Administrative Measures for Drug Registration
Administrative Measures for Drug Registration
Measures for Drug Registration
Order of the State Food and Drug Administration No.17
February 28, 2005
Adopted at the executive meeting of the State Food and Drug Administration, the Administrative Measures for Drug Registration is hereby promulgated and implemented as of May 1, 2005.
Administrative Measures for Drug Registration
Chapter I General Provisions
Article 1 For the purposes of guaranteeing the safety, effectiveness and quality controllability of drugs and regulating the drug registration, these Measures are formulated in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as Drug Administration Law) and the Implementing Regulations of the Drug Administration Law of the People's Republic of China (hereinafter referred to as the Implementing Regulations of the Drug Administration Law).
Article 2 These Measures shall apply to the application for drug clinical trials, drug production or import, as well as the relevant drug registration, inspection, supervision and administration undertaken within the People's Republic of China.
Article 3 The drug registration refers to the examination and approval process during which the State Food and Drug Administration (hereinafter referred to as the SFDA) conducts, at the drug registration application filed by an applicant, a systematic evaluation of the safety, effectiveness and quality controllability of the drug to be marketed and makes the decision on whether or not to approve the application in accordance with the statutory procedures.
Article 4 The state encourages the study and development of new drugs, and employs the system of expedite examination and approval to new drugs developed, new drugs for treating complicated and serious diseases as well as the drugs badly needed for emergencies.
Article 5 The State Food and Drug Administration shall be in charge of the administration of drug registration throughout the country, and be responsible for the examination and approval of drug clinical trial, drug manufacturing and import.
The (food) drug administrations of the provinces, autonomous regions and municipalities directly under the Central Government shall verify the research and development as well as the conditions, examine the completeness, standardization and authenticity of the application materials for drug registration, and organize a test of trial samples.
Article 6 An applicant for drug registration (hereinafter referred to as the applicant) refers to an institution that files an application for drug registration, bears the corresponding legal liabilities, and holds the drug approval certification documents after the application is approved.
A domestic applicant shall be an institution that is lawfully registered within China and can bear civil liabilities independently, while an overseas applicant is a lawful overseas drug manufacturer. Where an overseas applicant applies for the registration of drug import, its office based in China or an agency within China entrusted thereby shall go through the formalities for the registration of the imported drugs.
The personnel handling the applications for drug registration shall be professionals in corresponding fields, and shall be home with the laws and regulations and technical requirements for the administration of drug registration.
Chapter II Application for Drug Registration
Article 7 The applications for drug registration shall include the applications for new drugs, applications for drugs for which there are already state standards, applications for imported drugs and supplementary applications thereof. For a domestic applicant, the procedures for filing applications for new drug and for filing applications for drugs with existing state standards shall be followed; for an overseas applicant, the procedures for the application for imported drugs shall be followed.
Article 8 The "applications for new drugs" shall refer to the applications for the registration of drugs that haven't been marketed within China. If the type of preparation or the route of administration of any drugs that have been marketed is changed, or if the range of indications thereof is newly expanded, the said drugs shall be treated as new drugs.
The applications for drugs with existing state standards shall refer to the applications for the registration of the drugs for which the SFDA has promulgated formal standards.
The applications for imported drugs shall refer to the applications for registration of the drugs that are manufactured overseas and marketed in China.
The supplementary applications shall refer to the applications for changing, adding or canceling the originally approved matters or contents after the applications for new drugs, drugs with existing state standards or imported drugs have been approved.
Article 9 An applicant shall file an application for drug registration with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where it is located, and shall submit relevant materials and drug samples. In the case of an application for registration of imported drugs, the applicant shall file the application with the SFDA.
The applicant shall be responsible for the genuineness of all the contents of the application materials.
Article 10 If two or more entities, as a joint applicant, apply for the registration of a new drug, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the drug manufacturing enterprise is located. If all the applicant entities are drug manufacturing enterprises, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the drug manufacturing enterprise that applies for the preparation is located. If none of the applicant entities is a drug manufacturing enterprise, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the samples are trial-produced.
