Provisions for In-vitro Diagnostic Reagent Registration

(Decree No.5 of China Food and Drug Administration)

The Provisions for In-vitro Diagnostic Reagent Registration, adopted at the executive meeting of China Food and Drug Administration on June 27, 2014, is hereby promulgated and shall be effective as of October 1, 2014.

Minister: Zhang Yong

July 30, 2014

Provisions for In-Vitro Diagnostic Reagent Registration

Chapter I　General Provisions

Article 1 The Provisions is formulated in accordance with the Regulations on Supervision and Administration of Medical Devices, with a view to standardizing the administration on registration and filing of in-vitro diagnostic reagents and ensuring the safety and effectiveness of in-vitro diagnostic reagents.

Article 2 All in-vitro diagnostic reagents sold and used within the territory of the People's Republic of China shall apply for registration or filing according to the Provisions.

Article 3 The in-vitro diagnostic reagents mentioned herein refer to in-vitro diagnostic reagents administered as medical devices, including reagents, reagent kits, calibrators, control materials, etc. for in-vitro examination of specimens derived from human body in the course of disease forecast, prevention, diagnosis, treatment monitoring, prognosis observation, health status evaluation, which can be used independently or in combination with instruments, devices, equipment or systems.

The in-vitro diagnostic reagents used for blood screening and the in-vitro diagnostic reagents labeled by radionuclide, which are subjected to drug administration, do not belong to the administration scope of the Provisions.

Article 4 In-vitro diagnostic reagent registration refers to the prescribed procedures conducted by the food and drug regulatory department upon an application submitted by the registration applicant to decide whether the medical device to be marketed can be sold based on a comprehensive evaluation of the research and results of its safety and effectiveness.

In-vitro diagnostic reagent filing is a process that the filing entity submits the filing documents to the food and drug regulatory department and the food and drug regulatory department files the filing documents submitted by the filing entity.

Article 5 The in-vitro diagnostic reagent registration and filing shall be conducted under the principles of publicity, equity and justice.

Article 6 Class I in-vitro diagnostic reagents are subject to filing administration and class II and class III in-vitro diagnostic reagents are subject to registration administration.

To apply for filing of class I in-vitro diagnostic reagent, the filing entity shall submit the filing documents to the food and drug regulatory department of the city consisting of districts .

Class II in-vitro diagnostic reagents shall be reviewed by the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government, and the medical device registration certificate shall be issued after approval.

Class III domestic in-vitro diagnostic reagents shall be reviewed by China Food and Drug Administration, and the medical device registration certificate shall be issued after approval.

To apply for filing of import class I in-vitro diagnostic reagents, the filing entity shall submit the filing documents to China Food and Drug Administration.

Import class II and class III in-vitro diagnostic reagents shall be reviewed by China Food and Drug Administration, and the medical device registration certificate shall be issued after approval.

The in-vitro diagnostic reagents from Hong Kong, Macao and Taiwan shall be registered and filed by reference to the import medical devices.

Article 7 Where a registration applicant or filing entity of an in-vitro diagnostic reagent brings the products to the market in his own name, he shall take responsibilities for the product.

Article 8 The food and drug regulatory department shall publicize relevant information on in-vitro diagnostic reagent registration and filing promptly in accordance with laws. The applicant can look up the approval progress and relevant results as well as the public can look up the result of approval.

Article 9 The State encourages the research and innovation of in-vitro diagnostic reagents, implements special review for innovative medical devices, accelerates the popularization and application for new technologies of in-vitro diagnostic reagents and promotes the development of medical device industry.

Chapter II　Essential Requirements

Article 10 The registration applicant and filling entity of in-vitro diagnostic reagents shall establish the quality management system related to product research, development and manufacture and shall keep its effective operation.

Where applying for registration of a in-vitro diagnostic reagent subject to the special review procedures for innovative medical devices and its sample production is entrusted to another enterprise, the applicant shall entrust a medical device manufacturer having corresponding production range. Where the domestic medical device applied for registration is not subject to the special review procedures for innovative medical devices, the sample production shall not be entrusted to another enterprise.

Article 11 The persons undertaking registration or filing for in-vitro diagnostic reagents shall have corresponding specialized knowledge and be familiar with the laws, rules, regulations and technical requirements of the administration on registration or filing of in-vitro diagnostic reagent.

Article 12 The research and development of in-vitro diagnostic reagents involves main raw materials selection and preparation, manufacturing process determination, product technical requirements drafting, product stability study, positive judgment value or reference range determination, product analysis performance evaluation and clinical evaluation, etc..

