SFDA State Food and Drug
Administration
Circular on Printing and Issuing the Measures for the Administration of
In-vitro Diagnosis Reagents (Interim)
Authorized by MD Dept. SFDA [2007] No. 229
The appropriate food and drug administrations (drug administrations) in provinces,
autonomous regions and municipalities directly under the central government,
The Measures for the Administration of In-vitro Diagnosis Reagents (Interim) was
approved by the State Food and Drug Administration of the People’s Republic of China on
April 3rd, 2007 and is hereby printed and issued, and shall be observed and implemented
accordingly.
State Food and Drug Administration
April 19, 2007
Measures for the Administration of In-vitro Diagnosis Reagents (Interim)
Chapter 1 General Provisions
Article 1 The Measures for the Administration of In-vitro Diagnosis Reagents (Interim) is
formulated in accordance with the Regulations on the Supervision & Administration of
Medical Devices and the Measures for the Administration of Medical Device Registration,
with a view to regulating the administration of in-vitro diagnosis reagents.
Article 2 The Measures applies to the R&D, clinical trials, registration inspection, product
registration and supervision & administration of in-vitro diagnosis reagents.
Article 3 The in-vitro diagnosis reagents mentioned in these Measures refer to the in-vitro
diagnosis reagents administered as medical devices, including the reagents, reagent
cartridges, calibrators, quality controls, etc. for in-vitro inspection of human body
specimen (various body fluids, cells, tissue specimen, etc.) in the course of disease
prevention, diagnosis, treatment monitoring, prognosis observation, health status
evaluation and inherited disease prediction, which can be used independently or in
combination with instruments, devices, equipment or systems.
The in-vitro diagnosis reagents legitimately stipulated by the state for use in blood
screening and radionuclide-labeled in-vitro diagnosis reagents do not belong to the
administration scope of the Measures.
Article 4 Registration of in-vitro diagnosis reagents refers to the approving process in
which the authorities of drug supervision and administrations implement a systematic
evaluation on the research conducted by the registration applicant as regards the safety,
effectiveness and quality controllability of the products to be put on market and its results,
and determine whether to approve such application, in accordance with legal procedures
and the application of the registration applicant.
Article 5 The State implements classified registration administration of in-vitro diagnosis
reagents.
Class I in-vitro diagnosis reagents made within territory shall be examined by drug
supervision and administration authorities having districts established therein where such
authorities reside, and medical device registration certificates shall be issued after
approval.
Class II in-vitro diagnosis reagents made within territory shall be examined by authorities
of drug supervision and administrations in provinces, autonomous regions and
municipalities directly under the central government, and medical device registration
certificates shall be issued after approval.
Class III in-vitro diagnosis reagents made within territory shall be examined by the State
Food and Drug Administration, and medical device registration certificates shall be issued
after approval.
In-vitro diagnosis reagents made abroad shall be examined by the State Food and Drug
Administration, and medical device registration certificates shall be issued after approval.
The registration of in-vitro diagnosis reagents manufactured in Taiwan, Hong Kong or
Macao shall be carried out with reference to the relevant provisions in connection with
foreign medical devices.
Article 6 The authorities of drug supervision and administrations in provinces, autonomous
regions and municipalities directly under the central government are responsible for
verification of the R&D status and production conditions of the applied products in their
own administrative areas, assessment of the quality management system of the
manufacturing enterprise, and implementation of supervision and administration for the
products put on the market.
Article 7 The applicant for the registration of in-vitro diagnosis reagents (hereinafter
referred to as the “applicant”) refers to any manufacturing enterprise that puts forward the
application for the registration of in-vitro diagnosis reagents, assumes corresponding legal
responsibilities, and holds the registration certificate after such application is approved.
Domestic applicants refer to manufacturing enterprises legitimately registered within
Chinese territory.
Foreign applicants refer to manufacturing enterprises legitimately registered outside
Chinese territory.
Foreign applicants shall carry out the registration of in-vitro diagnosis reagents through
their offices located within Chinese territory or by entrusting agencies within Chinese
territory.
Personnel who handle the issues concerning the application for the registration of in-vitro
diagnosis reagents shall have corresponding professional knowledge, and are familiar
with the laws, regulations, rules and technical requirements as regards the registration
administration of in-vitro diagnosis reagents.
