, the applicant shall sign a contract with the authorized party, and make notes in the application dossier. The applicant is responsible for the truthfulness of the drug study data used in the application dossier. .Article 25: When an application is only made for registration of preparation,

37、the raw materials of the investigative drug substance used for this preparation must have a Drug Approval Number, Imported Drug Certificate or Pharmaceutical Product Certificate, and must have been obtained from legal channels. Any investigative drug substance which does not have a Drug Approval Num

38、ber, Imported drug Certificate or Pharmaceutical Product Certificate must be approved by SFDA. Article 26: If an applicant uses the drug study data from a foreign drug research for a drug registration application, an explanation for the study items, and referencing the page numbers issued by this in

39、stitution shall be provided, and notarized certificate of the institution's legal overseas registration shall be attached. Only after the documents are authenticated by SFDA may they be included in the registration documents. SFDA may send people to conduct on-site inspections, if necessary.Arti

40、cle 27: During the verification of drug studies, drug authorities may request the applicant or the drug research institute that conducted the experiments to repeat an experiment for any items by using the methods and data listed in the application dossier. SFDA may also designate other drug control

41、institutes or drug research institutions to repeat the experiments or to validate the methodology. Article 28: Drug study shall be conducted in accordance with relevant technical guidelines issued by SFDA. If the applicant conducts the experiments according to other methods and techniques, the appli

42、cant shall provide information to evidence that the methods and techniques are scientific. Article 29: After obtaining the drug approval number, the applicant should produce the drug according to the process approved by SFDA. Drug administrations shall monitor the production according to the approve

43、d production process and standards. Chapter 3: Clinical Trials of DrugsArticle 30: Clinical study of drugs, including bioequivalence trials, must be approved by SFDA, and must be conducted in accordance with Good Clinical Practice (GCP).Drug administrations shall monitor the approved clinical studie

44、s.Article 31: Clinical trials should be conducted for the registration of a new drug. For registration application of generic drugs and supplemental application, clinical trails should be conducted in accordance with provisions specified in Appendix of this Regulation. Clinical trials are divided in

45、to Phase I, Phase II, Phase III and Phase IV. Phase I: Basic clinical pharmacology and human safety evaluation studies. To observe tolerance in human bodies and pharmacokinetics, providing a basis for a drug administration program.Phase II: A preliminary exploration on the therapeutic efficacy. The

46、purpose is to evaluate the safety and efficacy of a new drug on patients within the target indication of the drugs, and providing the basis to devise Phase III Clinical Trial and to determine a drug administration program. Phase II Clinical Trial may be conducted in many ways including randomized bl

47、ind controlled clinical trial in accordance with the purpose of the study.Phase III: The phase to confirm the therapeutic efficacy. The purpose is to further verify the safety and efficacy of a new drug for patients with targeted indication, to evaluate the benefit and risks relationship, and finall

48、y to provide sufficient data to support the registration approval of the drug. The trials usually are randomized, blind and controlled clinical trial with a large number of sample subjects. Phase IV: A new drug post-marketing study, conducted by the applicant. The objective is to investigate the eff

49、icacy and adverse reactions under the conditions of wide use, and to evaluate the benefit and risk relationship when used by ordinary and special groups of patients and to improve dosage of the drug. Bioequivalence trials means those human trails to determine if there is any statistical difference i

50、n absorption and absorption speed of active component between the same or different dosage form of the same drugs under the same test conditions, by using methodology of bioavailability study and with pharmacokinetic parameters. Article 32: The number of human subjects in the clinical study of a dru

51、g should be decided in accordance with the objective of the clinical trials and shall meet both the statistical requirements and the minimal cases required by this Regulation for a clinical study. For a drug used for the treatment of rare and special diseases or other special circumstances, any requ

52、irements for reduction in the number of human subjects in the clinical study or exemption should be made at the same time of clinical trial application and be approved by SFDA. Article 33: For a vaccine and other special drugs prepared during the strains selection stage, if there is indeed neither s

53、uitable animal experimental model nor a way to evaluate the efficacy of the drugs in laboratory study, application of clinical trials may made to SFDA, provided that safety of the subjects can be ensured.Article 34: After approval of a clinical study, the applicant shall select from the institutions

54、 qualified for drug clinical trial to conduct the clinical study. Article 35: The investigational drugs shall be produced in a workshop which meets GMP requirements and the production process shall be strictly in accordance with the requirements of GMP. The applicant is responsible for the drug qual

55、ity of the investigational drugs Article 36: The applicant may inspect the investigational drug itself in accordance with the drug's standards for its selected drugs for clinical trial, or authorize a drug control institute designated by this Regulation to conduct the quality test. Vaccine, bloo

56、d products and other bio-products designated by SFDA must be inspected by a drug control institute designated by SFDA. The drug must not be used for Clinical Trails before it has passed the inspection. Drug administration authorities may conduct a random inspection for the investigational drug.Artic

57、le 37: Before conducting the clinical study, the applicant shall file with SFDA information such as the clinical study protocol, name of the principle investigator of the leading institution, participating institutions and investigators, approval letter from ethics committee, and the sample of the I

58、nformed Consent Form, also providing a copy to the PDA where the institutions are located and PDA where the application was filed. Article 38: If an applicant discovers that an institution conducting clinical study is in violation of relevant regulations, or is not following the clinical study protocol, the applicant shall try to have the situation corrected. For serious violation, the applicant may request to suspend or stop the clinical study and shall submit a written report to SFDA and the relevant PDA. Article 39: Upon the completion of the c