The applicant or filing entity may conduct product research and development with reference to the relevant technical guidelines, and may also adopt different test methods or technical means while it is required to describe their reasonableness.

Article 13 When applying for registration or filing, the applicant or filing entity shall complete the research and development of in-vitro diagnostic reagents in accordance with the essential requirements for safety and effectiveness of in-vitro diagnostic reagents and make sure the research and development process is true and standardized and all the data is authentic, complete and traceable.

Article 14 The documents for registration application or filing shall be in Chinese, where they are translated from a foreign language, the original documents shall also be provided at the same time. When referring to unpublished literature, the applicant shall provide documents proving of the owner's permission to use the information.

The applicant and filing entity shall take full responsibility for the authenticity of the documents submitted.

Article 15 An import in-vitro diagnostic reagents being applied for registration shall be one which has already got permission for distribution in the country (region) where the applicant or filing entity is registered or the manufacture is carried out.

If the product is not managed as medical device in the country (region) where the applicant or filing entity is registered or the manufacture is carried out, the applicant or filing entity shall provide relevant proof documents, including the permission for distribution of sold product in the country (region) where the applicant or filing entity is registered or the manufacture is carried out.

Article 16 An overseas applicant or filing entity shall conduct related work with the support of its representative office established in China or an enterprise legal person in China designated by it as its agent.

The agent shall undertake the following liabilities in addition to conducting in-vitro diagnostic reagents registration or filing:

(I) Contacting with corresponding food and drug regulatory department and overseas applicant or filing entity.

(II) Delivering related laws and regulations and technical requirements to the applicant of filing entity in a truthful and faithful manner.

(III) Collecting post-market adverse event information of in-vitro diagnostic reagents and sending feedback to overseas registrants or filing entity, meanwhile, reporting to relevant food and drug regulatory department.

(IV) Coordinating the in-vitro diagnostic reagents post-market product recall and reporting to relevant food and drug regulatory department.

(V) Other joint liabilities related to product quality and after-sales service.

Chapter III　Product Classification and Naming

Article 17 According to product risk degree in the order of lower to higher, in-vitro diagnostic reagents shall be classified into class I, class II and class III products.

(I) Class I products

1. Microorganism culture medium (not applicable to microorganism identification and drug sensitivity testing).

2. Products for specimen treatment, e.g. hemolytic agents, diluents, staining solutions, etc.

(II) Class II products

Products not clearly defined as class I and class III products are class II products, mainly including:

1. Reagents used for protein testing.

2. Reagents used for carbohydrate testing.

3. Reagents used for hormone testing.

4. Reagents used for enzymes testing.

5. Reagents used for esters testing.

6. Reagents used for vitamin testing.

7. Reagents used for inorganic ion testing.

8. Reagents used for the testing of drugs and drug metabolites.

9. Reagents used for auto-antibody testing.

10. Reagents used for microorganism identification and medicine sensitivity experiment.

11. Reagents used for indices inspection such as physiological indices, biochemical indices and immune functions indices.

(III) Class III products

1. Reagents related to the testing of antigen, antibody and nucleic acid, etc. for pathogen.

2. Reagents related to blood grouping and tissue typing.

3. Reagents related to human genetic testing.

4. Reagents related to inherited diseases.

5. Reagents related to the testing of narcotic drugs, psychotropic drugs and toxic drugs for medical use.

6. Reagents related to the testing of targets of curative drugs.

7. Reagents related to the testing of tumor markers.

8. Reagents related to allergy (allergen).

Article 18 If a class II product listed in Article 17 is used for monitoring of diagnosis, auxiliary diagnosis and treatment process of tumors, or for diagnosis and auxiliary diagnosis, etc. of inherited diseases, it shall be registered and managed as a class III product. For reagents used for inspection of drugs and drug metabolites, if the drugs belong to the scope of narcotic drugs, psychotropic drugs and toxic drugs for medical use, they shall be registered and managed as class III products.

Article 19 For the calibrators and quality controls used in conjunction with in-vitro diagnostic reagents, the applicant may submit an application for registration of such calibrators and control materials together with the in-vitro diagnostic reagent or submit separate application for registration.

The calibrators and control materials used in conjunction with class I in-vitro diagnostic reagents are registered as class II products. When separate applications are submitted for registration of some calibrators and control materials used in conjunction with class II and III in-vitro diagnostic reagents, such calibrators and control materials shall be registered according to the same class as that of the reagents. Calibrators or control materials for multiple analyses, registration will be made according to the highest class.

Article 20 China Food and Drug Administration shall be responsible for compiling and adjusting the classification catalogue of in-vitro diagnostic reagents.

