Administrative Measures for Drug Registration
Administrative Measures for Drug Registration
Administrative Measures for Drug Registration
Order of the State Administration for Market Regulation No. 27
January 22, 2020
The Administrative Measures for Drug Registration, which were deliberated and adopted at the first executive meeting of 2020 of the State Administration for Market Regulation on January 15, 2020, are hereby issued and shall come into force as of July 1, 2020.
Xiao Yaqing, Director
Administrative Measures for Drug Registration
(Issued as Order of the State Administration for Market Regulation No. 27 on January 22, 2020)
Chapter I General Provisions
Article 1 These Measures are formulated in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as the "Drug Administration Law"), the Law of the People's Republic of China on Traditional Chinese Medicine, the Vaccine Administration Law of the People's Republic of China (hereinafter referred to as the "Vaccine Administration Law"), the Administrative Licensing Law of the People's Republic of China, the Implementing Regulations on the Drug Administration Law of the People's Republic of China and other laws and administrative regulations with a view to regulating drug registration and ensuring drug safety, efficacy and quality controllability.
Article 2 These Measures shall apply to those engaging in drug development and registration as well as the supervision and management thereof for the purpose of the marketing of drugs within the territory of the People's Republic of China.
Article 3 Drug registration refers to an activity where an applicant for drug registration (hereinafter referred to as "applicant") submits an application for drug clinical trial, marketing authorization and re-registration, among others, as well as supplementary application as per legal procedures and in line with relevant requirements, and the medical products administration conducts examinations in terms of safety, efficacy and quality controllability, etc. based on laws, regulations and existing scientific cognition to decide whether to approve the application.
After obtaining the drug registration certificate, the applicant shall be the marketing authorization holder (hereinafter referred to as "MAH").
Article 4 Drug registration shall be subject to classified registration administration in terms of traditional Chinese medicines, chemical drugs and biological products, etc.
Registration of traditional Chinese medicines shall be classified by innovative traditional Chinese medicines, modified new traditional Chinese medicines, traditional Chinese medicine compound preparations of ancient classical prescriptions and medicines with the same names and the same prescriptions, etc.
Registration of chemical drugs shall be classified by innovative chemical drugs, modified new chemical drugs and generic drugs, etc.
Registration of biological products shall be classified by innovative biological products, modified new biological products and marketed biological products (including biosimilars), etc.
Refined classification of traditional Chinese medicines, chemical drugs and biological products, etc., and the corresponding requirements for application materials shall be formulated upon organization by the National Medical Products Administration (hereinafter referred to as the "NMPA") according to the product characteristics, innovation level, and review management needs of registered drugs, and shall be made public.
The application for registration of drugs manufactured overseas shall be subject to refined classification of drugs and the corresponding requirements for application materials.
Article 5 The NMPA shall be in charge of the administration of drug registration all over the country and be responsible for establishing administrative systems and regimes for drug registration, formulating administrative practices on drug registration, and legally organizing drug registration review and approval and relevant supervision and management. The Center for Drug Evaluation of the NMPA (hereinafter referred to as the "CDE") shall be responsible for reviewing applications for drug clinical trials, applications for marketing authorization, supplementary applications and applications for re-registration of drugs manufactured overseas, among others. The National Institutes for Food and Drug Control (hereinafter referred to as the "NIFDC"), the Chinese Pharmacopoeia Commission (hereinafter referred to as the "ChP"), the Center for Food and Drug Inspection of the NMPA (hereinafter referred to as the "CFDI"), the Center for Drug Reevaluation of the NMPA (hereinafter referred to as the "CDR"), the Center for Administrative Matter Acceptance Service and Complaint Report of the NMPA, the Center for Information of the NMPA (hereinafter referred to as the "IC") and other drug-related professional technical institutions shall undertake the drug registration inspection, generic name approval, verification, monitoring and evaluation, certificate production and service, relevant information construction and management, and other relevant work which are required for implementation of drug registration administration in accordance with the law.
