Order of the State Administration for Market Regulation

No. 48

The "Management Measures for the Registration and Filing of In Vitro Diagnostic Reagents" was passed at the 11th executive meeting of the State Administration of Market Regulation on July 22, 2021, and is now announced. It will come into effect on October 1, 2021.

Director Zhang Gong

August 26, 2021

Management Measures for Registration and Filing of In Vitro Diagnostic Reagents

Chapter 1 General Provisions

Article 1: In order to standardize the registration and filing of in vitro diagnostic reagents, ensure the safety, effectiveness, and controllable quality of in vitro diagnostic reagents, this method is formulated in accordance with the Regulations on the Supervision and Administration of Medical Devices.

Article 2: These Measures shall apply to the registration, filing, and supervision and management activities of in vitro diagnostic reagents carried out within the territory of the People's Republic of China.

Article 3: The term "in vitro diagnostic reagents" as used in these Measures refers to in vitro diagnostic reagents managed according to medical devices, including reagents, kits, calibration materials, quality control materials and other products used for in vitro testing of human samples in the process of disease prediction, prevention, diagnosis, treatment monitoring, prognosis observation, and health status evaluation. These reagents can be used alone or in combination with instruments, appliances, equipment, or systems.

In vitro diagnostic reagents used for blood source screening and in vitro diagnostic reagents labeled with radioactive nuclides under drug management are not within the scope of this regulation.

Article 4: In vitro diagnostic reagent registration refers to the activity in which the applicant for in vitro diagnostic reagent registration (hereinafter referred to as the applicant) submits an application for in vitro diagnostic reagent registration in accordance with legal procedures and requirements, and the drug regulatory department conducts safety, effectiveness, and quality controllability reviews based on scientific knowledge in accordance with laws and regulations, to decide whether to agree to their application.

In vitro diagnostic reagent filing refers to the activity where the in vitro diagnostic reagent filing person (hereinafter referred to as the filing person) submits filing materials to the drug regulatory department in accordance with legal procedures and requirements, and the drug regulatory department archives the submitted filing materials for future reference.

Article 5: The National Drug Administration is responsible for the registration and filing management of in vitro diagnostic reagents nationwide, responsible for establishing a system for the registration and filing management of in vitro diagnostic reagents, organizing the review and approval of domestic Class III and imported Class II and III in vitro diagnostic reagents in accordance with the law, as well as the filing and related supervision and management of imported Class I in vitro diagnostic reagents, and providing supervision and guidance for local in vitro diagnostic reagent registration and filing work.

Article 6: The Medical Device Technical Evaluation Center of the State Drug Administration (hereinafter referred to as the National Device Evaluation Center) is responsible for the technical evaluation of domestic Class III and imported Class II and III in vitro diagnostic reagent product registration applications, change registration applications, and continuation registration applications.

Other professional and technical institutions such as the Medical Device Standards Management Center of the National Drug Administration, the China Food and Drug Control Research Institute, the Food and Drug Audit and Inspection Center of the National Drug Administration (hereinafter referred to as the National Bureau Audit and Inspection Center), the Drug Evaluation Center of the National Drug Administration, the Administrative Matters Acceptance Service and Complaint Reporting Center of the National Drug Administration, and the Information Center of the National Drug Administration, Responsible for the standard management, classification and definition, inspection, verification, monitoring and evaluation, certification and delivery, as well as corresponding information construction and management of in vitro diagnostic reagents required for the implementation of in vitro diagnostic reagent supervision and management.

Article 7: The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall be responsible for the management of the registration of in vitro diagnostic reagents within their respective administrative regions:

（1） Registration, review and approval of Class II in vitro diagnostic reagents in China;

（2） Verification of the quality management system for Class II and Class III in vitro diagnostic reagents in China;

（3） Organize medical device clinical trial institutions and supervise and manage clinical trials in accordance with the law;

（4） Supervision and guidance on the filing of Class I in vitro diagnostic reagents within the jurisdiction of the municipal drug supervision and management department in the district.

Medical device professional technical institutions established or designated by the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall be responsible for the technical review, inspection, verification, monitoring, and evaluation required for the supervision and management of in vitro diagnostic reagents.

The department responsible for drug supervision and management at the municipal level with districts is responsible for the filing and management of Class I in vitro diagnostic reagent products in China.

Article 8: The registration and filing of in vitro diagnostic reagents shall follow the principles of law, science, openness, fairness, and impartiality.

Article 9: The first category of in vitro diagnostic reagents shall be subject to product filing management. The second and third types of in vitro diagnostic reagents are subject to product registration management.

For the filing of Class I in vitro diagnostic reagents in China, the filing person shall submit the filing materials to the department responsible for drug supervision and management at the municipal level with districts.

The second type of in vitro diagnostic reagents in China shall be reviewed and approved by the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government, and then issued with a medical device registration certificate.

The third type of in vitro diagnostic reagents in China shall be reviewed and approved by the State Administration for Drug Administration, and a medical device registration certificate shall be issued after approval.

For the filing of imported Class I in vitro diagnostic reagents, the filing person shall submit the filing materials to the National Drug Administration.

The import of Class II and Class III in vitro diagnostic reagents shall be reviewed by the National Drug Administration, and after approval, a medical device registration certificate shall be issued.

Article 10: The registrant and registrant of in vitro diagnostic reagents shall strengthen the quality management throughout the entire life cycle of in vitro diagnostic reagents, and shall be legally responsible for the safety, effectiveness, and quality controllability of in vitro diagnostic reagents throughout their development, production, operation, and use.

Article 11: The National Drug Administration shall prioritize the approval of in vitro diagnostic reagents that are urgently needed in clinical practice, and implement special approval for innovative in vitro diagnostic reagents. Encourage the research and innovation of in vitro diagnostic reagents, and promote the high-quality development of the medical device industry.