Article 8 Foreign applicants shall entrust legitimate organizations within Chinese territory
as their agencies, and if the foreign applicants have set up offices within Chinese territory,
their agents shall be such offices; if the foreign applicants have no office within Chinese
territory, they shall entrust other independent legal entities as their agents. The agents
shall perform the following duties:
(I) Liaison with competent authorities and foreign applicants for application;
(II) Faithful and accurate conveying of relevant regulations and technical requirements to
the applicant;
(III) Gathering of information about unfavorable incidents related to medical devices after
being put on the market and feedback to foreign applicants, and in the meantime reporting
to China’s corresponding medical device supervision and administration departments.
Article 9 In case the applicant entrusts a registration agency to handle issues concerning
the registration of in-vitro diagnosis reagents, except for the application for changing the
agent or registration agency, other issues of application shall be concretely handled by
such registration agency.
Article 10 The quality management system of the manufacturing enterprise of in-vitro
diagnosis reagents shall comply with the requirements of Detailed Rules for the
Implementation of the Production of In-vitro Diagnosis Reagents, and foreign
manufacturing enterprise shall also conform to the requirements of quality management
system in the country or region of production.
Article 11 The manufacturing enterprise of in-vitro diagnosis reagents shall have after-sale
service ability in technical training, consultancy, etc. that matches its products applying for
registration.
Foreign manufacturing enterprises can carry out after-sale service in technical training,
consultancy, etc. through their offices that reside within Chinese territory or by entrusting
agencies within Chinese territory.
Chapter 2 Product Classification and Naming Principles
Article 12 According to the product risk degree, in-vitro diagnosis reagents are
successively classified into Class III, Class II and Class I products.
(I) Class III products:
1. Reagents related to the inspection of antigen, antibody and nucleic acid, etc. for
pathogen;
2. Reagents related to blood group and tissue typing;
3. Reagents related to the inspection of human gene;
4. Reagents related to inherited diseases;
5. Reagents related to the inspection of narcotic drugs, psychotropic drugs and toxic
drugs for medical use;
6. Reagents related to the inspection of targets sites of curative drugs;
7. Reagents related to the inspection of tumor markers;
8. Reagents related to allergy (allergen).
(II) Class II products: products not clearly defined as Class III and Class I products are
Class II products, mainly including:
1. Reagents used for protein inspection;
2. Reagents used for carbohydrate inspection;
3. Reagents used for hormone inspection;
4. Reagents used for enzymes inspection;
5. Reagents used for esters inspection;
6. Reagents used for vitamin inspection;
7. Reagents used for inorganic ion inspection;
8. Reagents used for the inspection of drugs and drug metabolites;
9. Reagents used for auto-antibody inspection;
10. Reagents used for microorganism identification and medicine sensitivity experiment;
11. Reagents used for the inspection of indexes for other physiological, biochemical and
immune functions.
(III) Class I products:
1. Microorganism culture medium (not used for microorganism identification and medicine
sensitivity experiment);
2. Products for specimen treatment, e.g. hemolytic agents, diluents, staining solutions,
etc.
Article 13 If the inspection of some Class II products, e.g. protein, carbohydrate, hormone,
enzymes, etc. is used for the monitoring of tumor diagnosis, auxiliary diagnosis and
treatment process, or used for diagnosis and auxiliary diagnosis, etc. of inherited diseases,
these products are registered and administered as Class III products. Among the reagents
for inspection drugs and drug metabolites, if the drugs belong to the scope of narcotic
drugs, psychotropic drugs and toxic drugs for medical use, they are registered and
administered as Class III products.
Article 14 For in-vitro diagnosis reagents such as calibrators and quality controls, if not
sold independently, the registration needn’t be applied for independently; if sold
independently, the registration needs to be applied for independently, and their class is
the same as those in-vitro diagnosis reagents in clinical use in the meantime. As for
multiple calibrators and quality controls, their class is the same as higher-class in-vitro
diagnosis reagents used in the meantime.
Article 15 For products only used for research, not used for clinical diagnosis, the
registration needn’t be applied for, but their instruction manuals and package labels must
indicate the words “For research only, not for clinical diagnosis”.
For special substances that do not have diagnosis functions without any modification, and
can become compositions of in-vitro diagnosis reagents only after marking or optimization,
the registration needn’t be applied for. When put on the market for sales, such substances
shall be furnished with information about their origins, compositions, titers or active units,
etc. and indicated with the words “For research only, not for clinical diagnosis” in the
meantime.