For a newly developed in-vitro diagnostic reagent not yet listed in the classification catalogue, the applicant may directly apply for a class III in-vitro diagnostic reagent registration, or, after determining the class of the product in accordance with the classification rules and applying for class confirmation to the China Food and Drug Administration, apply for registration or for filing.

Where a class III in-vitro diagnostic reagent registration is directly applied for, China Food and Drug Administration shall determine the class based on its risk degree. Where a domestic in-vitro diagnostic reagent is determined as class II, China Food and Drug Administration shall forward the application materials to the food and drug regulatory department of the province, autonomous region, or municipality directly under the central government where the applicant is located for evaluation and approval. Where a domestic in-vitro diagnostic reagent is determined as class I, China Food and Drug Administration shall forward the application materials to the food and drug regulatory department of the city consisting of districts where the applicant is located.

Article 21 Naming for in-vitro diagnostic reagents shall comply with the following principles:

Product names of in-vitro diagnostic reagents are generally composed of three parts. The first part shall be the name of the substance tested. The second part shall be the usage, e.g. diagnosis serum, diagnostic regent kit, control materials, etc.. The third part shall be the method or mechanism, e.g. enzyme-linked immunosorbent assay, colloidal gold assay, etc., and this part shall be listed in parentheses.

If the substance to be tested has many components or is under special circumstances, the substance can adopt the indication name related to the product or other substitute names.

Class I products, calibrators and control materials shall be named according to their intended use.

Chapter IV　Technical Requirements and Registration Testing

Article 22 The applicant or the filling entity shall, under the preconditions of stable raw material quality and manufacturing process, draft the technical requirements of the product basing on the results of product development and clinical evaluation, etc., and in accordance with national standards, industry standards and related literature.

Product technical requirements mainly include the performance indicators and testing method of the finished in-vitro diagnostic reagents. Performance indicators refer to functional and safety indicators and other quality control indicators of finished in-vitro diagnostic reagents that can be measured objectively.

In the technical requirements for class III in-vitro diagnostic reagents, it is required to make clear the requirements for main raw materials, manufacturing process and in-process products in the form of annex.

The product technical requirements for class I in-vitro diagnostic reagents shall be submitted to the food and drug regulatory department at the time of filing by filing entity. The product technical requirements for class II and class III in-vitro diagnostic reagents shall be approved by the food and drug regulatory department at the time of registration approval.

The in-vitro diagnostic reagents marketed in China shall comply with the product technical requirements which are approved by registration or filed.

Article 23 When applying for class II and class III in-vitro diagnostic reagent registration, registration testing shall be conducted, and class III products shall conduct registration testing on samples in three continuous manufacture batches. The medical device testing institutions shall carry out relevant registration testing on the products in accordance with the product technical requirements.

The production of samples for registration testing shall comply with relevant requirements of quality management system for medical devices. Clinical trials or registration application can be carried out only after the products passed the registration testing.

For the filing of class I in-vitro diagnostic reagent, the filing entity may submit the product self-testing report.

Article 24 For the application of registration testing, the applicant shall submit relevant technical documents and samples for registration testing, product technical requirements and standard products or reference materials as required according to the registration testing to the testing institutions.

For a domestic applicant, the samples for registration testing shall be drawn out by the food and drug regulatory department.

Article 25 For the products with national standard products and reference products, it is required to use national standard products and reference materials for registration testing. National Institutes for Food and Drug Control is responsible for organizing the preparation and calibration of national standard products and reference materials.

Article 26 Medical device testing institutions shall have the relevant qualification of medical device testing, and perform testing within their specified testing scope. It shall carry out pre-evaluation of the product technical requirements. The pre-evaluation opinions together with the medical device registration testing report shall be submitted to the applicant.

For the medical devices having not included in the testing scope of any medical device testing institutions, the corresponding registration department shall designate a testing institution which has the capability to conduct the testing.

Article 27 Where one registration application includes different packaging sizes, it is allowed to conduct registration testing on the product of one packaging size.

Chapter V　Clinical Evaluation

Article 28 Clinical evaluation of in-vitro diagnostic reagents refers to the process that the applicant or filing entity validates whether the products under registration can meet their intended use and indications based on the information of clinical literature, clinical experience data and clinical trials.

Article 29 Clinical evaluation materials refer to the documents developed through clinical evaluation by the applicant or filing entity.

The clinical trial of in-vitro diagnostic reagents (including the comparative study made with the marketed products) refers to the systematic study on the clinical performance of in-vitro diagnostic reagents in the corresponding clinical environment.

