2. Regulatory Pre-evaluation of In Vitro Diagnostics

 

Chinese agent

 

For foreign manufacturer without Chinese entity, a legal representative named Chinese agent is needed. He should act as liaison between authority and manufacturer in term of registration and post market activities.

 

Determine classification of IVD

 

There are three classification of IVD in China:

Class I

such as hemolytic reagents, diluents, staining solutions, nucleic acid extraction reagents, buffer, substrate solution, enhancement solution

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Class II

1. Reagents for protein detection;

2. Reagents for sugar detection;

3. Reagents for hormone detection;

4. Reagents for enzyme detection;

5. Reagents for ester detection;

6. Reagents for vitamin testing;

7. Reagents for inorganic ion detection;

8. Reagents for detection of drugs and drug metabolites;

9. Reagents for autoantibody detection;

10. Reagents used for microbial identification or drug susceptibility testing, as well as cell culture media used for cell proliferation and culture, which have the functions of selecting, inducing, and differentiating cells, and the cultured cells are used for in vitro diagnosis;

11. Reagents for allergy (allergen) detection;

12. Reagents used for the detection of other physiological, biochemical or immune function indicators.

 

Class III

1. Reagents related to the detection of pathogenic pathogen antigens, antibodies, and nucleic acids;

2. Reagents related to blood type and tissue matching;

3. Reagents related to human genetic testing;

4. Reagents related to genetic disease detection;

5. Reagents related to the detection of narcotic drugs, psychotropic drugs, and medical toxic drugs;

6. Reagents related to detection of therapeutic drug action targets and companion diagnostic reagents;

 

The key to determine IVDs classification in China is intended use matching “In vitro diagnostic reagent classification catalog”. There are mainly 20 IVD groups.

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3. Important registration steps

 

Product technical requirement and Type testing

 

Product technical requirement (PTR) is a document submitted to testing institutes by manufacturer. As described in Chinese certificate it is a characteristic part of product indicating all key specifications and testing methods derived from Chinese standards whereby the testing institutes check own testing capability and accept the application of type testing by manufacturer.

 

Type testing is unique Chinese, it is also called in-country testing or product/sample testing.

 

Type testing applies to class II and III IVD. The final testing report is one of the important documents among submission dossiers. The revised PTR with functional specifications will be reviewed by authority and issued as annex with stamp together with product certificate after product approval.

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Technical documentation in predetermined table of content

 

The structure and requirements of Chinese technical documentation of IVD are transparent clear in Chna. The electronic technical documentation is structured (herby only to second level of chapter):

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1. Administration information 1.1 Application form 1.2 List of terms and abbreviations 1.3 List of products 1.4 Related documents 1.5 Contact information and communication records with regulatory agencies before application 1.6 Declaration of conformity

 

2. Summary material 2.1 Table of contents 2.2 Overview 2.3 Product description 2.4 Intended use 2.5 Application marketing history 2.6 Other contents that need to be explained

 

3. Non-clinical data 3.1 Table of contents 3.2 Product risk management data 3.3 List of basic principles for safety and performance of in vitro diagnostic reagents 3.4 Product technical requirements and inspection reports 3.5 Analytical performance evaluation data 3.6 Product stability study 3.7 Positive judgment value or reference interval 3.8 Other data

 

4. Clinical evaluation data 4.1 Table of contents 4.2 Clinical evaluation data

 

5. Instruction for use and label 5.1 Chapter table of contents 5.2 Product label 5.3 Instruction for use

 

6. Quality management system procedures 6.1 Overview 6.2 Table of contents 6.3 Regulatory information 6.4 Quality management system procedures 6.5 Management responsibility procedures 6.6 Resource management procedures 6.7 Product realization procedures

6.8 Quality management system measurement, analysis and improvement procedures 6.9 Other quality system procedure information 6.10 Quality management system verification information

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4. Post-market activities of In Vitro Diagnostics in China

 

Besides following vigilance in Chinese regulation, manufacturer has not only submit Periodic risk evaluation - and quality management annual report, but also control product change in term of design control.

 

Periodic risk evaluation report and quality management annual report

 

Periodic risk evaluation report is quasi Chinese Periodic Safety Update Report. It is annually to submit in the first 5 years Chinese lifecycle after approval.

 

The authority provides a relative clear template for manufacturers.

 

It contains worldwide marketing history, vigilance summary, literature evaluation and risk analysis related to adverse effects, adverse events and recalls.

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The quality management annual report is one report per one Chinese agent for approved products.

So there are 8 chaptels for overseas manufacturer in main template and 8 annexes:

 

• Basic info

• Change assessment

• Post market surveillance

• Adverse event and PRER

• Sample inspection

• Centralized procurement

• Punishment in China

• Internal audit and management review

 

When to change registration

 

We want to limit the change registration among significant design change. These are in regulation mentioned significant changes:

 

• Design, raw materials, production process, scope of application and method of use

• Product name, packaging specification, main component, intended use, technical requirements of the product, product specification, production address

 

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