Article 12: The National Drug Administration shall establish and improve systems such as in vitro diagnostic reagent standards and technical guidance principles in accordance with the law, regulate the technical evaluation and quality management system verification of in vitro diagnostic reagents, and guide and serve the research and development of in vitro diagnostic reagents and registration applications.

Article 13: The drug regulatory department shall promptly disclose relevant information on the registration and filing of in vitro diagnostic reagents in accordance with the law. Applicants may inquire about the approval progress and results, and the public may access the approval results.

Without the consent of the applicant, personnel such as drug regulatory departments, professional technical institutions, and their staff, as well as experts participating in the review, shall not disclose trade secrets, undisclosed information, or confidential business information submitted by the applicant or the filing person, except as otherwise provided by law or involving national security or significant social public interests.

Chapter 2 Basic Requirements

Article 14: The registration and filing of in vitro diagnostic reagents shall comply with relevant laws, regulations, rules, and mandatory standards, follow the basic principles of safety and performance of in vitro diagnostic reagents, and refer to relevant technical guidelines to prove that the registered and filed in vitro diagnostic reagents are safe, effective, and of controllable quality, ensuring the authenticity, accuracy, completeness, and traceability of information.

Article 15: The applicant and registrant shall be an enterprise or research and development institution that can bear corresponding legal responsibilities.

Overseas applicants and registrants shall designate corporate legal persons within China as agents to handle the registration and filing of relevant in vitro diagnostic reagents. The agent shall assist the registrant and registrant in fulfilling their obligations under Article 20, Paragraph 1 of the Regulations on the Supervision and Administration of Medical Devices in accordance with the law, and assist overseas registrants and registrants in fulfilling their corresponding legal responsibilities.

Article 16: Applicants and filers shall establish a quality management system related to product development and production, and maintain effective operation.

Article 17: Personnel handling the registration and filing of in vitro diagnostic reagents shall possess relevant professional knowledge and be familiar with the laws, regulations, rules, and registration management regulations related to in vitro diagnostic reagent registration and filing management.

Article 18: When applying for registration or filing, relevant materials shall be submitted in accordance with the requirements of the National Drug Administration for registration and filing. The applicant and the filing person are responsible for the authenticity of the materials.

Registration and filing materials should be in Chinese. If translated based on foreign language materials, the original text should also be provided. When citing unpublished literature and materials, documents licensed by the data rights holder should be provided.

Article 19: To apply for the registration of imported in vitro diagnostic reagents and to handle the registration of imported in vitro diagnostic reagents, proof documents from the competent authorities of the country (region) where the applicant or the registrant is registered or where the production is located that permit their listing for sale shall be submitted.

If the country (region) where the applicant or registrant is registered or produced does not manage the product as a medical device, the applicant or registrant must provide relevant documents, including proof that the country (region) where the registration or production is located allows the product to be marketed.

In vitro diagnostic reagents that have not been listed in the country (region) where the applicant or registrant is registered or where the production is located and approved according to the innovative product registration procedure do not need to submit relevant documents.

Article 20 In vitro diagnostic reagents shall comply with applicable mandatory standards. If the product's structural characteristics, technical principles, expected uses, usage methods, etc. are inconsistent with the scope of application of mandatory standards, the applicant and registrant shall provide an explanation of the non application of mandatory standards and provide relevant information.

If there are no mandatory standards, applicants and filers are encouraged to adopt recommended standards.

Article 21: The registration and filing of in vitro diagnostic reagents shall comply with the relevant requirements of the classification rules and catalog of in vitro diagnostic reagents.

Article 22: The drug regulatory authorities shall continue to promote the reform of the review and approval system, strengthen regulatory scientific research, establish a technical system for in vitro diagnostic reagent registration management led by technical review, supported by verification, inspection, monitoring, and evaluation, optimize the review and approval process, improve the review and approval ability, and improve the quality and efficiency of review and approval.

Article 23: Medical device professional technical institutions shall establish a sound communication and exchange system, clarify the form and content of communication and exchange, and organize communication and exchange with applicants according to work needs.

Article 24 Medical device professional technical institutions shall establish an expert consultation system according to work needs, listen to expert opinions on major issues during the review, verification, inspection, and other processes, and fully leverage the technical support role of experts.

Chapter 3 Registration of in vitro diagnostic reagents

Section 1 Product Development

Article 25: The development of in vitro diagnostic reagents shall follow the principles of risk management, take into account the existing recognized technological level, ensure that all known and foreseeable risks and unexpected impacts of the product are minimized and acceptable, and ensure that the benefits of the product in normal use outweigh the risks.

Article 26: Engaging in the development and experimental activities of in vitro diagnostic reagent products shall comply with the requirements of relevant laws, regulations, and mandatory standards in China.

Article 27: Applicants and registrants shall prepare product technical requirements for applying for registration or filing in vitro diagnostic reagents.

The product technical requirements mainly include the functional and safety indicators and testing methods that can be objectively judged for the finished product of in vitro diagnostic reagents.

The product technical requirements for the third type of in vitro diagnostic reagents should be clearly defined in the form of an appendix for the main raw materials and production process requirements.

In vitro diagnostic reagents should meet the registered or registered product technical requirements.

Article 28: The applicant and the registrant shall prepare product manuals and labels for in vitro diagnostic reagents for registration or filing.

The product manual and label should comply with the requirements of Article 39 of the Regulations on the Supervision and Administration of Medical Devices and relevant regulations.

Article 29: In the development of in vitro diagnostic reagents, non clinical research on in vitro diagnostic reagents shall be conducted based on the expected use and technical characteristics of the product.

Non clinical research refers to the testing or evaluation of in vitro diagnostic reagents under laboratory conditions, including the selection and preparation of main raw materials, product production processes, product analysis performance, positive judgment values or reference intervals, and product stability research.