Article 16 The State Food and Drug Administration is responsible for defining the
classification of in-vitro diagnosis reagents, and making adjustment according to such
circumstances as product risk.
As for in-vitro diagnosis reagents that cannot be defined according to the above
classification principles, the registration applicant shall put forward the application for
classification definition with the State Food and Drug Administration. The application for
classification definition shall be submitted together with the general summary materials,
product instructions, and information about the classification of similar products in
domestic and foreign registration and administration.
Article 17 In-vitro diagnosis reagents applying for registration shall adopt general names in
compliance with the naming principles.
Naming principles for in-vitro diagnosis reagents: product names of in-vitro diagnosis
reagents are generally composed of three parts:
First part: name of the substance tested.
Second part: usage, e.g. diagnosis serum, diagnostic reagent cartridge, quality control,
etc.
Third part: method or principle, e.g. enzyme linked immunity method, colloidal gold
method, etc., this part shall be listed in parentheses.
If the substance for inspection have too many components or under special circumstances,
the substance can adopt the indication name related to the product or other substitute
names.
Chapter 3 Product Research and Development
Article 18 Organizations engaged in the research and development of in-vitro diagnosis
reagents shall have the personnel, site, equipment, instruments and management system
that match the project of experiment and research, use laboratory animals, reagents and
raw materials, etc. that comply with relevant requirements and provisions, and guarantee
the authenticity of all the experimental data and materials.
Article 19 The product research and development work done for applying for the
registration of in-vitro diagnosis reagents shall include: selection and preparation of main
raw materials; determination of the product manufacturing process; formulation of
registered product standards; product stability research, reference value (reference scope)
determination, product performance evaluation, etc. The applicant can either carry out
product research and development by referring to relevant technical guidance principles,
or adopt different experimental methods or technical means, but shall explain their
reasonableness.
Article 20 Product performance evaluation refers to the evaluation on the analytical
performance and clinical performance of the in-vitro diagnosis reagents.
Analytical performance mainly includes analytical sensitiveness, analytical specificity,
diagnostic scope, diagnostic accuracy, within-run imprecision, between-run imprecision,
etc.
Analytical performance mainly includes clinical sensitiveness, clinical specificity, etc.
Article 21 The registration applicant can either independently accomplish or entrust
relevant research organizations to accomplish the research and development of in-vitro
diagnosis reagents, and the evaluation of analytical performance. The registration
applicant shall provide application materials indicating the name list of entrusted items,
attached with agreement of both parties, and guarantee the authenticity of all the
experimental data and materials.
Article 22 The clinical performance evaluation of in-vitro diagnosis reagents shall be
accomplished through clinical experiments. The clinical experiments of in-vitro diagnosis
reagents shall be accomplished by the applicant before putting forward the application.
The relevant provisions in Chapter 4 of the Measures apply to the requirements on clinical
experiments.
Article 23 The State Food and Drug Administration and authorities of drug supervision and
administrations in provinces, autonomous regions and municipalities directly under the
central department carry out verification on the product research and development
situation in their administrative areas when necessary, require the applicants or research
organizations undertaking the experiments to conduct experiments repeatedly according
to the material items, methods and data for the application, and assign personnel to verify
the experiment process on the site, or entrust relevant research organizations to conduct
the experiments repeatedly.
Chapter 4 Clinical Experiment
Article 24 The clinical experiment of in-vitro diagnosis reagents (clinical validation
including comparative research with the products already put on the market) refers to the
systematic research on the clinical performance of in-vitro diagnosis reagents in
corresponding clinical environment.
Article 25 The specimens for clinical experiment shall be prepared at the workshops that
conform to the requirements of the Detailed Rules for the Implementation of the
Production of In-vitro Diagnosis Reagents, and the production process shall be in strict
compliance with the requirements of the Detailed Rules for the Implementation of the
Production of In-vitro Diagnosis Reagents.
Article 26 The applicant can either independently conduct the inspection of specimens for
clinical experiment according to the product standards formulated, or entrust other
competent inspection organizations to conduct the inspection, and only after qualifying for
the inspection can the specimens be used for clinical experiment.
Article 27 When the same registration application includes different packaging
specifications, the specimens of one packaging specification can be adopted to conduct
the clinical experiment.