Article 11 For the drug applied for registration or the prescription,techniques or uses of the drug, the applicant shall provide its patent or the patent of any other person in China as well as the explanations on its ownership; if any patent of any other person exists within China, the applicant shall submit a statement of no infringement upon the patent of others.
Article 12 Where any dispute arises after the application for drug registration is approved, the parties concerned shall settle the dispute through negotiation by themselves, or through the patent administrative department or the people's court pursuant to the relevant laws and regulations.
A patentee may, on the basis of the final ruling made by the patent administrative department or valid judgment affirming infringement as made by the people's court, file with the SFDA for canceling the registered approval number of the drug. Accordingly, the SFDA shall write off the drug approval certification documents of the infringer.
Article 13 As for a drug of which the Chinese patent has been obtained by any other person, an applicant may file a registration application within 2 years before the expiration of the patent of that drug. The SFDA shall conduct an examination pursuant to these Measures, and, if the applicant meets the relevant conditions, it shall issue to it the registered number of drug approval, an Imported Drug Registration Certificate or the Pharmaceutical Product Registration Certificate after the patent expires.
Article 14 Where a producer or seller, who has obtained a permit to produce or sell an drug containing any new chemical ingredient, submits any undisclosed experimental data or other data obtained by itself, the SFDA shall not, within 6 years after it grants this permit, approve any other application for using the undisclosed data unless it is consented to by the applicant who has obtained the aforesaid permit, unless the data submitted by the other applicant is obtained by itself.
Chapter III Pre-clinical trial of New Drugs
Article 15 The pre-clinical trial of new drugs for applying for drug registration shall include synthetic techniques, extraction methods, physical and chemical properties, purity, choice of form of this drug, selection of prescriptions, preparation techniques, inspection methods, quality indicators, stability, pharmacology, toxicology, nuclein animal dynamics, etc. As for Chinese traditional medicine preparations, the sources and processing of the original medicine materials, etc. shall also be included; as for biologic products, the sources, quality standards, preservation conditions, biological features, inheritance stability and immunological study of the primary raw materials such as microbial and toxic species, cell line or organism, etc. shall also be included.
Article 16 The relevant administrative provisions shall be executed in the pre-clinical trial of new drugs, and the Criterions for the Quality Control of Non-clinical Study of Drugs must be executed in the safety evaluation study.
Article 17 An institution engaging in drug study and development must have the personnel, site, equipment, instruments and management system that can meet the requirements for the experiment and study projects. The animals, reagents, and raw materials for experiment use shall conform to the relevant provisions and requirements of the state, and shall ensure the authenticity of all the experiment data and materials.
Article 18 As to a separate application for the registration of a drug preparation, the applicant shall have, for the raw material medicines used for the study of the drug preparation, the registered number of drug approval, an Imported Drugs Registration Certificate or Pharmaceutical Product Registration Certificate, and the raw material medicines must be obtained through legal channels. If, for the raw material medicines, the applicant does not have the registered number of drug approval, anImported Drug Registration Certificate or Pharmaceutical Product Registration Certificate, such applicant shall be subject to the approval of the SFDA.
Article 19 Where an applicant entrusts any other institution to conduct drug study, separate experiment, testing, trial manufacturing or production of samples etc, it shall enter into a contract with the trustee. The applicant shall be responsible for the authenticity of the drug study data in the application materials.
Article 20 If the application materials for drug registration include any drug experiment and study materials submitted by any overseas drug study institution, there must be attached with the explanations produced by that overseas drug study institution on the projects and the page numbers of the materials provided, and the certifications which can prove that the institution has been legally registered and notarized overseas, and the attached materials may be used as the application materials unless they have been acknowledged by the SFDA. The SFDA shall send personnel to make on-spot inspection where necessary.
Article 21 When inspecting drug study according to the needs, the SFDA and the (food) drug administration of a province, autonomous region or municipality directly under the Central Government may request the applicant or the drug study institution undertaking the experiment to conduct an experiment again according to the projects, methods and data specified in the application materials, and shall send personnel to oversee the experiment on the spot; or an institute for drug control or other drug study institution may be entrusted to make an experiment again.
Article 22 The pre-clinical study of new drugs shall be conducted by referring to the relevant technical guiding principles promulgated by the SFDA. Where an applicant adopts other evaluation methods and techniques in the experiment, it shall submit the materials that can prove their scientificness.