Article 6 Medical products administrations of all provinces, autonomous regions and municipalities directly under the Central Government shall be responsible for the following drug registration-related administration within their respective administrative regions:
1. acceptance, examination and approval of the applications for re-registration of drugs manufactured at home;
2. management of the filing and reporting matters concerning post-marketing alterations of drugs;
3. organization of the routine regulation of drug non-clinical safety evaluation and research institutions and drug clinical trial institutions, and investigation and punishment of violations of laws;
4. taking part in such work as drug registration verification and inspection organized by the NMPA; and
5. relevant matters concerning drug registration to be implemented under the delegation of the NMPA.
Medical products administrations of provinces, autonomous region and municipalities directly under the Central Government shall set up or designate drug-related professional technical institutions to undertake such work as review, inspection, verification, monitoring and evaluation required for implementing drug supervision and management in accordance with the law.
Article 7 Drug registration administration shall follow the principles of openness, fairness and impartiality and be oriented towards clinical value to encourage the research and creation of new drugs and actively promote the development of generic drugs.
The NMPA shall constantly promote the reform of the review and approval system, optimize the review and approval procedures, improve the efficiency of review and approval, and establish a drug registration administration system led by review and with the support of inspection, verification, monitoring and evaluation, etc.
Chapter II Basic Systems and Requirements
Article 8 Whoever is engaged in drug development and drug registration shall abide by pertinent laws, regulations, rules, standards and practices; whoever adopts other evaluation methods and technologies with reference to relevant technical guidelines shall prove the scientificity and applicability thereof. It shall be ensured that information in the whole course is authentic, accurate, complete and traceable.
Drugs shall conform to national drug standards and the drug quality standards approved by the NMPA. Drug quality standards approved by the NMPA shall be drug registration standards, which shall comply with the general technical requirements of the Pharmacopoeia of the People's Republic of China, and shall not be lower than the provisions of the Pharmacopoeia of the People's Republic of China. If any testing item or indicator of a variety for which the registration application has been submitted is not applicable to the Pharmacopoeia of the People's Republic of China, the applicant shall provide sufficient supporting data.
The CDE and other professional technical institutions shall formulate and make public technical guidelines and procedures in light of scientific advances, industry development actualities and drug supervision and management needs.
Article 9 Applicants shall be those enterprises or drug development institutions, etc. that can assume corresponding legal responsibilities. An overseas applicant shall designate a business corporation within the territory of China to handle matters related to drug registration.
Article 10 An applicant shall complete relevant research work in terms of pharmacy, pharmacology and toxicology, and drug clinical trials, etc. before applying for drug marketing registration. Non-clinical drug safety evaluation research shall be carried out in an institution that has passed the certification of the Good Laboratory Practice for Non-clinical Laboratory Studies (hereinafter referred to as the "GLP") and comply with the GLP. Drug clinical trials shall be approved, in which bioequivalence trials shall be filed; a drug clinical trial shall be conducted in a drug clinical trial institution that complies with relevant regulations, and shall conform to the Good Clinical Practice (hereinafter referred to as the "GCP").
Whoever applies for drug registration shall submit authentic, sufficient and reliable data, materials and samples to prove the safety, efficacy and quality controllability of the drug.
Where any overseas research material or data is submitted in support of drug registration, the source thereof, research institution or laboratory conditions, quality system requirements as well as other management conditions shall comply with the prevailing principles of the International Council for Harmonization and with relevant Chinese requirements for the administration of drug registration.
Article 11 An applicant shall, in the case of any alteration to any item or content contained in the original drug registration approval certificate or appendixes thereto, in accordance with regulations and with reference to relevant technical guidelines, carry out sufficient research and validation of the drug alteration, fully assess the possible impacts of the alteration on the safety, efficacy and quality controllability of the drug, and submit a supplementary application, and carry out filing or reporting in accordance with the alteration procedures. (Relevant article: 1 review)
Article 12 A drug registration certificate shall be valid for five years. Within the validity period of a drug registration certificate, the MAH shall continually ensure the safety, efficacy and quality controllability of the drug marketed and shall apply for drug re-registration six months prior to the expiry date of the certificate. (Relevant article: 1 review)
Article 13 The NMPA shall establish a system for accelerating drug marketing registration to support clinical value-oriented drug innovation. As for acceptable applications for drug registration, the applicants may apply for access to the procedures for breakthrough therapy designation ("BTD") drugs, conditional approval, priority review and approval or special approval. During drug development and registration, medical products administrations and their respective professional technical institutions shall provide necessary policies and technical supports such as technical guidance, communication, priority in resource allocation and shortened time limit for review.