When applying for registration or filing, non clinical evidence generated during research and development activities should be submitted.

Article 30: The functional and safety indicators and methods determined during non clinical research of in vitro diagnostic reagents shall be suitable for the expected use conditions and purposes of the product, and the research samples shall be representative and typical. If necessary, methodological validation and statistical analysis should be conducted.

Article 31: When applying for registration or filing, an inspection shall be conducted in accordance with the technical requirements of the product and an inspection report shall be submitted. Only those who pass the inspection can conduct clinical trials or apply for registration or filing.

Article 32: When the same registration application includes different packaging specifications, only one packaging specification product can be inspected. The inspection products should represent the safety and effectiveness of the registered or registered products, and their production should comply with the relevant requirements of medical device production quality management standards.

Article 33: The inspection report submitted for registration or filing may be the self inspection report of the applicant or the filing person, or the inspection report issued by a qualified medical device inspection institution entrusted.

The third type of in vitro diagnostic reagents should provide inspection reports for three different production batches of products.

Article 34: For reagents with applicable national standards, national standards shall be used for testing. The China Food and Drug Control Research Institute is responsible for organizing the preparation and calibration of national standard products.

Section 2 Clinical Evaluation

Article 35: Clinical evaluation of in vitro diagnostic reagents refers to the process of analyzing and evaluating clinical data using scientific and reasonable methods, confirming whether the product meets the usage requirements or intended use, in order to prove the safety and effectiveness of in vitro diagnostic reagents.

Article 36: Clinical trials of in vitro diagnostic reagents refer to systematic research on the clinical performance of in vitro diagnostic reagents in corresponding clinical environments.

The National Drug Administration has formulated guidelines for in vitro diagnostic reagent clinical trials, clarifying the requirements for conducting clinical trials and writing clinical trial reports.

Article 37: In conducting clinical evaluations of in vitro diagnostic reagents, clinical trials shall be conducted to demonstrate the safety and effectiveness of in vitro diagnostic reagents.

Clinical trials may be exempted if:

（1） The reaction principle is clear, the design is finalized, the production process is mature, and the same variety of in vitro diagnostic reagents have been clinically used for many years without serious adverse event records, without changing their conventional use;

（2） By comparing the methodology of the same variety, it can be proven that the in vitro diagnostic reagent is safe and effective.

The list of Class II and Class III in vitro diagnostic reagents exempt from clinical trials shall be formulated, adjusted, and published by the National Drug Administration.

Article 38: For in vitro diagnostic reagents that are exempt from clinical trials, the applicant shall demonstrate the safety and effectiveness of the product by conducting methodological comparisons with the same variety of clinical samples that meet the intended use.

The National Drug Administration has formulated guidelines for the clinical evaluation of in vitro diagnostic reagents exempt from clinical trials.

Article 39: The clinical evaluation data of in vitro diagnostic reagents refer to the documents formed by the applicant's clinical evaluation.

For conducting clinical trials, the clinical trial data includes clinical trial protocols, ethics committee opinions, informed consent forms, clinical trial reports, and relevant data.

In vitro diagnostic reagents listed as exempt from clinical trials, clinical evaluation data includes comparative analysis with similar marketed products, methodological comparison data, relevant literature data analysis, and empirical data analysis.

Article 40: When the same registration application includes different packaging specifications, only one packaging specification of the product may be used for clinical evaluation. The products used for clinical evaluation shall represent the safety and effectiveness of the registered or registered products.

Clinical evaluation materials do not need to be submitted for the registration of calibration and quality control products separately.

Article 41: Clinical trials of in vitro diagnostic reagents shall be conducted in accordance with the requirements of the quality management standards for clinical trials of medical devices, in medical device clinical trial institutions that meet the corresponding conditions and are registered in accordance with regulations. Before the start of a clinical trial, the clinical trial applicant shall file a clinical trial with the drug regulatory department of the province, autonomous region, or municipality directly under the central government where it is located. The production of in vitro diagnostic reagents for clinical trials should comply with the relevant requirements of quality management standards for medical device production.

Article 42: For serious adverse events or other serious safety risk information related to in vitro diagnostic reagents during clinical trials, clinical trial applicants shall, in accordance with relevant requirements, report to the drug regulatory authorities of the province, autonomous region, or municipality where the clinical trial institution is located and take risk control measures. If no risk control measures have been taken, the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall order the applicants to take corresponding risk control measures in accordance with the law.

Article 43: In case of serious adverse events or other major safety issues related to in vitro diagnostic reagents in large-scale clinical trials, the applicant shall suspend or terminate the clinical trial of in vitro diagnostic reagents and report to the drug regulatory authorities of the province, autonomous region, or municipality directly under the Central Government where the clinical trial institution is located and the place where it is located. If not suspended or terminated, the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall order the applicants to take corresponding risk control measures in accordance with the law.

Article 44: When conducting clinical evaluations of in vitro diagnostic reagents intended for personal use by consumers, the applicant shall also evaluate the cognitive ability of consumers without medical background to the product manual.

Article 45: In vitro diagnostic reagents used in ongoing clinical trials to diagnose diseases that pose a serious threat to life and do not have effective diagnostic methods may benefit patients through medical observation. After ethical review and informed consent, they may be used for free in institutions conducting clinical trials of in vitro diagnostic reagents for other patients with similar conditions. Their safety data can be used for in vitro diagnostic reagent registration applications.

Section 3 Registration System Verification

Article 46: Applicants shall submit quality management system related materials related to product development and production when applying for registration. If the drug regulatory department that accepts the registration application deems it necessary to verify the quality management system during the product technical review, it shall organize quality management system verification and may access the original materials as needed.