Article 28 The applicants for Class III products shall choose no less than 3 (including 3)
provincial-level health & medical institutions, and the applicants for Class II products shall
choose no less than 2 (including 2) provincial-level health & medical institutions to carry
out the clinical experiment.
For special-purpose products, the clinical experiment can be conducted at such
organizations as disease control centers, specialized hospitals or inspection & quarantine
institutes and detoxification centers above the municipal level that meet the requirements.
Article 29 The organizations of clinical experiment shall have the personnel, site,
equipment, instruments and management system that match the research project, and
guarantee the authenticity of all the research data and materials.
The organizations and personnel participating in the clinical experiment shall understand
the responsibilities and obligations of the personnel of clinical experiment, and make
records of clinical experiment in a timely way, accurately and faithfully.
Article 30 The applicant shall sign a clinical experiment contract with the clinical
experiment organization, formulate and perfect the clinical experiment scheme by
referring to relevant technical guidance principles, provide specimens for clinical
experiment free of charge, and pay the expenses for clinical experiment.
Article 31 The number of cases for clinical experiment shall be determined according to
the purpose of clinical experiment, statistical requirements, and by referring to relevant
technical guidance principles. Technical guidance principles for clinical experiment are
issued separately.
For rare diseases, special diseases and other circumstances, if the applicant requests to
decrease the number of cases for clinical experiment or not to perform clinical experiment,
the applicant shall submit the materials for registration application together with the
application for decreasing the number of cases for clinical experiment or exempting the
clinical experiment, and explain the reasons in a detailed way. The technical review
organization of authorities of drug supervision and administration shall make the decision
after all-round technical review of the materials for registration application, and if clinical
experiment needs to be supplemented, shall inform the applicant in the form of
supplementary materials.
Article 32 When applying for foreign product registration, foreign clinical experiment
materials are required. The applicant shall consider at the same time many factors such
as the epidemiological background, characteristics of pathogenic microorganisms in
different countries or regions, and normal reference values (or reference scope)
applicable to crowds of different species, and carry out corresponding clinical experiments
within Chinese territory in accordance with the requirements of clinical experiment.
Article 33 After accomplishing the clinical experiment, the organizations of clinical
experiment shall respectively issue the reports of clinical experiment. The applicant or the
unit leading the clinical experiment shall summarize the results of clinical experiment and
complete the summary report of clinical experiment in accordance with relevant technical
guidance principles.
Article 34 If the organization of clinical experiment is found to have breached relevant
provisions or fail to execute the scheme of clinical experiment, the applicant shall urge the
organization to correct; if the circumstances are serious, the applicant can require the
organization to suspend or terminate the clinical experiment, and report to the
provincial-level authorities of drug supervision and administration in the locality and the
State Food and Drug Administration.
Article 35 If the applicant breaches relevant provisions or requests to change the data,
conclusions of the experiment, the organizations and personnel participating in the clinical
experiment shall report to the provincial-level authorities of drug supervision and
administration in the locality and the State Food and Drug Administration.
Article 36 The State Food and Drug Administration and authorities of drug supervision and
administrations in provinces, autonomous regions and municipalities directly under the
central government need to carry out supervision and inspection on the implementation
status of the clinical experiment.
Chapter 5 Assessment on Quality Management System of Manufacturing enterprise
Article 37 The manufacturing enterprise of in-vitro diagnosis reagents shall establish
corresponding quality management system, form files and records, implement them and
maintain effective operation.
Article 38 The assessment on quality management system of manufacturing enterprise
refers to the process of all-round assessment conducted by the authorities of drug
supervision and administration on the circumstances of establishment and fundamental
operation of the quality management system of the manufacturing enterprise.
Article 39 Before applying for the registration of Class II and Class III products and
re-registration, the applicant shall pass the assessment on quality management system by
the authorities of drug supervision and administration. For the first registration application,
the assessment on quality management system also includes onsite verification of the
research and development situation of the products applying for the registration. In case
of applying for the registration of Class I products, the applicant shall independently
organize the verification of the quality management system.
Article 40 The concrete requirements for the assessment on the quality management
system of the manufacturing enterprise shall be separately stipulated by the State Food
and Drug Administration.
Article 6 Product Standards and Registration Inspection
Article 41 The product standards for in-vitro diagnosis reagents refer to technical
requirements on standard substances, quality indexes and production process, etc.,
stipulated for ensuring the product quality of in-vitro diagnosis reagents, including national
standards, industrial standards and registered product standards.