Article 14 The NMPA shall establish a system for bundling review and approval of chemical active pharmaceutical ingredients ("APIs"), pharmaceutical excipients, packaging materials and containers in direct contact with drugs. During approval of pharmaceutical preparations, the chemical APIs shall be reviewed and approved together, and relevant pharmaceutical excipients, packaging materials and containers in direct contact with drugs shall also be reviewed. The CDE shall establish an information registration platform for APIs, pharmaceutical excipients, and packaging materials and containers in direct contact with drugs to publicize relevant registration information for selection by relevant applicants or MAHs, and for bundling review during review of the applications for registration of relevant pharmaceutical preparations.
Article 15 Prescription drugs and over-the-counter ("OTC") drugs are subject to classified registration and conversion administration. The CDE shall formulate and make public relevant technical guidelines and procedures with respect to the marketing registration of OTC drugs according to the characteristics thereof. The CDR shall formulate and make public relevant technical requirements and procedures with respect to the post-marketing conversion of prescription drugs and OTC drugs.
Article 16 Applicants may, before applying for drug clinical trials, during drug clinical trials, before applying for marketing authorization and at other key stages, communicate with the CDE and other professional technical institutions about key issues. During drug registration, the CDE and other professional technical institutions may, in light of work needs, organize communication with the applicants.
The CDE and other professional technical institutions shall, in light of their functions, formulate and make public the procedures, requirements and time limit for communication separately.
Article 17 The CDE and other professional technical institutions shall, in light of work needs, establish an expert consultation system and set up an expert consultation committee, hear experts' opinions on major issues in the process of review, verification, inspection and generic name approval, etc., and give full play to the experts' role of technical support.
Article 18 The NMPA shall establish a catalog of chemical drugs that are newly approved for marketing and those which have passed the consistency evaluation of the quality and efficacy of generic drugs, stating the drug name, active ingredients, dosage form and specifications, reference preparation or not, the MAH and other relevant information. The catalog of chemical drugs shall be updated in a timely manner and made public. The collection procedures and requirements for the catalog of chemical drugs shall be formulated and made public by the CDE.
Article 19 The NMPA shall support the inheritance and innovation of traditional Chinese medicines, establish and improve the registration administration system and technical evaluation system that conform to the characteristics of traditional Chinese medicine, encourage the use of modern science and technology and traditional research methods to develop traditional Chinese medicine, strengthen the quality control of traditional Chinese medicine, and improve the level of clinical trials of traditional Chinese medicine.
For the purpose of application for registration of traditional Chinese medicine, applicants shall assess clinical value and resources, highlight clinical value as the guide, and promote the sustainable use of resources. (Relevant article: 1 review)
Chapter III Drug Marketing Registration
Section 1 Drug Clinical Trial
Article 20 For the purpose of these Measures, drug clinical trial refers to drug research which is to be conducted in humans to determine the safety and efficacy of drugs for the purpose of drug marketing registration.
Article 21 Drug clinical trials shall be divided into Phase I clinical trial, Phase II clinical trial, Phase III clinical trial, Phase IV clinical trial, and bioequivalence trial. According to the drug characteristics and research objectives, the research content shall include clinical pharmacology research, exploratory clinical trials, confirmatory clinical trials and post-marketing research.
Article 22 Drug clinical trials shall be conducted in drug clinical trial institutions that have appropriate conditions and have registered in accordance with regulations. Specifically, vaccine clinical trials shall be implemented or organized for implementation by Grade-III medical institutions or disease prevention and control institutions at or above the provincial level that meet the conditions prescribed by the NMPA and the National Health Commission.
Article 23 An applicant that applies for a drug clinical trial after completion of the pharmaceutical, pharmacological and toxicological research, etc., which support the drug clinical trial, shall submit relevant research materials according to the requirements for application materials.