For the clinical trial of in-vitro diagnostic reagents are not required, the applicant shall evaluate the clinical performance of in-vitro diagnostic reagents through non-clinical trial methods such as evaluation on the clinical samples covering intended use and interference factors as well as comprehensive literatures. The applicant or filing entity shall ensure that the clinical samples for evaluation are traceable.

Article 30 For filing of a class I in-vitro diagnostic reagent, clinical trial is not required. For application for registration of a class II or class III in-vitro diagnostic reagent, clinical trial shall be conducted; however,

In one of the following circumstances, clinical trial may be exempted:

(1) Where the reaction principle is definite, the design is finalized, the production process is well-established, and the marketed in-vitro diagnostic reagent of the same variety has been in clinical use for years and no serious adverse events are recorded, and its conventional purposes of use are not changed, and the applicant can provide the equivalence evaluation data to the marketed products.

(2) Where the safety and effectiveness of an in-vitro diagnostic reagent can be proved through the evaluation on the clinical samples covering intended use and interference factors.

The catalogue of in-vitro diagnostic reagent that is exempted from clinical trial shall be compiled, adjusted and published by China Food and Drug Administration.

Article 31 Where one registration application includes different packaging sizes, it is allowed to make clinical evaluation on the samples of one packaging size.

Article 32 The applicant of class III products shall select no less than 3 qualified clinical institutions, the applicant of class II products shall select no less than 2 qualified clinical institutions to carry out clinical trials according to relevant requirements. The production of the samples for clinical trials shall comply with the relevant requirements of the in-vitro diagnostic reagent quality management system.

Article 33 The applicant shall conclude and sign the contract of clinical trial with the clinical trial institution, prepare and improve the clinical trial protocol by referring to the related technical guidelines, provide samples for clinical trial for free, and assume the costs of clinical trials.

Article 34 The number of clinical trial cases shall be determined according to the clinical trial objective, requirements of statistics and referring to the related technical guidelines. The technical guideline for the clinical trial is issued separately.

For an in-vitro diagnostic reagent which is used to treat a rare disease or is urgently needed in dealing with emergent public health incidents, which requires cases number reduction or clinical trial exempt, the applicant shall apply for trial exempt and provide detailed reasons while submitting the application materials. The technical evaluation institution of food and drug regulatory departments shall perform comprehensive technical evaluation to the registration application materials, and inform the applicant by notice for supplements or corrections in the case that clinical trial is required.

Article 35 The documents of overseas clinical evaluation shall be provided for the registration of import in-vitro diagnostic reagent. The applicant shall perform targeted clinical evaluation within the territory of China according to the requirements for clinical evaluation, in consideration of epidemics background, characteristics of different diseases, positive judgment value or reference range, etc. suitable for people of different species in different countries or regions.

Article 36 The clinical trial institution shall respectively provide the clinical trial report after completing the clinical trial. The applicant or leading unit of clinical trial shall summarize the results of clinical trials and complete the final report according to the relevant technical guidelines.

Article 37 For the in-vitro diagnostic reagents used by the consumer himself, the evaluation on cognitive competence of instructions by the consumer without medical science background shall be included during clinical trial.

Article 38 Where the applicant finds that the clinical trial institution violates relevant regulations or fails to performs the clinical trial protocol, it shall supervise and urge the clinical trial institution to correct; In case of severe conditions, the applicant can require suspending or terminating the clinical trial, and report to the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government where the clinical trial institution is located and China Food and Drug Administration.

Article 39 Where the applicant violates relevant regulations or requires change of trial data and conclusion, the participating institution and its personnel shall report to the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government where the applicant is located and China Food and Drug Administration.

Article 40 The clinical trial of in-vitro diagnostic reagents shall be filed with the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government where the applicant is located. The food and drug regulatory department accepting the filling shall report to the food and drug regulatory department and the competent health and family planning department at the same level where the clinical trial institution is located.

China Food and Drug Administration and the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government shall supervise and inspect the implementation situation of clinical trial according to necessity.

Chapter VI　Product Registration

Article 41 To apply for in-vitro diagnostic reagent registration, the applicant shall submit application materials to the food and drug regulatory department in accordance with relevant requirements.

Article 42 The food and drug regulatory department shall conduct formal review after accepting an application, and handle respectively according to the following circumstances:

(I) Where the application is within functions and duties of department, and the application materials are complete and meet the preliminary review requirements.

(II) Where the application materials have errors that may be corrected on the spot, the applicant shall be allowed to correct them on the spot.

(III) Where the application materials are incomplete or do not meet the preliminary review requirements, the applicants shall be informed one-off of all the supplements or corrections required within 5 workdays. Where the application is not informed, the application shall be deemed as accepted from the date the application materials are received.