The standard substances of in-vitro diagnosis reagents refer to the substances for the
inspection of in-vitro diagnosis reagents, which have determined characteristic quantity
values and are used for evaluating diagnostic methods, including standards and
references.
Article 42 The applicant shall formulate the standards for the applicant products under the
precondition of stable quality of raw materials and stable production process, in
accordance with the results of product research and development, clinical experiment,
etc., and by referring to relevant documents, national standards and industrial standards,
etc. The product standards formulated by the applicant shall not be lower than national
standards or industrial standards.
Article 43 The product standards formulated by the applicant will become registered
product standards after being approved by the authorities of drug supervision and
administration and being registered, and the manufacturing enterprises must execute
such registered product standards.
Article 44 The registration inspection refers the process in which the medical device
inspection organization (hereinafter referred to as “inspection organization”), recognized
by the State Food and Drug Administration and having corresponding inspection scope,
puts forward suggestions on the science and reasonableness of the standards or
references adopted for the product standards submitted by the applicant, in terms of the
items and indexes, in accordance with relevant research data, standards of domestic and
foreign similar products and relevant national requirements, and carry out the inspection
of specimens submitted for inspection, and issue test reports.
Article 45 As for the application for the first registration of in-vitro diagnosis reagents,
registration inspection is generally not required for Class I products; registration inspection
shall be carried out for Class II and Class III products; registration inspection with
specimens of 3 consecutive production batches shall be carried out for Class III products.
The specimens for registration inspection of domestic manufacturing enterprises are
drawn out on site after being qualified for the assessment on the quality management
system of the manufacturing enterprise by the authorities of drug supervision and
administration. The specimens for registration inspection of domestic manufacturing
enterprises are drawn out by the applicant independently.
Article 46 When carrying out the registration inspection, the applicant shall submit written
application to the inspection organization, and provide the necessary relevant technical
materials, specimens and standards or references.
When the same registration application involves different packaging specifications, the
registration inspection can be carried out for products of one packaging specification only.
Article 47 The medical device inspection organizations shall carry out the work of
registration inspection within the authorized inspection scope, and shall issue test report
within specified working time period.
For products not listed in the authorized inspection scope of the inspection organization,
the State Food and Drug Administration shall designate the inspection organization with
the ability to undertake the inspection to carry out the inspection.
Chapter 7 Registration Application and Approval
Article 48 The registration application mentioned in this chapter refers to the registration
application put forward by the applicant for its manufactured in-vitro diagnosis reagents
not put on the market within Chinese territory, i.e. the first registration application.
Article 49 According to the classification principles of in-vitro diagnosis reagents, in case
the domestic applicant plans to apply for the registration of Class III and Class II products,
the applicant shall put forward the application to the corresponding authorities of drug
supervision and administration after accomplishing the product research and development,
clinical experiment, registration inspection and passing the assessment on the quality
management system, and submit materials for registration application according to the
requirements in Appendix I of these Measures.
In case of applying for the registration of Class I products, the applicant shall put forward
the application to the corresponding authorities of drug supervision and administration
after accomplishing the research and development work, and submit the materials for
registration application according to the requirements in Appendix 1 of these Measures.
Article 50 According to the classification principles of in-vitro diagnosis reagents, in case
the foreign applicant plans to apply for the registration of Class III and Class II products,
the applicant can put forward the application for product registration to the State Food and
Drug Administration according to these Measures after accomplishing the clinical
experiment and registration inspection for the products. In case of applying for the
registration of Class I products, the applicant shall put forward the application for product
registration to the State Food and Drug Administration according to these Measures.
In case of applying for the registration of overseas products, such products shall be
granted overseas medical device marketing approval; for overseas products not required
to be granted medical device marketing approval, relevant documents proving that such
products are not registered and administered as medical devices and that such products
are legally marketed in the country of origin shall be provided.
Article 51 The registration units of in-vitro diagnosis reagents shall be single reagents or
single reagent cartridges, and one registration unit can include different packaging
specifications.
Article 52 The materials for registration application shall be written in Chinese. The
application materials translated according to materials in foreign languages shall be
provided with original text in the meantime. The materials for registration application shall
be complete, standardized, and the data must be authentic and reliable. When the
documents not publicly published are cited, the documents proving that the owner of
materials allows the usage shall be provided.