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Order of the State Administration for Market Regulation No. 27
January 22, 2020
The Administrative Measures for Drug Registration, which were deliberated and adopted at the first executive meeting of 2020 of the State Administration for Market Regulation on January 15, 2020, are hereby issued and shall come into force as of July 1, 2020.
Xiao Yaqing, Director
Administrative Measures for Drug Registration
(Issued as Order of the State Administration for Market Regulation No. 27 on January 22, 2020)
Chapter I General Provisions
Article 1 These Measures are formulated in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as the "Drug Administration Law"), the Law of the People's Republic of China on Traditional Chinese Medicine, the Vaccine Administration Law of the People's Republic of China (hereinafter referred to as the "Vaccine Administration Law"), the Administrative Licensing Law of the People's Republic of China, the Implementing Regulations on the Drug Administration Law of the People's Republic of China and other laws and administrative regulations with a view to regulating drug registration and ensuring drug safety, efficacy and quality controllability.
Article 2 These Measures shall apply to those engaging in drug development and registration as well as the supervision and management thereof for the purpose of the marketing of drugs within the territory of the People's Republic of China.
Article 3 Drug registration refers to an activity where an applicant for drug registration (hereinafter referred to as "applicant") submits an application for drug clinical trial, marketing authorization and re-registration, among others, as well as supplementary application as per legal procedures and in line with relevant requirements, and the medical products administration conducts examinations in terms of safety, efficacy and quality controllability, etc. based on laws, regulations and existing scientific cognition to decide whether to approve the application.
After obtaining the drug registration certificate, the applicant shall be the marketing authorization holder (hereinafter referred to as "MAH").
Article 4 Drug registration shall be subject to classified registration administration in terms of traditional Chinese medicines, chemical drugs and biological products, etc.
Registration of traditional Chinese medicines shall be classified by innovative traditional Chinese medicines, modified new traditional Chinese medicines, traditional Chinese medicine compound preparations of ancient classical prescriptions and medicines with the same names and the same prescriptions, etc.
Registration of chemical drugs shall be classified by innovative chemical drugs, modified new chemical drugs and generic drugs, etc.
Registration of biological products shall be classified by innovative biological products, modified new biological products and marketed biological products (including biosimilars), etc.
Refined classification of traditional Chinese medicines, chemical drugs and biological products, etc., and the corresponding requirements for application materials shall be formulated upon organization by the National Medical Products Administration (hereinafter referred to as the "NMPA") according to the product characteristics, innovation level, and review management needs of registered drugs, and shall be made public.
The application for registration of drugs manufactured overseas shall be subject to refined classification of drugs and the corresponding requirements for application materials.
Article 5 The NMPA shall be in charge of the administration of drug registration all over the country and be responsible for establishing administrative systems and regimes for drug registration, formulating administrative practices on drug registration, and legally organizing drug registration review and approval and relevant supervision and management. The Center for Drug Evaluation of the NMPA (hereinafter referred to as the "CDE") shall be responsible for reviewing applications for drug clinical trials, applications for marketing authorization, supplementary applications and applications for re-registration of drugs manufactured overseas, among others. The National Institutes for Food and Drug Control (hereinafter referred to as the "NIFDC"), the Chinese Pharmacopoeia Commission (hereinafter referred to as the "ChP"), the Center for Food and Drug Inspection of the NMPA (hereinafter referred to as the "CFDI"), the Center for Drug Reevaluation of the NMPA (hereinafter referred to as the "CDR"), the Center for Administrative Matter Acceptance Service and Complaint Report of the NMPA, the Center for Information of the NMPA (hereinafter referred to as the "IC") and other drug-related professional technical institutions shall undertake the drug registration inspection, generic name approval, verification, monitoring and evaluation, certificate production and service, relevant information construction and management, and other relevant work which are required for implementation of drug registration administration in accordance with the law.