(IV) Where an application is not within the functions and duties of the department, the applicant shall be notified immediately of unacceptance.

The food and drug regulatory department shall issue a dated acceptance or rejection notice affixed with its special seal to indicate its acceptance or rejection of the in-vitro diagnostic reagent registration application.

Article 43 The food and drug regulatory department accepting the registration application shall forward the application materials to technical evaluation institution within 3 workdays from the date of acceptance.

The technical evaluation institution shall complete the technical evaluation within 60 workdays for class II in-vitro diagnostic reagent registration, and within 90 workdays for class III in-vitro diagnostic reagent registration.

Where experts shall be invited for an evaluation, the time spent shall not be calculated in the overall evaluation time. The technical evaluation institution shall notify the applicant of the time needed in writing.

Article 44 The food and drug regulatory department may refer to the original research data when organizing a technical evaluation for product registration, and organize an inspection of the applicant’s quality management system concerning product research, development and production.

For domestic class II and class III medical device registration, the quality management system shall be inspected by the food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government. In case the quality management system inspection is for a domestic class III medical device, the technical evaluation institution of China Food and Drug Administration shall notify the food and drug regulatory department of the corresponding province, autonomous region and municipality directly under the central government to carry out the inspection, and participate in the inspection when necessary. The food and drug regulatory department of the province, autonomous region or municipality directly under the central government shall complete the inspection within 30 workdays according to relevant requirements.

When conducting technical evaluation for an import class II or class III in-vitro diagnostic reagent, if the technical evaluation institution of China Food and Drug Administration deems it necessary to conduct a quality management system inspection, it shall notify the technical institution for quality management system inspection of China Food and Drug Administration to carry out the inspection according to relevant requirements. The technical evaluation institution shall participate in the inspection when necessary.

The time for quality management system inspection shall not be calculated in the overall evaluation time.

Article 45 Where supplementary and correction materials are required during technical evaluation, the technical evaluation institution shall inform the applicant one-off of all the supplements to be completed. The applicant shall submit all necessary supplementary and correction materials one-off within one year according to the supplementation notice. The technical evaluation institution shall complete the technical evaluation within 60 workdays from the date of acceptance of the supplements. The time spent by applicant for supplementing such materials shall not be calculated in the overall evaluation time.

Where the applicant has an objection to the content of the notice for supplements or corrections, it may submit its written opinions to the corresponding technical evaluation institution, to explain its reasons and provide corresponding technical supporting materials.

Where the applicant fails to submit the supplementary materials within the specified timeline, the technical evaluation institution shall terminate the technical evaluation and come up with a disapproval suggestion, and China Food and Drug Administration shall make a disapproval decision after confirmation.

Article 46 The food and drug regulatory department accepting the registration application shall make a decision within 20 workdays after technical evaluation. For that meeting safety and effectiveness requirements, the registration shall be approved, and a medical device registration certificate shall be issued within 10 workdays from the date of approval, and the approved product technical requirements and product instructions shall be issued as an attachment to the applicant. For that disapproved, reasons shall be given in writing, and the applicant shall be informed of its right to apply for a re-evaluation and for an administrative reconsideration or administrative litigation in accordance with laws and regulations.

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

Article 47 In-vitro diagnostic reagent registration items include permission items and registry items. The permission items include product name, packaging size, main composition ingredient, intended use, product technical requirements, product instructions, period of validity, the manufacture is carried out for an import in-vitro diagnostic reagent, etc.. The registry items include the name and residence of the registrant, the name and residence of the agent and the manufacture is carried out of domestic in-vitro diagnostic reagent, etc..

Article 48 For a in-vitro diagnostic reagent which is used to treat a rare disease or is urgently needed in dealing with emergent public health incidents, the food and drug regulatory department may require its applicant to further complete relevant work after the product is put on market, and specify the requirements on the medical device registration certificate.

Article 49 For accepted registration applications, where one of the following circumstances exists, the food and drug regulatory department shall decide to reject the application and notify the applicant:

(I) The research conducted by the applicant and its result cannot prove the safety and effectiveness of the in-vitro diagnostic reagent to be sold on the market.

(II) The registration application materials are spurious.

(III) The registration application materials have confused or inconsistent contents.

(IV) The registration application materials are obviously inconsistent with application items.

(V) Other circumstances under which the registration application shall not be approved.

Article 50 For an accepted registration application, the applicant may, prior to the administrative permission decision is made, withdraw the registration application and relevant materials, and give reasons to the food and drug regulatory department which accepted the application.