Chapter IV Clinical Trial of Drugs
Section 1 Basic Requirements
Article 23 The clinical trial of drugs (including bioequivalence experiments) shall be subject to the approval of the SFDA and shall follow the Criterions for the Quality Control of Clinical Trials of Drugs.
Article 24 An applicant shall conduct clinical trials when applying for the registration of a new drug. The clinical trials are classified into four phases: I, II, III and IV. Before a new drug is approved for marketing, phases I, II, and III clinical trials shall be conducted. Under certain circumstances, the applicant may, upon approval, only conduct phases II and III clinical trials or only phase III clinical trials.
The phase I clinical trials: the preliminary trials on clinical pharmacology and human body safety evaluation, which aim to observe the degree of tolerance of human body against the new drug and the drug dynamics, and provide the basis for working out the dosage administration scheme.
The phase II clinical trials: the preliminary evaluation of the treating effects, which aim to preliminarily evaluate the treating effect and safety of the drug on the target patients with the applicable disease, and also to provide the basis for the determination of study design and dosage administration scheme for the clinical trial in phase III. Various methods may be employed for the study design of this phase in light of the specific study purpose, including the randomized controlled trial.
The phase III clinical trials: the confirmation phase of the treating effect, which aim to further verify the treating effect and safety of the drug on the target patient with the applicable disease, to evaluate the relationship between interest and risk, and to eventually provide adequate basis for the examination of the drug registration application. Generally, the trials shall be randomly controlled ones with sufficient samples.
The phase IV clinical trials: the phase of application study conducted by the applicant independently after the new drug comes into the market, which aim to examine the curative effect of the drug and the adverse reactions when it is widely used, to evaluate the relationship between interest and risk when the drug is used in ordinary or special groups and to improve the dosage administration, etc.
Article 25 Generally speaking, it is not required to conduct any clinical trial for the registration of drugs with existing state standards. Among those which require a clinical trial, a bioequivalence trial shall be conducted for chemical drugs. For a drug whose quality needs to be controlled by techniques and standards, clinical trials shall be conducted. In a supplementary application, the applicant shall conduct clinical trials if new indications are added for any drug already on the market or if the manufacturing techniques of the drug are altered significantly.
The bioequivalence trial is, under the same testing conditions, to compare the statistical disparities of the absorption extent and speed of the active substances of the identical dosage or of different dosages of the same drug in the human body through the approach of bio-availability study and by considering the parameters of drug dynamics as the indicators.
Article 26 The number of cases experimented in drug clinical trials shall be in line with the purpose of the drug clinical trials, shall meet the relevant statistical requirements and shall not be less than the minimum clinical trial case number as specified in these Measures. As for a rare disease, special disease or any other circumstance where it is needed to reduce clinical trial cases or to exempt the clinical trial, the examination and approval of the SFDA is required.
Article 27 With respect to the bacteria or other special drugs prepared during the phase of selecting bacteria or virus species, if it is unable to evaluate the curative effect thereof due to lack of suitable animal model and laboratory, the applicant may apply for clinical trial with the SFDA on the precondition that the safety of the experimented person is secured.
Section 2 Requirements Before Trial
Article 28 After a drug clinical trial has been approved, the applicant shall select, from the institutions qualified for drug clinical trials, an institution to undertake the drug clinical trial, decide through consultation the entity responsible for the clinical trial, the major researchers and the entities participating in the clinical trial.
Article 29 The applicant shall conclude a clinical trial contract with the selected entity responsible for and the entities participating in the clinical trial, provide the researchers with manuals, and together with the researchers, design and perfect the clinical trial scheme by referring to the relevant technical guiding principles.
The clinical trial scheme shall be subject to the examination of the ethic committee of the clinical trial institution.
Article 30 The applicant shall provide the selected clinical trial entities with free medicines for clinical trial use and drugs for comparison use (except for clinical trials in phase IV), to which it shall attach a sample inspection report, and bear the expenses needed for the clinical trial.