The applicant shall take full responsibility for the authenticity of the materials for
registration application.
Article 53 The administrative acceptance organization of the authorities of drug
supervision and administration shall carry out the form examination for materials for
registration application. If the materials meet the acceptance requirements, the
organization shall accept the materials and issue the acceptance notice; if the materials
fail to meet the requirements, the organization shall not accept the materials, and inform
the applicant in writing.
Article 54 The technical review organization of the authorities of drug supervision and
administration shall carry out all-round technical review on the materials for registration
application, and can recall the original research materials when necessary. In case expert
consultancy or hearing is required during the review, the technical review organization
shall inform the applicant in writing. The time required for consulting with experts or
conducting the hearing is not calculated into the time period of the review.
Article 55 When the technical review organization conducts technical review on the
materials for registration application, if the applicant is required to supplement the
materials, the technical review organization shall issue the written notice of supplementing
materials only one time. The applicant shall submit supplementary materials only one time
within 60 working days according to the requirements of the notice of supplementing
materials. The time required for the applicant to supplement the materials is not calculated
into the time period of review.
Article 56 If the applicant has objection to the content of the notice of supplementing the
materials, the applicant can put forward the written suggestions to corresponding
technical review organization, explain the reasons and provide corresponding materials of
technical support.
Article 57 For the products examined as conforming to provisions and approved for
registration, the corresponding authorities of drug supervision and administration shall
issue the Medical Device Registration Certificate within specified time period. The
registered product standards and product instructions shall be approved by corresponding
authorities of drug supervision and administration according to the application materials of
the applicant, and sent to the applicant in the form of appendix.
The Medical Device Registration Certificate remains effective for 4 years.
Article 58 If the products are deemed as not conforming to the provisions after
examination, the authorities of drug supervision and administration shall make the
decision not to register and explain the reasons, notify the applicant in writing within
stipulated time period, and in the meantime inform the applicant that the applicant enjoys
the right of reexamination and applying for administrative reconsideration or lodging
administrative litigation.
Article 59 According to the provisions of Article 23 in these Measures, if repeated
experiment is required but the applicant refuses, and the authorities of drug supervision
and administration orders the applicant to correct but the applicant refuses to correct, the
registration application for this product will not be accepted any longer; for products
already accepted, the authorities of drug supervision and administration will make the
decision not to register.
Article 60 The authorities of drug supervision and administration shall publicize the
approving process and results, and shall declare to the society and conduct the hearing as
regards important issues of permission involving public interests.
Article 61 After in-vitro diagnosis reagents are put on the market, their product standards
and instructions must be consistent with the contents approved by the authorities of drug
supervision and administration.
The applicant shall trace the safety and effectiveness of the products put on the market,
and shall put forward timely application for modifying the product standards or instructions
when necessary. The applicant shall take full responsibility for the correctness and
accuracy of the product standards and instructions.
Chapter 8 Change Application and Approval
Article 62 After the registration application of in-vitro diagnosis reagents is approved, in
case of change of the issues concerning registration and permission, the applicant shall
put forward the change application to corresponding authorities of drug supervision and
administration according to the provisions in Article 5 of these Measures. In case of
change of registration issues, the applicant shall put forward the change application within
30 days since the change takes place; in case of change of permission issues, the
applicant shall put forward the change application and implement the change after the
change application is approved. When handling the issues concerning change
applications, the applicant shall submit the application materials according to
corresponding requirements in Article 2 of these Measures.
Article 63 The change of registration issues includes the following circumstances:
(I) Change of the name of manufacturing enterprise;
(II) Change of the registered address of manufacturing enterprise;
(III) Change of registration agency;
(IV) Change of agent.
Article 64 The change of permission issues includes the following circumstances:
(I) Change of main materials such as antigen and antibody in the course of production;
(II) Change of inspection conditions and reference values (or reference scope), etc.;
(III) Change of the items, indexes, experimental methods, etc. set in the registered
product standards;
(IV) Change of the contents in product instructions, e.g. change or addition of packaging
specifications, addition of applicable models, etc.;
(V) Change of product storage conditions and/or product warranty period;
(VI) Increase of the clinical application scope, e.g. increase of clinical indications, increase
of the types of specimens for clinical diagnosis, etc.;
(VII) Change of production address (material change of production site);
(VIII) Other changes that could influence the safety and effectiveness of products.
