Order of the State Administration for Market Regulation
No. 27
The Measures for the Administration of Drug Registration was deliberated and adopted at the first executive meeting of the State Administration for Market Regulation in 2020 on January 15, 2020. It is hereby promulgated and shall come into effect as of July 1, 2020.
Director Xiao Yaqing
January 22, 2020
Measures for the Administration of Drug Registration
(Announced by Order No. 27 of the State Administration for Market Regulation on January 22, 2020)
Chapter One General Provisions
Article 1: To standardize the behavior of drug registration and ensure the safety, efficacy and controllable quality of drugs, This measure is formulated in accordance with the "Pharmaceutical Administration Law of the People's Republic of China" (hereinafter referred to as the "Pharmaceutical 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 "Regulations for the Implementation of the Pharmaceutical Administration Law of the People's Republic of China" and other laws and administrative regulations.
rticle 2 This measure shall apply to the activities of drug research and development, registration and supervision and administration for the purpose of drug marketing within the territory of the People's Republic of China.
Article 3 Drug registration refers to the activity where a drug registration applicant (hereinafter referred to as the "applicant") submits applications for drug clinical trials, drug marketing authorization, re-registration, etc., as well as supplementary applications in accordance with legal procedures and relevant requirements, and the drug regulatory department reviews the safety, efficacy and quality controllability based on laws, regulations and existing scientific understanding, and decides whether to approve the application.
After obtaining the drug registration certificate, the applicant becomes the marketing authorization holder of the drug (hereinafter referred to as the "holder").
Article 4 Drug registration shall be classified and managed in accordance with the categories of traditional Chinese medicine, chemical drugs and biological products, etc.
The registration of traditional Chinese medicine is classified into innovative traditional Chinese medicine drugs, improved new traditional Chinese medicine drugs, traditional Chinese medicine compound preparations based on ancient classic prescriptions, and drugs with the same name and formula.
Chemical drug registration is classified into innovative chemical drugs, improved new chemical drugs, generic drugs, etc.
Biological product registration is classified into innovative biological products, improved new biological products, and marketed biological products (including biosimilars), etc.
The detailed classification of drugs such as traditional Chinese medicine, chemical drugs and biological products, as well as the corresponding requirements for application materials, shall be formulated by the National Medical Products Administration based on the product characteristics, innovation level and review management needs of the registered drugs, and shall be made public to the society.
The registration application for drugs produced overseas shall be carried out in accordance with the detailed classification of drugs and the corresponding requirements for declaration materials.
Article 5 The National Medical Products Administration is in charge of the national drug registration management work, responsible for establishing the drug registration management work system and regulations, formulating drug registration management norms, organizing drug registration review and approval in accordance with the law, and related supervision and management work. The Center for Drug Evaluation of the National Medical Products Administration (hereinafter referred to as the Center for Drug Evaluation) is responsible for the review of applications for drug clinical trials, applications for drug marketing authorization, supplementary applications, and applications for re-registration of drugs produced overseas. The National Institutes for Food and Drug Control (hereinafter referred to as NIFU), the National Medical Products Administration's Pharmacopoeia Commission (hereinafter referred to as Pharmacopoeia Commission), the Center for Food and Drug Evaluation of the National Medical Products Administration (hereinafter referred to as the Center for Drug Evaluation), the Center for Drug Evaluation of the National Medical Products Administration (hereinafter referred to as the Center for Drug Evaluation), and the administrative affairs acceptance service and complaint and reporting of the National Medical Products Administration The center, the Information Center of the National Medical Products Administration (hereinafter referred to as the Information Center), and other professional technical institutions for drugs undertake the relevant work required for the implementation of drug registration management in accordance with the law, including drug registration inspection, generic name approval, verification, monitoring and evaluation, certificate production and delivery, as well as the corresponding information construction and management.
Article 6 The drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall be responsible for the following drug registration-related management work within its administrative region:
(1) Acceptance, examination and approval of re-registration applications for drugs produced within the territory;
(2) Management of filing and reporting matters related to post-marketing changes of drugs;
(3) Organize the daily supervision of research institutions for non-clinical safety evaluation of drugs and drug clinical trial institutions, as well as the investigation and handling of illegal acts;
(4) Participate in the drug registration verification, inspection and other work organized by the National Medical Products Administration;
(V) Matters related to drug registration entrusted by the National Medical Products Administration.
The drug professional technical institutions established or designated by the drug regulatory authorities of provinces, autonomous regions and municipalities directly under the Central Government shall undertake the review, inspection, verification, monitoring and evaluation and other work required for the implementation of drug supervision and administration in accordance with the law.
Article 7 The administration of drug registration shall follow the principles of openness, fairness and impartiality, be oriented towards clinical value, encourage research and creation of new drugs, and actively promote the development of generic drugs.
The National Medical Products Administration has been continuously promoting the reform of the review and approval system, optimizing the review and approval procedures, enhancing the efficiency of review and approval, and establishing a drug registration management system with review as the leading force and inspection, verification, monitoring and evaluation as the supporting measures.