Article 51 For an accepted registration application, where there are evidences indicating that the registration application materials may be spurious, the food and drug regulatory department shall suspend the evaluation and approval process. After investigation, the food and drug regulatory department shall determine to continue the process or to reject the registration application in accordance with the investigation conclusion.

Article 52 Where an applicant has an objection to the disapproval decision of the food and drug regulatory department, it may submit a re-evaluation application within 20 workdays after receiving the disapproval notice to the food and drug regulatory department that made the decision. Contents of the re-evaluation application shall be limited to original application items and original application materials.

The food and drug regulatory department shall make a re-evaluation decision within 30 workdays after accepting the re-evaluation application and inform the applicant. Where the original decision shall be maintained, the food and drug regulatory department shall not accept further application for re-evaluation by the applicant.

Article 53 Where the applicant has an objection to the disapproval decision of the food and drug regulatory department, and has applied for an administrative reconsideration or administrative litigation, the food and drug regulatory department shall not accept its re-evaluation application.

Article 54 Where a medical device registration certificate is lost, the registrant shall publish a loss declaration immediately at the media specified by the original certificate-issuing authority, and apply after 1 month of declaration to the original certificate-issuing authority for re-issuing the certificate. The original certificate-issuing authority shall re-issue the medical device registration certificate within 20 workdays.

Article 55 Where the in-vitro diagnostic reagent is put on market, the technical requirements and product instructions must be consistent with the contents approved by the food and drug regulatory department. The registrant and filling entity shall track the safety and effectiveness of post-market product, and timely provide application for modifying the technical requirements or instructions when necessary.

Article 56 Where major interest relationship between the applicant and others is directly involved in the application for in-vitro diagnostic reagent registration, the food and drug regulatory department shall inform the applicant and the interested party of their right to apply for a hearing in accordance with laws, regulations and other provisions of China Food and Drug Administration. During the process of reviewing the application for in-vitro diagnostic reagent registration, if the food and drug regulatory department believes there are major licensing issues concerning public interests, it shall make a public announcement and hold a hearing.

Article 57 Where a patent dispute arises during the registration review or after approval, it shall be dealt with according to relevant laws and regulations.

Chapter VII　Registration Alteration

Article 58 For a registered class II or class III in-vitro diagnostic reagent, if the content of the medical device registration certificate and its attachment(s) has an alteration, the registrant shall apply to the original registration department for registration alteration and submit application materials according to relevant requirements.

Where the alteration is for name, residence of the applicant and the agent, the registrant shall apply to the original registration department for change of registry items. Where the alteration is for production address of a domestic in-vitro diagnostic reagent, the registrant shall apply for change of registry items after the corresponding production license is changed.

If the following items contained in the medical device registration certificate and annexes thereto change, the applicant shall make an application for changing the permission items:

(1) Change of suppliers of main materials such as antigen and antibody, etc..

(2) Change of inspection conditions, positive judgment value or reference range.

(3) Change of the items, indices, experimental methods, set in the registered product technical requirements.

(4) Change of packaging sizes, applicable models.

(5) Change of storage conditions or period of validity of the product.

(6) Addition of the intended purposes, e.g. addition of the clinical indications, addition of the types of specimens for clinical diagnosis, etc..

(7) Change of manufacturing address of import in-vitro diagnostic reagents.

(8) Other changes that may influence the safety and effectiveness of product.

Article 59 The following circumstances are not within the change of application items, registration application shall be conducted:

(1) Change of basic reaction principles of products.

(2) Change of positive judgment value or reference range of products, which also has new significance of clinical diagnosis.

(3) Other significant changes that influence the product performance.

Article 60 Where the application materials for change of registry items conform to the requirements, the food and drug regulatory department shall issue the medical device registration alteration document within 10 workdays. Where the application materials are not complete or do not meet the requirements for preliminary review, the food and drug regulatory department shall inform the applicant one-off of all the supplements to be completed.

Article 61 For the change of permission items, technical evaluation institution shall focus on evaluating both the changed parts and their effects on product performance and evaluate the product safety and effectiveness after the change.

The food and drug regulatory department accepting the application for change of permission items shall organize technical evaluation within the period specified in Chapter VI of the Provisions.

Article 62 The medical device registration alteration document shall be used in conjunction with the original medical device registration certificate and its period of validity shall be the same with that of the original registration certificate. After obtaining the registration alteration document, the registrant shall alter the product technical requirements, instructions and labels by himself.

Article 63 Where provisions concerning acceptance and approval procedures of the application for change of permission items are not available in this chapter, Chapter VI of the Provisions shall prevail.