Article 65 In case of applying for the change of production address (material change of
production site), the applicant shall apply for assessment on the quality management
system of the new production site. When the quality management system meets the
requirements after assessment, the applicant shall submit the application materials
according to corresponding requirements in Article 2 of these Measures.
Article 66 The following circumstances do not belong to the issues of change application
as stipulated in this chapter, and shall be handled as the first registration application:
(I) Change of basic reaction principles of the products already put on the market;
(II) Change of analytical sensitiveness of the products already put on the market, which
also has new significance of clinical diagnosis.
Article 67 If the change of permission issues takes place within 6 months before the
registration certificate expires, the applicant can put forward the application together with
the re-registration.
Article 68 The authorities of drug supervision and administration shall carry out the
examination of the issues of change application, and approve the change application in
the form of Approval of Change Application for In-vitro Diagnosis Reagents. The effective
period of the Approval of Change Application for In-vitro Diagnosis Reagents is the same
as the original registration certificate, and the applicant shall apply for re-registration when
the effective period expires.
Article 69 The relevant provisions in Chapter 7 of these Measures apply to the accepting
and approving procedures for the change application.
Chapter 9 Application and Approval of Re-registration
Article 70 The re-registration of in-vitro diagnosis reagents refers to the approving process
implemented for continuing the production and sales of the products after the product
registration certificate expires.
Article 71 The applicant shall put forward the re-registration application to the
corresponding authorities of drug supervision and administration according to the
provisions in Article 5 of these Measures within 6 months before the product registration
certificate expires, and submit the application materials according to corresponding
requirements in Appendix 3 of these Measures.
In case the applicant puts forward the re-registration application and issues of change
application at the same time, the applicant shall make explanation and submit the
application materials according to the provisions concerning re-registration application
and change application.
Article 72 For the product re-registration, if the product has no change whatsoever
compared to the approved contents of the original registration, the registration inspection
is generally not required.
Article 73 If the applicant fails to put forward the re-registration application before the
registration certificate expires but needs to continue the production and sales of the
products, the product registration shall be handled according to the procedures and
requirements for the first registration application.
Article 74 The re-registration will not be accepted under any one of the following
circumstances:
(I) Failure to comply with the requirements put forward by the authorities of drug
supervision and administration when approving the marketing of the products;
(II) Failure to fulfill the responsibilities for product quality, failure to report serious adverse
events, or failure to effectively deal with the serious consequences caused by the
products;
(III) The quality management system of manufacturing enterprise fails to comply with the
requirements;
(IV) It is deemed that the safety and effectiveness of the products cannot be guaranteed
after re-evaluation of the authorities of drug supervision and administration;
(V) Other circumstances not complying with the provisions of the authorities of drug
supervision and administration.
Article 75 The relevant provisions in Chapter 7 of these Measures apply to the accepting
and approving procedures for the re-registration application.
Chapter 10 Withdrawal, Return and Review of Registration Application
Article 76 For the accepted registration application, the applicant can apply for the
withdrawal of the registration application with the corresponding authorities of drug
supervision and administration at any stage of the approving procedure. In case the
registration application is actively withdrawn, the registration can be applied for again.
Article 77 If the accepted registration application comes under any one of the following
circumstances, the authorities of drug supervision and administration shall return the
application, explain the reasons in writing and inform that the applicant enjoys the right of
review and administrative reconsideration.
(I) The applicant fails to submit the supplementary materials within the specified time
period;
(II) The products applying for registration do not belong to the scope stipulated by these
Measures;
(III) Other circumstances requiring the return of application.
Article 78 If the applicant has any objection to the decision made by the authorities of drug
supervision and administration to return the application or not to approve the registration,
the applicant can put forward the review application with the corresponding authorities of
drug supervision and administration within 10 working days since the day of receiving the
notice that the application is returned or the registration is not approved.
The contents of review application are limited to the original application issues and the
original application materials.
Article 79 After receiving the review application, the authorities of drug supervision and
administration shall make the review decision within the specified time period, and notify
the applicant in writing. If the original decision is maintained, the authorities of drug
supervision and administration will not accept the review application put forward again by
the applicant.