Chapter Two Basic Systems and Requirements
Article 8 Those engaged in drug research and development and drug registration activities shall abide by relevant laws, regulations, rules, standards and norms; Where other evaluation methods and techniques are adopted in accordance with relevant technical guidelines, their scientificity and applicability shall be proved. The information throughout the entire process should be ensured to be true, accurate, complete and traceable.
Drugs shall comply with the national drug standards and the drug quality standards approved by the National Medical Products Administration. The drug quality standards approved by the National Medical Products Administration are the drug registration standards. The standards for drug registration 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 the testing items or indicators of the varieties declared for registration do not apply to the Pharmacopoeia of the People's Republic of China, the applicant shall provide sufficient supporting data.
Professional technical institutions such as drug evaluation centers shall formulate technical guidance principles and procedures in accordance with scientific progress, the actual development of the industry and the needs of drug supervision and administration work, and make them public to the society.
Article 9 The applicant shall be an enterprise or a drug research and development institution, etc. that is capable of bearing corresponding legal responsibilities. Overseas applicants shall designate enterprise legal persons within the territory of China to handle relevant drug registration matters.
Article 10 Before applying for the marketing registration of a drug, the applicant shall complete relevant research work such as pharmacy, pharmacology and toxicology, and drug clinical trials. Non-clinical safety evaluation studies of drugs should be conducted in institutions that have been certified by the Good Clinical Practice for Drug Research and comply with the Good Clinical Practice for Drug Research. Drug clinical trials shall be approved, among which bioequivalence trials shall be filed. Drug clinical trials shall be conducted in drug clinical trial institutions that comply with relevant regulations and abide by the Good Clinical Practice for Drugs.
When applying for drug registration, one should provide true, sufficient and reliable data, materials and samples to prove the safety, efficacy and quality controllability of the drug.
Where foreign research materials and data are used to support drug registration, their sources, research institutions or laboratory conditions, quality system requirements and other management conditions shall comply with the common principles of the International Committee on Harmonization of Technical Requirements for Pharmaceuticals for Human Use and the relevant requirements of China's drug registration management.
Article 11 Where the matters or contents stated in the original drug registration approval document and its annexes are to be changed, the applicant shall, in accordance with the regulations and in reference to relevant technical guidelines, conduct thorough research and verification on the drug change, fully assess the possible impact of the change on the safety, efficacy and quality controllability of the drug, and submit supplementary applications, filings or reports in accordance with the change procedures.
Article 12 The validity period of the drug registration certificate is five years. During the validity period of the drug registration certificate, the holder shall continuously ensure the safety, efficacy and quality controllability of the marketed drug, and apply for re-registration of the drug six months before the expiration of the validity period.
Article 13 The National Medical Products Administration shall establish a system for accelerating the registration of drugs for market entry and support drug innovation oriented towards clinical value. For drug registration applications that meet the conditions, applicants may apply for the application of breakthrough therapy drugs, conditional approval, priority review and approval, and special approval procedures. During the process of drug research and development and registration, the drug regulatory authorities and their professional technical institutions provide necessary technical guidance, communication and exchanges, priority allocation of resources, and shortened review time limits, among other policies and technical support.
Article 14 The National Medical Products Administration shall establish an associated review and approval system for chemical active pharmaceutical ingredients, excipients and packaging materials and containers that come into direct contact with drugs. When approving drug preparations, chemical active pharmaceutical ingredients should be reviewed and approved simultaneously, as well as related excipients, packaging materials and containers that come into direct contact with the drugs. The Center for Drug Evaluation establishes an information registration platform for chemical active pharmaceutical ingredients, excipients, and packaging materials and containers that come into direct contact with drugs. It publicizes the relevant registration information for the selection of relevant applicants or holders, and links it to the review of relevant drug preparation registration applications.
Article 15 Prescription drugs and over-the-counter drugs shall be subject to classified registration and conversion management. The Center for Drug Evaluation formulates relevant technical guidelines and procedures for the marketing registration of over-the-counter drugs based on their characteristics and makes them public to the society. The Center for Drug Evaluation formulates the technical requirements and procedures for the post-marketing conversion of prescription drugs and over-the-counter drugs and makes them public to the society.
Article 16 At critical stages such as before the application for a drug clinical trial, during the drug clinical trial process, and before the application for drug marketing authorization, the applicant may communicate and exchange views on major issues with professional technical institutions such as the Center for Drug Evaluation. During the drug registration process, professional technical institutions such as the Center for Drug Evaluation may organize communication and exchanges with the applicants as needed for their work.
The procedures, requirements and time limits for communication and exchange shall be formulated respectively by professional technical institutions such as the Center for Drug Evaluation in accordance with their functions and made public to the society.
Article 17 Professional technical institutions such as the Center for Drug Evaluation shall, as required by their work, establish an expert consultation system and form an expert consultation committee. During the processes of review, verification, testing, and approval of generic names, they shall listen to the opinions of experts on major issues and give full play to the technical support role of experts.