Article 47: The quality management system verification of Class III in vitro diagnostic reagents within the territory of China shall be carried out by the Drug Evaluation Center of the National Bureau, which shall notify the drug regulatory department of the province, autonomous region, or municipality directly under the central government where the applicant is located.

The quality management system verification of Class II in vitro diagnostic reagents in China shall be organized and carried out by the drug regulatory department of the province, autonomous region, or municipality directly under the central government where the applicant is located.

Article 48: The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall conduct quality management system inspections in accordance with the requirements of the quality management standards for medical device production, with a focus on verifying whether the applicant has established a quality management system that is suitable for the product in accordance with the requirements of the quality management standards for medical device production, as well as the design and development, production management, quality control, and other related contents related to product development and production.

During the verification process, the authenticity of the inspection products and clinical trial products should be verified simultaneously, with a focus on reviewing relevant records of the design and development process, as well as the production process of the inspection products and clinical trial products.

When submitting a self inspection report, a key verification should be conducted on the inspection capabilities and results of the applicant, registrant, or entrusted institution during the development process.

Article 49: The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government may conduct quality management system verification through data review or on-site inspection. Based on the specific situation of the applicant, the supervision and inspection situation, and the comparison between the production conditions and processes of the products registered in this application and those that have been verified in the past, determine whether to conduct on-site inspections and the inspection content to avoid duplicate inspections.

Article 50: When the National Bureau's Equipment Evaluation Center conducts technical evaluations of imported Class II and Class III in vitro diagnostic reagents, if it deems it necessary to conduct quality management system verification, it shall notify the National Bureau's Audit and Inspection Center to conduct verification according to relevant requirements.

Section 4 Product Registration

Article 51: After completing the safety and effectiveness research supporting the registration of in vitro diagnostic reagents and preparing for quality management system verification, the applicant shall submit an application for in vitro diagnostic reagent registration and submit the following registration application materials to the drug regulatory department through online registration applications and other channels in accordance with relevant requirements:

（1） Product risk analysis data;

（2） Product technical requirements;

（3） Product inspection report;

（4） Clinical evaluation data;

（5） Product manual and label sample;

（6） Quality management system documents related to product development and production;

（7） Other materials required to prove the safety and effectiveness of the product.

Article 52: After receiving the application, the drug regulatory department shall review the application materials and handle them according to the following situations:

（1） If the application matters fall within the scope of the authority of this administrative agency, and the application materials are complete and meet the requirements for formal review, they shall be accepted;

（2） If there are errors in the application materials that can be corrected on the spot, the applicant should be allowed to correct them on the spot;

（3） If the application materials are incomplete or do not comply with the legal form, the applicant shall be notified of all the necessary corrections on the spot or within 5 days. If the applicant fails to inform within the time limit, it shall be deemed accepted from the date of receiving the application materials;

（4） If the application matters do not fall within the scope of the administrative authority in accordance with the law, a decision on rejection shall be made immediately and the applicant shall be notified to apply to the relevant administrative authority.

If the drug regulatory department accepts or refuses to accept the application for registration of in vitro diagnostic reagents, it shall issue a notice of acceptance or refusal stamped with the special seal of the administrative authority and dated.

After the application for registration of in vitro diagnostic reagents is accepted, if the applicant needs to pay fees, the applicant shall pay the fees in accordance with regulations. If the applicant fails to pay the fees within the prescribed time limit, it shall be deemed that the applicant has voluntarily withdrawn the application, and the drug regulatory department shall terminate its registration process.

Article 53: In the process of technical evaluation, if the applicant needs to supplement and correct the information, the technical evaluation institution shall inform the applicant of all the content that needs to be supplemented and corrected at once. The applicant shall provide supplementary information in accordance with the requirements of the correction notice within one year after receiving it; After receiving the supplementary information, the technical review institution shall complete the technical review within the prescribed time limit.

If the applicant has objections to the content of the correction notice, they may submit written opinions to the corresponding technical evaluation institution, explain the reasons, and provide corresponding technical support materials.

If the applicant fails to submit supplementary materials within the prescribed time limit, the technical evaluation shall be terminated, and the drug regulatory department shall make a decision not to register.

Article 54: For a registered application that has been accepted, the applicant may, before the administrative licensing decision is made, apply to the drug regulatory department that has accepted the application to withdraw the registration application and relevant materials, and explain the reasons. If the applicant agrees to withdraw the application, the drug regulatory department shall terminate its registration process.

If any illegal behavior such as concealing the true information or providing false information is found during the review, verification, and approval process, it shall be dealt with in accordance with the law, and the applicant shall not withdraw the registration application.

Article 55: If there is evidence indicating that the registration application materials that have been accepted may be false, the drug regulatory department may suspend the review and approval. After verification, continue the review or make a decision not to register based on the verification conclusion.

Article 56: During the evaluation period of the application for registration of in vitro diagnostic reagents, if a review conclusion is to be made that does not pass, the technical evaluation institution shall inform the applicant of the reasons for the failure. The applicant may raise objections to the technical evaluation institution within 15 days, and the objection content is limited to the original application items and the original application materials. The technical evaluation institution shall conduct a comprehensive evaluation based on the applicant's objections and provide feedback to the applicant. The time for handling objections is not included in the review deadline.

Article 57: The drug regulatory department that accepts registration applications shall make a decision on whether to approve or not after the technical review is completed. For those that meet the requirements of safety, effectiveness, and controllable quality, registration is granted and a medical device registration certificate is issued. The approved product technical requirements and product manual are sent to the applicant in the form of attachments. For those who refuse to register, they shall provide a written explanation and inform the applicant of their right to apply for administrative reconsideration or file an administrative lawsuit in accordance with the law.

The validity period of the medical device registration certificate is 5 years.

