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In order to strengthen the supervision and guidance of the registration of medical device products and further improve the quality of registration and review, the State Food and Drug Administration has formulated a hepatitis C virus RNA testing reagent

Guidelines for the technical review of HCV RNA assay reagents

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In order to strengthen the supervision and guidance of the registration of medical device products and further improve the quality of registration and review, the State Food and Drug Administration has formulated a hepatitis C virus RNA testing reagent

This guideline is intended to guide registration applicants in the preparation and writing of registration information for hepatitis C virus (HCV) ribonucleic acid (RNA) assay reagents, and also to review registration reports for technical review departments Information provided for reference.

This guideline is a general requirement for HCV ribonucleic acid assay reagents. Applicants should determine whether the content is applicable based on the specific characteristics of the product. If it is not applicable, the reason and corresponding scientific basis shall be specified, and the specific product Features enrich and refine the content of registration application materials. If the applicant believes that it is necessary to add research content that is not included in this guideline, he can supplement it by himself.

This Guiding Principle is a guidance document for applicants and reviewers. It does not involve administrative matters such as registration approval, nor is it enforced as a regulation. If other methods can meet the requirements of the regulation, it can also be used, but detailed research should be provided. Information and verification information. This guideline should be used in compliance with relevant regulations.

This guideline is formulated under the current regulations, standard system and current cognitive level. With the continuous improvement of regulations and standards and the continuous development of science and technology, the relevant content of this guideline will also be adjusted in due course.

Chinese name

Guidelines for the technical review of HCV RNA assay reagents

Posting time

November 16, 2015

Issuing authority

State Food and Drug Administration

Issue number

No. 93 of 2015

(1) Clinical background

Hepatitis C is a blood-borne disease. Chronic infection with hepatitis C virus can lead to chronic inflammatory necrosis and fibrosis of the liver. Some patients can develop cirrhosis or even hepatocellular carcinoma, which is extremely harmful to the health and life of patients. Has become a serious social and public health problem.

(II) Distribution of hepatitis C infection

Hepatitis C is a global epidemic and is the leading cause of end-stage liver disease in countries such as Europe, America and Japan. According to World Health Organization statistics (2014), approximately 185 million people worldwide are infected with HCV, of which approximately 150 million are chronic infections, 350,000 to 500,000 die each year from complications of hepatitis C, and approximately 3 to 4 million new infections occur each year. example.
HCV1b and 2a genotypes are more common in China, of which 1b is the main type; some regions have reported 1a, 2b, and 3b types; type 6 is mainly found in Hong Kong and Macau, and this genotype can also be seen in southern border provinces.

(Three) characteristics of HCV

HCV belongs to the family Flaviviridae. Its genome is a single-stranded positive-stranded RNA, which is susceptible to mutation. It can be divided into 6 genotypes and more than 50 different subtypes. According to internationally accepted methods, HCV genotypes are expressed in Arabic numerals. The lowercase English letters indicate the gene subtype (such as 1a, 2b, 3c, etc.). Genotype 1 is globally distributed and accounts for more than 70% of all HCV infections.

The HCV genome contains an open reading frame (ORF), encoding more than 10 structural and non-structural (NS) proteins. NS3 protein is a multifunctional protein with protease activity at the amino terminus and helicase / triphosphate core at the carboxyl terminus. Glycosidase activity; NS5B protein is an RNA-dependent RNA polymerase, necessary for HCV replication, and an important target for antiviral therapy. It has nucleotide transferase activity at the end, but cannot correct mismatches due to the lack of corrective function of RNase After multiple replications, it can easily lead to a variety of HCV mutations.

(IV) Quantitative detection of HCVRNA

HCVRNA quantitative detection methods include real-time fluorescent reverse transcription polymerase chain reaction (qRT-polymerasechain reaction, qRT-PCR), branched DNA (bDNA), and so on. The HCVRNA assay reagents referred to in this guideline refer to the nucleic acid detection technology using the qRT-PCR method. The HCV gene sequence is used as the detection target for the in vitro quantitative detection of HCVRNA in human serum, plasma and other human samples. Evidence of HCV infection and observational indicators of antiviral efficacy evaluation.

Other similar nucleic acid quantitative detection methods can refer to this guideline, but the specific content should be determined according to the characteristics of the product. If it is not applicable, another technical requirement or evaluation method that meets its own methodological characteristics should be selected. This guideline applies to products undergoing first registration filings and related licensing changes.

This guideline does not apply to HCVRNA detection reagents for blood source screening applications that are administered in accordance with medicines.

(I) Summary data

The review materials mainly include the intended use of the product, the product description, the description of the biosafety, the summary and evaluation of the main research results of the product, and other contents. Among them, the other includes the situation of similar products approved for marketing at home and abroad. It should focus on methodology And detection limits, etc., indicate the main differences between the product to be declared and the similar products that have been approved on the market. It shall comply with the relevant provisions of the "Administrative Measures for the Registration of In Vitro Diagnostic Reagents" (Order of the State Food and Drug Administration No. 5) and the "Requirements and Instructions for the Declaration and Application of In Vitro Diagnostic Reagent Registration" (State Food and Drug Administration Announcement No. 44 of 2014) Claim. ^[1]

Accuracy: The degree of agreement between a measured value and an acceptable reference value.

Precision: The degree of consistency between independent test results under specified conditions. The degree of precision is expressed in a numerical form of the measurement imprecision obtained by statistical methods, such as standard deviation (SD) and coefficient of variation (CV).

Linearity: The ability of a given measurement result to be proportional to the value of the object actually present in the sample within a given measurement range. Linearity is a property that describes the measurement indication or measurement result of a measurement system in relation to the value of the sample in accordance with a straight line.

Analytical specificity: The ability of a measurement program to measure only the object being measured. Analytical specificity is used to describe the ability of a test procedure to measure only the measured object in the presence of other substances in the sample. It is usually described as a list of potential interferences that are evaluated, and gives an analysis of the degree of interference at a specific medically relevant concentration level (potential interferences include interferences and cross-reactants). ^[1]