Article 6 Medical products administrations of all provinces, autonomous regions and municipalities directly under the Central Government shall be responsible for the following drug registration-related administration within their respective administrative regions:
1. acceptance, examination and approval of the applications for re-registration of drugs manufactured at home;
2. management of the filing and reporting matters concerning post-marketing alterations of drugs;
3. organization of the routine regulation of drug non-clinical safety evaluation and research institutions and drug clinical trial institutions, and investigation and punishment of violations of laws;
4. taking part in such work as drug registration verification and inspection organized by the NMPA; and
5. relevant matters concerning drug registration to be implemented under the delegation of the NMPA.
Medical products administrations of provinces, autonomous region and municipalities directly under the Central Government shall set up or designate drug-related professional technical institutions to undertake such work as review, inspection, verification, monitoring and evaluation required for implementing drug supervision and management in accordance with the law.
Article 7 Drug registration administration shall follow the principles of openness, fairness and impartiality and be oriented towards clinical value to encourage the research and creation of new drugs and actively promote the development of generic drugs.
The NMPA shall constantly promote the reform of the review and approval system, optimize the review and approval procedures, improve the efficiency of review and approval, and establish a drug registration administration system led by review and with the support of inspection, verification, monitoring and evaluation, etc.
Chapter II Basic Systems and Requirements
Article 8 Whoever is engaged in drug development and drug registration shall abide by pertinent laws, regulations, rules, standards and practices; whoever adopts other evaluation methods and technologies with reference to relevant technical guidelines shall prove the scientificity and applicability thereof. It shall be ensured that information in the whole course is authentic, accurate, complete and traceable.
Drugs shall conform to national drug standards and the drug quality standards approved by the NMPA. Drug quality standards approved by the NMPA shall be drug registration standards, which shall comply with the general technical requirements of the Pharmacopoeia of the People's Republic of China, and shall not be lower than the provisions of the Pharmacopoeia of the People's Republic of China. If any testing item or indicator of a variety for which the registration application has been submitted is not applicable to the Pharmacopoeia of the People's Republic of China, the applicant shall provide sufficient supporting data.
The CDE and other professional technical institutions shall formulate and make public technical guidelines and procedures in light of scientific advances, industry development actualities and drug supervision and management needs.
Article 9 Applicants shall be those enterprises or drug development institutions, etc. that can assume corresponding legal responsibilities. An overseas applicant shall designate a business corporation within the territory of China to handle matters related to drug registration.
Article 10 An applicant shall complete relevant research work in terms of pharmacy, pharmacology and toxicology, and drug clinical trials, etc. before applying for drug marketing registration. Non-clinical drug safety evaluation research shall be carried out in an institution that has passed the certification of the Good Laboratory Practice for Non-clinical Laboratory Studies (hereinafter referred to as the "GLP") and comply with the GLP. Drug clinical trials shall be approved, in which bioequivalence trials shall be filed; a drug clinical trial shall be conducted in a drug clinical trial institution that complies with relevant regulations, and shall conform to the Good Clinical Practice (hereinafter referred to as the "GCP").
Whoever applies for drug registration shall submit authentic, sufficient and reliable data, materials and samples to prove the safety, efficacy and quality controllability of the drug.
Where any overseas research material or data is submitted in support of drug registration, the source thereof, research institution or laboratory conditions, quality system requirements as well as other management conditions shall comply with the prevailing principles of the International Council for Harmonization and with relevant Chinese requirements for the administration of drug registration.
Article 11 An applicant shall, in the case of any alteration to any item or content contained in the original drug registration approval certificate or appendixes thereto, in accordance with regulations and with reference to relevant technical guidelines, carry out sufficient research and validation of the drug alteration, fully assess the possible impacts of the alteration on the safety, efficacy and quality controllability of the drug, and submit a supplementary application, and carry out filing or reporting in accordance with the alteration procedures. (Relevant article: 1 review)
Article 12 A drug registration certificate shall be valid for five years. Within the validity period of a drug registration certificate, the MAH shall continually ensure the safety, efficacy and quality controllability of the drug marketed and shall apply for drug re-registration six months prior to the expiry date of the certificate. (Relevant article: 1 review)
Article 13 The NMPA shall establish a system for accelerating drug marketing registration to support clinical value-oriented drug innovation. As for acceptable applications for drug registration, the applicants may apply for access to the procedures for breakthrough therapy designation ("BTD") drugs, conditional approval, priority review and approval or special approval. During drug development and registration, medical products administrations and their respective professional technical institutions shall provide necessary policies and technical supports such as technical guidance, communication, priority in resource allocation and shortened time limit for review.