Chapter VIII　Registration Renewal

Article 64 Where it is required to extend the period of validity of the medical device registration certificate, the registrant shall submit application for registration renewal to the food and drug regulatory department six months before the expiration of period of validity and submit application documents according to corresponding requirements.

Except for the situations specified in Article 65, the food and drug regulatory department receiving the application for registration renewal shall make a decision for the renewal before the expiration of period of validity of the medical device registration certificate. If the decision is not made within the specified time, the renewal is considered approved.

Article 65 The registration renewal shall not be approved in any of the following circumstances:

(1) The applicant fails to submit the application for registration renewal within the specified period.

(2) The mandatory standard(s) of in-vitro diagnostic reagents have been revised or national standard products and reference products have been established, and the in-vitro diagnostic reagent fails to meet the requirements of the new standards.

(3) For an in-vitro diagnostic reagent which is used to treat a rare disease or is urgently needed in dealing with emergent public health incidents, the registrant fails to complete items stated in medical device registration certificate within specified time as required by registration department upon approving such registration.

Article 66 Where provisions concerning acceptance and approval procedures of application for registration renewal of medical device are not available in this chapter, Chapter VI of the Provisions shall prevail.

Chapter IX　Product Filing

Article 67 Filing for a class I in-vitro diagnostic reagent shall be conducted prior to production.

Article 68 For an in-vitro diagnostic reagent filing, the filing entity shall submit the filing materials in accordance with Article 9 of the Regulations on Supervision and Administration of Medical Devices.

Where the filing documents meet the requirements, the food and drug regulatory department shall complete the filing on the spot. Where the filing documents are not complete or do not meet the filing requirements, the filing entity shall be informed of all the supplements and corrections to be made one- off, for filing after supplements and corrections.

For a filed in-vitro diagnostic reagent, the food and drug regulatory department shall make filing certificates according to the format in relevant requirements and publish the information from the filing information form for medical device on their website.

Article 69 For a filed in-vitro diagnostic reagent, where the contents set forth in the filing information form for in-vitro diagnostic reagent changed, the filing entity shall submit a description of the change and related supporting documents to the original filing department and apply for change of filing. Where the filing materials meet the formal requirements, the food and drug regulatory department shall put the changes in the information of changes, and file a record.

Article 70 Where the management classification of a filed in-vitro diagnostic reagent is adjusted, the filing entity shall apply to the food and drug regulatory department for cancellation of the original filing. Where the management classification is adjusted to a class II or class III in-vitro diagnostic reagent, the filing entity shall apply for registration in accordance with the Provisions.

Chapter X　Supervision and Administration

Article 71 China Food and Drug Administration shall be responsible for the supervision and administration of in-vitro diagnostic reagent registration and filing nationwide, and supervise and guide the in-vitro diagnostic reagent registration and filing by local food and drug regulatory departments.

Article 72 The food and drug regulatory department of the provinces, autonomous regions and municipalities directly under the central government shall be responsible for supervision and administration of in-vitro diagnostic reagent registration and filing within their administrative areas, and organize supervision and inspection and report relevant situations to China Food and Drug Administration.

Article 73 The food and drug regulatory departments of the provinces, autonomous regions and municipalities directly under the central government shall, in accordance with the principle of territorial administration, perform routine supervision and administration over the work concerning registration and filing done by agents for import in-vitro diagnostic reagents.

Article 74 The food and drug regulatory departments of the cities consisting of districts shall perform regular examination over the filing of in-vitro diagnostic reagents and timely report relevant information to the food and drug regulatory departments of the provinces, autonomous regions and municipalities directly under the central government.

Article 75 Where, for a registered in-vitro diagnostic reagent, there exists a revocation situation in accordance with laws and regulations, or a registrant applies for revocation before the expiration of a registration certificate, the food and drug regulatory department shall revoke the registration certificate according to law and disclose to the society.

Article 76 Where, for a registered in-vitro diagnostic reagent, the management classification is adjusted from a higher class to a lower one, the registration certificate within its period of validity shall remain valid. Where a renewal is needed, the registrant shall apply for registration renewal or filing on changed classification to corresponding food and drug regulatory department six months prior to the expiration of period of validity of the registration certificate.

Where, the in-vitro diagnostic reagent classification is adjusted from a lower class to a higher one, the registrant shall apply for registration on changed classification to the corresponding food and drug regulatory department in accordance with the provisions in Chapter VI hereof. China Food and Drug Administration shall specify a time limit for completing the adjustment in the notice on adjusting management classification.

Article 77 Where a food and drug regulatory department of a province, autonomous region or municipality directly under the central government conducts an in-vitro diagnostic reagent registration by violating the Provisions, China Food and Drug Administration shall order it to correct within a deadline. Where it fails to correct before the deadline, China Food and Drug Administration may directly announce a revocation of the medical device registration certificate.