Article 31 The drugs for clinical trial use shall be produced and prepared in workshops meeting the conditions as provided for in the Good Manufacturing Practices (GMP) for Pharmaceutical Products. The process of production and preparation shall strictly follow the Good Manufacturing Practices (GMP) for Pharmaceutical Products.
The SFDA or the entrusted (food) drug administration of the province, autonomous region or municipality directly under the Central Government may conduct on-the-spot checks where it so requires.
Article 32 An applicant may inspect the drugs for clinical trial use by itself according to the drug standards determined by the SFDA, or entrust an institute to do the drug control as specified in Articles 147 and 148 to conduct the inspection. The drugs shall not be used in clinical trial unless they have passed the drug inspection.
The SFDA may designate an institute for drug control to make a selective inspection over the drugs for clinical trial use.
The vaccine products, blood products, and other biological products as well as overseas-manufactured drugs for clinical trial use as provided for by the SFDA, shall be subject to the inspection by the institutes for drug control designated by the SFDA. They shall not be used in the clinical trial unless they have passed the aforesaid drug inspection.
The applicant shall be liable for the quality of the drugs for clinical trial use.
Article 33 An applicant shall, before carrying out the clinical trial of a drug, submit the clinical trial scheme and the names of the principal researchers of the entity responsible for the clinical trial, the list of the participating entities and the researchers thereof, the letter of approval of the ethics committee, the sample of the letter of consent and knowledge to the SFDA for record, and shall submit copies of the aforesaid materials to the (food) drug administrations of the provinces, autonomous regions or municipalities directly under the Central Government where the clinical trial entities are located and where the application is accepted.
Section 3 Administration of Clinical Trials
Article 34 In the course of clinical trial of a drug, the applicant shall appoint a supervisor to supervise the course of trial in pursuance of the Criterions for the Quality Control of Clinical Trial of Drugs.
Article 35 If the applicant finds out that any clinical researcher violates the relevant provisions or fails to carry out the clinical trial scheme, it shall urge the researcher to make corrections; if the circumstances are serious, it may demand suspension or termination of the clinical trial, and shall report the relevant situation to the SFDA and the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government.
Article 36 After finishing each phase of clinical trial, the applicant shall submit a clinical trial and statistical analysis report to the SFDA and to the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government. Moreover, after it finishes the clinical trial in phase IV, it shall submit a summary report to the SFDA.
If the period of clinical trial exceeds 1 year, the applicant shall submit a report on the progress of the clinical trial to the SFDA and the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government every year as of the date of approval.
Article 37 The clinical trials of a drug shall be carried out within 3 years from the date of approval. If it fails to be carried out within that period, the original certifications of approval shall be invalidated automatically. A new application shall be filed if it is still needed to carry out clinical trials.
Article 38 The entities and personnel participating in the clinical trials shall be familiar with the nature, functions, curative effect and safety of the drugs for clinical trial use, shall understand the responsibilities and obligations of clinical researchers, shall obtain the letter of consent and knowledge voluntarily signed by the experimented person, and shall make clinical trial records genuinely, accurately, completely, timely and truthfully.
Article 39 If any applicant violates the Criterions for the Quality Control of Clinical Trial of Drugs or requests for changing the data or conclusion of the trial, the entities and personnel participating in the clinical trial shall report it to the (food) drug administration of the relevant province, autonomous region, or municipality directly under the Central Government and the SFDA.
Article 40 The entities undertaking the clinical trials and the clinical researchers are obliged to take necessary measures to guarantee the safety of the experimented person.
The clinical researchers shall pay close attention to the occurrence of any adverse reaction case involving the drugs for clinical trial use, take proper treating measures for the experimented person without delay, and shall make records.
If any serious adverse reaction case occurs in the course of a clinical trial, the researchers shall, within 24 hours, report it to the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government and the SFDA, and shall timely report it to the ethics committee.
Article 41 The SFDA and the (food) drug administrations of the relevant provinces, autonomous regions and municipalities directly under the Central Government shall conduct supervision and inspection over the clinical trials that have been approved.
Article 42 If any of the following cases occurs in the course of a clinical trial, the SFDA may request the applicant to modify the clinical trial scheme, or to suspend or terminate the clinical trial:
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Order of the State Food and Drug Administration No.17
February 28, 2005
Adopted at the executive meeting of the State Food and Drug Administration, the Administrative Measures for Drug Registration is hereby promulgated and implemented as of May 1, 2005.