Article 58: For the registration application that has been accepted, if one of the following situations occurs, the drug regulatory department shall make a decision not to register and inform the applicant:

（1） The applicant's research on the safety, effectiveness, and quality controllability of in vitro diagnostic reagents intended for sale and its results cannot prove the safety, effectiveness, and quality controllability of the product;

（2） The quality management system verification fails, and the applicant refuses to accept the on-site inspection of the quality management system;

（3） The registration application materials are false;

（4） The content of the registration application materials is chaotic and contradictory, and the content of the registration application materials is clearly inconsistent with the application items, which cannot prove that the product is safe, effective, and controllable in quality;

（5） Other situations where registration is not allowed.

Article 59: For matters that require a hearing in the implementation of administrative licensing according to laws, regulations, and rules, or other major administrative licensing matters that involve public interests that the drug regulatory department deems necessary, the drug regulatory department shall make a public announcement and hold a hearing. If the application for medical device registration directly involves a significant interest relationship between the applicant and others, the drug regulatory department shall inform the applicant and interested parties of the right to request a hearing before making an administrative licensing decision.

Article 60: For in vitro diagnostic reagents used for rare diseases, serious life-threatening diseases without effective diagnostic methods, and urgently needed in response to public health events, the drug regulatory department may make a conditional approval decision, and specify in the medical device registration certificate the validity period, research work that needs to be continued after being launched, and completion time limit.

Article 61: For conditionally approved in vitro diagnostic reagents, the registrant shall collect relevant data on benefits and risks after the in vitro diagnostic reagents are launched, continuously monitor and evaluate the benefits and risks of the products, take effective measures to actively control risks, and complete the research and submit relevant materials as required within the specified time limit.

Article 62: For conditionally approved in vitro diagnostic reagents, if the registrant fails to complete the research as required or cannot prove that the benefits outweigh the risks, the registrant shall promptly apply for the cancellation of the medical device registration certificate. The drug regulatory department may cancel the medical device registration certificate in accordance with the law.

Article 63: For newly developed in vitro diagnostic reagents that have not been included in the classification catalog of in vitro diagnostic reagents, the applicant may directly apply for the registration of Class III in vitro diagnostic reagent products, or determine the product category according to the classification rules and apply to the National Drug Administration for category confirmation before applying for product registration or filing.

For those who directly apply for the registration of Class III in vitro diagnostic reagents, the National Drug Administration shall determine the category based on the degree of risk. If domestic in vitro diagnostic reagents are determined as Class II or Class I, the applicant shall be notified to apply for registration or filing with the corresponding drug regulatory department.

Article 64: If the management category of registered in vitro diagnostic reagents is adjusted from high category to low category, the medical device registration certificate shall continue to be valid during its validity period. If the validity period needs to be extended, the registrant shall apply for registration extension or filing with the corresponding drug regulatory department according to the adjusted category 6 months before the expiration of the medical device registration certificate.

If the management category of in vitro diagnostic reagents is adjusted from low to high, the registrant shall apply for registration with the corresponding drug regulatory department according to the changed category. The National Drug Administration shall specify the time limit for completing the adjustment in the notice of management category adjustment.

Article 65: If the medical device registration certificate and its attachments are lost or damaged, the registrant shall apply to the original issuing authority for reissuing them, and the original issuing authority shall verify and reissue them.

Article 66: If a patent dispute arises during the examination process of a registration application or after approval, it shall be handled in accordance with the provisions of relevant laws and regulations.

Chapter 4 Special Registration Procedures

Section 1 Innovative Product Registration Procedure

Article 67: Applicants may apply for the application of innovative product registration procedures for in vitro diagnostic reagents that meet the following requirements:

（1） The applicant, through its leading technological innovation activities, legally owns the core technology invention patent right of the product in China, or obtains the invention patent right or its use right in China through transfer in accordance with the law, and the time for applying for the applicable innovative product registration procedure is within 5 years from the date of patent authorization announcement; Or the application for patent for core technology invention has been disclosed by the patent administration department under the State Council, and the patent search and consultation center of the China National Intellectual Property Administration has issued a search report, indicating that the core technology solution of the product has novelty and creativity;

（2） The applicant has completed preliminary research on the product and has a basic finalized product. The research process is real and controlled, and the research data is complete and traceable;

（3） The main working principle or mechanism of the product is the first in China, and the performance or safety of the product has been fundamentally improved compared to similar products. The technology is at the international leading level and has significant clinical application value.

Article 68: If an applicant applies for the registration procedure of innovative products, they shall submit an application for the examination of innovative medical devices to the National Drug Administration after the product is basically finalized. The National Drug Administration organizes experts for review, and those that meet the requirements will be included in the innovative product registration process.

Article 69: For in vitro diagnostic reagent registration applications that are subject to innovative product registration procedures, the National Drug Administration and the institutions responsible for relevant technical work shall designate dedicated personnel to be responsible for timely communication and provide guidance according to their respective responsibilities.

For in vitro diagnostic reagents included in the registration process of innovative products, the National Bureau of Device Evaluation Center can communicate and exchange with applicants on major technical issues, major safety issues, clinical trial plans, and summary and evaluation of phased clinical trial results in product development before and during the registration application acceptance process.

Article 70: If the applicant voluntarily requests the termination of in vitro diagnostic reagents included in the innovative product registration procedure, or if the National Drug Administration finds that they no longer meet the requirements of the innovative product registration procedure, the National Drug Administration may terminate the innovative product registration procedure for the relevant products and notify the applicant.

Article 71: In vitro diagnostic reagents included in the innovative product registration procedure shall no longer be subject to the innovative product registration procedure if the applicant fails to submit a registration application within the prescribed period.