Article 80 If the applicant has any objection to the decision made by the authorities of drug
supervision and administration to return the application or not to approve the registration,
and has applied for administrative reconsideration or lodged administrative litigation, the
authorities of drug supervision and administration will not accept the review application put
forward by the applicant,
Chapter 11 Supervision and Administration
Article 81 Any dispute of patent right, which arises during the examination of the
registration application for in-vitro diagnosis reagents or after the application is approved,
can either be resolved by the parties concerned through friendly consultation, or resolved
by departments managing the patent work or people’s court in accordance with the
provisions of relevant laws and regulations.
Article 82 In case of circumstances stipulated in Article 69 of the Administrative License
Law of the People’s Republic of China, the authorities of drug supervision and
administration can withdraw the approving documents for relevant products according to
the request of interested person or according to its duties.
Article 83 After the registration of in-vitro diagnosis reagents is approved, if the quality
management system of the manufacturing enterprise for in-vitro diagnosis reagents is not
effectively operating, the provincial-level authorities of drug supervision and administration
of the region where the enterprise resides shall order the enterprise to correct or rectify
within specified period according to the seriousness degree of the case.
Article 84 If the agent entrusted by the overseas applicant fails to perform corresponding
responsibilities, refuses to report serious adverse events of the products, or fails to
effectively deal with the serious consequences caused by the products, the authorities of
drug supervision and administration shall punish the agent according to relevant laws and
regulations, and release the product risk information to the society.
Article 85 Under any one of the following circumstances, the authorities of drug
supervision and administration will cancel the documents approving the product
registration.
(I) The documents approving the product registration expired but not renewed;
(II) Termination by legal entity or other organizations in accordance with the law;
(III) The documents approving the product registration are cancelled, withdrawn, or
revoked according to the law;
(IV) Other circumstances under which the administrative license shall be canceled
according to relevant laws and regulations.
Article 86 If the Medical Device Manufacturing enterprise License of the manufacturing
enterprise is cancelled, the product registration certificate held by the enterprise will be
annulled automatically, and the authorities of drug supervision and administration will
cancel its documents approving the product registration, and make public.
Article 87 Any breach of other relevant provisions in these Measures will be punished by
the authorities of drug supervision and administration in accordance with the Regulations
for the Supervision and Administration of Medical Devices and the Provision on Medical
Device Registration.
Chapter 12 Supplementary Provisions A
Article 88 The product registration No. in the registration certificate is arranged as follows:
×（×）1（Food）YJX（×2）××××3 No.×4××5××××6. Among them:
×1 is the abbreviation for the location of the authority in charge of registration examination
and approval:
The word of “Guo” is the abbreviation for a Class Ⅲ medical device manufactured
domestically or abroad, as well as those from Taiwan, Hong Kong and Macao;
The abbreviations of provinces, autonomous regions or municipalities directly under the
central government where authorities in charge of registration examination and approval
reside for Class II medical device made within the territory;
And the combination of abbreviations for provinces, autonomous regions, municipalities
directly under the central government where authorities responsible for the registration
and approval of a ClassⅠmedical device and abbreviations for city-level administrative
areas having districts established therein where such authorities reside shall be
expressed as ××1 (In cases where there is no corresponding city-level administrative
areas without districts divided therein, the abbreviation shall only be used for provinces,
autonomous regions or municipalities directly under the central government);
×2 is the type of registration (Zhun, Jin and Xu): The word of “Zhun” shall apply to a
domestic medical device; The word of “Jin” shall apply to a foreign medical device; The
word of “Xu” shall be applicable to medical devices from Taiwan, Hong Kong or Macao;
××××3 is the year in which the registration is approved;
×4 is the product class classified for administration convenience;
××5 is the code for a specific variety of product (that for in-vitro diagnosis reagents is: 40);
××××6 is the serial number of registration.
Article 89 The time period for examination of in-vitro diagnosis reagents by the authorities
of drug supervision and administration shall be specified according to the provisions
concerning the time period of examination in Provision on Medical Device Registration.
Article 90 The variety scope of the in-vitro diagnosis reagents legitimately stipulated by the
state for use in blood screening, and the reagents related to the inspection of narcotic
drugs, psychotropic drugs and toxic drugs for medical use, both of which are mentioned in
these Measures, shall comply with relevant provisions of the state.
Article 91: The right of interpretation of these Measures shall be vested with the State
Food and Drug Administration of the People’s Republic of China.
Article 92 These Measures shall become effective as of June 1, 2007.