Administrative Measures for Drug Registration
Chapter I General Provisions
Article 1 For the purposes of guaranteeing the safety, effectiveness and quality controllability of drugs and regulating the drug registration, these Measures are formulated in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as Drug Administration Law) and the Implementing Regulations of the Drug Administration Law of the People's Republic of China (hereinafter referred to as the Implementing Regulations of the Drug Administration Law).
Article 2 These Measures shall apply to the application for drug clinical trials, drug production or import, as well as the relevant drug registration, inspection, supervision and administration undertaken within the People's Republic of China.
Article 3 The drug registration refers to the examination and approval process during which the State Food and Drug Administration (hereinafter referred to as the SFDA) conducts, at the drug registration application filed by an applicant, a systematic evaluation of the safety, effectiveness and quality controllability of the drug to be marketed and makes the decision on whether or not to approve the application in accordance with the statutory procedures.
Article 4 The state encourages the study and development of new drugs, and employs the system of expedite examination and approval to new drugs developed, new drugs for treating complicated and serious diseases as well as the drugs badly needed for emergencies.
Article 5 The State Food and Drug Administration shall be in charge of the administration of drug registration throughout the country, and be responsible for the examination and approval of drug clinical trial, drug manufacturing and import.
The (food) drug administrations of the provinces, autonomous regions and municipalities directly under the Central Government shall verify the research and development as well as the conditions, examine the completeness, standardization and authenticity of the application materials for drug registration, and organize a test of trial samples.
Article 6 An applicant for drug registration (hereinafter referred to as the applicant) refers to an institution that files an application for drug registration, bears the corresponding legal liabilities, and holds the drug approval certification documents after the application is approved.
A domestic applicant shall be an institution that is lawfully registered within China and can bear civil liabilities independently, while an overseas applicant is a lawful overseas drug manufacturer. Where an overseas applicant applies for the registration of drug import, its office based in China or an agency within China entrusted thereby shall go through the formalities for the registration of the imported drugs.
The personnel handling the applications for drug registration shall be professionals in corresponding fields, and shall be home with the laws and regulations and technical requirements for the administration of drug registration.
Chapter II Application for Drug Registration
Article 7 The applications for drug registration shall include the applications for new drugs, applications for drugs for which there are already state standards, applications for imported drugs and supplementary applications thereof. For a domestic applicant, the procedures for filing applications for new drug and for filing applications for drugs with existing state standards shall be followed; for an overseas applicant, the procedures for the application for imported drugs shall be followed.
Article 8 The "applications for new drugs" shall refer to the applications for the registration of drugs that haven't been marketed within China. If the type of preparation or the route of administration of any drugs that have been marketed is changed, or if the range of indications thereof is newly expanded, the said drugs shall be treated as new drugs.
The applications for drugs with existing state standards shall refer to the applications for the registration of the drugs for which the SFDA has promulgated formal standards.
The applications for imported drugs shall refer to the applications for registration of the drugs that are manufactured overseas and marketed in China.
The supplementary applications shall refer to the applications for changing, adding or canceling the originally approved matters or contents after the applications for new drugs, drugs with existing state standards or imported drugs have been approved.
Article 9 An applicant shall file an application for drug registration with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where it is located, and shall submit relevant materials and drug samples. In the case of an application for registration of imported drugs, the applicant shall file the application with the SFDA.
The applicant shall be responsible for the genuineness of all the contents of the application materials.
Article 10 If two or more entities, as a joint applicant, apply for the registration of a new drug, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the drug manufacturing enterprise is located. If all the applicant entities are drug manufacturing enterprises, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the drug manufacturing enterprise that applies for the preparation is located. If none of the applicant entities is a drug manufacturing enterprise, they shall file an application with the (food) drug administration of the province, autonomous region or municipality directly under the Central Government where the samples are trial-produced.
Article 11 For the drug applied for registration or the prescription,techniques or uses of the drug, the applicant shall provide its patent or the patent of any other person in China as well as the explanations on its ownership; if any patent of any other person exists within China, the applicant shall submit a statement of no infringement upon the patent of others.