Section 2 Priority Registration Procedure

Article 72 In vitro diagnostic reagents that meet one of the following conditions may apply for priority registration procedures:

（1） Medical devices that diagnose rare diseases, malignant tumors, and have obvious clinical advantages, are specific to the elderly and have multiple diseases, and currently have no effective diagnostic methods. They are specifically designed for children and have obvious clinical advantages, or are urgently needed in clinical practice and have not been approved for registration of similar products in China;

（2） Medical devices included in national major scientific and technological projects or national key research and development plans;

（3） Other medical devices that can be subject to priority registration procedures as stipulated by the National Drug Administration.

Article 73: When applying for the priority registration procedure, the applicant shall submit an application for the priority registration procedure to the State Drug Administration when submitting the application for in vitro diagnostic reagent registration. If the situation falls under the first item of Article 72, the State Drug Administration shall organize experts to conduct an audit. If it meets the requirements, it shall be included in the priority registration procedure; If it falls under the second item of Article 72, it shall be reviewed by the Equipment Evaluation Center of the National Bureau, and if it meets the requirements, it shall be included in the priority registration procedure; In the case of the third item of Article 72, the State Drug Administration shall widely listen to opinions and organize expert argumentation to determine whether to include it in the priority registration procedure.

Article 74: For in vitro diagnostic reagent registration applications included in the priority registration procedure, the National Drug Administration shall give priority to review and approval, and the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall give priority to arranging registration quality management system verification.

During the technical evaluation process of medical device products included in the priority registration procedure, the National Bureau of Medical Device Evaluation Center shall actively communicate and exchange with applicants in accordance with relevant regulations, and may arrange special exchanges if necessary.

Section 3 Emergency Registration Procedure

Article 75: The National Drug Administration may, in accordance with the law, implement emergency registration for in vitro diagnostic reagents that are required for emergency response to public health emergencies and have not yet been marketed in China, or that, although similar products have already been marketed in China, their supply cannot meet the emergency response needs of public health emergencies.

Article 76: When applying for the application of emergency registration procedures, the applicant shall submit an emergency registration application to the State Drug Administration. Those that meet the conditions will be included in the emergency registration procedure.

Article 77: For the registration application of in vitro diagnostic reagents for emergency registration, the National Drug Administration shall handle it in accordance with the requirements of unified command, early intervention, on-site review, and scientific approval, and carry out in parallel the inspection of in vitro diagnostic reagent products, system verification, technical evaluation, and other work.

Chapter 5 Change of Registration and Continuation of Registration

Section 1 Change of Registration

Article 78: The registrant shall actively conduct post market research on in vitro diagnostic reagents, further confirm the safety, effectiveness, and quality controllability of in vitro diagnostic reagents, and strengthen the continuous management of in vitro diagnostic reagents that have already been listed.

If there are substantial changes in the design, raw materials, production process, scope of application, and methods of use of Class II and Class III in vitro diagnostic reagent products that have been registered, which may affect the safety and effectiveness of the in vitro diagnostic reagent, the registrant shall apply to the original registration department for registration change procedures; If other changes occur, they shall be filed with the original registration department within 30 days from the date of the change.

The product name, packaging specifications, main components, expected use, product technical requirements, product manual, and production address of imported in vitro diagnostic reagents specified in the registration certificate belong to the items that require registration changes as stipulated in the preceding paragraph. The name and address of the registrant, the name and address of the agent, and other matters that need to be filed as stipulated in the preceding paragraph. If the production address of in vitro diagnostic reagents in China changes, the registrant shall apply for registration after applying for the corresponding production license change.

If other changes occur, the registrant shall carry out relevant work in accordance with the requirements of the quality management system and report to the drug regulatory department in accordance with regulations.

Article 79: If a registered Class II or Class III in vitro diagnostic reagent undergoes substantial changes in the core technical principles of the product, or undergoes other significant changes that have a significant impact on the safety and effectiveness of the product, and substantially constitute a new product, it shall not be subject to the change application matters specified in this chapter and shall be handled in accordance with the provisions of the registration application.

Article 80: For changes in registration applications, the technical evaluation institution shall focus on the evaluation of the changed parts, and form evaluation opinions on whether the products after the changes are safe, effective, and controllable in quality.

When conducting a technical review of a change of registration application, if it is deemed necessary to verify the quality management system, the drug regulatory department shall organize a quality management system verification.

Article 81: The registration documents for changes in medical devices shall be used in conjunction with the original medical device registration certificate, and the expiration date shall be the same as the original medical device registration certificate.

Section 2 Continuation of Registration

Article 82: If the validity period of the medical device registration certificate expires and the registration needs to be extended, the registrant shall apply for the extension of registration to the original registration department 6 months before the expiration of the medical device registration certificate, and submit application materials in accordance with relevant requirements.

Except for the circumstances specified in Article 83 of these Measures, the drug regulatory department that receives the application for renewal of registration shall make a decision to approve the renewal before the expiration of the validity period of the medical device registration certificate. If a decision is not made within the prescribed time limit, it shall be deemed that the extension is granted.

Article 83: In any of the following circumstances, the registration shall not be renewed:

（1） Failure to submit an application for renewal of registration within the prescribed time limit;

（2） New mandatory standards or national standards for in vitro diagnostic reagents have been released and implemented, and in vitro diagnostic reagents that apply for registration extension cannot meet the new requirements;

（3） Conditionally approved in vitro diagnostic reagents that have not completed the items specified in the medical device registration certificate within the specified period.

Article 84: If the approval time for continuing registration is within the validity period of the original registration certificate, the starting date of the validity period of the continued registration certificate shall be the day after the expiration date of the original registration certificate; If the approval time is not within the validity period of the original registration certificate, the starting date of the validity period of the continued registration certificate shall be the date of approval for the continued registration.

Article 85: If there are no provisions in this chapter regarding the acceptance and approval procedures for the application for registration change or renewal of in vitro diagnostic reagents, the relevant provisions in Chapter 3 of these Measures shall apply.