Article 78 The food and drug regulatory department, relevant technical institutions and their staff shall be liable for the confidentiality of the trial or testing data and know-how submitted by the applicant of filing entity.

Chapter XI　Legal Responsibilities

Article 79 Where a medical device registration certificate is obtained by providing spurious documents or by other deception means, punishments shall be imposed according to Paragraph 1, Article 64 of the Regulations on Supervision and Administration of Medical Devices.

Where a filing is done by providing spurious documents, punishments shall be imposed according to Paragraph 2, Article 65 of the Regulations on Supervision and Administration of Medical Devices.

Article 80 Where a medical device registration certificate is falsified, altered, bought or sold, leased or lent, punishments shall be made according to Paragraph 2, Article 64 of the Regulations on Supervision and Administration of Medical Devices.

Article 81 Where, in violation of the Provisions, a change of filing for a class I in-vitro diagnostic reagent is not performed, or a registration alteration of registry items for a class II or class III in-vitro diagnostic reagent is not performed according to law, punishments shall be imposed according to the situation concerning fail in filing in the Regulations on Supervision and Administration of Medical Devices.

Article 82 Where, in violation of the Provisions, a registration alteration of permission items for an in-vitro diagnostic reagent is not performed according to law, punishments shall be imposed according to the situation concerning not obtaining a medical device registration certificate in the Regulations on Supervision and Administration of Medical Devices.

Article 83 Where a clinical trial performed by an applicant is not in accordance with the Regulations on Supervision and Administration of Medical Devices and the Provisions, the food and drug regulatory department at or above the county level shall order for rectifications and may impose a penalty of less than 30,000 yuan(RMB). In case of severe conditions, the clinical trial shall be stopped immediately.

Chapter XII　Supplementary Provisions

Article 84 The registration or filing unit of in-vitro diagnostic reagent shall be a single reagent or a single reagent kit. One registration or filing unit may include different packaging sizes.

Article 85 The format of the medical device registration certificate shall be prepared by China Food and Drug Administration.

The registration numbers shall be arranged in the following form:

×1 XZ ×2××××3×4××5××××6. Among which,

×1 shall be the abbreviation of the place where the registration authority is located.

The letter "G" shall refer to domestic class III in-vitro diagnostic reagents and import class II and III medical devices.

The abbreviation of the provinces, autonomous regions and municipalities directly under the central government where the registration authority is located shall be adopted for domestic class II in-vitro diagnostic reagents.

×2 shall indicate the form of registration:

“Z” is applicable to domestic in-vitro diagnostic reagents.

“J” is applicable to import in-vitro diagnostic reagents.

“X” is applicable to in-vitro diagnostic reagents from Hong Kong, Macao and Taiwan.

××××3 shall indicate the year of initial registration.

×4 shall indicate the classification.

××5 shall indicate the product classification code.

××××6 shall indicate the serial number of initial registration.

For the registration renewal, ××××3 and ××××6 shall remain the same. In case of the management classification changed, a new registration number shall be issued.

Article 86 The filing certificate for class I in-vitro diagnostic reagent shall be arranged in the following form:

×1 XB ××××2××××3. Among which,

×1 shall be the abbreviation of the place where the filing department is located:

The letter "G" shall refer to import class I in-vitro diagnostic reagents.

The abbreviation of the provinces, autonomous regions and municipalities directly under the central government combines the abbreviation of city divided into districts where filing department is located (if there is no corresponding city divided into districts, only use the abbreviation of province, autonomous region or municipality directly under the central government) shall be adopted for domestic class I in-vitro diagnostic reagent.

××××2 shall indicate the year of filing.

××××3 shall indicate the serial number of filing.

Article 87 The emergency approval and the innovation special approval for in-vitro diagnostic reagents shall be executed according to emergency approval procedure for medical device and special approval procedure for innovative medical device formulated by China Food and Drug Administration.

Article 88 China Food and Drug Administration may, according to necessity, authorize the food and drug regulatory departments or technical organizations of provinces, autonomous regions and municipalities directly under the central government and relevant social organizations to conduct the specific work related to the registration of in-vitro diagnostic reagents.

Article 89 The charging items and the charging standards for in-vitro diagnostic reagent registration shall be determined in accordance with the relevant regulations formulated by the competent finance department and the competent pricing department of the State Council.

Article 90 The Provisions shall be effective as of October 1, 2014.

Note: In case of any difference in interpretation between the English version and the Chinese version, the Chinese version shall prevail.