Article 12 Where any dispute arises after the application for drug registration is approved, the parties concerned shall settle the dispute through negotiation by themselves, or through the patent administrative department or the people's court pursuant to the relevant laws and regulations.
A patentee may, on the basis of the final ruling made by the patent administrative department or valid judgment affirming infringement as made by the people's court, file with the SFDA for canceling the registered approval number of the drug. Accordingly, the SFDA shall write off the drug approval certification documents of the infringer.
Article 13 As for a drug of which the Chinese patent has been obtained by any other person, an applicant may file a registration application within 2 years before the expiration of the patent of that drug. The SFDA shall conduct an examination pursuant to these Measures, and, if the applicant meets the relevant conditions, it shall issue to it the registered number of drug approval, an Imported Drug Registration Certificate or the Pharmaceutical Product Registration Certificate after the patent expires.
Article 14 Where a producer or seller, who has obtained a permit to produce or sell an drug containing any new chemical ingredient, submits any undisclosed experimental data or other data obtained by itself, the SFDA shall not, within 6 years after it grants this permit, approve any other application for using the undisclosed data unless it is consented to by the applicant who has obtained the aforesaid permit, unless the data submitted by the other applicant is obtained by itself.
Chapter III Pre-clinical trial of New Drugs
Article 15 The pre-clinical trial of new drugs for applying for drug registration shall include synthetic techniques, extraction methods, physical and chemical properties, purity, choice of form of this drug, selection of prescriptions, preparation techniques, inspection methods, quality indicators, stability, pharmacology, toxicology, nuclein animal dynamics, etc. As for Chinese traditional medicine preparations, the sources and processing of the original medicine materials, etc. shall also be included; as for biologic products, the sources, quality standards, preservation conditions, biological features, inheritance stability and immunological study of the primary raw materials such as microbial and toxic species, cell line or organism, etc. shall also be included.
Article 16 The relevant administrative provisions shall be executed in the pre-clinical trial of new drugs, and the Criterions for the Quality Control of Non-clinical Study of Drugs must be executed in the safety evaluation study.
Article 17 An institution engaging in drug study and development must have the personnel, site, equipment, instruments and management system that can meet the requirements for the experiment and study projects. The animals, reagents, and raw materials for experiment use shall conform to the relevant provisions and requirements of the state, and shall ensure the authenticity of all the experiment data and materials.
Article 18 As to a separate application for the registration of a drug preparation, the applicant shall have, for the raw material medicines used for the study of the drug preparation, the registered number of drug approval, an Imported Drugs Registration Certificate or Pharmaceutical Product Registration Certificate, and the raw material medicines must be obtained through legal channels. If, for the raw material medicines, the applicant does not have the registered number of drug approval, anImported Drug Registration Certificate or Pharmaceutical Product Registration Certificate, such applicant shall be subject to the approval of the SFDA.
Article 19 Where an applicant entrusts any other institution to conduct drug study, separate experiment, testing, trial manufacturing or production of samples etc, it shall enter into a contract with the trustee. The applicant shall be responsible for the authenticity of the drug study data in the application materials.
Article 20 If the application materials for drug registration include any drug experiment and study materials submitted by any overseas drug study institution, there must be attached with the explanations produced by that overseas drug study institution on the projects and the page numbers of the materials provided, and the certifications which can prove that the institution has been legally registered and notarized overseas, and the attached materials may be used as the application materials unless they have been acknowledged by the SFDA. The SFDA shall send personnel to make on-spot inspection where necessary.
Article 21 When inspecting drug study according to the needs, the SFDA and the (food) drug administration of a province, autonomous region or municipality directly under the Central Government may request the applicant or the drug study institution undertaking the experiment to conduct an experiment again according to the projects, methods and data specified in the application materials, and shall send personnel to oversee the experiment on the spot; or an institute for drug control or other drug study institution may be entrusted to make an experiment again.
Article 22 The pre-clinical study of new drugs shall be conducted by referring to the relevant technical guiding principles promulgated by the SFDA. Where an applicant adopts other evaluation methods and techniques in the experiment, it shall submit the materials that can prove their scientificness.