Chapter 6 Filing of in vitro diagnostic reagents

Article 86 Before the production of Class I in vitro diagnostic reagents, product registration shall be conducted.

Article 87: For the registration of in vitro diagnostic reagents, the registrant shall submit the registration materials to the drug regulatory department in accordance with the provisions of the Regulations on the Supervision and Administration of Medical Devices, and obtain the registration number.

Article 88: If there is a change in the content and technical requirements of the registered in vitro diagnostic reagents in the registration information form, the registrant shall change the registration to the original registration department and submit an explanation of the change and relevant documents. The drug regulatory department shall record the changes in the record keeping information.

Article 89: If the management category of in vitro diagnostic reagents that have been filed is adjusted to Class II or Class III in vitro diagnostic reagents, registration shall be applied for in accordance with the provisions of these Measures.

Chapter 7 Work Time Limit

Article 90 The time limit specified in these Measures is the maximum time for the acceptance, technical evaluation, verification, approval, and other work of in vitro diagnostic reagent registration. The working time limit related to the special registration procedure shall be executed in accordance with the relevant provisions of the special registration procedure.

Professional technical institutions such as the National Bureau's Equipment Evaluation Center shall clearly define their own work procedures and time limits, and make them public to the society.

Article 91: After receiving an application for registration of in vitro diagnostic reagents, the drug regulatory department shall, within 3 days from the date of acceptance, transmit the application materials to the technical evaluation institution.

Article 92: The time limit for technical evaluation of in vitro diagnostic reagent registration shall be implemented in accordance with the following provisions:

（1） The technical review time limit for the registration application, change registration application, and extension registration application of the second type of in vitro diagnostic reagents is 60 days, and the technical review time limit after the application materials are supplemented and corrected is 60 days;

（2） The technical review time limit for the registration application, change registration application, and extension registration application of the third type of in vitro diagnostic reagents is 90 days, and the technical review time limit for the corrected application materials is 60 days.

Article 93: The verification time limit for the quality management system of Class III in vitro diagnostic reagents in China shall be implemented in accordance with the following provisions:

（1） The National Bureau's Device Evaluation Center shall notify the relevant drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government to initiate verification within 10 days after the acceptance of the application for in vitro diagnostic reagent registration;

（2） The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall, in principle, complete the inspection within 30 days after receiving the inspection notice, and provide feedback on the inspection situation, results, and other relevant materials to the National Bureau of Device Evaluation Center.

Article 94: The drug regulatory department that accepts registration applications shall make a decision within 20 days from the date of receiving the evaluation opinions.

Article 95: The drug regulatory department shall issue and deliver relevant administrative licensing documents within 10 days from the date of making the decision on the registration and approval of in vitro diagnostic reagents.

Article 96: If it is necessary to extend the time limit due to special circumstances such as product characteristics and technical review and verification, the extension time limit shall not exceed half of the original time limit. After approval by the head of relevant technical institutions such as medical device technical review and verification, the technical institution that extended the time limit shall notify the applicant in writing and notify other relevant technical institutions.

Article 97: The original issuing authority shall reissue the medical device registration certificate within 20 days from the date of receiving the application.

Article 98: The following time shall not be included in the relevant work time limit:

（1） The time taken by the applicant for supplementary information, rectification after verification, etc;

（2） Delayed verification due to the applicant's reasons;

（3） The time required for external expert consultation, expert consultation meetings, and joint evaluation with drug evaluation institutions;

（4） If the review and approval process is suspended according to regulations, the time occupied during the suspension of the review and approval process;

（5） The time taken for quality management system verification.

Article 99: The time limit specified in these Measures shall be calculated based on working days.

Chapter 8 Supervision and Management

Article 100: The drug regulatory department shall strengthen the supervision and inspection of the development activities of in vitro diagnostic reagents. If necessary, extended inspections may be conducted on units and individuals providing products or services for the development of in vitro diagnostic reagents. Relevant units and individuals shall cooperate, provide relevant documents and materials, and shall not refuse, conceal, or obstruct.

Article 101: The National Drug Administration shall establish and implement a unique identification system for medical devices step by step. Applicants and registrants shall submit information related to the unique identification in accordance with relevant regulations to ensure the authenticity, accuracy, and traceability of the data.

Article 102: The State Drug Administration shall promptly report the information of the agent to the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where the agent is located. The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall carry out daily supervision and management of agent organizations within their respective administrative regions.

Article 103: The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall organize post registration supervision and inspection of clinical trial institutions that have already been registered within their respective administrative regions based on the registration status of medical device clinical trial institutions. For newly registered medical device clinical trial institutions, supervision and inspection should be carried out within 60 days after registration.

The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the central government shall organize daily supervision and inspection of the compliance of medical device clinical trial institutions with the quality management standards for medical device clinical trials within their respective administrative regions, and supervise their continuous compliance with the prescribed requirements. The National Drug Administration shall supervise and inspect clinical trial institutions for medical devices as needed.

Article 104 If the drug regulatory department deems it necessary, it may conduct on-site inspections on the authenticity, accuracy, completeness, standardization, and traceability of clinical trials.

Article 105: If the drug regulatory department responsible for the registration of Class I in vitro diagnostic reagent products discovers that the registration materials are not standardized during post registration supervision, it shall order the registrant to make corrections within a specified period of time.

Article 106: If the drug regulatory department fails to timely discover systemic or regional risks in the registration and management of in vitro diagnostic reagents within its administrative region, or fails to timely eliminate systemic or regional hidden dangers in the registration and management of in vitro diagnostic reagents within its administrative region, the superior drug regulatory department may hold interviews with the main responsible persons of the subordinate drug regulatory department.