Article 18 The National Medical Products Administration shall establish a directory collection of newly approved chemical drugs for marketing and those that have passed the consistency evaluation of quality and efficacy of generic drugs, including relevant information such as the drug name, active ingredient, dosage form, specification, whether it is a reference preparation, and the holder. It shall be updated in a timely manner and made public to the society. The procedures and requirements for the inclusion of the chemical drug catalogue shall be formulated by the Center for Drug Evaluation and made public to the society.
Article 19 The National Medical Products Administration supports the inheritance and innovation of traditional Chinese medicine, establishes and improves a registration management system and technical evaluation system that are in line with the characteristics of traditional Chinese medicine, encourages the application of modern science and technology and traditional research methods in the development of traditional Chinese medicine, strengthens the quality control of traditional Chinese medicine, and improves the level of clinical trials of traditional Chinese medicine.
When applying for the registration of traditional Chinese medicine, the applicant should conduct an assessment of clinical value and resources, highlighting the orientation of clinical value to promote the sustainable utilization of resources.
Chapter Three Drug Marketing Registration
Section 1 Drug Clinical Trials
Article 20 The term "drug clinical trial" as used in these Measures refers to drug research conducted on humans for the purpose of drug marketing and registration to determine the safety and efficacy of the drug.
Article 21 Drug clinical trials are classified into Phase I clinical trials, Phase II clinical trials, Phase III clinical trials, Phase IV clinical trials and bioequivalence trials. According to the characteristics of the drug and the research purpose, the research contents 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 the corresponding conditions and have been filed as required. Among them, clinical trials of vaccines shall be carried out or organized by tertiary medical institutions that meet the conditions stipulated by the National Medical Products Administration and the National Health Commission, or disease prevention and control institutions at or above the provincial level.
Article 23 Where an applicant has completed the pharmaceutical, pharmacological and toxicological research that supports the clinical trial of a drug and then submits an application for a clinical trial of a drug, he or she shall submit the relevant research materials in accordance with the requirements of the application materials. After a formal review, if the application materials meet the requirements, they will be accepted. The Center for Drug Evaluation shall organize pharmaceutical, medical and other technical personnel to review the applications for drug clinical trials that have been accepted. A decision on whether to approve the application for a drug clinical trial shall be made within 60 days from the date of acceptance, and the approval result shall be notified to the applicant through the website of the Center for Drug Evaluation. If no notice is given within the prescribed time limit, it shall be deemed as consent, and the applicant may conduct the drug clinical trial in accordance with the submitted plan.
The applicant who is approved to conduct a drug clinical trial is the sponsor of the drug clinical trial (hereinafter referred to as the sponsor).
Article 24 Where an applicant intends to conduct a bioequivalence test, it shall complete the filing of the bioequivalence test on the website of the Center for Drug Evaluation as required, and then carry out relevant research work in accordance with the filed plan.
Article 25 The conduct of drug clinical trials shall be subject to the review and approval of the ethics committee.
The management of drugs used in clinical trials shall comply with the relevant requirements of the Good Clinical Practice for Drugs.
Article 26 Where a drug clinical trial is approved to be conducted, the sponsor shall formulate a corresponding drug clinical trial plan before conducting subsequent phased drug clinical trials. The plan shall be carried out after being reviewed and approved by the ethics committee, and the corresponding drug clinical trial plan and supporting materials shall be submitted on the website of the Center for Drug Evaluation.
Article 27 Where a drug approved for clinical trials intends to add indications (or main functions and indications) or to add combination therapy with other drugs, the applicant shall submit a new application for clinical trials of the drug. The new clinical trials of the drug may only be conducted after approval.
If a drug that has been approved for marketing needs to conduct drug clinical trials to add indications (or functions and main treatments), a new application for drug clinical trials shall be submitted.
Article 28 The sponsor shall regularly submit safety update reports during the research and development period on the website of the Center for Drug Evaluation. The safety update report during the research and development period shall be submitted once a year, within two months after each full year following the approval of the drug clinical trial. The Center for Drug Evaluation may, based on the review situation, require the sponsor to adjust the reporting cycle.
For suspicious and unexpected serious adverse reactions and other potential serious safety risk information that occur during drug clinical trials, the sponsor shall report to the Center for Drug Evaluation in a timely manner in accordance with relevant requirements. Depending on the severity of the safety risk, the sponsor can be required to take measures such as adjusting the drug clinical trial protocol, informed consent form, and investigator's manual to enhance risk control. When necessary, the sponsor can be required to suspend or terminate the drug clinical trial.
The specific requirements for the safety update report during the research and development period shall be formulated and published by the Center for Drug Evaluation.
Article 29 During a drug clinical trial, if there are changes to the drug clinical trial protocol, non-clinical or pharmaceutical changes, or new discoveries, the sponsor shall, in accordance with the regulations and by referring to relevant technical guidelines, fully assess the impact on the safety of the subjects.
If the sponsor assesses that it does not affect the safety of the subjects, it can be directly implemented and under research and development