Chapter IV Clinical Trial of Drugs
Section 1 Basic Requirements
Article 23 The clinical trial of drugs (including bioequivalence experiments) shall be subject to the approval of the SFDA and shall follow the Criterions for the Quality Control of Clinical Trials of Drugs.
Article 24 An applicant shall conduct clinical trials when applying for the registration of a new drug. The clinical trials are classified into four phases: I, II, III and IV. Before a new drug is approved for marketing, phases I, II, and III clinical trials shall be conducted. Under certain circumstances, the applicant may, upon approval, only conduct phases II and III clinical trials or only phase III clinical trials.
The phase I clinical trials: the preliminary trials on clinical pharmacology and human body safety evaluation, which aim to observe the degree of tolerance of human body against the new drug and the drug dynamics, and provide the basis for working out the dosage administration scheme.
The phase II clinical trials: the preliminary evaluation of the treating effects, which aim to preliminarily evaluate the treating effect and safety of the drug on the target patients with the applicable disease, and also to provide the basis for the determination of study design and dosage administration scheme for the clinical trial in phase III. Various methods may be employed for the study design of this phase in light of the specific study purpose, including the randomized controlled trial.
The phase III clinical trials: the confirmation phase of the treating effect, which aim to further verify the treating effect and safety of the drug on the target patient with the applicable disease, to evaluate the relationship between interest and risk, and to eventually provide adequate basis for the examination of the drug registration application. Generally, the trials shall be randomly controlled ones with sufficient samples.
The phase IV clinical trials: the phase of application study conducted by the applicant independently after the new drug comes into the market, which aim to examine the curative effect of the drug and the adverse reactions when it is widely used, to evaluate the relationship between interest and risk when the drug is used in ordinary or special groups and to improve the dosage administration, etc.
Article 25 Generally speaking, it is not required to conduct any clinical trial for the registration of drugs with existing state standards. Among those which require a clinical trial, a bioequivalence trial shall be conducted for chemical drugs. For a drug whose quality needs to be controlled by techniques and standards, clinical trials shall be conducted. In a supplementary application, the applicant shall conduct clinical trials if new indications are added for any drug already on the market or if the manufacturing techniques of the drug are altered significantly.
The bioequivalence trial is, under the same testing conditions, to compare the statistical disparities of the absorption extent and speed of the active substances of the identical dosage or of different dosages of the same drug in the human body through the approach of bio-availability study and by considering the parameters of drug dynamics as the indicators.
Article 26 The number of cases experimented in drug clinical trials shall be in line with the purpose of the drug clinical trials, shall meet the relevant statistical requirements and shall not be less than the minimum clinical trial case number as specified in these Measures. As for a rare disease, special disease or any other circumstance where it is needed to reduce clinical trial cases or to exempt the clinical trial, the examination and approval of the SFDA is required.
Article 27 With respect to the bacteria or other special drugs prepared during the phase of selecting bacteria or virus species, if it is unable to evaluate the curative effect thereof due to lack of suitable animal model and laboratory, the applicant may apply for clinical trial with the SFDA on the precondition that the safety of the experimented person is secured.
Section 2 Requirements Before Trial
Article 28 After a drug clinical trial has been approved, the applicant shall select, from the institutions qualified for drug clinical trials, an institution to undertake the drug clinical trial, decide through consultation the entity responsible for the clinical trial, the major researchers and the entities participating in the clinical trial.
Article 29 The applicant shall conclude a clinical trial contract with the selected entity responsible for and the entities participating in the clinical trial, provide the researchers with manuals, and together with the researchers, design and perfect the clinical trial scheme by referring to the relevant technical guiding principles.
The clinical trial scheme shall be subject to the examination of the ethic committee of the clinical trial institution.
Article 30 The applicant shall provide the selected clinical trial entities with free medicines for clinical trial use and drugs for comparison use (except for clinical trials in phase IV), to which it shall attach a sample inspection report, and bear the expenses needed for the clinical trial.