Chapter 9 Legal Liability

Article 107: Those who violate the provisions of Article 78 of these Measures and fail to file changes as required shall be ordered to make corrections within a specified period of time; Those who fail to make corrections within the time limit shall be fined not less than 10000 yuan but not more than 30000 yuan.

Article 108: If a clinical trial of in vitro diagnostic reagents fails to comply with clinical trial quality management standards, punishment shall be imposed in accordance with Article 94 of the Regulations on the Supervision and Administration of Medical Devices.

Article 109: If a medical device technical evaluation institution fails to fulfill its responsibilities in accordance with the provisions of these Measures, resulting in significant errors in the evaluation work, the department responsible for drug supervision and management shall order it to make corrections, circulate a notice of criticism, and give a warning; If serious consequences are caused, the legal representative, main responsible person, directly responsible supervisor, and other responsible personnel of the illegal unit shall be punished in accordance with the law.

Article 110: Personnel of the department responsible for drug supervision and management who violate regulations, abuse their power, neglect their duties, or engage in favoritism and fraud shall be punished in accordance with the law.

Chapter 10 Supplementary Provisions

Article 111 The naming of in vitro diagnostic reagents shall follow the following principles:

The product name of in vitro diagnostic reagents generally consists of three parts. Part 1: Name of the tested substance; Part 2: Purpose, such as assay kits, quality control products, etc; Part 3: Methods or principles, such as magnetic particle chemiluminescence immunoassay, fluorescence PCR, fluorescence in situ hybridization, etc., should be listed in parentheses in this section.

If there are many components of the tested substance or there are other special circumstances, the indication name or other alternative name related to the product can be used.

The first category of products, calibration products, and quality control products are named based on their intended use.

Article 112: The registration or filing unit for in vitro diagnostic reagents shall be a single reagent or a single reagent kit, and a registration or filing unit may include different packaging specifications.

Calibration and quality control products can be registered together with in vitro diagnostic reagents used in combination, or they can be registered separately.

Article 113: In vitro diagnostic reagents that have been approved for registration refer to in vitro diagnostic reagents that are consistent with the limited content of the medical device registration certificate and attachments and are produced within the validity period of the medical device registration certificate.

Article 114: The independent reagent components specified in the "Main Components" column of the medical device registration certificate, which are used for the original registered product, may be sold separately.

Article 115: Applicants may obtain authorization from the owner of the medical device main document to refer to the registered medical device main document when applying for in vitro diagnostic reagent product registration or change registration. The main document of medical devices shall be registered by its owner or agency, and the relevant work procedures shall be stipulated separately.

Article 116: The format of the medical device registration certificate shall be uniformly formulated by the State Drug Administration.

The arrangement of registration certificate numbers is as follows:

× 1 mechanical note × two ×××× three × four ×× five ×××× 6. Among them:

× 1 is the abbreviation for the location of the registration and approval department:

The third category of in vitro diagnostic reagents, imported second and third categories of in vitro diagnostic reagents in China are referred to as "national";

The second type of in vitro diagnostic reagents in China are abbreviated as the province, autonomous region, or municipality where the registration and approval department is located;

× 2 is the registration form:

The word 'accurate' is applicable to in vitro diagnostic reagents within China;

The word 'jin' is applicable to imported in vitro diagnostic reagents;

The word 'Xu' is applicable to in vitro diagnostic reagents in Hong Kong, Macau, and Taiwan;

×××× 3 is the year of initial registration;

× 4 is the product management category;

×× 5 is the product classification code;

×××× 6 is the first registration serial number.

Continuing registration, ×××× 3 and ×××× The number 6 remains unchanged. If the product management category is adjusted, it should be renumbered.

Article 117 The arrangement of the filing numbers for Class I medical devices is as follows:

× 1 Equipment ×××× two ×××× 3. Among them:

× 1 is the abbreviation for the location of the filing department:

The first category of imported in vitro diagnostic reagents is labeled as "national";

The first type of in vitro diagnostic reagents in China are the abbreviation of the province, autonomous region, or municipality where the filing department is located, plus the abbreviation of the city level administrative region where the registration department is located (in the absence of a corresponding city level administrative region, only the abbreviation of the province, autonomous region, or municipality directly under the central government);

×××× 2 is the year of filing;

×××× 3 is the registration serial number.

Article 118 The electronic documents of the medical device registration certificate and change registration documents produced by the drug regulatory department shall have the same legal effect as the paper documents.

Article 119: According to work needs, the National Drug Administration may entrust drug regulatory departments, technical institutions, and social organizations of provinces, autonomous regions, and municipalities directly under the central government to undertake specific work in accordance with the law.

Article 120: The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government may refer to the provisions of Chapter 4 of these Measures to formulate special registration procedures for Class II in vitro diagnostic reagents within their respective administrative regions, and report them to the National Drug Administration for record keeping.

Article 121: The registration fees and standards for in vitro diagnostic reagent products shall be implemented in accordance with the relevant regulations of the finance and pricing authorities of the State Council.

Article 122: The relevant regulations for the emergency use of in vitro diagnostic reagents shall be formulated separately by the State Administration for Drug Administration in conjunction with relevant departments.

Article 123: There are no products of the same variety listed in China, and medical institutions develop in vitro diagnostic reagents based on the clinical needs of their own units and use them within their own units under the guidance of licensed physicians. The relevant management regulations shall be separately formulated by the State Drug Administration in conjunction with relevant departments.

Article 124 The registration and filing of in vitro diagnostic reagents in Hong Kong, Macau, and Taiwan shall be handled with reference to imported in vitro diagnostic reagents.

Article 125: These measures shall come into effect from October 1, 2021. The "In Vitro Diagnostic Reagent Registration Management Measures" promulgated by Order No. 5 of the former State Food and Drug Administration on July 30, 2014 shall be abolished simultaneously.