Article 14 The NMPA shall establish a system for bundling review and approval of chemical active pharmaceutical ingredients ("APIs"), pharmaceutical excipients, packaging materials and containers in direct contact with drugs. During approval of pharmaceutical preparations, the chemical APIs shall be reviewed and approved together, and relevant pharmaceutical excipients, packaging materials and containers in direct contact with drugs shall also be reviewed. The CDE shall establish an information registration platform for APIs, pharmaceutical excipients, and packaging materials and containers in direct contact with drugs to publicize relevant registration information for selection by relevant applicants or MAHs, and for bundling review during review of the applications for registration of relevant pharmaceutical preparations.
Article 15 Prescription drugs and over-the-counter ("OTC") drugs are subject to classified registration and conversion administration. The CDE shall formulate and make public relevant technical guidelines and procedures with respect to the marketing registration of OTC drugs according to the characteristics thereof. The CDR shall formulate and make public relevant technical requirements and procedures with respect to the post-marketing conversion of prescription drugs and OTC drugs.
Article 16 Applicants may, before applying for drug clinical trials, during drug clinical trials, before applying for marketing authorization and at other key stages, communicate with the CDE and other professional technical institutions about key issues. During drug registration, the CDE and other professional technical institutions may, in light of work needs, organize communication with the applicants.
The CDE and other professional technical institutions shall, in light of their functions, formulate and make public the procedures, requirements and time limit for communication separately.
Article 17 The CDE and other professional technical institutions shall, in light of work needs, establish an expert consultation system and set up an expert consultation committee, hear experts' opinions on major issues in the process of review, verification, inspection and generic name approval, etc., and give full play to the experts' role of technical support.
Article 18 The NMPA shall establish a catalog of chemical drugs that are newly approved for marketing and those which have passed the consistency evaluation of the quality and efficacy of generic drugs, stating the drug name, active ingredients, dosage form and specifications, reference preparation or not, the MAH and other relevant information. The catalog of chemical drugs shall be updated in a timely manner and made public. The collection procedures and requirements for the catalog of chemical drugs shall be formulated and made public by the CDE.
Article 19 The NMPA shall support the inheritance and innovation of traditional Chinese medicines, establish and improve the registration administration system and technical evaluation system that conform to the characteristics of traditional Chinese medicine, encourage the use of modern science and technology and traditional research methods to develop traditional Chinese medicine, strengthen the quality control of traditional Chinese medicine, and improve the level of clinical trials of traditional Chinese medicine.
For the purpose of application for registration of traditional Chinese medicine, applicants shall assess clinical value and resources, highlight clinical value as the guide, and promote the sustainable use of resources. (Relevant article: 1 review)
Chapter III Drug Marketing Registration
Section 1 Drug Clinical Trial
Article 20 For the purpose of these Measures, drug clinical trial refers to drug research which is to be conducted in humans to determine the safety and efficacy of drugs for the purpose of drug marketing registration.
Article 21 Drug clinical trials shall be divided into Phase I clinical trial, Phase II clinical trial, Phase III clinical trial, Phase IV clinical trial, and bioequivalence trial. According to the drug characteristics and research objectives, the research content shall include clinical pharmacology research, exploratory clinical trials, confirmatory clinical trials and post-marketing research.
Article 22 Drug clinical trials shall be conducted in drug clinical trial institutions that have appropriate conditions and have registered in accordance with regulations. Specifically, vaccine clinical trials shall be implemented or organized for implementation by Grade-III medical institutions or disease prevention and control institutions at or above the provincial level that meet the conditions prescribed by the NMPA and the National Health Commission.
Article 23 An applicant that applies for a drug clinical trial after completion of the pharmaceutical, pharmacological and toxicological research, etc., which support the drug clinical trial, shall submit relevant research materials according to the requirements for application materials.
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