Article 31 The drugs for clinical trial use shall be produced and prepared in workshops meeting the conditions as provided for in the Good Manufacturing Practices (GMP) for Pharmaceutical Products. The process of production and preparation shall strictly follow the Good Manufacturing Practices (GMP) for Pharmaceutical Products.
The SFDA or the entrusted (food) drug administration of the province, autonomous region or municipality directly under the Central Government may conduct on-the-spot checks where it so requires.
Article 32 An applicant may inspect the drugs for clinical trial use by itself according to the drug standards determined by the SFDA, or entrust an institute to do the drug control as specified in Articles 147 and 148 to conduct the inspection. The drugs shall not be used in clinical trial unless they have passed the drug inspection.
The SFDA may designate an institute for drug control to make a selective inspection over the drugs for clinical trial use.
The vaccine products, blood products, and other biological products as well as overseas-manufactured drugs for clinical trial use as provided for by the SFDA, shall be subject to the inspection by the institutes for drug control designated by the SFDA. They shall not be used in the clinical trial unless they have passed the aforesaid drug inspection.
The applicant shall be liable for the quality of the drugs for clinical trial use.
Article 33 An applicant shall, before carrying out the clinical trial of a drug, submit the clinical trial scheme and the names of the principal researchers of the entity responsible for the clinical trial, the list of the participating entities and the researchers thereof, the letter of approval of the ethics committee, the sample of the letter of consent and knowledge to the SFDA for record, and shall submit copies of the aforesaid materials to the (food) drug administrations of the provinces, autonomous regions or municipalities directly under the Central Government where the clinical trial entities are located and where the application is accepted.
Section 3 Administration of Clinical Trials
Article 34 In the course of clinical trial of a drug, the applicant shall appoint a supervisor to supervise the course of trial in pursuance of the Criterions for the Quality Control of Clinical Trial of Drugs.
Article 35 If the applicant finds out that any clinical researcher violates the relevant provisions or fails to carry out the clinical trial scheme, it shall urge the researcher to make corrections; if the circumstances are serious, it may demand suspension or termination of the clinical trial, and shall report the relevant situation to the SFDA and the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government.
Article 36 After finishing each phase of clinical trial, the applicant shall submit a clinical trial and statistical analysis report to the SFDA and to the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government. Moreover, after it finishes the clinical trial in phase IV, it shall submit a summary report to the SFDA.
If the period of clinical trial exceeds 1 year, the applicant shall submit a report on the progress of the clinical trial to the SFDA and the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government every year as of the date of approval.
Article 37 The clinical trials of a drug shall be carried out within 3 years from the date of approval. If it fails to be carried out within that period, the original certifications of approval shall be invalidated automatically. A new application shall be filed if it is still needed to carry out clinical trials.
Article 38 The entities and personnel participating in the clinical trials shall be familiar with the nature, functions, curative effect and safety of the drugs for clinical trial use, shall understand the responsibilities and obligations of clinical researchers, shall obtain the letter of consent and knowledge voluntarily signed by the experimented person, and shall make clinical trial records genuinely, accurately, completely, timely and truthfully.
Article 39 If any applicant violates the Criterions for the Quality Control of Clinical Trial of Drugs or requests for changing the data or conclusion of the trial, the entities and personnel participating in the clinical trial shall report it to the (food) drug administration of the relevant province, autonomous region, or municipality directly under the Central Government and the SFDA.
Article 40 The entities undertaking the clinical trials and the clinical researchers are obliged to take necessary measures to guarantee the safety of the experimented person.
The clinical researchers shall pay close attention to the occurrence of any adverse reaction case involving the drugs for clinical trial use, take proper treating measures for the experimented person without delay, and shall make records.
If any serious adverse reaction case occurs in the course of a clinical trial, the researchers shall, within 24 hours, report it to the (food) drug administration of the relevant province, autonomous region or municipality directly under the Central Government and the SFDA, and shall timely report it to the ethics committee.
Article 41 The SFDA and the (food) drug administrations of the relevant provinces, autonomous regions and municipalities directly under the Central Government shall conduct supervision and inspection over the clinical trials that have been approved.
Article 42 If any of the following cases occurs in the course of a clinical trial, the SFDA may request the applicant to modify the clinical trial scheme, or to suspend or terminate the clinical trial:
1.
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